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4.
Skinmed ; 22(2): 138-143, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39090000

RESUMEN

Libtayo® (cemiplimab-rwlc) injection for intravenous use was recently approved by the US Food and Drug Administration (FDA) for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC), both being the advanced stages of BCC. In the past, it was approved by the FDA for the treatment of metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC), both being the advanced stages of CSCC. Cemiplimab is a monoclonal antibody that works by blocking the programmed death-1 pathway. In two open-label, single-arm, phase 2 studies, cemiplimab was investigated for the treatment of advanced stages of BCC (study 1620, NCT03132636) and advanced stages of CSCC (study 1540, NCT02760498). The primary endpoint was objec-tive response rate (ORR) per independent central review. In the study 1620, both mBCC and laBCC received cemiplimab 350 mg every 3 weeks. ORR was 21% (6/28) and 31% (26/84) in the mBCC and laBCC groups, respectively. In the study 1520, mCSCC was divided into two groups: one receiving cemiplimab 350 mg every 3 weeks (Q3W) and another receiving 3-mg/kg cemiplimab every 2 weeks (Q2W); the third group, laCSCC, received cemiplimab 3 mg/kg every 2 weeks. ORR was 41% (23/56) in the Q3W group, 49% (29/59) in the Q2W group, and 44% (34/78) in the laCSCC group. An acceptable safety profile and antitumor activity was discovered in patients treated with cemiplimab. The recommended dosage for cemiplimab to treat advanced stages of BCC and CSCC is 350 mg every 3 weeks administered intravenously over 30 min.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma Basocelular/tratamiento farmacológico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Inyecciones Intravenosas , Femenino , Masculino , Persona de Mediana Edad
5.
J Cutan Pathol ; 51(9): 714-723, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39091243

RESUMEN

BACKGROUND: Nail squamous cell carcinoma (NSCC) is the most frequent ungual malignant tumor, but its incidence remains low. The histopathological description is sparse. We aim to characterize NSCC histopathological aspects, search for a correlation with clinical subtypes, and investigate immunohistochemistry expression of p16, p53, and Ki67. METHODS: This retrospective study collected NSCC diagnosed in our dermatology department between 2007 and 2021. The histopathological features were correlated with the clinical signs and immunohistochemistry. RESULTS: A total of 48 patients were included, and immunohistochemistry was available for 36 of them. Two histopathological patterns became prominent: a blue-basaloid type characterized by koilocytosis (p < 0.001), and a pink-keratinizing type. Mean ages were similar when comparing basaloid and periungual versus keratinizing and subungual (p < 0.001). p16 was positive in 31 of 36 cases: 18 basaloid and 13 keratinizing (p = 0.167). p53 and Ki67 were all abnormal. CONCLUSIONS: Our study described two histopathological NSCC subtypes and associated them with the two clinical subtypes: the blue-basaloid type, HPV-induced, in situ, of periungual localization in younger males; and the pink-keratinizing type, non-HPV-induced, invasive, of subungual site, in elderly. Immunohistochemistry was not contributing on its own, but p16 positivity associated with basaloid histopathological profile helps support HPV etiology.


Asunto(s)
Carcinoma de Células Escamosas , Inmunohistoquímica , Antígeno Ki-67 , Enfermedades de la Uña , Neoplasias Cutáneas , Humanos , Masculino , Femenino , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Persona de Mediana Edad , Estudios Retrospectivos , Inmunohistoquímica/métodos , Anciano , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Enfermedades de la Uña/patología , Enfermedades de la Uña/metabolismo , Adulto , Anciano de 80 o más Años , Antígeno Ki-67/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Uñas/patología , Uñas/metabolismo , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis
6.
BMC Cancer ; 24(1): 944, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095743

