Monosomy 22 and del(10)(p12) in an ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland

Short-term cultures of a collagenase disaggregated ameloblastoma previously diagnosed as an adenoid cystic carcinoma of the salivary gland were shown by cytogenetic analysis to have the clonal karyotype 45,XY,del(10)(p12), -22. The data may indicate that the loss of genes of chromosome 22, as well as of 10p, could be a critical event in the evolutionary pattern of odontogenic neoplasias. (C) Elsevier B.V., 1996

Cytogenetic alterations in chagasic achalasia compared to esophageal carcinoma

Patients with chagasic achalasia (megaesophagus) are liable to have an additional 1.7-20% possibility of developing esophageal squamous cell carcinoma (ESCC). We applied a fluorescence in situ hybridization technique in 20 such patients and found aneuploidies of chromosomes 7, 11, and 17 in 60% (12 of 20 specimens) and deletion of the TP53 gene in 54.5% (6 of 11 specimens; it was only possible to obtain data by FISH technique from 11 of the 20 achalasia patients). The main aneuploidies detected were chromosome 7 monosomy or trisomy (35%) in mid-third megaesophagus cases, and chromosome 17 monosomy or trisomy (25%) in distal-third cases. TP53 gene deletion was more frequent in mid-third (62.5%) than in distal-third megaesophagus cases (40%). In chagasic megaesophagus, no amplification of the cyclin D1 gene (CCND1) was observed. Comparing chagasic megaesophagus to ESCC, we found a higher frequency of aneuploidies in all 10 tumors. The main alterations were trisomy or tetrasomy of chromosomes 17 (90%), 11 (70%), and 7 (70%). Amplification of CCND1 was evidenced as a cluster in 70% of the tumors (22-99% of nuclei), while TP53 gene deletion occurred in 100%. To our knowledge, this is the first cytogenetic analysis of chagasic megaesophagus to show that aneuploidies of chromosomes 7, 11, and 17, and TP53 gene deletion might be related to increased risk for malignancy. (C) 2004 Elsevier B.V. All rights reserved.

Multiple cytogenetic clones in a basal cell carcinoma

Chromosome analysis of short-term culture of a basal cell carcinoma showed five clonal chromosome abnormalities, t(9;14)(q12 or q13;p11), del(1)(q23 or q25), trisomy 5, trisomy 7, and monosomy X. In addition, several nonclonal structural and numerical changes were seen in the tumor cells.

Translocation (4;14) and concomitant inv(14) in a basal cell carcinoma

Chromosome analysis of short-term cultures from a basal cell carcinoma was performed. The analyzed karyotypes showed a pseudodiploid clone characterized by a der(4)t(4;14)(p14;p11) and a concomitant inversion of the same chromosome 4 involved in the t(4;14) with the breakpoints at p14 and q25.

Frequent p53 mutations and occasional loss of chromosome 4 in invasive bladder carcinoma induced by N-butyl-N-(4-hydroxybutil)nitrosamine in B6D2F1 mice

B6D2F1 mice (45/group) were treated with N-butyl-N-(4- hydroxybutyl)nitrosamine (BBN) or uracil as follows: Group 1 received 0.05% BBN in drinking water for the entire experiment, Group 2 received 5 mg of BBN by gastric gavage in 0.1 mL of 20% ethanol twice per week for 10 wk, Group 3 received a 2.5% uracil-containing diet for the entire experiment, and Group 4 was controls (received 0.1 mL of 20% ethanol by gavage twice per week for 10 wk). The surviving mice in Group 1 were killed after week 26 and those in the other groups after week 30. By week 15, three of 11 Group 1 and one of 15 Group 2 mice had bladder carcinoma. By 26 and 30 wk, respectively, invasive carcinomas were observed in 33 of 34 and six of 21 mice in Groups 1 and 2 and renal pelvic carcinomas in 11 of 34 and three of 21 mice in Groups 1 and 2. Four of 19 uracil-treated mice had bladder nodular hyperplasia. By polymerase chain reaction-single-strand conformation polymorphism and sequence analyses, 16 of 20 and two of five bladder carcinomas from Groups 1 and 2, respectively, showed mutations in the p53 gene. Ha-ras mutation was present in one case. Loss of heterozygosity analysis with simple-sequence length polymorphism markers for chromosome 4 showed that 10 of 21, two of 15, and nine of 13 mice in Groups 1-3, respectively, had heterozygous or homozygous deletions. B6D2F1 mice are therefore susceptible to the urothelial carcinogenic effects of BBN and develop frequent p53 mutations and chromosome 4 deletions. Chromosome 4 deletions were also seen with uracil.

