Carcinoma de células escamosas y el rol discutido de la irritación mecánica crónica. Informe de un caso / Squamous oral cell carcinoma and the discussed role of chronic mechanical irritation. Report of a case

Resumen Objetivo Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico Un paciente de 41 años de edad, argentino, con antecedentes de fisura labio alvéolo palatina, diabetes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odontología del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias semanas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, falleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evidencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación mecánica crónica en la carcinogénesis.

Abstract Aim To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation appears to play a significant role in carcinogenesis. Clinical case A 41-year-old patient, from Argentina, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospital for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he rejected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcinogenesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alcohol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion develops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relationship of chronic mechanical irritation in the development of carcinogenesis.

Modelos pré-clínicos de câncer hepático / Preclinical models of liver câncer

ABSTRACT Background: This manuscript provides an overview of liver carcinogenesis in murine models of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Objective: A review through MEDLINE and EMBASE was performed to assess articles until August 2022. Methods: Search was conducted of the entire electronic databases and the keywords used was HCC, CCA, carcinogenesis, animal models and liver. Articles exclusion was based on the lack of close relation to the subject. Carcinogenesis models of HCC include HCC induced by senescence in transgenic animals, HCC diet-induced, HCC induced by chemotoxicagents, xenograft, oncogenes, and HCC in transgenic animals inoculated with B and C virus. The models of CCA include the use of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), thioacetamide (TAA), and carbon tetrachloride (CCl4). CCA murine models may also be induced by: CCA cells, genetic manipulation, Smad4, PTEN and p53 knockout, xenograft, and DEN-left median bile duct ligation. Results: In this review, we described different murine models of carcinogenesis that reproduce the key points for HCC and CCA genesis allowing a better understanding of its genetic, physiopathological, and environmental abnormalities. Conclusion: Each model has its advantages, disadvantages, similarities, and differences with the corresponding human disease and should be chosen according to the specificity of the study. Ultimately, those models can also be used for testing new anticancer therapeutic approaches.

RESUMO Contexto: Este manuscrito fornece uma visão geral da carcinogênese hepática em modelos murinos de carcinoma hepatocelular (CHC) e colangiocarcinoma (CCA). Objetivo: Realizar uma revisão de artigos científicos até agosto de 2022 utilizando as bases de dados MEDLINE e EMBASE. Métodos: A busca foi realizada em todas as bases de dados eletrônicas e as palavras-chave usadas foram CHC, CCA, carcinogenesis, modelos animais e fígado. A exclusão dos artigos baseou-se na falta de estreita relação com o assunto. Os modelos de carcinogênese do CHC incluíram: CHC induzido por senescência em animais transgênicos, CHC induzido por dieta, CHC induzido por agentes quimiotóxicos, xenoenxerto, oncogenes e CHC em animais transgênicos inoculados com vírus B e C. Os modelos de CCA incluíram: o uso de dimetilnitrosamina (DMN), dietilnitrosamina (DEN), tioacetamida (TAA) e tetracloreto de carbono (CCl4). Os modelos murinos de CCA induzidos por incluir: células de CCA, manipulação genética, animais nocaute para Smad4, PTEN e p53, xenoenxerto e ligadura do ducto biliar mediano esquerdo. Resultados: Nesta revisão, descrevemos diferentes modelos murinos de carcinogênese que reproduzem os pontos-chave para a gênese do CHC e do CCA, permitindo uma melhor compreensão de suas anormalidades genéticas, fisiopatológicas e ambientais. Conclusão: Cada modelo tem suas vantagens, desvantagens, semelhanças e diferenças com a doença humana correspondente e deve ser escolhido de acordo com a especificidade do estudo. Em última análise, esses modelos também podem ser utilizados para testar novas abordagens terapêuticas anticancerígenas.

Quantification of human polyomaviruses MCPyV and HPyV6 in malignant and non-malignant skin lesions

Abstract Background: Human Polyomaviruses such as MCPyV and HPyV6 are frequently found as part of healthy skin microbiota and have been associated with Merkel cell carcinoma (MCC), pruritic and dyskeratotic dermatoses, respectively. Their presence in other types of skin conditions varies greatly depending on lesion type and population. Objectives: To analyse comparatively the presence of MCPyV and HPyV6 in nonmelanoma skin cancers and healthy skin. Methods: The authors utilized qPCR techniques to quantify these pathogens in NMSC, premalignant diseases, and healthy skin of 87 patients. Results: MCPyV was detected in over 40% of samples, while HPyV6 was in 9.6%. MCPyV load was higher in squamous cell carcinomas (SCC) compared to basal cell carcinomas (BCC) (p = 0.016) and HPyV6 showed a higher percentage of infected cells in areas of low solar exposure as well as normal skin (p = 0.012). A fair agreement (kappa = 0.301) was found between MCPyV detection in lesions and their respective perilesional skin, indicating a random process of local dissemination of the virus. Study limitations: The lack of a larger sampling of different lesion types and protein expression analyses limits the correlation findings. Conclusions: This is the first report of HPyV6 detection in the healthy skin of a Brazilian population, but the role of both polyomaviruses in NMSC has yet to be demonstrated.

