Maria Angelica Ehara Watanabe

Genome of Herbaspirillum seropedicae Strain SmR1, a Specialized Diazotrophic Endophyte of Tropical Grasses

The molecular mechanisms of plant recognition, colonization, and nutrient exchange between diazotrophic endophytes and plants are scarcely known. Herbaspirillum seropedicae is an endophytic bacterium capable of colonizing intercellular spaces of grasses such as rice and sugar cane. The genome of H. seropedicae strain SmR1 was sequenced and annotated by The Paraná State Genome Programme—GENOPAR. The genome is composed of a circular chromosome of 5,513,887 bp and contains a total of 4,804 genes. The genome sequence revealed that H. seropedicae is a highly versatile microorganism with capacity to metabolize a wide range of carbon and nitrogen sources and with possession of four distinct terminal oxidases. The genome contains a multitude of protein secretion systems, including type I, type II, type III, type V, and type VI secretion systems, and type IV pili, suggesting a high potential to interact with host plants. H. seropedicae is able to synthesize indole acetic acid as reflected by the four IAA biosynthetic pathways present. A gene coding for ACC deaminase, which may be involved in modulating the associated plant ethylene-signaling pathway, is also present. Genes for hemagglutinins/hemolysins/adhesins were found and may play a role in plant cell surface adhesion. These features may endow H. seropedicae with the ability to establish an endophytic life-style in a large number of plant species.

The possible involvement of virus in breast cancer.

It is well known that the etiology of human breast cancer is significantly affected by environmental factors. Virus-associated cancer refers to a cancer where viral infection results in the malignant transformation of the host’s infected cells. Human papillomaviruses (HPV), mouse mammary tumor virus (MMTV) and Epstein–Barr (EBV) virus are prime candidate viruses as agents of human breast cancer. The precise role that viruses play in tumorigenesis is not clear, but it seems that they are responsible for causing only one in a series of steps required for cancer development. The idea that a virus could cause breast cancer has been investigated for quite some time, even though breast cancer could be a hereditary disease; however, hereditary breast cancer is estimated to account for a small percentage of all breast cancer cases. Based on current research, this review present at moment, substantial, but not conclusive, evidence that HPV, EBV and MMTV may be involved in breast cancer.

Cytotoxic constituents of propolis inducing anticancer effects: a review.

Objectives  Propolis is a honeybee product used extensively in traditional medicine for its antioxidant, anti‐inflammatory, immunomodulatory and anticancer effects. Propolis exhibits a broad spectrum of biological activities because it is a complex mixture of natural substances. In this review, the antitumour effects of propolis extracts and its constituents (e.g. flavonoids, terpenes and caffeic acid phenethyl ester) are discussed.

Regulatory T cells and breast cancer: implications for immunopathogenesis

Current understanding of the role of several cancer risk factors is more comprehensive, as reported for a number of sites, including the brain, colon, breasts, and ovaries. Despite such advances, the incidence of breast cancer continues to increase worldwide. Signals from the microenviroment have a profound influence on the maintenance or progression cancers. Although T cells present the most important immunological response in tumor growth in the early stages of cancer, they become suppressive CD4+ and CD8+ regulatory T cells (Tregs) after chronic stimulation and interactions with tumor cells, thus promoting rather than inhibiting cancer development and progression. Tregs have an important marker protein which is FoxP3, though it does not necessarily confer a Treg phenotype when expressed in CD4+ T lymphocytes. High Treg levels have been reported in peripheral blood, lymph nodes, and tumor specimens from patients with different types of cancer. The precise mechanisms by which Tregs suppress immune cell functions remain unclear, and there are reports of both direct inhibition through cell–cell contact and indirect inhibition through the secretion of anti-inflammatory mediators such as interleukin. In this review, we present the molecular and immunological aspects of Treg cells in the metastasis of breast cancer.

Molecular Markers for Breast Cancer: Prediction on Tumor Behavior

Breast cancer is one of the most common cancers with greater than 1,300,000 cases and 450,000 deaths each year worldwide. The development of breast cancer involves a progression through intermediate stages until the invasive carcinoma and finally into metastatic disease. Given the variability in clinical progression, the identification of markers that could predict the tumor behavior is particularly important in breast cancer. The determination of tumor markers is a useful tool for clinical management in cancer patients, assisting in diagnostic, staging, evaluation of therapeutic response, detection of recurrence and metastasis, and development of new treatment modalities. In this context, this review aims to discuss the main tumor markers in breast carcinogenesis. The most well-established breast molecular markers with prognostic and/or therapeutic value like hormone receptors, HER-2 oncogene, Ki-67, and p53 proteins, and the genes for hereditary breast cancer will be presented. Furthermore, this review shows the new molecular targets in breast cancer: CXCR4, caveolin, miRNA, and FOXP3, as promising candidates for future development of effective and targeted therapies, also with lower toxicity.

