Biomarkers in Non-Small Cell Lung Cancer: Perspectives of Individualized Targeted Therapy.

INTRODUCTION: The understanding of cancer has evolved into a complex disease, which has heterogeneous characteristics between different patients, and more than that, a broad range of genetically distinct cells in the same tumor. Chronic and non-transmissible diseases such as cancer have become even more important worldwide and advances in their characterization and properties are running out. In a suitable setting, early diagnosis of cancer and proper treatment are essential to overcome the barriers of tumor healing and quality assurance of the patient's life. The studies included in the analysis were independently retrieved by the authors. The text words included "Non-Small Cell Lung Cancer," "NSCLC," "biomarkers in NSCLC" and "gene in NSCLC"." We were used to perform a systematic literature search in the PubMed and Web of Science databases. There was limit on the start date for published articles (2001), and the search ended in December 2017. For a more comprehensive analysis, articles were only in English. Non-small Cell Lung Cancer (NSCLC) Microenvironment: This review focuses on lung cancer, especially NSCLC, one of the most worldwide common cancer types, showing the importance of tumor microenvironment in this disease. NSCLC Biomarkers: This review shows a molecular aspect of NSCLC biomarkers used in clinical approaches, such as EGFR, KRAS, MET, indicating mutations that are crucial for cancer progression and related to treatment properties. We also describe 11 drugs commonly used in cancer treatment that are correlated with the patient genetic profile. CONCLUSION: This review highlights the importance of molecular diagnosis of mutations in lung cancer, driving to individualized therapy with the intent of getting a better response to treatment and improving patients' quality of life.

The prognostic value of regulatory T cells infiltration in HER2-enriched breast cancer microenvironment.

Breast cancer represents a complex and heterogeneous disease that comprises distinct disease conditions, histological features, and clinical outcome. Since many years, it has been demonstrated as an association between HER2 amplification and poor prognosis, because its overexpression is associated with an aggressive phenotype of breast tumor cells. A significant proportion of cases have developed resistance to the current therapies available. Consequently, new prognostic markers are urgently needed to identify patients who are at the highest risk for developing metastases. During the past decade, new insights provided valuable knowledge regarding mechanisms underlying the dynamic interplayed between immune cells and tumor progression. It has been shown that the presence of a lymphocytic infiltrate, particularly of regulatory T cells, in cancer tissue, is associated with clinical outcome promoting rather than inhibiting cancer development and progression. It has been also verified that the clinical value of lymphocytic infiltration in breast cancers could be subtype-dependent, including the HER2-enriched subtype. In this context, this work summarizes proposed to discuss the prognostic value of regulatory T cell infiltration in microenvironment of HER2-enriched breast cancer.

Propolis reduces Leishmania amazonensis-induced inflammation in the liver of BALB/c mice.

Experimental models of mouse paw infection with L. amazonensis show an induction of a strong inflammatory response in the skin, and parasitic migration may occur to secondary organs with consequent tissue injury. There are few studies focusing on the resolution of damage in secondary organs caused by Leishmania species-related cutaneous leishmaniasis. We investigated the propolis treatment effect on liver inflammation induced by Leishmania amazonensis infection in the mouse paw. BALB/c mice were infected in the hind paw with L. amazonensis (10(7)) promastigote forms. After 15 days, animals were treated daily with propolis (5 mg/kg), Glucantime (10 mg/kg), or with propolis plus Glucantime combined. After 60 days, mice were euthanized and livers were collected for inflammatory process analysis. Liver microscopic analysis showed that propolis reduced the inflammatory process compared to untreated infected control. There was a decrease of liver myeloperoxidase and N-acetyl-ß-glucosaminidase activity levels, collagen fiber deposition, pro-inflammatory cytokine production, and plasma aspartate transaminase and alanine transaminase levels. Furthermore, propolis treatment enhanced anti-inflammatory cytokine levels and reversed hepatosplenomegaly. Our data demonstrated that daily low doses of Brazilian propolis reduced the secondary chronic inflammatory process in the liver caused by L. amazonensis subcutaneous infection in a susceptible mice strain.

Increased oxidative stress in foam cells obtained from hemodialysis patients.

Premature atherosclerosis represents the main cause of mortality among end-stage renal disease patients (ESRD). Increased inflammation and oxidative stress are involved in initiation and progression of the atherosclerotic plaque. As foam cells are capable of producing significant amounts of inflammatory mediators and free radicals, we hypothesized that foam cells from uremic patients could produce more inflammation and oxidative stress than foam cells from normal people and be, somehow, involved in the accelerated atherosclerosis of uremia. To test this hypothesis, the levels of a few markers of inflammation and oxidative stress: Tumor necrosis factor-α, inducible nitric oxide synthase, malondialdehyde, nitric oxide by-products were measured in the supernatants of macrophage-derived foam cells cultures from 18 hemodialysis patients and 18 apparently healthy individuals controls. Malondialdehyde levels in the supernatant of cell cultures (macrophages stimulated or not with native and oxidized lipoprotein) were significantly increased in uremic patients; no statistically significant difference was found between the supernatant concentrations of nitric oxide by-products, inducible nitric oxide synthase activity, and tumor necrosis factor-α between patients and controls. Our results, obtained with human macrophages and macrophage-derived foam cells, are compatible with the theory that increased cellular oxidative stress and inflammatory activity in ESRD patients could accelerate the atherosclerotic process. The present culture protocol showed it is possible to use human mononuclear cells to evaluate the oxidative metabolism of foam cells, which are considered to be the initial step of atherosclerotic lesions.

Serological evidence of Paracoccidioides brasiliensis infection in chickens from Paraná and Mato Grosso do Sul States, Brazil.

The objective of this study was to detect antibodies against Paracoccidioides brasiliensis in free-range and caged chickens Gallus domesticus. Initially, the humoral immune response of two chickens immunized with P. brasiliensis was evaluated. Both animals showed the production of antibodies to gp43, the major P. brasiliensis antigen. The seroepidemiological survey was conducted in chickens from the Pantanal region in Mato Grosso do Sul State (free-range n = 40) and from northern region of Paraná State (free-range n = 100, caged n = 43). The serum samples were analyzed by indirect ELISA using gp43 as antigen. The positivity observed in free-range chickens from Mato Grosso do Sul (55%) was significantly higher (P = 0.0001) than in free-range chickens from Paraná State (16%). In contrast to the free-range chickens, no positivity was observed in the caged chickens (P = 0.003). This is the first report showing serological evidence of P. brasiliensis infection in chickens. The results suggest that free-range chickens are more frequently infected by P. brasiliensis, probably due to the constant contact with soil than caged chickens and could be useful as epidemiological markers of paracoccidioidomycosis.

Involvement of regulatory T cells in HIV immunopathogenesis.

Recently, a mechanism of negative regulation of immune responses by a specialized population of so-called regulatory T cells (Tregs) has become a focus of intense investigation. Through the discovery of transcription factor Foxp3 as a central molecular determinant of Tregs differentiation and function, the complex biology of these cells, including maintenance of immunological tolerance to "self" and regulation of immune responses to pathogens, commensals, and tumors, has become the focus of intense investigation. The ability to control the infection and to delay the progression of the infection to AIDS and/or death is probably regulated by a balance between host factors, such as immunologic response and viral factors. Different rates of disease progression among HIV-1 infected individuals have been observed. In this context, Tregs may play an important role in the immunopathology of HIV-1 infection due to their potent suppressive activity of both T cell activation and effector function. In this review, we present the molecular and immunological aspects of Tregs in the HIV system and the association between Tregs and highly active antiretroviral therapy (HAART).