Serum levels of interleukin-6, tumor necrosis factor-alpha and interferon-gama in infants with and without dengue

This study compared the serum levels of IL-6, TNF-alpha and IFN-gamma, in children under 1 year of age with and without dengue. Sera were collected from a total of 41 children living in the Department of Antioquia, Colombia (27 patients with dengue and 14 controls). The results showed higher cytokine levels in children with dengue than without dengue, with statistically significant differences for IL-6 and IFN-gamma. No statistically significant differences were found between clinical forms, although IL-6 and IFN-gamma levels were higher in dengue fever cases than in dengue hemorrhagic fever cases. On the other hand, TNF-alpha levels were higher in dengue hemorrhagic fever than in dengue fever. The levels of IL-6 and TNF-alpha were higher in secondary infection than in primary infection, although IFN-gamma levels were higher in primary infection. These results suggest that IL-6, TNF-alpha and IFN-gamma are involved in dengue infection independently of the clinical form.

Simultaneous occurrence of brain tumor and myeloradiculopathy in schistosomiasis mansoni: case report

Simultaneous occurrence of brain tumor and myeloradiculopathy in cases of Manson's schistosomiasis have only rarely been described. We report the case of a 38-year-old man who developed seizures during a trip to Puerto Rico and in whom a brain tumor was diagnosed by magnetic resonance imaging: brain biopsy revealed the diagnosis of schistosomiasis. He was transferred to a hospital in the United States and, during hospitalization, he developed sudden paraplegia. The diagnosis of myeloradiculopathy was confirmed at that time. He was administered praziquantel and steroids. The brain tumor disappeared, but the patient was left with paraplegia and fecal and urinary dysfunction. He has now been followed up in Brazil for one year, and his clinical state, imaging examinations and laboratory tests are presented here.

Genital schistosomiasis mansoni: tubal tumor and parietal peritoneum involvement diagnosed during laparoscopy

Female genital schistosomiasis is not uncommon in endemic areas for schistosomiasis, but there are few reports in the Brazilian medical literature. Here, we describe the case of a 31-year-old woman with lower abdominal pain who was diagnosed as presenting a fallopian tube tumor caused by Manson's schistosomiasis. The diagnosis was delayed because her symptoms were considered nonspecific. Involvement of the parietal peritoneum of the ovarian fossa was observed during laparoscopy and confirmed by histological analysis. The left tube and the tumor were excised and schistosomiasis was treated with praziquantel. She presented a full recovery and options for future reproduction are under evaluation.

Actinomicose pulmonar simulando tumor de Tobias-Pancoast

A actinomicose é uma infecção rara que pode envolver diversos órgãos. O envolvimento torácico é incomum (10-20%). No presente trabalho, é descrito o caso de um paciente de 33 anos, HIV negativo, com dor torácica posterior à esquerda em queimação com irradiação para membro superior esquerdo e diminuição da força com parestesias. A tomografia computadorizada evidenciou uma massa em contato com a parede torácica. Após realização de toracotomia foi visualizada lesão pulmonar sólida vascularizada aderida no lobo superior esquerdo, infiltrando a parede torácica posterior e ápice da cavidade. A biopsia incisional da lesão e o estudo microbiológico evidenciaram actinomicose.

Glucocorticoid-induced tumor necrosis factor receptor expression in patients with cervical human papillomavirus infection

Introduction The progression of human papillomavirus (HPV) infection in the anogenital tract has been associated with the involvement of cells with regulatory properties. Evidence has shown that glucocorticoid-induced tumor necrosis factor receptor (GITR) is an important surface molecule for the characterization of these cells and proposes that GITR ligand may constitute a rational treatment for many cancer types. We aimed to detect the presence of GITR and CD25 in cervical stroma cells with and without pathological changes or HPV infection to better understand the immune response in the infected tissue microenvironment. Methods We subjected 49 paraffin-embedded cervical tissue samples to HPV DNA detection and histopathological analysis, and subsequently immunohistochemistry to detect GITR and CD25 in lymphocytes. Results We observed that 76.9% of all samples with high GITR expression were HPV-positive regardless of histopathological findings. High GITR expression (77.8%) was predominant in samples with ≥1,000 RLU/PCB. Of the HPV-positive samples negative for intraepithelial lesion and malignancy, 62.5% had high GITR expression. High GITR expression was observed in both carcinoma and high-grade squamous intraepithelial lesion (HSIL) samples (p = 0.16). CD25 was present in great quantities in all samples. Conclusions The predominance of high GITR expression in samples with high viral load that were classified as HSIL and carcinoma suggests that GITR+ cells can exhibit regulatory properties and may contribute to the progression of HPV-induced cervical neoplasia, emphasizing the importance of GITR as a potential target for immune therapy of cervical cancer and as a disease evolution biomarker.