RESUMEN

BACKGROUNDS: Currently, family with sequence similarity 65 member A (FAM65A) is reported as a pivotal regulator in various cancers. However, the effect of FAM65A in lung squamous cell carcinoma (LSCC) is still unclear, the prime objective of this research is to explore the role of FAM65A in LSCC. METHODS: Gene expression data and correlated clinical information were downloaded from the public database and the expression of FAM65A was detected. The expression of FAM65A was also detected in our collected clinical samples and LSCC cell lines. Survival package of R language was used to determine the survival significance of FAM65A. Proteins expression level was determined via western blot assay. Cell function experiments and in vivo experiments were performed to explore the effect of FAM65A on LSCC cell biological behaviors. RESULTS: FAM65A expression was significantly increased in LSCC clinical samples and cell lines. High FAM65A expression predicted poor prognosis in LSCC patients. After silencing FAM65A, the ability of LSCC cell proliferation, invasion and migration was decreased, and LSCC cell cycle was blocked. Moreover, in vivo experiments revealed that silencing FAM65A could inhibit LSCC cell proliferation. CONCLUSIONS: High FAM65A expression could enhance proliferative, invasive and migratory abilities of LSCC. FAM65A might be a novel biomarker of LSCC.


Asunto(s)
Carcinoma de Células Escamosas , Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidad , Proliferación Celular/genética , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Ratones , Línea Celular Tumoral , Masculino , Movimiento Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Progresión de la Enfermedad , Pronóstico , Persona de Mediana Edad , Ratones Desnudos , Invasividad Neoplásica
7.
BMC Cancer ; 24(1): 946, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095812

RESUMEN

BACKGROUND: Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer-related death in men in Algeria. Little is known about the characteristics of lung cancer in Algeria. This study aimed to determine the clinicopathological characteristics and prognosis of non-small cell lung cancer (NSCLC) patients in Algeria. METHODS: This retrospective study was performed on 269 pathologically confirmed cases of NSCLC at the Benbadis University Hospital of Constantine (2015-2023). Of these, 95 patients were included in the survival analysis. The clinicopathological and outcome data were investigated based on the patients' medical records. RESULTS: This study showed male predominance with sex ratio of 5.7, with a mean age of 61.8 years. Histologically, 67.3% of cases had adenocarcinoma (ADC) and 22.7% squamous cell carcinoma (SCC). ADC and SCC occurred more frequently in female (p = 0.02) and male (p = 0.003) patients, respectively. Smoking was estimated at 82.2% in men. Over 28% were non-smokers, of which 50.7% were women, and presented at younger age (p = 0.04). Most of our patients (75.5%) have an advanced stage at diagnosis. Around 70% of patients underwent chemotherapy (CT) as first-line treatment, with medians diagnostic and treatment delays of 4 and 1 months, respectively. The median overall survival (mOS) was estimated at 10.3 and 6.7 months in I-III and IV stages, respectively. Other factors that negatively impact OS were age > 65 years (p = 0.01), and the presence of symptoms (p = 0.005) and comorbidity (p = 0.004) in stage IV, and delayed treatment (p = 0.03) and receiving CT alone (p = 0.03) in stages I-III cases. Medians progression free survival (mPFS) in stage IV, III, and II patients were 4.1, 5.2, and 8.3 months, respectively, and negatively affected by the comorbidity (stage IV, p = 0.03) and receiving CT alone (stages II-III, p = 0.03). CONCLUSIONS: NSCLC presents at an early age and advanced stage in Algerian patients. ADC is the most frequent histological subtype and smoking remains the most important risk factor in men. Furthermore, the prognostic factors affecting survival are stage, age, comorbidity, symptoms, and treatment. Thus, tobacco control, early detection program, and access to novel therapies may be the best strategies to reduce NSCLC morbidity and mortality.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Masculino , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/epidemiología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Femenino , Persona de Mediana Edad , Argelia/epidemiología , Estudios Retrospectivos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/terapia , Pronóstico , Anciano , Adulto , Estadificación de Neoplasias , Anciano de 80 o más Años , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/terapia , Análisis de Supervivencia
8.
Medicine (Baltimore) ; 103(31): e39070, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39093764

