Genomics and proteomics approaches to the study of cancer-stroma interactions.

BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.

Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant.

BACKGROUND: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrP(c)) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrP(c) might be related to epilepsy. OBJECTIVE: To evaluate the genetic contribution of PRNP to MTLE-HS. METHODS: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. RESULTS: A variant allele at position 171 (Asn-->Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). CONCLUSIONS: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.

[Toxoplasmosis of the central nervous system in a patient without immunosupression: case report]. / Toxoplasmose do sistema nervoso central em paciente sem evidência de imunossupressão: relato de caso.

The clinical manifestations of acquired toxoplasmosis in the immunocompetent patient rarely include localized neurological signs, which are frequent in the immunosuppressed patient (Aids). The objective of this paper is to report the case of a woman with Toxoplasma gondii brain abscess, without an identified cause of immunosuppression.

[Epidemiologic study on tegumentary leishmaniasis in the municipality of Corguinho, Mato Grosso do Sul -- Studies in the human population]. / Estudo epidemiológico sobre leishmaniose tegumentar (LT) no município de Corguinho, Mato Grosso do Sul-Estudos na população humana.

A study on the resident population of 150 inhabitants of Boa Sorte in the Municipality of Corguinho, Mato Grosso do Sul State, Brazil was made, from March 1991 to March 1994, to establish the prevalence of South American Cutaneous Leishmaniasis (SACL), and to characterize the affected population, in an area of recent transmission. Twelve of the inhabitants showed lesions suspected to be SACL, and in 8 cases it was possible to confirm this by biopsy and parasitology. The mucosal form was found in one patient only, the rest showed the following cutaneous forms: ulcerated (3), ulcero-verrucose (1), hyperkeratotic ulcer (1), infiltrated maccule (1), nodule with florid regional adenopathy (1). All patients reacted favorably to treatment with glucantime, with lesion scarring. Side-effects were rare. The parasite isolated from all patients was identified as Leishmania (Viannia) braziliensis. The Montenegro skin test, applied to the 150 inhabitants, showed 32 reactive ones. Of these, six were carriers of the disease, 21 showed sequelae suggestive of the disease and five showed no signs of infection. The age grouping of the cohort ranged from 22 to 78 years, 75% being male. To date, transmission is suspected to be in the peridomicile.