Associação entre lesões de hpv e os carcinomas genitais e da cavidade oral: uma revisão narrativa / Association between hpv lesions and genital and oral cavity carcinomas: a narrative review / Asociación entre lesiones por vph y carcinomas genitales y de cavidad oral: una revisión narrativa

Os Papilomavírus Humano (HPVs) são membros da família Papilomaviridae. O vírus destaca-se pelo seu tropismo por células epiteliais, infectando exclusivamente mucosa epitelial e cutânea. O HPV-16 e HPV-18 são subtipos classificados como de alto risco, conhecidos por sua oncogenicidade, fortemente associados aos cânceres anais, genitais e de orofaringe. Lesões por HPV representam um grande grupo de doenças sexualmente transmissíveis. O objetivo do presente estudo consistiu em realizar uma revisão narrativa sobre a associação entre lesões por HPV e carcinomas genitais e da cavidade oral. Realizamos uma busca na base de dados eletrônicos PubMed, Lilacs, Scielo, Medline e Google Scholar, sendo utilizados artigos publicados entre os anos de 2017-2021, ao fim, foram selecionados 36 artigos. Grande parte das infecções por HPV são subclínicas, ou seja, não apresentam sintomatologia importante e tendem a desaparecer espontaneamente. Desta forma, faz-se necessário ter conhecimento a respeito dos aspectos clínicos e comportamentais dessas lesões, possibilitando o diagnóstico precoce, evitando a evolução para estágios mais invasivos, favorecendo um tratamento efetivo e melhor prognóstico.

Human Papillomaviruses (HPVs) are members of the Papilomaviridae family. The virus stands out for its tropism for epithelial cells, exclusively infecting epithelial and cutaneous mucosa. O HPV-16 and HPV-18 are subtypes classified as high risk, known for their oncogenicity, strongly associated with anal, genital and oropharyngeal cancers. HPV lesions represent a large group of sexually transmitted diseases. The objective of this study was to carry out a narrative review on the association between HPV lesions and genital and oral cavity carcinomas. We carried out a search in the electronic databases PubMed, Lilacs, Scielo, Medline and Google Scholar, using articles published between the years of 2017-2021, at the end, foram selected 36 articles. A large part of HPV infections are subclinical, or seem to, do not present significant symptoms and tend to disappear spontaneously. In this way, it is necessary to be aware of the two clinical and behavioral aspects of these injuries, enabling early diagnosis, avoiding evolution to more invasive stages, favoring effective treatment and better prognosis.

Los virus del papiloma humano (VPH) son miembros de la familia Papillomaviridae. El virus destaca por su tropismo por las células epiteliales, infectando exclusivamente mucosas epiteliales y cutáneas. El VPH-16 y el VPH-18 son subtipos clasificados como de alto riesgo, conocidos por su oncogenicidad, fuertemente asociados con cánceres anales, genitales y orofaríngeos. Las lesiones por VPH representan un gran grupo de enfermedades de transmisión sexual. El objetivo del presente estudio fue realizar una revisión narrativa sobre la asociación entre las lesiones por VPH y los carcinomas genitales y de cavidad oral. Realizamos una búsqueda en la base de datos electrónica PubMed, Lilacs, Scielo, Medline y Google Scholar, utilizando artículos publicados entre los años 2017-2021, al final se seleccionaron 36 artículos. La mayoría de las infecciones por VPH son subclínicas, es decir, no presentan síntomas importantes y tienden a desaparecer espontáneamente. Por lo tanto, es necesario tener conocimiento sobre los aspectos clínicos y conductuales de estas lesiones, que permitan un diagnóstico precoz, evitando la progresión a estadios más invasivos, favoreciendo un tratamiento eficaz y un mejor pronóstico.

The role of TNF-α and NFkß in an experimental model of intestinal carcinogenesis with 1, 2-dimethyhydrazine

ABSTRACT Purpose: To analyze the potential of tumor necrosis factor-α (TNF-α) and factor nuclear kappa B (NF-κB) as colorectal cancer (CRC) biomarkers in an experimental model of intestinal carcinogenesis with 1,2-dimethyhydrazine (1,2-DMH). Methods: Twenty-four male Wistar rats were divided into two groups: sham and 1,2-DMH. First, 1,2-DMH (20 mg/kg/week) was administered for 15 consecutive weeks. In the 25th week, proctocolectomy was conducted. Histopathological analysis, immunohistochemistry, and gene expression of TNF-α and NF-κB were performed. Statistical analysis was performed using GraphPad Prism. The location of aberrant crypt foci (ACF) was analyzed by Kruskal-Wallis' test. For analyses with two groups with parametric data, the t-test was used; for non-parametric data, the Mann-Whitney's test was used. P < 0.05 was considered significant. Results: The number of ACF and macroscopic lesions was significantly higher (p < 0.5) in the 1,2-DMH group compared to the sham group, and most ACF were concentrated in the distal segment of the colon. There was a statistically significant increase (p < 0.5) in protein and gene expression of TNF-α and NF-κB in the 1,2-DMH group compared to the sham group. Conclusions: Our results provide supportive evidence that TNF-α and NF-κB pathways are strongly involved in CRC development in rats and might be used as early biomarkers of CRC pathogenesis in experimental studies.

Controversy and consideration of gallbladder adenomyomatosis / 中华肝胆外科杂志

The detection rate of gallbladder adenomyomatosis has gradually increased, but the accuracy of preoperative diagnosis is low. Most doctors tend to expand the operation indications because they are worried about the carcinogenesis. But there are still great controversies on the key issues such as whether it is cancerous, operation indications and how to follow up for non-surgical patients. This article will review these key issues.

