A meta-analysis evaluating the role of calcium channel alpha-2 delta-1 subunit in carcinogenesis

There is hardly found any study accumulating all the experiments reported with the expression of alpha-2 delta-1 (?2?-1) in cancer cells. This meta-analysis aimed to advance our knowledge about the role of calcium channel alpha2 delta-1 subunit in carcinogenesis in the present time. PubMed searches for peer-reviewed articles were conducted using the keywords “?2?-1 protein in oncogenesis”, “?2?-1 protein expression in cancer cells”, and “?2?-1 protein as cancer cell marker”. The databases were developed in accordance with PRISMA guidelines. Seventeen studies out of 80 citations met the inclusion criteria pertaining to ?2?-1 expression in different cancer cells. The cancer patterns were hepatocellular carcinoma in 41%, non-small cell lung carcinoma in 12% and laryngeal squamous cell carcinoma in 12%. The remaining studies included small-cell lung cancer (6%), gastric cancer (6%), pancreatic cancer (6%), hypopharyngeal squamous cell carcinoma (6%), breast cancer (6%) and glioblastoma multiforme (6%). ?2?-1+ cells had a higher sphere-forming and tumorigenic efficiency in 76.5% of experiments. 58.8% experiments explored mechanistically in self-renewal efficiency and tumorigenesis of ?2?-1+ cancer cells. The cancer cells expressing ?2?-1 have the potential to serve as cell surface markers for tumour-initiating cells and cancer stem cells. These intriguing findings open up a promising avenue for future research, focusing on the targeting of ?2?-1 as a potential therapeutic strategy for cancer treatment.

Pathogenesis of hepatitis B-associated intrahepatic cholangiocarcinoma / 临床肝胆病杂志

Intrahepatic cholangiocarcinoma （ICC） is a type of primary liver cancer that accounts for about 10%‍ — ‍15% of the total cases， and its incidence and mortality rates tend to increase significantly around the world， especially in Asian countries. At present， radical liver resection is the only possible cure for ICC， but with a fairly high postoperative recurrence rate and a poorer prognosis than hepatocellular carcinoma. Therefore， it is urgently needed to further investigate the mechanisms of the development and progression of ICC and search for more effective treatment methods. Some epidemiological data suggest that chronic hepatitis B virus infection is one of the most important predisposing factors for ICC， yet little is known about its oncogenic effects. This article summarizes the epidemiological evidence that links the two diseases and briefly elaborates on the mechanisms of the development and progression of HBV-associated ICC， so as to help to gain a better understanding of the role of HBV in the development and progression of ICC.

Doença hepática gordurosa não-alcoólica e neoplasias extra-hepáticas: uma revisão narrativa / Non-alcoholic fatty liver disease and extra-hepatic cancer: a narrative review

ABSTRACT Background: Recently, significant associations between non-alcoholic fatty liver disease (NAFLD) and extra-hepatic cancer have been reported. Objective: To carry out a comprehensive review of the current evidence in the literature on the association between NAFLD and extra-hepatic cancer. Methods: A narrative literature review was performed through an online search for the MeSH terms "fatty liver" and "cancer" in MEDLINE (via PubMed) and LILACS (via BVS). Original studies that described the impact of NAFLD on different types of extra-hepatic malignancies were included. Results: After careful analysis, nine prospective cohort studies, one retrospective cohort study, three case-control studies, and three cross-sectional studies were selected. Conclusion: There is consistent evidence on the association between NAFLD and extra-hepatic carcinogenesis, especially in relation to colorectal, gastric, pancreatic, breast, prostate, and bladder cancers.

RESUMO Contexto: Recentemente, associações significativas entre a doença hepática gordurosna não-alcoólica (DHGNA) e neoplasias extra-hepáticas têm sido descritas. Objetivo: Realizar uma revisão abrangente acerca das evidências atuais na literatura sobre a associação entre DHGNA e neoplasias extra-hepáticas. Métodos: Uma revisão narrativa de literatura foi realizada através da busca on-line pelos descritores "fígado gorduroso" e "câncer" em MEDLINE (através do PubMed) e LILACS (através da BVS). Estudos originais que descreveram o impacto da DHGNA em diferentes tipos de neoplasias malignas extra-hepáticas foram incluídos. Resultados: Após análise criteriosa, nove estudos prospectivos de coorte, um coorte histórica, três estudos de caso-controle, e três estudos transversais foram selecionados. Conclusão: Existem evidências consistentes a respeito da associação entre DHGNA e a carcinogênese extra-hepática, especialmente em relação aos cânceres de cólon e reto, estômago, pâncreas, mama, próstata e bexiga.