RESUMEN

RATIONALE: To investigate T lymphoma invasion and metastasis inducing factor 2 (Tiam2) protein for expression in esophageal carcinoma and relationship with clinical features among cases with tumors. PATIENT CONCERNS: In primary esophageal cancer patients, surgical resection of tumor tissue was performed in 65 cases and adjacent normal esophageal tissue in 20 cases. DIAGNOSES: Primary esophageal carcinoma (57 cases squamous cell carcinoma, 8 cases adenosquamous carcinoma). INTERVENTIONS: The expression level of Tiam2 protein in esophageal carcinoma tissues and normal esophageal tissues by SP immunohistochemical method. The expression intensity was quantitatively analyzed by using Image-pro plus software for image analysis, while SPSS26.0 software was used for a statistical analysis on the data. OUTCOMES: Tiam2 was highly expressed in esophageal squamous cell carcinoma and adenosquamous cell carcinoma, but low expressed in normal esophageal tissue. The expression level of Tiam2 protein was not correlated with gender and age of patients (P > .05), but was correlated with lymph node metastasis of esophageal carcinoma, TNM stage and differentiation degree of esophageal squamous cell carcinoma (P < .05). Tiam2 was positively correlated with Tiam1 for protein expression in esophageal carcinoma (r = .704, P < .001). LESSONS: The increased expression of Tiam2 protein in esophageal cancer may be an early molecular event of esophageal cancer. Tiam2 protein has a high expression level in esophageal carcinoma related to lymph node metastasis, TNM stage and differentiation degree, which suggests that Tiam2 protein plays an important role in the invasion and metastasis of esophageal carcinoma. There is a positive correlation between Tiam2 and Tiam1 protein expressions in esophageal carcinoma, suggesting that the 2 proteins may have a definite internal relationship.


Asunto(s)
Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Factores de Intercambio de Guanina Nucleótido/metabolismo , Metástasis Linfática , Carcinoma Adenoescamoso/patología , Carcinoma Adenoescamoso/metabolismo , Proteína 1 de Invasión e Inducción de Metástasis del Linfoma-T/metabolismo , Carcinoma de Células Escamosas de Esófago/metabolismo , Carcinoma de Células Escamosas de Esófago/patología , Biomarcadores de Tumor/metabolismo , Adulto , Estadificación de Neoplasias , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Inmunohistoquímica
9.
Mol Genet Genomics ; 299(1): 76, 2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39097557

RESUMEN

Lung Squamous Cell Carcinoma is characterised by significant alterations in RNA expression patterns, and a lack of early symptoms and diagnosis results in poor survival rates. Our study aimed to identify the hub genes involved in LUSC by differential expression analysis and their influence on overall survival rates in patients. Thus, identifying genes with the potential to serve as biomarkers and therapeutic targets. RNA sequence data for LUSC was obtained from TCGA and analysed using R Studio. Survival analysis was performed on DE genes. PPI network and hub gene analysis was performed on survival-relevant genes. Enrichment analysis was conducted on the PPI network to elucidate the functional roles of hub genes. Our analysis identified 2774 DEGs in LUSC patient datasets. Survival analysis revealed 511 genes with a significant impact on patient survival. Among these, 20 hub genes-FN1, ACTB, HGF, PDGFRB, PTEN, SNAI1, TGFBR1, ESR1, SERPINE1, THBS1, PDGFRA, VWF, BMP2, LEP, VTN, PXN, ABL1, ITGA3 and ANXA5-were found to have lower expression levels associated with better patient survival, whereas high expression of SOX2 correlated with longer survival. Enrichment analysis indicated that these hub genes are involved in critical cellular and cancer-related pathways. Our study has identified six key hub genes that are differentially expressed and exhibit significant influence over LUSC patient survival outcomes. Further, in vitro and in vivo studies must be conducted on the key genes for their utilisation as therapeutic targets and biomarkers in LUSC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Mapas de Interacción de Proteínas/genética , Redes Reguladoras de Genes , Perfilación de la Expresión Génica , Análisis de Supervivencia , Pronóstico , Transcriptoma/genética , Bases de Datos Genéticas
10.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 206-211, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39097873