Research advance on ubiquitin-specific protease 14 as novel carcinogenesis biomarker / 环境与职业医学

Hazardous environmental factors as well as occupational factors can lead to elevated incidence of diseases including tumors, and specific molecular biomarkers are needed to guide the diagnosis and treatment of diseases. In recent years, ubiquitin-specific protease 14 (USP14) has gradually attracted the attention of researchers. USP14 is widely expressed in various organs of human body and regulates the stability and degradation of important proteins in various signaling pathways. Studies have shown that its abnormal expression is highly correlated with tumors, neurodegenerative diseases, autophagy, immune response, and viral infections, and is involved in the regulation of various classic signaling pathways. It has been shown to play a key role in the development of various human diseases and can be used as a diagnostic and prognostic molecular biomarker and therapeutic target in the development of tumors. This paper reviewed the current status of research on the structure and regulation of USP14 and its function in physiological and pathological processes, with the aim of providing a reference for research on diseases or injuries caused by environmental and occupational factors.

HIV and neoplasms: What do we know so far?

ABSTRACT Introduction The human immunodeficiency virus (HIV) pandemic remains an important issue. In 2020, approximately 37.7 million people were living with the disease and there were more than 680 thousand deaths due to complications linked to the disease. Despite these exorbitant numbers, the introduction of highly active antiretroviral therapy has marked a new era, changing the epidemiological profile of the infection and related pathologies, including neoplasms. Objective We performed a literature review to assess the role of neoplasms in patients with HIV after the introduction of antiretroviral therapy. Methods A literature review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, searching the MEDLINE, LILACS, and COCHRANE databases for articles published from 2010 onwards. Results Using specific key terms, 1,341 articles were identified; two were duplicates, 107 were selected for full-text evaluation, and 20 were included in the meta-analysis. The selected studies included 2,605,869 patients. Fifteen of the 20 articles indicated a reduction in the global incidence of AIDS-defining neoplasms and 12 indicated an overall increase in non-AIDS-defining cancers after the introduction of antiretrovirals. This growth trend could be explained by a range of factors including the aging population with HIV, risky behaviors, and coinfection with oncogenic viruses. Conclusions There was a decreasing trend in the incidence of AIDS-defining neoplasms and increasing trend in non-AIDS-defining neoplasms. However, the carcinogenic effect of antiretrovirals could not be confirmed. In addition, studies focusing on the oncogenic role of HIV and screening for neoplasms in individuals with HIV are required.

Virus de Epstein-Barr: más que una mononucleosis infecciosa / Epstein-Barr virus: more than infectious mononucleosis

El virus de Epstein-Barr (VEB) fue el primer virus asociado a neoplasias en humanos. Infecta el 95 % de la población mundial, y aunque usualmente es asintomático, puede causar mononucleosis infecciosa y se relaciona con más de 200.000 casos de neoplasias al año. De igual forma, se asocia con esclerosis múltiple y otras enfermedades autoinmunes. A pesar de ser catalogado como un virus oncogénico, solo un pequeño porcentaje de los individuos infectados desarrollan neoplasias asociadas a VEB. Su persistencia involucra la capacidad de alternar entre una serie de programas de latencia, y de reactivarse cuando tiene la necesidad de colonizar nuevas células B de memoria, con el fin de sostener una infección de por vida y poder transmitirse a nuevos hospederos. En esta revisión se presentan las generalidades del VEB, además de su asociación con varios tipos de neoplasias, como son el carcinoma nasofaríngeo, el carcinoma gástrico, el linfoma de Hodgkin y el linfoma de Burkitt, y la esclerosis múltiple. Adicionalmente, se describen los mecanismos fisiopatológicos de las diferentes entidades, algunos de ellos no completamente dilucidados

Epstein-Barr virus (EBV) was the first virus associated with human cancer. It infects 95% of the world's population, and although it is usually asymptomatic, it causes infectious mononucleosis. It is related to more than 200,000 cases of cancer per year, and is also associated with multiple sclerosis and other autoimmune diseases. Despite being classified as an oncogenic virus, only a small percentage of infected individuals develop EBV-associated cancer. Its persistence involves the ability to alternate between a series of latency programs, and the ability to reactivate itself when it needs to colonize new memory B cells, in order to sustain a lifelong infection and be able to transmit to new hosts. In this review, the general characteristics of EBV are presented, in addition to its association with various types of cancers, such as nasopharyngeal carcinoma, gastric carcinoma, Hodgkin's lymphoma and Burkitt's lymphoma, and multiple sclerosis. Additionally, the pathophysiological mechanisms of the different entities are described, some of them not completely elucidated yet

Lifestyle and breast cancer: review article

The aim of this study was to improve our knowledge about carcinogenesis and lifestyle, given their impact on the occurrence of breast cancer, emphasizing the importance of lifestyle changes as a preventive factor in the development of the disease. We conducted a bibliographic review with the analysis of 31 articles in English and Portuguese. As a result, the articles selected for study showed that factors such as diet, alcohol intake, smoking, obesity, physical activity, occupational exposure, hormonal factors (hormone therapy, contraceptives) and reproductive factors (menarche, menopause, nulliparity, pregnancy, breastfeeding) have a protective or risk effect on breast cancer. We conclude that eating healthy, with fruits, vegetables and greens, practicing moderate physical activity, avoiding alcoholic beverages and breastfeeding exclusively reduce the risk of developing breast cancer by 28%. Therefore, it is necessary to make the public aware of these modifiable risk factors