Blocking tumor exosome release using nanovectorization systems

Exosomes are small membrane vesicles secreted by most cell types, either normal or malignant and are found in most body fluids such as saliva, plasma and breast milk. In the past decade, the interest in these vesicles has been growing more and more since it was found that besides their beneficial functions such as the removal of cellular debris and unnecessary proteins during cell maturation process, they can also interact with other cells and transfer information between them, thus helping diseases like cancer to progress. The present work intended to use gold nanoparticles as vehicles for gene silencing in an attempt to reduce the tumor-derived exosome secretion, regulated by Rab27a protein, and also aimed to compare the exosome secretion between two breast cell lines, MCF7 and MDA. Changes in RAB27A gene expression were measured by Real-time Quantitative PCR and it was revealed a decreased in RAB27A gene expression, as expected. Exosomes were isolated and purified by two different methods, ultracentrifugation and the commercial kit ExoQuick™ Solution, and further characterized using Western Blot analysis. ExoQuick™ Solution was proven to be the most efficient method for exosome isolation and it was revealed that MDA cells secrete more exosomes. Furthermore, the isolated MCF7-derived exosomes were placed together with a normal bronchial/tracheal epithelial cell line (BTEC) for an additional assay, which aimed to observe the uptake of exosomes by other cells and the exosomes’ capability of promoting cell-cell communication. This observation was made based on alterations in the expression levels of c-Myc and miR-21 genes and the fact that they both have an increased expression in BTEC cells incubated with tumor-derived exosomes when compared to control cells (without incubation with the exosomes) lead us to the conclusion that the exosome uptake and exchange of information between the exosomes and the normal cells did occurred.

The use of a modular titanium endoprosthesis in skeletal reconstructions after bone tumor resections: method presentation and analysis of 37 cases

We analyzed 37 patients who underwent segmental wide resection of bone tumors and reconstruction with a modular titanium endoprosthesis at the Orthopaedic Oncology Group, between 1992 and 1998. Twelve patients were male and 25 were female, with a mean age of 30 years (9 - 81). The mean follow-up was 14 months (2 - 48). The diagnoses were: osteosarcoma (14 cases), metastatic carcinoma (10), Ewing's sarcoma (4), giant cell tumor (4), malignant fibrous histiocytoma (3), chondrosarcoma (1), and aneurysmal bone cyst (1). Eleven articulated total knee, 8 partial proximal femur with bipolar acetabulum, 8 partial proximal humerus, 3 total femur, 2 partial proximal tibia, 2 diaphyseal femur, 2 diaphyseal humerus, and 1 total proximal femur with cementless acetabulum endoprosthesis implant procedures were done. The complications related to the procedure included: infection (5 cases), dislocation (3), module loosening (1), and ulnar nerve paresthesia (1). We used the following criteria for the clinical evaluation: presence of pain, range of motion, reconstruction stability, surgical and oncologic complications, and patient acceptance. The results were good in 56.8% of the cases, regular in 32.4% and poor in 10.8%.

Hypothyroidism following struma ovarii tumor resection: a case report

Struma ovarii is an infrequent ovarian tumor, and there are only few reports with detailed data of thyroid function. In several cases, malignant struma ovarii have been shown to produce hyperthyroidism, but there is no reported case of hypothyroidism following struma ovarii tumor resection. A 62-year-old white woman underwent right ovary resection that had a pathologic diagnosis of struma ovarii. After 6 days, she developed weakness, myalgia, somnolence, nausea, and arterial hypotension. Laboratory tests showed a high level of thyroid-stimulating hormone (TSH) and a decreased level thyroxin. Thyroxin replacement therapy was initiated, and the patient became completely asymptomatic. This is the first reported case of a previously asymptomatic woman who developed a definite clinical hypothyroidism after resection of a struma ovarii tumor.

Meningeal carcinomatosis as the initial manifestation of a gallbladder adenocarcinoma associated with a Krukenberg tumor

A case of malignant neoplasm is described in which the initial manifestations were mental dysfunction and meningeal irritation, mimicking chronic or subacute meningitis. Physical examination showed cranial nerve involvement and a pelvic tumor. There was progressive deterioration, and death occurred in 2 weeks. The autopsy revealed a gallbladder adenocarcinoma, meningeal carcinomatosis, and ovarian metastasis presenting as a Krukenberg tumor. The authors emphasize the importance of including meningeal carcinomatosis as a possibility in the differential diagnosis of non-characteristic clinical pictures, as well as the importance of the cerebrospinal fluid cytologic examination, repeated as needed, in order to confirm this diagnosis.