RESUMEN

The objective of this study was to investigate the impact of ethyl pyruvate (EP), an HMGB1 inhibitor, on ESCC cells both in vitro and in vivo. The viability of ESCC cells was assessed using the MTT method to evaluate the correlation between EP and cell viability. A scratch test was used to investigate the relationship between EP and cell migration and invasion. The effects of EP on tumor growth and survival in cancerous nude mice were examined using a tumor formation model. Immunohistochemical staining was performed to evaluate the expression levels of HMGB1, TLR4, and MyD88 in tumor tissues. EP, an anti-HMGB1 inhibitor, inhibited ESCC cell proliferation and metastasis in vitro and in vivo. Furthermore, compared with the control treatment, EP improved the activity, diet, and drinking behaviour of nude mice; inhibited tumour growth; and led to lower protein expression levels of HMGB1, TLR4, and MyD88. EP has the potential to regulate the HMGB1/TLR4-MyD88 signaling pathway, thereby inhibiting the proliferation and metastasis of ESCC, suppressing tumor growth, improving quality of life, and serving as an effective drug for ESCC treatment.


Asunto(s)
Carcinoma de Células Escamosas , Proliferación Celular , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Proteína HMGB1 , Ratones Desnudos , Factor 88 de Diferenciación Mieloide , Piruvatos , Receptor Toll-Like 4 , Animales , Piruvatos/farmacología , Humanos , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Línea Celular Tumoral , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/metabolismo , Proliferación Celular/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Movimiento Celular/efectos de los fármacos , Ratones , Transducción de Señal/efectos de los fármacos , Ratones Endogámicos BALB C , Supervivencia Celular/efectos de los fármacos , Masculino
11.
Cell Mol Biol (Noisy-le-grand) ; 70(7): 193-199, 2024 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-39097875

RESUMEN

Fructose-6-phosphate 2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a crucial enzyme in the glycolysis pathway, possessing both kinase and phosphatase capabilities. Although it has emerged as an important oncogene in various cancer types, its function in oral squamous cell carcinoma (OSCC) is still not well understood. In our research, PFKFB4 expression was assessed via immunohistochemical (IHC) staining of tissue microarrays and OSCC patient specimens. The transcriptional expression of PFKFB4 in OSCC was analyzed by utilizing The Cancer Genome Atlas (TCGA) dataset. Correlation between PFKFB4 expression and clinicopathological features was examined using the χ2 test. Prognostic investigation of PFKFB4 was conducted via Kaplan-Meier and Cox analyses. PFKFB4 levels were notably elevated in OSCC samples in comparison to adjacent normal tissues (P < 0.001). Elevated PFKFB4 expression was associated with higher histologic grade (P = 0.0438), higher T stage (P = 0.031), and more advanced clinical stage (P = 0.0063). The ROC curve demonstrated the diagnostic potential of PFKFB4 (AUC = 0.827). Increased levels of PFKFB4 were linked to decreased overall survival (OS) (P = 0.04), poorer disease-specific survival (DSS) (P = 0.04), and shorter progression-free interval (PFI) (P < 0.001). PFKFB4 expression was identified as an independent risk factor for OS based on Cox regression analysis [hazard ratio (HR) = 1.517, P = 0.044)]. An OS nomogram was constructed with a concordance index of 0.690. Our findings reveal that upregulated PFKFB4 expression in OSCC tissues could serve as a potential prognostic biomarker.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Estimación de Kaplan-Meier , Neoplasias de la Boca , Fosfofructoquinasa-2 , Humanos , Fosfofructoquinasa-2/genética , Fosfofructoquinasa-2/metabolismo , Femenino , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/diagnóstico , Masculino , Pronóstico , Persona de Mediana Edad , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidad , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Curva ROC , Modelos de Riesgos Proporcionales , Regulación Neoplásica de la Expresión Génica , Anciano , Inmunohistoquímica
12.
BMC Urol ; 24(1): 165, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39090582