Mecanismos de Acción de la Microbiota Oral en el Desarrollo del Cáncer. Revisión Sistemática Exploratoria

En esta revisión sistemática exploratoria, presentamos la evidencia registrada en la literatura, de que la microbiota oral puede generar una acción carcinogénica, actuando a través de tres mecanismos principales: sobre el medio extracelular, activando vías de señalización intracelular y/o generando acción directa sobre el DNA, y que las principales bacterias estudiadas corresponden a Fusobacterium nucleatum y Porphyromona gingivalis. En la actualidad hay evidencia suficiente acerca de la asociación entre microbiota oral y distintos tipos de cáncer, sin embargo, no hay gran conocimiento de los mecanismos por los cuales esta microbiota participa en su desarrollo. Presentamos una recopilación de los diversos mecanismos de acción que utilizan las bacterias de la cavidad oral en el proceso de carcinogénesis en cuatro tipos diferentes de cáncer. Es de gran importancia aumentar el conocimiento acerca del rol etiológico de la microbiota oral en el desarrollo de la enfermedad de cáncer debido a que se establecería como un nuevo agente carcinogénico y su conocimiento podría ser utilizado como una herramienta valiosa en la detección y tratamiento de esta enfermedad.

In this Scoping Review, we present the evidence recorded in the literature about that oral microbiota can generate a carcinogenic action, acting through three main mechanisms: on the extracellular space, activating intracellular signaling pathways and/or generating direct action on DNA, and that the principal pathogens studied are Fusobacterium nucleatum and Porphyromona gingivalis. Nowadays, there is sufficient evidence about the association between oral microbiota and several types of cancer, however, there is not much knowledge about the mechanisms by which this microbiota participates in its development. We present a compilation of different mechanisms of action used by oral cavity bacteria in the process of carcinogenesis in four different types of cancer. It is of great importance to increase the knowledge about the etiological role of the oral microbiota in the development of cancer disease because it would be established as a new carcinogenic agent and its knowledge could be used as a valuable tool in the detection and treatment of this disease.

Chemopreventive agents on a mouse skin carcinogenesis model: an integrative review / Agentes quimiopreventivos em um modelo de carcinogênese de pele em camundongos: uma revisão integrativa / Agentes quimiopreventivos en un modelo de carcinogénesis cutánea en ratón: una revisión integradora

Squamous cell carcinoma (SCC) is a non-melanoma skin cancer, with chronic sun exposure as the main risk factor. Excisional surgery is the most indicated treatment; however, patients can suffer functional, aesthetic, and psychological damage depending on the lesion site. Topical administration of 7,12-dimethylbenz[a]anthracene (DMBA) and 12-O-Tetradecanoylphorbol-13- acetate (TPA) induce to the appearance of benign skin tumors in mice, some of which develop into SCC. This protocol has been used to analyze the effects of many chemopreventive agents that may block or inhibit the mechanisms of action of chemical carcinogenesis. We compared the effects of chemopreventive agents in an induced skin carcinogenesis animal model. In the Scopus, PubMed, and EMBASE databases, we searched for manuscripts published between June 16, 2011, and June 16, 2021. We excluded studies conducted in vitro or on transgenic mice; in addition, studies without drug dosage, route of administration, or tumor incidence were excluded. We selected 26 studies and analyzed their main characteristics and the outcomes of tumorigenesis analysis. Most chemopreventive agents have shown excellent potential to inhibit the development of skin tumors. This review also discusses the standardization of studies in animal models to ensure better responses and future randomized clinical trials for cancer treatment and prevention.

O carcinoma espinocelular cutâneo (CEC) é um câncer de pele não melanoma, com a exposição solar crônica como o principal fator de risco. A cirurgia excisional é o tratamento mais indicado; entretanto, os pacientes podem sofrer danos funcionais, estéticos e psicológicos dependendo do local da lesão. A administração tópica de 7,12-dimetilbenz[a]antraceno (DMBA) e 12-O- Tetradecanoilforbol-13-acetato (TPA) induz ao aparecimento de tumores cutâneos benignos em camundongos, alguns dos quais evoluíram para CEC. Este protocolo tem sido utilizado para analisar os efeitos de muitos agentes quimiopreventivos que podem bloquear ou inibir os mecanismos de ação da carcinogênese química. Comparamos os efeitos de agentes quimiopreventivos em um modelo animal que foi induzido à carcinogênese de pele. Nas bases de dados Scopus, PubMed e EMBASE, buscamos manuscritos publicados entre 16 de junho de 2011 e 16 de junho de 2021. Excluímos estudos realizados in vitro ou em camundongos transgênicos; além disso, estudos sem dosagem de drogas, via de administração ou incidência de tumores foram excluídos. Selecionamos 26 estudos e analisamos suas principais características e os resultados da análise da tumorigênese. A maioria dos agentes quimiopreventivos tem demonstrado excelente potencial para inibir o desenvolvimento de tumores cutâneos. Esta revisão também discute a padronização de estudos em modelos animais para garantir melhores respostas e futuros ensaios clínicos randomizados para tratamento e prevenção do câncer.