P53 and Rb tumor suppressor gene alterations in gastric cancer

Inactivation of tumor suppressor genes has been frequently observed in gastric carcinogenesis. Our purpose was to study the involvement of p53, APC, DCC, and Rb genes in gastric carcinoma. METHOD: Loss of heterozygosity of the p53, APC, DCC and Rb genes was studied in 22 gastric cancer tissues using polymerase chain reaction; single-strand conformation polymorphism of the p53 gene exons 5-6 and exons 7-8 was studied using 35S-dATP, and p53 expression was detected using a histological immunoperoxidase method with an anti-p53 clone. RESULTS AND DISCUSSION: No loss of heterozygosity was observed in any of these tumor suppressor genes; homozygous deletion was detected in the Rb gene in 23% (3/13) of the cases of intestinal-type gastric carcinoma. Eighteen (81.8%) cases showed band mobility shifts in exons 5-6 and/or 7-8 of the p53 gene. The presence of the p53 protein was positive in gastric cancer cells in 14 cases (63.6%). Normal gastric mucosa showed negative staining for p53; thus, the immunoreactivity was likely to represent mutant forms. The correlation of band mobility shift and the immunoreactivity to anti-p53 was not significant (P = .90). There was no correlation of gene alterations with the disease severity. CONCLUSIONS: The inactivation of Rb and p53 genes is involved in gastric carcinogenesis in our environment. Loss of the Rb gene observed only in the intestinal-type gastric cancer should be further evaluated in association with Helicobacter pylori infection. The p53 gene was affected in both intestinal and diffuse histological types of gastric cancer.

Evaluating biomaterial-and microfluidic-based 3D tumor models

Cancer is a major cause of morbidity and mortality worldwide, with a disease burden estimated to increase in the coming decades. Disease heterogeneity and limited information on cancer biology and disease mechanisms are aspects that 2D cell cultures fail to address. We review the current "state-of-the-art" in 3D Tissue Engineering (TE) models developed for and used in cancer research. Scaffold-based TE models and microfluidics, are assessed for their potential to fill the gap between 2D models and clinical application. Recent advances in combining the principles of 3D TE models and microfluidics are discussed, with a special focus on biomaterials and the most promising chip-based 3D models.

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Longitudinal analysis of tumor marker CEA of breast cancer patients from Braga's hospital

Allied to an epidemiological study of population of the Senology Unit of Braga’s Hospital that have been diagnosed with malignant breast cancer, we describe the progression in time of repeated measurements of tumor marker Carcinoembryonic antigen (CEA). Our main purpose is to describe the progression of this tumor marker as a function of possible risk factors and, hence, to understand how these risk factors influences that progression. The response variable, values of CEA, was analyzed making use of longitudinal models, testing for different correlation structures. The same covariates used in a previous survival analysis were considered in the longitudinal model. The reference time used was time from diagnose until death from breast cancer. For diagnostic of the models fitted we have used empirical and theoretical variograms. To evaluate the fixed term of the longitudinal model we have tested for a changing point on the effect of time on the tumor marker progression. A longitudinal model was also fitted only to the subset of patients that died from breast cancer, using the reference time as time from date of death until blood test.

Tumor primário de pulmão simulando doença de Alzheimer: relato de caso

RESUMO Retratamos o relato de um homem de 61 anos que apresentava um glioblastoma multiforme em região do giro têmporo-occipital lateral esquerdo que rechaça cranialmente o hipocampo e o corno temporal do ventrículo lateral correspondente. Não havia sinais e sintomas neurológicos e o quadro clínico lembrava a demência de Alzheimer. Havia comprometimento de memória e alterações comportamentais com duração de três meses. Foram afastadas inicialmente outras causas de demência rapidamente progressivas e a ressonância magnética revelou a etiologia tumoral dos sintomas neuropsiquiátricos. Foi submetido à bateria de testes neuropsicométricos com pontuação compatível com doença de Alzheimer (DA). Em razão de extensa área de edema, foi introduzida dexametasona com reversão completa dos sintomas neuropsiquiátricos iniciais e a repetição da bateria neuropsicológica mostrou melhora acentuada em todos os testes. Optou-se por tratamento conservador, após biópsia por agulha, com evolução para óbito em cinco meses.

Ontological representation of tumor-node-metastasis classification and an ontology-driven classifier: a study on colorectal cancer

Dissertação de mestrado integrado em Engenharia Biomédica (área de especialização em Informática Médica)