RESUMEN

BACKGROUND: We investigated the feasibility of the tertiary lymphoid structure (TLS) as a prognostic marker for penile squamous cell carcinoma(SCC). METHODS: We retrospectively collected data from 83 patients with penile squamous cell carcinoma. H&E-stained slides were reviewed for TLS density. In addition, clinical parameters were analyzed, the prognostic value of these parameters on overall survival (OS) was evaluated using ‒ Kaplan-Meier survival curves, and the prognostic value of influencing factors was evaluated using Cox multifactor design nomogram analysis. RESULT: BMI, T, N, and M are significant in the survival curve with or without tertiary lymphoid structure. BMI, T, N, M and TLS were used to construct a prognostic model for penile squamous cell carcinoma, and the prediction accuracy reached a consensus of 0.884(0.835-0.932), and the decision consensus reached 0.581(0.508-0.655). CONCLUSION: TLS may be a positive prognostic factor for penile squamous cell carcinoma, and the combination of BMI, T, N and M can better evaluate the prognosis of patients.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Pene , Estructuras Linfoides Terciarias , Masculino , Neoplasias del Pene/patología , Neoplasias del Pene/mortalidad , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/mortalidad , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Estructuras Linfoides Terciarias/patología , Adulto , Tasa de Supervivencia
13.
Sci Rep ; 14(1): 17804, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39090162

RESUMEN

Limited treatment options and poor prognosis present significant challenges in the treatment of lung squamous cell carcinoma (LUSC). Disulfidptosis impacts cancer progression and prognosis. We developed a prognostic signature using disulfidptosis-related long non-coding RNAs (lncRNAs) to predict the prognosis of LUSC patients. Gene expression matrices and clinical information for LUSC were downloaded from the TCGA database. Co-expression analysis identified 209 disulfidptosis-related lncRNAs. LASSO-Cox regression analysis identified nine key lncRNAs, forming the basis for establishing a prognostic model. The model's validity was confirmed by Kaplan-Meier and ROC curves. Cox regression analysis identified the risk score (RS) as an independent prognostic factor inversely correlated with overall survival. A nomogram based on the RS demonstrated good predictive performance for LUSC patient prognosis. The relationship between RS and immune function was explored using ESTIMATE, CIBERSORT, and ssGSEA algorithms. According to the TIDE database, a negative correlation was found between RS and immune therapy responsiveness. The GDSC database revealed that 49 drugs were beneficial for the low-risk group and 25 drugs for the high-risk group. Silencing C10orf55 expression in SW900 cells reduced invasiveness and migration potential. In summary, this lncRNA model based on TCGA-LUSC data effectively predicts prognosis and assists clinical decision-making.


Asunto(s)
Carcinoma de Células Escamosas , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Pronóstico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Biomarcadores de Tumor/genética , Masculino , Nomogramas , Femenino , Estimación de Kaplan-Meier , Línea Celular Tumoral , Perfilación de la Expresión Génica
14.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000164