El carcinoma de células escamosas (CCE) es un cáncer de piel no melanoma, cuyo principal factor de riesgo es la exposición crónica al sol. La cirugía de escisión es el tratamiento más indicado; sin embargo, los pacientes pueden sufrir daños funcionales, estéticos y psicológicos dependiendo de la localización de la lesión. La administración tópica de 7,12-dimetilbenz[a]antraceno (DMBA) y 12-O-Tetradecanoilforbol-13-acetato (TPA) inducen a la aparición de tumores cutáneos benignos en ratones, algunos de los cuales se convierten en CCE. Este protocolo se ha utilizado para analizar los efectos de muchos agentes quimiopreventivos que pueden bloquear o inhibir los mecanismos de acción de la carcinogénesis química. Comparamos los efectos de los agentes quimiopreventivos en un modelo animal de carcinogénesis cutánea inducida. En las bases de datos Scopus, PubMed y EMBASE, se buscaron los manuscritos publicados entre el 16 de junio de 2011 y el 16 de junio de 2021. Se excluyeron los estudios realizados in vitro o en ratones transgénicos; además, se excluyeron los estudios sin dosis de fármacos, vía de administración o incidencia tumoral. Se seleccionaron 26 estudios y se analizaron sus características principales y los resultados del análisis de la tumorigénesis. La mayoría de los agentes quimiopreventivos han mostrado un excelente potencial para inhibir el desarrollo de tumores cutáneos. Esta revisión también analiza la estandarización de los estudios en modelos animales para garantizar mejores respuestas y futuros ensayos clínicos aleatorios para el tratamiento y la prevención del cáncer.

Experimental carcinogenesis with 7, 12-dimethylbenz(a)anthrazene (DMBA) and its inhibition with isothi-ocyanates / Carcinogénesis experimental con 7, 12-dimetilbenzantraceno (DMBA) y su inhibición con isitiocianatos

Introduction: DMBA is a chemical carcinogen that induces carcinomas within a few weeks of its application. We developed an experimental model of carcinogenesis induced by DMBA dissolved in 0,5% paraffin oil (DMBA-PO), verifying the inhibitory effect of the carcinogenicity of phenyl isothiocyanate (PhITC), phenethyl (PhnITC) and benzyl isothiocyanate (BITC). Material and Methods: For this, 88 hamsters were distributed into three groups: one exposed to DMBA-PO (Group 1, n=12), three subgroups (n=12) exposed to PhITC, PhnITC, BITC and DMBA-PO (Group 2, n=36) and four control subgroups (n=10) that were not exposed to the carcinogen in which PO (paraffin oil) and isothiocyanates were applied (Group 3, n=40). Results: The experiment had a duration of 20 weeks, at the end of which the inhibitory effect was established by comparing the lesions developed in the groups that received isothiocyanates with the group that was only treated with DMBA-PO. The carcinogenic effect of DMBA-PO is 100% (35 carcinomas) and the inhibitory effect was 0, whereas in the presence of isothiocyanates the carcinogenic effect decreases, with an inhibitory effect of 86% for BITC (5 carcinomas) and 74% for PhITC (9 carcinomas). Conclusion: The inhibitory effect for PhnITC is 80% in relation to invasive OSCC (1 carcinoma).

Introducción: El DMBA es un carcinógeno químico que induce carcinomas a las pocas semanas de su aplicación. Desarrollamos un modelo experimental de carcinogénesis inducida por DMBA disuelto en aceite de parafina al 0,5% (DMBA-Ap) comprobando el efecto inhibidor de la carcinogénesis de los isotiocianatos fenil (PhITC), fenetil (PhnITC) y bencil isotiocianato (BITC). Material y Métodos: Para ello, se distribuyeron 88 hámsteres en 3 grupos: uno expuesto al DMBA-Ap (Grupo 1, n=12), tres subgrupos (n=12) expuestos a PhITC, PhnITC, BITC y DMBA-Ap (Grupo 2, n=36) y cuatro subgrupos controles (n=10), no expuestos al carcinógeno en el que se aplicaron Ap e isotiocianatos (Grupo 3, n=40). Resultados:El experimento tuvo una duración de 20 semanas, al final de la cual se establece de forma comparativa el efecto inhibidor comparando las lesiones desarrolladas en los grupos que recibieron isotiocianatos con respecto al grupo tratado sólo con DMBA-Ap. El efecto carcinógeno del DMBA-Ap es del 100% (35 carcinomas) y el efecto inhibidor 0, mientras que en presencia de isotiocianatos el efecto carcinógeno disminuye, con un efecto inhibidor del 86% para BITC (5 carcinomas) y del 74% para el PhITC (9 carcinomas). Conclusión:El efecto inhibidor del PhnITC es del 80% en relación con el COCE invasivo (1 carcinoma).

Human papillomavirus and head and neck squamous cell carcinoma in a UK population: Is there an association?

