RESUMO

Introduction: Worldwide, breast cancer is the most important cancer in incidence and prevalence in women. Different risk factors interact to increase the probability of developing it. Biological agents such as helminth parasites, particularly their excretory/secretory antigens, may play a significant role in tumor development. Helminths and their antigens have been recognized as inducers or promoters of cancer due to their ability to regulate the host's immune response. Previously in our laboratory, we demonstrated that chronic infection by Toxocara canis increases the size of mammary tumors, affecting the systemic response to the parasite. However, the parasite does not invade the tumor, and we decided to study if the excretion/secretion of antigens from Toxocara canis (EST) can affect the progression of mammary tumors or the pathophysiology of cancer which is metastasis. Thus, this study aimed to determine whether excretion/secretion T. canis antigens, injected directly into the tumor, affect tumor growth and metastasis. Methods: We evaluated these parameters through the monitoring of the intra-tumoral immune response. Results: Mice injected intratumorally with EST did not show changes in the size and weight of the tumors; although the tumors showed an increased microvasculature, they did develop increased micro and macro-metastasis in the lung. The analysis of the immune tumor microenvironment revealed that EST antigens did not modulate the proportion of immune cells in the tumor, spleen, or peripheral lymph nodes. Macroscopic and microscopic analyses of the lungs showed increased metastasis in the EST-treated animals compared to controls, accompanied by an increase in VEGF systemic levels. Discussion: Thus, these findings showed that intra-tumoral injection of T. canis EST antigens promote lung metastasis through modulation of the tumor immune microenvironment.

Assuntos

Neoplasias da Mama , Parasitos , Toxocara canis , Toxocaríase , Humanos , Feminino , Animais , Camundongos , Antígenos de Helmintos , Injeções Intralesionais , Pulmão , Microambiente Tumoral

RESUMO

Breast cancer treatment failure is related to low response rates, high costs, and long-term toxicities. Thus, it is necessary to find less toxic, cheaper, and more effective treatments. In situ administration ensures drug delivery to tumor cells and decreases systemic toxic effects. The androstene-3ß, 17α-diol (α-AED) reduces breast tumor cell proliferation and is an ideal candidate to treat mammary tumors. This study aims to identify the in vitro and in vivo effects of α-AED on a triple-negative mammary tumor model. An in vitro biphasic steroid effect was observed in mouse and human mammary tumor cells treated with α-AED. In this sense, cells treated with higher doses (100 and 200 µM) showed an antiproliferative effect. The α-AED administrated intratumorally reduced average tumor weight and increased the percentage of natural killer cells (NK), plasmatic, and plasmablast cells in mice tumors. Of note, VEGF levels in all α-AED-treated tumors was lower than in the control and vehicle groups. The tumor in situ increased response was reflected systemically by higher anti-4T1 IgG concentration in serum from α-AED-treated mice, but no other associated systemic changes were detected. The reduction in tumor size for the local injection of α-AED is associated with the anti-proliferative effect of this steroid, and the lower local levels of VEGF may be related to the imperceptible macroscopic metastasis in α-AED-treated mice. The above suggests that α-AED may be used in clinical studies to prove its efficacy as an alternative breast tumor treatment or in conjunction with already established therapies.

Assuntos

Neoplasias da Mama , Neoplasias Pulmonares , Androstenos , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Imunoglobulina G , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Modelos Teóricos , Fator A de Crescimento do Endotélio Vascular

RESUMO

INTRODUCTION: Former studies have shown that hematologic parameters are affected by the SARS-CoV-2 infection which has caused a global health problem. Therefore, this research aims to identify the most frequent symptoms and comorbidities in SARS-CoV-2 infected outpatients; besides, to analyze hematological parameters and their correlation with cycle threshold (Ct) values. METHODS: We analyzed a total of sixty outpatients with SARS-CoV-2 infection. They were divided according to sex. Afterward, a questionnaire was carried out to find out their symptoms and comorbidities. Additionally, blood biometry data were correlated with the Ct value, respectively. RESULTS: Sixty patients were analyzed; the mean age was 43 years. All patients were from Nayarit, Mexico. The frequency index showed that the main symptoms were headache and anosmia, and the comorbidities were obesity and smoking. The analysis of blood biometry showed a clear increase in red blood cells (RBC) related parameters in women. In both sexes an increase in the number of white blood cells (WBC) was observed. Also, all the hematological alterations correlated with the grade of infection. CONCLUSION: Headache and anosmia are the most common symptoms according to the frequency index, the main comorbidities were obesity and smoking. Also, there is a Ct value correlation with hematological parameters (WBC, mean corpuscular volume, mean corpuscular hemoglobin, hemoglobin); they can be used as a prognostic marker of infection.

Assuntos

COVID-19/sangue , Adulto , Idoso , COVID-19/diagnóstico , COVID-19/epidemiologia , Contagem de Eritrócitos , Índices de Eritrócitos , Feminino , Hematócrito , Humanos , Contagem de Leucócitos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , SARS-CoV-2/isolamento & purificação , Adulto Jovem

RESUMO

Worldwide, breast cancer is the most important type of cancer in women with regard to incidence and prevalence. Several risk factors interact to increase the probability of breast cancer development. Biological environmental contaminants such as infectious agents play a significant role in tumor development, and helminths have been recognized as cancer enhancers or inducers due to their ability to regulate the host immune response. Toxocara canis is a zoonotic and cosmopolite nematode with immuno-regulatory abilities. T. canis infection has been related to T helper type-2 cell (Th2 or type 2) and regulatory responses. Type 2 and regulatory immune responses may favor the development of comorbidities that are usually controlled or eliminated through a type 1 response such as cancer. The aim of this study was to determine whether T. canis infection alters mammary tumor growth through modulation of the immune response. Infected mice developed larger tumors. Tumor immune cell milieu analysis revealed that infection reduced the proportions of CD8+ lymphocytes and increased the proportions of F4/80+ macrophages and CD19+ B cells. These changes were accompanied by a type 2 local response represented by increased amounts of IL-4 and VEGF and a regulatory microenvironment associated with higher IL-10 levels. Thus, this study demonstrates that T. canis infection enhances tumor development and suggests that this is through modulation of the tumor immune microenvironment.