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ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

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Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

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Objetivo: La histoplasmosis es una infección fúngica sistémica prevalente en la región del Río de la Plata. Puede exhibir manifestaciones orales, cutáneas y/o sistémicas. Las lesiones bucales significan un desafío diagnóstico debido a su semejanza clínica con el carcinoma oral de células escamosas (COCE). El objetivo de este trabajo fue presentar una serie de casos de histoplasmosis oral enfatizando la importancia del diagnóstico diferencial clínico con el COCE. Casos clínicos: Se describen casos de histoplasmosis oral diagnosticados en los últimos 5 años en la Cátedra de Estomatología "A" de la Facultad de Odontología de la Universidad Nacional de Córdoba, Córdoba, Argentina. En forma paralela, se realizó una revisión de la literatura de los últimos 10 años. Los casos corresponden a 9 pacientes, 6 varones y 3 mujeres, cuya edad promedio fue de 58,6 años. 4 pacientes eran VIH positivos. Se planteó la sospecha de COCE en 5 pacientes, cuya presentación clínica intraoral consistía en úlceras o lesiones ulcerovegetantes, mayormente únicas, ubicadas en la encía. La revisión bibliográfica arrojó un resultado de 48 artículos que incluyeron 60 casos de histoplasmosis oral, con una prevalencia mayor en hombres y similitudes clínicas con COCE en el 80% de los casos. La lesión más predominante fue la úlcera en el 85% de los casos, ubicada en lengua, seguido por el paladar. El diagnóstico de histoplasmosis oral es desafiante y requiere un amplio diferencial, ya que se asemeja a múltiples patologías, debiendo ser considerada ante lesiones ulcerativas orales. Un diagnóstico preciso, de manera interdisciplinaria, es esencial para un tratamiento efectivo.(AU)

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Aim: Histoplasmosis is a systemic fungal infection prevalent in the Río de la Plata region. It could present oral, cutaneous and/or systemic manifestations. Oral lesions represent a diagnostic challenge due to their clinical similarity to oral squamous cell carcinoma (OSCC). The objective of this work is to present a case series of oral histoplasmosis emphasizing the importance of clinical differential diagnosis with OSCC. Clinical cases: Cases of oral histoplasmosis diagnosed in the last 5 years in the Oral Medicine Department "A" of the Facultad de Odontología of the Universidad Nacional de Córdoba, Córdoba, Argentina are discribed. Alongside, a literature review of the last 10 years was carried out. 9 patients are described, 6 men and 3 women, whose average age was 58.6 years. 4 patients were HIV positive. The suspicion of OSCC was raised in 5 patients, whose intraoral clinical presentation consisted of single ulcers or vegetating ulcers, mostly single, located in the gingiva. The literature review included a total of 48 articles with 60 cases of oral histoplasmosis, with a higher prevalence in men and clinical similarities with OSCC in 80% of cases. The most predominant lesion was the ulcer in 85% of the cases, mostly located on the tongue, followed by the palate. The diagnosis of oral histoplasmosis is challenging and requires a wide differential, since it can mimic multiple pathologies, and should be considered in oral ulcerative lesions. An accurate diagnosis, in an interdisciplinary framework, is essential for effective treatment.(AU)

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PURPOSE: This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. METHODS: This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. RESULTS: Multivariate analysis revealed that an alpha-fetoprotein (AFP) level ⩾ 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) ⩽ 65.43 (HR 0.50; 95% CI 0.30-0.84; P < 0.01 ) and SII ⩽ 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP ⩾ 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII > 303.66 were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). CONCLUSION: SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

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OBJECTIVES: Chemoprevention can be a treatment for potentially malignant lesions (PMLs). We aimed to evaluate whether artemisinin (ART) and cisplatin (CSP) are associated with apoptosis and immunogenic cell death (ICD) in vitro, using oral leukoplakia (OL) and oral squamous cell carcinoma (OSCC) cell lines, and whether these compounds prevent OL progression in vivo. METHODS: Normal keratinocytes (HaCat), Dysplastic oral cells (DOK), and oral squamous cell carcinoma (SCC-180) cell lines were treated with ART, CSP, and ART + CSP to analyze cytotoxicity, genotoxicity, cell migration, and increased expression of proteins related to apoptosis and ICD. Additionally, 41 mice were induced with OL using 4NQO, treated with ART and CSP, and their tongues were histologically analyzed. RESULTS: In vitro, CSP and CSP + ART showed dose-dependent cytotoxicity and reduced SCC-180 migration. No treatment was genotoxic, and none induced expression of proteins related to apoptosis and ICD; CSP considerably reduced High-mobility group box-1 (HMGB-1) protein expression in SCC-180. In vivo, there was a delay in OL progression with ART and CSP treatment; however, by the 16th week, only CSP prevented progression to OSCC. CONCLUSION: Expression of proteins related to ICD and apoptosis did not increase with treatments, and CSP was shown to reduce immunogenic pathways in SCC-180, while reducing cell migration. ART did not prevent the malignant progression of OL in vivo; CSP did despite significant adverse effects.