Background: Human papillomavirus (HPV) is an evolving important risk factor for head and neck cancer (HNC) especially for individuals who do not smoke and drink alcohol. The aim of this study was to establish the prevalence of HPV infection and elucidate its association with head and neck squamous cell carcinoma (HNSCC) patients in UK population. Methods: The presence and association of HPV was investigated in HNSCC patients in this retrospective clinical study. Samples were obtained from archived biopsies and resections. HPV screening was performed by the use of polymerase chain reaction (PCR) using the GP5+/GP6+ and the SPF1/2 consensus as primers and by immunohistochemistry (IHC). Samples of viral warts that were IHC positive for HPV and fibroepethelial polyps (FEP) were used as positive and negative controls respectively. Results: The cohort included 124 patients with HNSCC with an age range of 27–97 years (median 60 years) and a male to female ratio of 2:1. Among the 124 HNSCC 43/124 (34.7%) were from the tongue 74/124 (60%) presented with advanced stage III or IV disease 112/124 (90%) had a conventional phenotype 84/124 (68%) were moderately differentiated and 89/124 (72%) had bands or cords at the invasive front. Of the 124 patients with HNSCC 84/124 (68%) demonstrated the presence of HPV 0/124 (0%) was for oral squamous cell carcinomas (OSCC). HPV16 was the associated virus type in all positive samples. However no significant association was observed between HPV positivity and other clinico-pathological variables including age and gender of the patients stage and malignancy differentiation. Conclusion: The results we provide suggest that HPV infection is low in HNSCC in general and absent in OSCC specifically in this UK population during this time period. This implies that HPV infection may not play an important role in HNSCC carcinogenesis compared to other risk factors in UK population. This information can aid in more effective treatment approaches for treating UK cases of HNSCC.

Progress of Research on the Relationship between Lung Microbiome and Lung Cancer / 中国肺癌杂志

The microbiota plays an important role in the biological functions of the human body and is associated with various disease states such as inflammation (gastritis, hepatitis) and cancer (stomach, cervical, liver). The Human Microbiome Project painted a panorama of human microorganisms in its first phase, incorporating body parts such as the nasal cavity, oral cavity, intestine, vagina and skin, while the lungs were considered a sterile environment. However, studies in recent years have confirmed the presence of a rich microbial community in the lung, and the association of this lung microbiota with lung disease has become a hot topic of research. Current research has found that patients with lung cancer have a specific microbiota compared to healthy individuals or patients with lung disease. Even in patients with lung cancer, a lung microbiota specific to the tumor site is present. In addition, different pathological types and metastatic status of lung cancer can lead to differences in microbiota. Mechanistic studies have found that the lung microbiota may influence lung cancer development by affecting the immune response. Clinical studies on lung microbiota and immunotherapy are still in the preliminary stage. More relevant studies are needed in the future to provide high-quality evidence to further understand the oncogenic mechanisms of lung microbiota and provide new ideas for clinical treatment. This paper briefly reviews the progress of lung microbiota research in terms of its relevance to lung cancer, possible molecular mechanisms and applications in clinical treatment, and provides an outlook for future research.
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Peroxidase from foxtail millet bran exerts anti-colorectal cancer activity via targeting cell-surface GRP78 to inactivate STAT3 pathway

Molecular targeted therapy has become an emerging promising strategy in cancer treatment, and screening the agents targeting at cancer cell specific targets is very desirable for cancer treatment. Our previous study firstly found that a secretory peroxidase of class III derived from foxtail millet bran (FMBP) exhibited excellent targeting anti-colorectal cancer (CRC) activity in vivo and in vitro, whereas its underlying target remains unclear. The highlight of present study focuses on the finding that cell surface glucose-regulated protein 78 (csGRP78) abnormally located on CRC is positively correlated with the anti-CRC effects of FMBP, indicating it serves as a potential target of FMBP against CRC. Further, we demonstrated that the combination of FMBP with the nucleotide binding domain (NBD) of csGRP78 interfered with the downstream activation of signal transducer and activator of transcription 3 (STAT3) in CRC cells, thus promoting the intracellular accumulation of reactive oxygen species (ROS) and cell grown inhibition. These phenomena were further confirmed in nude mice tumor model. Collectively, our study highlights csGRP78 acts as an underlying target of FMBP against CRC, uncovering the clinical potential of FMBP as a targeted agent for CRC in the future.

A bibliometric and visual analysis of research on carcinogenesis of nickel and nickel compounds / 环境与职业医学

Background Metallic nickel and nickel compounds are classified as possibly carcinogic and carninogic to humans respectively, but the exact carcinogenic mechanism has not been clarified. Objective To analyze the carcinogenic research trend and hotspots of nickel and nickel compounds, and provide research directions for this topic. Methods Literature search on the carcinogenesis of nickel and nickel compounds was conducted through authoritative databases at home and abroad: Wanfang, China National Knowledge Infrastructure, PubMed at the US National Library of Medicine, and Elsevier’s biomedical research database EMBASE. VOS viewer 1.6.17 visual analysis software was applied to perform the bibliometric analysis and present results with charts on annual number of publications, distribution of author’s affiliations, country/region distribution, journal distribution, and keywords of literature that meet a predetermined inclusion criteria. Results A total of 242 Chinese documents and 878 foreign documents (languages included English, German, and Japanese) related to the carcinogenic research of nickel and nickel compounds were found. In terms of Chinese articles, the earliest publication of relevant research was in 1974; Guangzhou Medical University (including Guangzhou Medical College and Institute of Chemical Carcinogenesis of Guangzhou Medical College) was the institution that published most articles in this field (35 articles); Industrial Health and Occupational Diseases was the journal that published the most articles (19 articles). In terms of foreign articles, the earliest publication was in 1950; the United States ranked the country having the highest number of published articles (304 articles), and China took the second place (83 articles); Cancer Research was the journal that published the most articles (40 articles). The keyword co-occurrence analysis showed that the domestic studies on the carcinogenesis of nickel and nickel compounds mainly focused on nickel smelting fume, nickel sulfate, nickel chloride, and other nickel and its compounds in association with DNA damage, DNA methylation, induction of human bronchial epithelial cell transformation, and other carcinogenic mechanisms. The international studies focused on population epidemiological studies on occupational risk factors, incidence, and mortality on carcinogenesis of nickel and nickel compounds, and studies on histone modification, oxidative stress, DNA damage, cell transformation, and other carcinogenic mechanisms. Conclusion Studies have shown that the hotspots of carcinogenic research on nickel and nickel compounds involved studies on carcinogenic mechanisms related to DNA damage, DNA methylation, histone modification, oxidative stress, and induction of human bronchial epithelial cell transformation, and population epidemiological studies on occupational risk factors, incidence, and mortality. In recent years, the number of published articles on the carcinogenesis of nickel and its compounds in China has been decreasing. In view of the large number of occupational nickel-exposed population in China, more efforts should be made to study the carcinogenesis of nickel and nickel compounds in the future.