RESUMEN

Skin cancer encompasses a range of cutaneous malignancies, with non-melanoma skin cancers (NMSCs) being the most common neoplasm worldwide. Skin exposure is the leading risk factor for initiating NMSC. Ultraviolet (UV) light induces various genomic aberrations in both tumor-promoting and tumor-suppressing genes in epidermal cells. In conjunction with interactions with a changed stromal microenvironment and local immune suppression, these aberrations contribute to the occurrence and expansion of cancerous lesions. Surgical excision is still the most common treatment for these lesions; however, locally advanced or metastatic disease significantly increases the chances of morbidity or death. In recent years, numerous pharmacological targets were found through extensive research on the pathogenic mechanisms of NMSCs, leading to the development of novel treatments including Hedgehog pathway inhibitors for advanced and metastatic basal cell carcinoma (BCC) and PD-1/PD-L1 inhibitors for locally advanced cutaneous squamous cell carcinoma (cSCC) and Merkel cell carcinoma (MCC). Despite the efficacy of these new drugs, drug resistance and tolerability issues often arise with long-term treatment. Ongoing studies aim to identify alternative strategies with reduced adverse effects and increased tolerability. This review summarizes the current and emerging therapies used to treat NMSC.


Asunto(s)
Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/patología , Carcinoma Basocelular/terapia , Carcinoma Basocelular/patología , Carcinoma Basocelular/tratamiento farmacológico , Nivel de Atención , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Microambiente Tumoral , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Animales
15.
Chem Biol Drug Des ; 104(1): e14597, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39044124

RESUMEN

Early detection of lung squamous cell carcinoma (LUSC) has a significant impact on clinical outcomes, and pterostilbene (PT) is a natural compound with promising anti-oncogenic activities. This study aimed to identify potential LUSC biomarkers through a series of bioinformatic analyses and clinical verification and explored the interaction between PT and selected biomarkers during the treatment of LUSC. The analysis of the expression profile of the clinical samples of LUSC was performed to identify dysexpressed genes (DEGs) and validated by IHC. The role of KANK3 in the anti-LUSC effects of PT was assessed with a series of in vitro and in vivo assays. 4335 DEGs were identified, including 1851 upregulated genes and 2484 downregulated genes. Survival analysis showed that KANK3 was significantly higher in patients with LUSC with an advanced tumor stage. In in vitro assays, PT suppressed cell viability, induced apoptosis, and inhibited migration and invasion in LUSC cell lines, which was associated with downregulation of KANK3. After the reinduction of the KANK3 level in LUSC cells, the anti-LUSC function of PT was impaired. In mice model, reinduction of KANK3 increased tumor growth and metastasis even under the treatment of PT. The findings outlined in the current study indicated that PT exerted anti-LUSC function in a KANK3 inhibition-dependent manner.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias Pulmonares , Estilbenos , Estilbenos/farmacología , Estilbenos/química , Estilbenos/uso terapéutico , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Animales , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Ratones , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Ratones Desnudos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/antagonistas & inhibidores , Proteínas Adaptadoras Transductoras de Señales/genética , Masculino , Femenino , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Proteínas del Citoesqueleto/metabolismo , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/antagonistas & inhibidores , Regulación hacia Abajo/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Proliferación Celular/efectos de los fármacos
16.
BMC Oral Health ; 24(1): 834, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39048985