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Apoptose , Artemisininas , Movimento Celular , Cisplatino , Progressão da Doença , Leucoplasia Oral , Neoplasias Bucais , Artemisininas/farmacologia , Animais , Leucoplasia Oral/patologia , Leucoplasia Oral/tratamento farmacológico , Humanos , Cisplatino/farmacologia , Camundongos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proteína HMGB1/metabolismo , Antineoplásicos/farmacologia

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Background: Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder marked by pathogenic variants in the MEN1 tumor suppressor gene, leading to tumors in the parathyroid glands, pancreas, and pituitary. The occurrence of ACTH-producing pancreatic neuroendocrine carcinoma is exceedingly rare in MEN1. Case presentation: This report details a Colombian family harboring a novel MEN1 variant identified through genetic screening initiated by the index case. Affected family members exhibited primary hyperparathyroidism (PHPT) symptoms from their 20s to 50s. Uniquely, the index case developed an ACTH-secreting pancreatic neuroendocrine carcinoma, a rarity in MEN1 syndromes. Proactive screening enabled the early detection of pituitary neuroendocrine tumors (PitNETs) as microadenomas in two carriers, with subsequent surgical or pharmacological intervention based on the clinical presentation. Conclusion: Our findings underscore the significance of cascade screening in facilitating the early diagnosis and individualized treatment of MEN1, contributing to better patient outcomes. Additionally, this study brings to light a novel presentation of ACTH-producing pancreatic neuroendocrine carcinoma within the MEN1 spectrum, expanding our understanding of the disease's manifestations.

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Hormônio Adrenocorticotrópico , Carcinoma Neuroendócrino , Neoplasia Endócrina Múltipla Tipo 1 , Neoplasias Pancreáticas , Linhagem , Humanos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/diagnóstico , Masculino , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/patologia , Colômbia , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/complicações , Feminino , Pessoa de Meia-Idade , Seguimentos , Hormônio Adrenocorticotrópico/sangue , Hormônio Adrenocorticotrópico/metabolismo , Adulto , Proteínas Proto-Oncogênicas/genética

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BACKGROUND: The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear. METHODS: We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations. RESULTS: We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425. CONCLUSIONS: These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies.

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BACKGROUND: Primary carcinoma of the ovary (OCs) are responsible for a significant number of deaths related to cancer, and have the highest rate of death related to cancers of the female reproductive organs. Programmed cell death 1 (PD1) protein, acts as an immune checkpoint, and has an important role in the down-regulation of the immune system by preventing the activation of T-cells, which will weaken the autoimmunity and increases self-tolerance. This study aimed at the evaluation of the immunohistochemical (IHC) expression of PD-L1 in various primary surface ovarian epithelial tumours and to test its correlation with different clinicopathological parameters together with the expression of a panel of P53, ER and PR. METHODS: A set of 102 cases of primary ovarian surface epithelial neoplasms (benign, borderline and malignant) were collected to construct Tissue Microarray (TMA) using 3 tissue cores from each case. IHC for PD-L1, p53, PR and ER was performed. The expression of PD-L1 was evaluated in relation to some clinicopathological parameters and to the expression patterns of other markers. RESULTS: Expression of PD-L1 was detected in about 51% (n = 36) of malignant tumours. The malignant group significantly showed PD-L1 positivity compared to borderline and benign groups. The malignant tumours significantly showed PD-L1 and total p53 positivity in comparison to borderline group. Also, malignant tumours significantly showed higher combined positivity of PD-L1 and either PR or ER compared to borderline and benign lesions. No significant correlation was appreciated between PD-L1 expression and with any of the studied clinicopathological parameters. CONCLUSIONS: This study showed a significant PD-L1 expression in malignant primary surface epithelial tumours. Construction of a panel of IHC markers, including PD-L1, could have a potential value to define patients those would benefit from the addition of immunotherapy to the treatment plan.

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Hepatocellular carcinoma (HCC) is one of the deadliest cancers. For patients with advanced HCC, liver function decompensation often occurs, which leads to poor tolerance to chemotherapies and other aggressive treatments. Therefore, it remains critical to develop effective therapeutic strategies for HCC. Etiological factors for HCC are complex and multifaceted, including hepatitis virus infection, alcohol, drug abuse, chronic metabolic abnormalities, and others. Thus, HCC has been categorized as a "genomically unstable" cancer due to the typical manifestation of chromosome breakage and aneuploidy, and oxidative DNA damage. In recent years, immunotherapy has provided a new option for cancer treatments, and the degree of genomic instability positively correlates with immunotherapy efficacies. This article reviews the endogenous and exogenous causes that affect the genomic stability of liver cells; it also updates the current biomarkers and their detection methods for genomic instabilities and relevant applications in cancer immunotherapies. Including genomic instability biomarkers in consideration of cancer treatment options shall increase the patients' well-being.

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Objectives: The aim of the present study was to examine the immunoexpression of CD44, p16 and VEGF in oral squamous cell carcinoma (OSCC) and correlate them to clinicopathological parameters and survival outcomes in order to clarify their prognostic impact. Material and Methods: A total of 68 individuals with OSCC recruited between 2011 and 2015 from two referral centres were enrolled in the study. The samples were placed on silanized glass slides and subjected to immunohistochemistry using anti-p16, anti-CD44 and anti-VEGF antibodies. The H Score was used for p16 and VEGF, while CD44 was scored according to the percentage of stained cells. Chi-square tests and Fisher's exact probability tests were used to compare clinicopathological characteristics according to the immunohistochemical expression, while overall survival and disease-free survival were estimated and compared using the Kaplan-Meier method and log-rank test, respectively. For all hypothesis tests, the level of significance was set at P ≤ 0.05. Results: No correlation was observed between the expression of tumour VEGF, p16 and CD44, and the clinicopathological characteristics analysed. Patients with high stromal VEGF expression had better disease-free survival than patients with low VEGF expression (P = 0.023). Conclusion: In summary, P16, CD44 and tumour VEGF did not prove to be good prognostic biomarkers. Stromal VEGF expression is suggested to be a good candidate prognostic biomarker, although additional studies are needed.