Lung histopathological changes in Swiss mice exposed to narghile smoke

ABSTRACT Objective To investigate the histological influence of waterpipe smoke exposure on lung tissues of Swiss mice during the periods of 7, 15, 30, 60, and 90 days. Methods The sample consisted of 60 animals, divided into 6 groups, one control group, exposed only to air, and the other experimental groups, daily submitted to water pipe smoke for 30 minutes through the whole body system, for 7, 15, 30, 60 and 90 days. After these periods, the mice were euthanized to obtain the tissue samples and subsequent preparation and analysis of histological slides. Results In the slide microscopy, the control group presented normal aspects. In experimental groups, exacerbation of inflammation was observed, there was a increased thickness of intra-alveolar septa, reduced alveolar lumen, areas of ciliary loss, and neovascular formation. And as the animals' exposure to smoke was extended, the progressive exacerbation of these pulmonary changes was noted. Conclusions The exposure to waterpipe smoke stimulates inflammation and cellular changes in lung tissues of Swiss mice and suggests that the longer the animals' exposure period, the more exacerbated this picture will appear.

Análise proteômica de células BEAS-2B expostas a benzo[α]pireno e nicotinamida ribosídeo / Proteomic Analysis of BEAS-2B cells exposed to benzo[α]pyrene and nicotinamide riboside

Responsável por milhões de óbitos anuais e um grande custo para a saúde pública, o câncer é a segunda maior causa de mortes no mundo. Dentre seus diversos tipos, o câncer de pulmão, além da alta incidência, é um dos mais letais. A exposição a substâncias tóxicas provenientes da combustão de matéria orgânica, assim como o consumo de cigarro, são os principais responsáveis pela alta incidência de câncer de pulmão. Dentre estas substâncias, está o benzo[α]pireno (B[α]P), um carcinógeno completo, ou seja, capaz de iniciar e promover o processo de carcinogênese. Resultados anteriores obtidos pelo grupo demonstraram que células BEAS-2B expostas a 1 µM de B[α]P apresentaram alterações das concentrações de metabólitos intracelulares, indução de estresse redox e hipermetilação do DNA. A exposição a 1 µM de nicotinamida ribosídeo (NR), um dos precursores de NAD+, foi capaz de proteger as células BEAS-2B contra a transformação induzida por B[α]P, além de impedir totalmente que células não expostas a B[α]P formassem colônias em soft-agar. A utilização da proteômica neste trabalho permitiu verificar a abundância das proteínas nos quatro diferentes grupos de exposição: Controle, B[α]P, B[α]P + NR e NR. Após 120 h de exposição as células foram coletadas, as proteínas extraídas e preparadas para análise. Foram descobertas 3024 proteínas posteriormente analisadas com o objetivo de elucidar vias possivelmente envolvidas na proteção contra o processo de transfomação maligna. Os grupos NR e Controle demonstram ser mais parecidos em relação ao seu conteúdo, enquanto os grupos B[α]P e B[α]P + NR foram mais semelhantes entre si. A análise de proteínas exclusivas revelou menos processos relacionados ao reparo de DNA no grupo tratado apenas com B[α]P quando comparado com B[α]P + NR. A análise estatística do total de proteínas utilizando o teste ANOVA (p < 0,05, N = 5) revelou 564 proteínas diferencialmente expressas entre os grupos. A clusterização nos permitiu observar a diferença na abundância de proteínas entre os quatro tratamentos. As proteínas estão envolvidas em funções como a regulação do metabolismo, resposta a estresse, transdução de sinal, regulação de expressão gênica e morte celular. Um dos clusters (cluster 1), contendo 59 proteínas, revelou poucos processos na análise de enriquecimento, mas as proteínas contidas nele apresentam funções como controle da divisão celular, apoptose e proteção ao estresse redox. Nele podemos observar que, no geral, o tratamento com B[α]P aumentou a abundância de algumas proteínas, o que foi revertido no grupo B[α]P + NR. O tratamento apenas com NR diminuiu a abundância das proteínas contidas nesse cluster. Outro cluster (cluster 4) apresentou 51 proteínas de abundância diminuída durante a exposição ao B[α]P, o que se reverteu no grupo B[α]P + NR. As proteínas desse cluster estão envolvidas em etapas importantes da via glicolítica, de crescimento, adesão, migração e invasão celular. Apesar de ser descrito que a exposição a NR pode aumentar a eficiência do reparo de DNA, os resultados apresentados nesse trabalho indicam que o efeito protetor pode estar relacionado com a modulação do ciclo celular ou alterações na adesão celular