RESUMEN

BACKGROUND: The scientific community has been particularly interested in oral squamous cell carcinoma (OSCC) because of the cancer's extremely high incidence and fatality rates worldwide. It has been proposed that paxillin is involved in certain malignancies as an oncogene. Additionally, several investigations have assessed paxillin expression and investigated its function in developing distinct human carcinomas, including squamous cell carcinoma. Furthermore, it was discovered that there is a strong link between paxillin levels and cancer progression and spread. OBJECTIVE: This investigation was carried out to analyze and compare the salivary paxillin levels between oral potentially malignant disorders (OPMDs), OSCC and the healthy controls to assess its potential role as a biomarker of oral cancer aiming for early diagnosis and better prognosis of OSCC. METHODS: Forty-five patients, ranging in age from thirty to seventy-five, were divided into three groups: fifteen patients with OPMDs, fifteen patients with OSCC, and fifteen controls. Paxillin was identified in saliva samples by using an ELISA kit. RESULTS: Patients with OSCC and OPMDs have considerably greater salivary Paxillin levels than the healthy control group. The receiver operating curve (ROC) analysis was used in our study to distinguish patients with OPMDs from those with OSCC. The ROC curve constructed with the OPMDs group as the positives had lower sensitivity and area under the curve (AUC) values [100% and 1] than the ROC curve with the malignant group as the positives [93.3% and 0.997], respectively. Furthermore, ROC analysis performed between OPMDs group and the malignant group showed a specificity of 73.3% and a cut-off value ≥ 7.9 . CONCLUSION: Paxillin can be considered a reliable biomarker for identifying and comparing OPMDs and OSCC cancerous changes. GOV IDENTIFIER: NCT06154551- 4/12/2023.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Neoplasias de la Boca , Paxillin , Saliva , Humanos , Paxillin/metabolismo , Paxillin/análisis , Neoplasias de la Boca/patología , Neoplasias de la Boca/metabolismo , Saliva/química , Saliva/metabolismo , Persona de Mediana Edad , Masculino , Femenino , Anciano , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Estudios de Casos y Controles , Lesiones Precancerosas/patología , Lesiones Precancerosas/metabolismo
17.
Technol Cancer Res Treat ; 23: 15330338241258596, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39043205

RESUMEN

INTRODUCTION: Postoperative radiotherapy can improve locoregional control (LC) in oral cavity squamous cell carcinoma (OCSCC) patients with positive resection margins. The present study aimed to evaluate the impact of surgical margin size on LC in this patient population. METHODS: This retrospective study involved 162 patients with OCSCC who underwent postoperative radiotherapy between 2000 and 2020 at the Department of Radiation Oncology, University Hospital Heidelberg and the German Cancer Research Center. The study aimed to determine the impact of different resection margins on LC, as well as overall survival (OS), progression-free survival (PFS), and treatment-related toxicity (CTCAE 4.03). RESULTS: Seventy-seven patients (47.5%) had involved (<1 mm) margins, 22 patients (13.6%) close (≤5 mm) margins, and 63 patients (38.9%) clear (>5 mm) margins. A surgical margin ≤ 5 mm was a significant predictor for worse LC (HR 2.6, 95% CI 1.2, 6.1), but not for OS (HR 1.2, CI 0.7, 1.9) or PFS (HR 1.2, 0.7, 2.0). CONCLUSION: Patients who have narrow resection margins (1-5 mm) experience poor local control and should receive postoperative radiotherapy. It is necessary to conduct further prospective studies to determine whether a narrower margin window could be achieved to better determine the appropriate indication for adjuvant radiotherapy.


Asunto(s)
Márgenes de Escisión , Neoplasias de la Boca , Humanos , Masculino , Femenino , Neoplasias de la Boca/radioterapia , Neoplasias de la Boca/patología , Neoplasias de la Boca/cirugía , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Radioterapia Adyuvante/métodos , Adulto , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/mortalidad , Anciano de 80 o más Años , Pronóstico , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/radioterapia , Resultado del Tratamiento
18.
Sci Rep ; 14(1): 16864, 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043845

RESUMEN

Long non-coding RNAs (lncRNAs) have emerged as important players in cancer progression. Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer with increasing incidence worldwide. The prognosis of the metastatic cSCC is poor, and currently there are no established biomarkers to predict metastasis risk or specific therapeutic targets for advanced or metastatic cSCC. To elucidate the role of lncRNAs in cSCC, RNA sequencing of patient derived cSCC cell lines and normal human epidermal keratinocytes was performed. The correlation analysis of differentially expressed lncRNAs and protein-coding genes revealed six distinct gene clusters with one of the upregulated clusters featuring genes associated with cell motility. Upregulation of the expression of lncRNAs linked to cSCC cell motility in cSCC and head and neck SCC (HNSCC) cells was confirmed using qRT-PCR. Elevated expression of HOTTIP and LINC00543 was also noted in SCC tumors in vivo and was associated with poorer prognosis in HNSCC and lung SCC cohorts within TCGA data, respectively. Altogether, these findings uncover a novel set of lncRNAs implicated in cSCC cell locomotion. These lncRNAs may serve as potential novel biomarkers and as putative therapeutic targets for locally advanced and metastatic cSCC.