Biologic and genetics aspects of chagas disease at endemic areas

The etiologic agent of Chagas Disease is the Trypanosoma cruzi, transmitted through blood-sucking insect vectors of the Triatominae subfamily, representing one of the most serious public health concerns in Latin America. There are geographic variations in the prevalence of clinical forms and morbidity of Chagas disease, likely due to genetic variation of the T. cruzi and the host genetic and environmental features. Increasing evidence has supported that inflammatory cytokines and chemokines are responsible for the generation of the inflammatory infiltrate and tissue damage. Moreover, genetic polymorphisms, protein expression levels, and genomic imbalances are associated with disease progression. This paper discusses these key aspects. Large surveys were carried out in Brazil and served as baseline for definition of the control measures adopted. However, Chagas disease is still active, and aspects such as host-parasite interactions, genetic mechanisms of cellular interaction, genetic variability, and tropism need further investigations in the attempt to eradicate the disease. Copyright 2012 Marilanda Ferreira Bellini et al.

Clinical, cytologic, and histologic features of a mammary micropapillary carcinoma in a dog

Mammary invasive micropapillary carcinoma is a rare variant of mammary carcinoma that was recently recognized in dogs. The cytologic features and biologic behavior of such neoplasms in dogs have not yet been widely discussed in the veterinary literature. We report the clinical, cytologic, and histologic features of a canine micropapillary carcinoma in a 13-year-old female mongrel dog. The mammary region presented with extreme local pain, severe edema and erythema, and multifocal epidermal ulceration, which is typical for an inflammatory mammary carcinoma. Fine-needle aspirates were highly cellular and consisted of individual cells and papillary cell clusters with characteristics of malignant epithelial cells. Histologic examination revealed neoplastic cells arranged in small papillae without fibrovascular cores, sometimes inside clear lymphatic spaces, indicating lymphovascular invasion. Regional lymph node evaluation revealed metastatic cells. Due to deteriorating clinical condition the dog was euthanatized 5 months after mastectomy. At necropsy, metastatic neoplastic mammary cells were found in popliteal and mediastinal lymph nodes, the right femoral biceps muscle, liver, heart, lungs, and urinary bladder. © 2013 American Society for Veterinary Clinical Pathology.

Identificação e caracterização de possiveis marcadores moleculares em carcinoma renal de células claras

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Estudo clínico e genético de uma família portadora de carcinoma medular de tireóide

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Genomic profile of a Li-Fraumeni-like syndrome patient with a 45,X/46,XX karyotype, presenting neither mutations in TP53 nor clinical stigmata of Turner syndrome

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

Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Identificação de genes de predisposição à síndrome dos carcinomas de mama e tireoide por sequenciamento total do exoma

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Endostatin gene therapy stimulates upregulation of ICAM-1 and VCAM-1 in a metastatic renal cell carcinoma model

One of the greatest challenges in urological oncology is renal cell carcinoma (RCC), which is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and respond positively to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of ES-based antiangiogenic therapy to activate tumor-associated endothelial cells in metastatic RCC (mRCC). Balb/c-bearing Renca cells were treated with NIH/3T3-LendSN or, as a control, with NIH/3T3-LXSN cells. The T-cell subsets and lymphocyte populations of tumors, mediastinal lymph nodes and the spleen were assessed by flow cytometry. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was assessed by real-time PCR, flow cytometry and immunohistochemistry analysis. ES gene therapy led to an increase in the percentage of infiltrating CD4-interferon (IFN)-gamma cells (P<0.05), CD8-IFN-gamma cells (P<0.01) and CD49b-tumor necrosis factor-alpha cells (P<0.01). In addition, ES therapy caused an increase at the mRNA level of ICAM-1 (1.4-fold; P<0.01) and VCAM-1 (1.5-fold) (control vs treated group; P<0.001). Through flow cytometry, we found a significant increase in the CD34/ICAM-1 cells (8.1-fold; P<0.001) and CD34/VCAM-1 cells (1.6-fold; P<0.05). ES gene therapy induced a significant increase in both T CD4 and CD8 cells in the lymph nodes and the spleen, suggesting that ES therapy may facilitate cell survival or clonal expansion. CD49b cells were also present in increased quantities in all of these organs. In this study, we demonstrate an antitumor inflammatory effect of ES in an mRCC model, and this effect is mediated by an increase in ICAM-1 and VCAM-1 expression in tumor-associated endothelial cells.

