Genomic and phenotypic profiles of two Brazilian breast cancer cell lines derived from primary human tumors

Breast cancer is the most common type of cancer among women worldwide. Research using breast cancer cell lines derived from primary tumors may provide valuable additional knowledge regarding this type of cancer. Therefore, the aim of this study was to investigate the phenotypic profiles of MACL-1 and MGSO-3, the only Brazilian breast cancer cell lines available for comparative studies. We evaluated the presence of hormone receptors, proliferation, differentiation and stem cell markers, using immunohistochemical staining of the primary tumor, cultured cells and xenografts implanted in immunodeficient mice. We also investigated the ability of the cell lines to form colonies and copy number alterations by array comparative genomic hybridization. Histopathological analysis showed that the invasive primary tumor from which the MACL-1 cell line was derived, was a luminal A subtype carcinoma, while the ductal carcinoma in situ (DCIS) that gave rise to the MGSO-3 cell line was a HER2 subtype tumor, both showing different proliferation levels. The cell lines and the tumor xenografts in mice preserved their high proliferative potential, but did not maintain the expression of the other markers assessed. This shift in expression may be due to the selection of an 'establishment' phenotype in vitro. Whole-genome DNA evaluation showed a large amount of copy number alterations (CNAs) in the two cell lines. These findings render MACL-1 and MGSO-3 the first characterized Brazilian breast cancer cell lines to be potentially used for comparative research. © 2013 Spandidos Publications Ltd. All rights reserved.

Effects of Ginkgo biloba on chemically-induced mammary tumors in rats receiving tamoxifen

Background: Ginkgo biloba extract (GbE) is used extensively by breast cancer patients undergoing treatment with Tamoxifen (TAM). Thus, the present study investigated the effects of GbE in female Sprague-Dawley (SD) rats bearing chemically-induced mammary tumors and receiving TAM.Methods: Animals bearing mammary tumors (≥1 cm in diameter) were divided into four groups: TAM [10 mg/kg, intragastrically (i.g.)], TAM plus GbE [50 and 100 mg/kg, intraperitoneally (i.p.)] or an untreated control group. After 4 weeks, the therapeutic efficacy of the different treatments was evaluated by measuring the tumor volume (cm3) and the proportions of each tumor that were alive, necrotic or degenerative (mm2). In addition, labeling indexes (LI%) were calculated for cell proliferation (PCNA LI%) and apoptosis (cleaved caspase-3 LI%), expression of estrogen receptor-alpha (ER-α) and p63 biomarkers.Results: Overall, the tumor volume and the PCNA LI% within live tumor areas were reduced by 83% and 99%, respectively, in all TAM-treated groups when compared to the untreated control group. GbE treatment (100 mg/kg) reduced the proportions of live (24.8%) and necrotic areas (2.9%) (p = 0.046 and p = 0.038, respectively) and significantly increased the proportion of degenerative areas (72.9%) (p = 0.004) in mammary tumors when compared to the group treated only with TAM. The expression of ER-α, p63 and cleaved caspase-3 in live tumor tissues was not modified by GbE treatment.Conclusions: Co-treatment with 100 mg/kg GbE presented a slightly beneficial effect on the therapeutic efficacy of TAM in female SD rats bearing mammary tumors. © 2013 Dias et al.; licensee BioMed Central Ltd.

In vivo assessment of intratumoral aspirin injection to treat hepatic tumors

AIM: To study the antineoplastic efficacy of 10% aspirin intralesional injection on VX2 hepatic tumors in a rabbit model. METHODS: Thirty-two male rabbits (age: 6-9 wk; body weight: 1700-2500 g) were inoculated with VX2 hepatic tumor cells (104 cells/rabbit) via supraumbilical median laparotomy. On day 4 post-implantation, when the tumors were about 1 cm in diameter, the rabbits were randomly divided into the following groups (n = 8 each group) to assess early (24 h) and late (7 d) antineoplastic effects of intratumoral injection of 10% bicarbonate aspirin solution (experimental groups) in comparison to intratumoral injection of physiological saline solution (control groups): group 1, 24 h control; group 2, 24 h experimental; group 3, 7 d control; group 4, 7 d experimental. The serum biochemistry profile (measurements of glycemia, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase) and body weight measurements were obtained for all animals at the following time points: D0, before tumor implant; D4, day of treatment; D5, day of sacrifice for groups 1 and 2; D11, day of sacrifice for groups 3 and 4. Gross assessments of the abdominal and thoracic cavities were carried out upon sacrifice. The resected liver tissues, including hepatic tumors, were qualitatively (general morphology, signs of necrosis) and quantitatively (tumor area) assessed by histopathological analysis. RESULTS: Gross examination showed no alterations, besides the left hepatic lobe tumors, had occurred in the thoracic and abdominal cavities of any animal at any time point evaluated. However, the features of the tumor foci were distinctive between the groups. Compared to the control groups, which showed normal unabated tumor progression, the aspirin-treated groups showed imprecise but limited tumor boundaries and a general red-white coloration (indicating hemorrhaging) at 24 h post-treatment, and development of yellow-white areas of a cicatricial aspect at 7 d after treatment. At all time points evaluated, all except one biochemical parameters tested within the reference range (P > 0.05); a significant increase was detected in the alkaline phosphatase level of the control group 3 on D11 (P < 0.05). At 24 h post-treatment, the aspirintreated groups showed extensive coagulation necrosis accompanied by a remarkable absence of viable tumor foci; at 7 d after treatment, the tumors had completely disappeared in these animals and fibrous necrotic nodules had developed. In contrast, throughout the study course, the tumors of the control groups remained unchanged, showing tumor nodules without necrosis at the time point corresponding to 24 h post-treatment and increased amounts of tumor nodules at the time point corresponding to 7 d post-treatment. Quantitative analysis of the remaining tumor area revealed that the aspirin-treated groups had significantly smaller tumor foci at 24 h post-treatment (8.5% ± 0.7%) andat 7 d after treatment (11.0% ± 4.2%), compared to those in the control groups (24 h: 98.5% ± 1.5% and 7 d: 94.0% ± 2.7%; both, P < 0.005). CONCLUSION: Intralesional injection of a 10% aspirin solution causes destruction of VX2 hepatic tumors in rabbits without evidence of relapse at 7 d after treatment administration. © 2013 Baishideng.