Asunto(s)
Biomarcadores de Tumor , Carcinoma de Células Escamosas , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Línea Celular Tumoral , Redes Reguladoras de Genes , Pronóstico , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Movimiento Celular/genética , Perfilación de la Expresión Génica
19.
Sci Prog ; 107(3): 368504241266087, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39044316

RESUMEN

The absence of improvement in survival rates across various cancers, including laryngeal cancer, has led to an increasing interest in understanding the immune response to cancer. In head and neck cancers, immune modulatory mechanisms such as immune microenvironment and immune infiltration are important in cancer pathogenesis. This study aims to explore the distribution of tumor-infiltrating lymphocyte (TIL) subgroups in the immune microenvironment and evaluate their impact on tumor histopathological characteristics and prognosis. The study included 50 patients who underwent laryngectomy for laryngeal squamous cell carcinoma, in Istanbul University - Cerrahpasa, Faculty of Medicine Department of Otorhinolaryngology, between January 2016 and January 2018. Pathology specimens were evaluated using immunohistochemistry to assess the expressions of the CD3, CD20, CD8, CD4, CD25, and FoxP3 markers, identifying subgroups of TILs. The investigation aimed to uncover how these subgroups influence tumor histopathological features and survival outcomes. The high infiltration of CD3, CD20, and CD4 had a positive impact on disease-specific survival, disease-free survival, and recurrence-free survival. In addition, overall survival was positively affected by high CD3 and CD4 infiltrations. However, no significant relationship was observed between the expressions of CD8, FoxP3, and CD25 and any of the survival parameters. The infiltration of CD3, CD20, and CD4 positive cells indicative of a robust antitumoral immune response-emerged as favorable prognostic factors in laryngeal cancer. These findings suggest that enhancing the infiltration of CD3, CD20, and CD4 lymphocytes could be a therapeutic strategy worth exploring in clinical trials.


Asunto(s)
Neoplasias Laríngeas , Linfocitos Infiltrantes de Tumor , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Neoplasias Laríngeas/inmunología , Neoplasias Laríngeas/patología , Pronóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Supervivencia sin Enfermedad , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Factores de Transcripción Forkhead/metabolismo , Adulto
20.
Rom J Morphol Embryol ; 65(2): 243-250, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39020538

RESUMEN

INTRODUCTION: Histological grading of cutaneous squamous cell carcinoma (cSCC) is crucial for prognosis and treatment decisions, but manual grading is subjective and time-consuming. AIM: This study aimed to develop and validate a deep learning (DL)-based model for automated cSCC grading, potentially improving diagnostic accuracy (ACC) and efficiency. MATERIALS AND METHODS: Three deep neural networks (DNNs) with different architectures (AlexNet, GoogLeNet, ResNet-18) were trained using transfer learning on a dataset of 300 histopathological images of cSCC. The models were evaluated on their ACC, sensitivity (SN), specificity (SP), and area under the curve (AUC). Clinical validation was performed on 60 images, comparing the DNNs' predictions with those of a panel of pathologists. RESULTS: The models achieved high performance metrics (ACC>85%, SN>85%, SP>92%, AUC>97%) demonstrating their potential for objective and efficient cSCC grading. The high agreement between the DNNs and pathologists, as well as among different network architectures, further supports the reliability and ACC of the DL models. The top-performing models are publicly available, facilitating further research and potential clinical implementation. CONCLUSIONS: This study highlights the promising role of DL in enhancing cSCC diagnosis, ultimately improving patient care.


Asunto(s)
Carcinoma de Células Escamosas , Aprendizaje Profundo , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/diagnóstico , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/diagnóstico , Clasificación del Tumor/métodos
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