CXCL12 rs1801157 Polymorphism in Patients with Breast Cancer, Hodgkin's Lymphoma, and Non-Hodgkin's Lymphoma

Chemokines and their receptors regulate the trafficking of immune cells during their development, inflammation, and tissue repair. The single‐nucleotide polymorphism (SNP) rs1801157 (previously known as CXCL12‐A/ stromal cell‐derived factor‐1 (SDF1)‐3′A) in CXCL12/SDF1 gene was assessed in breast cancer, Hodgkins lymphoma (HL), and non‐Hodgkins lymphoma (NHL), since the chemokine CXCL12, previously known as SDF1, and its receptor CXCR4 regulate leukocyte trafficking and many essential biological processes, including tumor growth, angiogenesis, and metastasis of different types of tumors. Genotyping was performed by PCR‐RFLP (polymerase chain reaction followed by restriction fragment length polymorphism) using a restriction enzyme HpaII cleavage. No significant difference was observed in genotype distribution between breast cancer patients (GG: 57.3%; GA: 39.8%; AA: 2.9%) and healthy female controls (GG: 62.9%; GA: 33%; AA: 4.1%) nor between HL patients (GG: 61.1%; GA:27.8%; AA: 11.1%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%), whereas a significant difference was observed in genotype distribution between NHL patients (GG: 51.4%; GA: 47.1%; AA: 1.5%) and healthy controls (GG: 65.6%; GA: 28.9%; AA: 5.5%). Further studies will be necessary to elucidate the cancer chemokine network. However, this study suggests that CXCL12 rs1801157 polymorphism may have important implications in the pathogenesis of NHL. J. Clin. Lab. Anal. 23:387–393, 2009.

Genetic polymorphisms associated with the development and clinical course of multiple sclerosis (Review)

Multiple sclerosis (MS) is an autoimmune disease characterized by areas of inflammation, demyelination and axonal damage. The etiology of MS is multifactorial with an interaction between genetic, environmental and geographical factors. The objective of this study was to review the physiopathology and the genetic polymorphisms associated with the development and clinical course of MS. Studies carried out in populations worldwide showed that polymorphisms in the genes of the major histocompatibility complex (MHC) class II and class III have been associated with susceptibility, resistance and clinical forms of MS. Considerable attention has been focused on studies evaluating disease-modifying effects in MS that identified seven genes of probable importance such as the HLA class II, ApoE, IL-1ra, IL-1β, TNF-α, TNF-β and CCR5 genes. However, the results described in the literature about genetic biomarkers in MS are not consistent in the worldwide population. The detection of a single nucleotide polymorphism involved in the etiology and physiopathology of MS is very difficult and, it is likely that, several genetic polymorphisms are involved, each with a small contribution to the susceptibility or resistance to MS. Taken together the results show the need for continued research in genetically heterogeneous populations to identify new biomarkers associated with MS that could be used as prognostic markers or as therapeutic targets to modulate the autoimmune response in MS patients. This information may contribute to a better understanding of the physiopathology and treatment of MS, with the possibility of developing different therapeutic strategies according to the genetic profile of each individual.

RNA from Borna disease virus in patients with schizophrenia, schizoaffective patients, and in their biological relatives

Numerous interactions of the immune system with the central nervous system have been described recently. Mood and psychotic disorders, such as severe depression and schizophrenia, are both heterogeneous disorders regarding clinical symptomatology, the acuity of symptoms, the clinical course, the treatment response, and probably also the etiology. Detection of p24 RNA from Borna disease virus (BDV) by the reverse transcriptase polymerase chain reaction in patients with schizophrenia, schizoaffective disorder, and in their biological relatives was evaluated. The subjects were 27 schizophrenic and schizoaffective patients, 27 healthy controls, 20 relatives without psychiatric disease, and 24 relatives with mood disorder, who attended the Psychiatric Ambulatory of Londrina State University, Paraná, Brazil. The subjects were interviewed by structured diagnostic criteria categorized according to the Diagnostic and Statistical Manual of Mental Disorders‐IV, axis I, (SCID‐IV). The mean duration of illness in schizophrenic and schizoaffective patients was 15.341±1.494 years and the median age at onset was 22.4±7.371 years. There were no significant differences in gender (P=0.297), age (P=0.99), albumin (P=0.26), and body mass index (kg/m2) (p=0.28), among patients, controls, and relatives. Patients and biological relatives had significantly higher positive p24 RNA BDV detection than controls (P=0.04); however, the clinical significance of BDV remains to be clarified. J. Clin. Lab. Anal. 22:314–320, 2008.

Toll-like receptor 3: involvement with exogenous and endogenous RNA.

The recognition of pathogens is assigned to an evolutionarily conserved family of receptors, the Toll-like receptors (TLRs). The investigation of RNA-based immunology has been reinvigorated with the observation that TLR3s interact with RNA (dsRNA of viral origin, poly (I:C) and endogenous RNA). Many RNAs, therefore, join the list of endogenous ligands for TLRs. The further finding that nucleoside modification alters RNA-mediated TLR signaling presents a mechanism for the long-observed differences in immunogenicity. The involvement of RNA modification in the pathogenesis of diseases, and its implications in the therapeutics, are still being studied, and will have important implications in the future.

Brazilian Propolis Antileishmanial and Immunomodulatory Effects

The antileishmanial and immunomodulatory effects of propolis collected in Botucatu, São Paulo State, Brazil, were evaluated in Leishmania (Viannia) braziliensis experimental infection. The antileishmanial effect of propolis on promastigote forms was verified by reducing growth and by promoting morphologic alterations observed by scanning electron microscopy. In in vitro immunomodulatory assays, macrophages were pretreated with propolis and then infected with L. (V.) braziliensis. In vivo, supernatants from liver cells and peritoneal exudate of BALB/c mice pretreated with propolis and infected with Leishmania (107/mL promastigotes) were collected, and TNF-α and IL-12 were measured by ELISA. Macrophages incubated with propolis showed a significant increase in interiorization and further killing of parasites. An increased TNF-α production was seen in mice pretreated with propolis, whereas IL-12 was downregulated during the infection. In conclusion, Brazilian propolis showed a direct action on the parasite and displayed immunomodulatory effects on murine macrophages, even though the parasite has been reported to affect the activation pathways of the cell. The observed effects could be associated with the presence of phenolic compounds (flavonoids, aromatic acids, and benzopyranes), di- and triterpenes, and essential oils found in our propolis sample.