Obstrução de vias lacrimais associada ao tratamento radioiodoterápico de carcinoma de tireoide

OBJETIVO: Descrever uma série de pacientes portadores de obstrução do sistema lacrimal associado à radioiodoterapia para tratamento de carcinoma de tireoide, revisar os dados clínicos e a resposta ao tratamento cirúrgico desta rara complicação. MÉTODOS: Foi realizada uma análise retrospectiva dos achados oftalmológicos de pacientes com histórico de carcinoma de tireoide previamente submetidos à tireoidectomia e à RIT que foram encaminhados para cirurgia de vias lacrimais. RESULTADOS: Dezessete pacientes com carcinoma de tireoide tratados com tireoidectomia e RIT apresentaram obstrução do ducto nasolacrimal sintomática após período médio de 13,2 meses do tratamento do câncer. Onze pacientes tiveram epífora bilateral, 8 com mucocele de saco lacrimal. A idade dos pacientes variou entre 30 e 80 anos, sendo 10 com idade menor ou igual a 49 anos. A dose cumulativa média de radioiodo administrada foi de 571 mCi (variação entre 200-1200 mCi). Sintomas de obstrução nasal e aumento de glândulas salivares ocorreram em 53% dos pacientes. Todos os pacientes foram submetidos à dacriocistorrinostomia. Observou-se ainda que nos 3 pacientes mais jovens houve maior sangramento intraoperatótio e dilatação de saco lacrimal. A resolução completa da epífora e da dacriocistite ocorreu em 82,4%, e foi parcial em 17,6% (3 pacientes mantiveram queixa unilateral após a correção da obstrução bilateralmente). O seguimento médio foi de 6 meses (intervalo: 2-24 meses). CONCLUSÕES: Alta dose cumulativa de radioiodo, disfunção nasal e de glândulas salivares estão associadas à obstrução das vias lacrimais. Observa-se uma maior porcentagem de pacientes mais jovens apresentando quadro de dacriocistite quando comparado à dacrioestenose idiopática. A absorção de iodo radioativo pela mucosa do ducto nasolacrimal com subsequente inflamação, edema e fibrose parece ter relação direta com a obstrução do ducto nasolacrimal. O conhecimento desta complicação é importante para o estudo e abordagem correta desses pacientes.

MicroRNA miR-146b-5p regulates signal transduction of TGF-beta by repressing SMAD4 in thyroid cancer

MicroRNAs (miRNA) are small non-coding RNAs involved in post-transcriptional gene regulation that have crucial roles in several types of tumors, including papillary thyroid carcinoma (PTC). miR-146b-5p is overexpressed in PTCs and is regarded as a relevant diagnostic marker for this type of cancer. A computational search revealed that miR-146b-5p putatively binds to the 3' untranslated region (UTR) of SMAD4, an important member of the transforming growth factor beta (TGF-beta) signaling pathway. The TGF-beta pathway is a negative regulator of thyroid follicular cell growth, and the mechanism by which thyroid cancer cells evade its inhibitory signal remains unclear. We questioned whether the modulation of the TGF-beta pathway by miR-146b-5p can contribute to thyroid tumorigenesis. Luciferase reporter assay confirmed the direct binding of miR-146b-5p on the SMAD4 3'UTR. Specific inhibition of miR-146b-5p with a locked nucleic acid-modified anti-miR-146b oligonucleotide significantly increased SMAD4 levels in the human papillary carcinoma cell lines, TPC-1 and BCPAP. Moreover, suppression of miR-146b-5p increased the cellular response to the TGF-beta anti-proliferative signal, significantly decreasing the proliferation rate. The overexpression of miR-146b-5p in normal rat follicular PCCL3 cells decreased SMAD4 levels and disrupted TGF-beta signal transduction. MiR-146b-5p overexpression in PCCL3 cells also significantly increased cell proliferation in the absence of thyroid-stimulating hormone and conferred resistance to TGF-beta-mediated cell-cycle arrest. Additionally, the activation of thyroid most common oncogenes RET/PTC3 and BRAF in PCCL3 cells upregulated miR-146b-5p expression. Our results confirm the oncogenic role of miR-146b-5p in thyroid follicular cells and contribute to knowledge regarding the modulation of TGF-beta signal transduction by miRNAs in PTCs. Oncogene (2012) 31, 1910-1922; doi:10.1038/onc.2011.381; published online 29 August 2011