Study of 138 vulvar lichen sclerosus patients and the malignant risk transformation

Abstract Objective To report the prevalence of malignant transformation of vulvar lichen sclerosus (VLS) and possible risk factors. Methods This is a cohort study with data analysis from medical records of 138 patients with histological diagnosis of VLS registered at the Vulvar Pathology Outpatient Clinic of the University Hospital, between 2007 and 2017. Predominance of risk factors was performed using logistic regression analysis. The variables studied were the length of follow-up, age, regular or irregular follow up; presence of symptoms (dyspareunia, pruritus and/or vulvar burning); histology characteristics, the presence of epithelial hyperplasia; and the presence of autoimmune diseases. Results There were 138 patients included in the study, and among them five progressed to malignant transformation. The patients had a median age of 59 years and 83% were symptomatic. The most frequent symptom was itching with 72%. Autoimmune diseases were present in 11.6%, the most prevalent being thyroid disease. All five case of malignant transformation (0.6%) had an irregular follow up. The logistic regression analysis was used among the studied variables, and no statistical significance was found among them (p ≥ 0.05). The relationship between hyperplasia and the clinical outcome of malignant transformation, in which non-significant but acceptable p value close to 0.05 was observed. Conclusion The prevalence of malignant transformation in patients with VLS was 0.6%, and common factors were the lack of adherence to medical treatments and the loss of follow-up.

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.

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

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, argen- tino, con antecedentes de fisura labio alvéolo palatina, diabe- tes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odonto- logía del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias sema- nas 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, fa- lleció 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 evi- dencia 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 me- cánica crónica en la carcinogénesis (AU)

Aim: To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation ap- pears to play a significant role in carcinogenesis. Clinical case: A 41-year-old patient, from Argenti- na, 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 Hospi- tal 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 re- jected, 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 carcino- genesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alco- hol. 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 devel- ops 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 relation- ship of chronic mechanical irritation in the development of carcinogenesis (AU)

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.

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.

Role of ABRACL in the occurrence and development of malignant tumors / 国际肿瘤学杂志

The ABRACL protein, the regulator of actin and cell motility, belongs to the HSPC280 family, and its conserved hydrophobic groove can interact with other proteins to facilitate actin motility and cellular activity. ABRACL is upregulated in tumor tissues and is closely linked with the proliferation and migration of tumor cells. A deeper understanding of the role of ABRACL in tumorigenesis and development may provide new ideas and insights for ABRACL to prevent or reverse tumor progression.

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 progress on metabolic activation of indirect carcinogens by CYP1A1 / 中国职业医学

Cytochrome P450 enzyme 1A1 (CYP 1A1) is one of the main members of CYP1A subfamily, which participates in metabolizing and activating a variety of indirect carcinogens. CYP1A1 can induce carcinogenesis by participating in activating exogenous compounds to produce intermediates or active metabolites that bind to specific biomolecules. CYP1A1 plays a critical role in the metabolic activation of benzo(a)pyrene e ［B(a)P］, and plays a key role in activating the toxic and carcinogenic effects of B(a)P. CYP1A1 involves in the metabolic activation of 7,12-dimethyl benzanthracene and 2-amino-1-methyl-6-phenylimidazo［4,5-b］pyridine (PhIP), and plays an important role in PhIP-induced genotoxicity. CYP1A1 is the main enzyme to metabolize and activate 7H-dibenzo［c,g］carbazole (DBC), a key factor in the carcinogenic effect of DBC. CYP1A1 is also associated with metabolic activation of indirect carcinogens such as aflatoxin B1, 3-nitrobenzene, and naphthalene. Inhibition of the catalytic activity of CYP1A1 can decrease the CYP1A1-mediated activity of carcinogens, thus playing a role in the prevention and treatment of malignant tumors.

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

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

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.

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.

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).