High-risk human papillomaviruses in two different primary tumors in the same patient

Abstract

Screening de polimorfismos e análise comparativa de alterações no número de copias do gene tp53 em gliomas

As neoplasias astrocitárias correspondem a cerca de (60%) dos tumores do sistema nervoso central, sendo que atingem principalmente adultos numa fase altamente produtiva da vida e com evoluções pouco satisfatórias apesar dos tratamentos disponíveis. Um melhor entendimento de sua biologia molecular se faz necessário na tentativa de compreender sua evolução e melhor planejar e tratamento, assim como na busca de novas terapias. Este trabalho teve como objetivo analisar modificações no gene TP53 com relação ao número de cópias e polimorfismos nos éxons de 4 a 11, considerados hotspots para mutações. Um total de 14 amostras de diferentes graus de malignidade foram analisadas por experimentos de FISH interfásico com sondas loco-específicas do gene TP53 e centroméricas para o cromossomo 17, e também pela técnica de SSCP para o screening de polimorfismos dos éxons 4-10. Foram comparados os resultados obtidos entre tumores de graus I e II (benignos) com aqueles de graus III e IV (malignos). Os resultados referentes às sondas loco-específicas (gene TP53 e centrômero do cromossomo 17) mostraram que a ocorrência de deleções ou amplificações, apesar de importantes estatisticamente em relação aos núcleos com número de marcações normais, não apresentou correlação com idade, sexo ou grau de malignação. Entretanto, as alterações foram encontradas com maior freqüência nos paciente portadores de astrocitomas de grau intermediário (III). A técnica de SSCP revelou polimorfismos nos éxons 5, 7 e 10, e apesar de não estarem associados à malignidade tumoral, os casos polimórficos corresponderam aos pacientes com menor sobrevida após tratamentos, sugerindo, uma associação entre mutações nesses éxons e uma maior agressividade tumoral.

Epigenetic alterations in human brain tumors in a Brazilian population

Aberrant methylation of CpG islands located in promoter regions represents one of the major mechanisms for silencing cancer-related genes in tumor cells. We determined the frequency of aberrant CpG island methylation for several tumor-associated genes: DAPK, MGMT, p14^ARF, p16^INK4a, TP73, RB1 and TIMP-3 in 55 brain tumors, consisting of 26 neuroepithelial tumors, 6 peripheral nerve tumors, 13 meningeal tumors and 10 metastatic brain tumors. Aberrant methylation of at least one of the seven genes studied was detected in 83.6% of the cases. The frequencies of aberrant methylation were: 40% for p14^ARF, 38.2% for MGMT, 30.9% for, p16^INK4a, 14.6% for TP73 and for TIMP-3, 12.7% for DAPK and 1.8% for RB1. These data suggest that the hypermethylation observed in the genes p14^ARF, MGMT and p16^INK4a is a very important event in the formation or progression of brain tumors, since the inactivation of these genes directly interferes with the cell cycle or DNA repair. The altered methylation rate of the other genes has already been reported to be related to tumorigenesis, but the low methylation rate of RB1 found in tumors in our sample is different from that so far reported in the literature, suggesting that perhaps hypermethylation of the promoter is not the main event in the inactivation of this gene. Our results suggest that hypermethylation of the promoter region is a very common event in nervous system tumors.

Expression of glutathione, glutathione peroxidase and glutathione S-transferase pi in canine mammary tumors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Epigenetic and expression analysis of TRAIL-R2 and BCL2: on the TRAIL to knowledge of apoptosis in ovarian tumors

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Low expression of sodium iodide symporter identifies aggressive thyroid tumors

A decreased radioiodine uptake is frequently detected in differentiated thyroid carcinomas (DTC) and is associated with high recurrence rate and reduced survival. We investigated the correlation between NIS mRNA expression levels in the primary tumor and patient outcome using a quantitative real-time RT-PCR method. NIS expression was decreased in 17 DTC (21.04 +/- 39.66 pg Eq) compared to four autoimune thyroid disease (180.51 +/- 92.63 pg Eq) and 14 normal tissues (75.71 +/- 66.98 pg Eq) (p < 0.0001). The 17 thyroid differentiated carcinoma patients were submitted to surgery complemented by radioiodine ablation and had at least 24 months of follow-up, under levothyroxine continued suppressive therapy. According to their outcome, we could characterize a group of papillary carcinoma patients with aggressive carcinomas, whose NIS mRNA levels were markedly lower than a group with non-aggressive carcinomas (0.62 +/- 0.79 versus 54.87 +/- 53.79: p < 0.005). We suggest that the quantification of NIS mRNA relative levels in the primary tumor may predict poor outcome. (C) 2003 Elsevier Ireland Ltd. All rights reserved.

Genomic screening of testicular germ cell tumors from monozygotic twins

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

HPV16-associated tumors control myeloid cell homeostasis in lymphoid organs, generating a suppressor environment for T cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of melatonin treatment in primary culture of canine mammary tumors

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)