Responsible for millions of annual deaths and a great health expense, cancer is the second leading cause of death in the world. Among its many types, lung cancer, besides its high incidence, is also one of the most lethal. Exposure to toxic substances resulting from the combustion of organic matter, as well as cigarette consumption, are the mainly responsible for the high incidence of lung cancer. One of these substances is benzo[α]pyrene (B[α]P), a complete carcinogen, able to initiate and promote the carcinogenesis process. Results obtained previously demonstrated that BEAS-2B cells exposed to 1 µM BaP presented alterations in the levels of intracellular metabolites, induction of oxidative stress, and hypermethylation of DNA. The exposure to 1 µM nicotinamide riboside (NR), one of the precursors of NAD+, was able to protect BEAS-2B cells against the transformation induced by B[α]P, moreover, it also totally prevented the colonies formation on soft agar in cells not exposed to B[α]P. The use of proteomics allowed us to verify the abundance of proteins in the four different exposure groups: Control, B[α]P, B[α]P + NR e NR. After 120h of exposure, the cells were collected followed by the extraction of the proteins. A total of 3024 proteins were identified and analyzed aiming to elucidate possible pathways involved in the protective effect against the malignant transformation induced by B[α]P. The NR and Control groups showed to be more similar, while B[α]P and B[α]P + NR were more similar. The analysis of exclusive proteins revealed fewer processes related to DNA repair in B[α]P when compared with B[α]P + NR. The statistical analysis of the total proteins using the ANOVA test (p <0.5, N = 5) revealed 564 proteins differentially expressed between the groups. The heatmap showed the difference in protein abundance between the four treatments. Proteins are involved in functionssuch asthe regulation of metabolism, stress response, signal transduction, regulation of gene expression, and cell death. One of the clusters (cluster 1), containing 59 proteins, revealed a few processes in the enrichment analysis, but the proteins contained in it have functions such as control of cell division, apoptosis, and protection from redox stress. It is possible to observe, in general, treatment with B[α]P increased the abundance of some proteins, which was partially reversed in group B[α]P + NR. On the other hand, the NR treatment decreased the abundance of proteins contained in this cluster. Another cluster (cluster 4) showed 51 proteins of decreased abundance during exposure to B [α] P, which was partially reversed in group B[α]P + NR. The proteins in this cluster are involved in important stages of the glycolytic pathway, also in growth, adhesion, migration, and cell invasion. Although it has been described that exposure to NR can increase the efficiency of DNA repair, the results presented in this work indicate that the protective effect may be related to the modulation of the cell cycle or cell adehsion modifications

Exposição a agrotóxicos e desenvolvimento de câncer no contexto da saúde coletiva: o papel da agroecologia como suporte às políticas públicas de prevenção do câncer / Exposure to pesticides and cancer development in the context of public health: the role of agroecology as a support for public cancer prevention policies

RESUMO Atualmente, a agricultura brasileira é caracterizada pelo crescente consumo de agrotóxicos e fertilizantes químicos, inserindo-se no modelo de produção baseado nos fundamentos do agronegócio. As novas técnicas de cultivo baseadas no agronegócio resultaram na expansão das monoculturas sobre os ecossistemas naturais, com o consequente desmatamento, desequilíbrio e perda da biodiversidade; e o aumento da contaminação do solo, da água e do ar pelos agrotóxicos. No que tange à saúde humana, a literatura científica tem demonstrado que a contaminação química decorrente do uso de agrotóxicos na agricultura implica adoecimento dos trabalhadores rurais expostos ocupacionalmente aos agrotóxicos, dos moradores da área rural, além de consumidores de alimentos contendo resíduos de agrotóxicos. Entre os efeitos sobre a saúde humana associados à exposição a agrotóxicos, os mais preocupantes são as intoxicações crônicas, caracterizadas por infertilidade, abortos, malformações congênitas, neurotoxicidade, desregulação hormonal, imunotoxicidade, genotoxicidade e câncer. Sendo assim, neste ensaio, apresenta-se uma revisão narrativa com dados presentes na literatura científica nacional e internacional referentes à associação entre a exposição a agrotóxicos e o desenvolvimento de câncer no contexto da saúde coletiva e o papel da alimentação saudável e da agroecologia como suporte às políticas públicas de prevenção do câncer.

ABSTRACT Currently, Brazilian agriculture is characterized by the growing consumption of pesticides and chemical fertilizers, forming part of the production model based on the fundamentals of agribusiness. The new farming techniques based on agribusiness resulted in the expansion of monocultures over natural ecosystems, with the consequent deforestation, imbalance, and loss of biodiversity; and the increased contamination of soil, water, and air by pesticides. With regard to human health, the scientific literature has shown that chemical contamination resulting from the use of pesticides in agriculture implies the illness of rural workers occupationally exposed to pesticides, of rural residents, in addition to consumers of food containing pesticide residues. Among the effects on human health associated with exposure to pesticides, the most worrying are chronic intoxications, characterized by infertility, abortions, congenital malformations, neurotoxicity, hormonal dysregulation, immunotoxicity, genotoxicity, and cancer. Therefore, in this essay, we will present a narrative review with data from national and international scientific literature regarding the association between exposure to pesticides and the development of cancer in the context of public health and the role of healthy eating and agroecology as a support for public cancer prevention policies.