Kras oncogene analysis of non-melanoma skin tumors in Southeastern Brazil

Skin cancers are the most common human malignant neoplasia and their incidence is growing, chiefly in tropical countries. There is evidence that ultraviolet (UV) radiation present in sunlight is important for genetic damage. Mutations due to such damage could be responsible for alterations in oncogenes and tumor suppressor genes. Recent studies have reported remarkable differences in mutation frequency of the RAS proto-oncogene in non-melanoma skin cancers. These findings may reflect differences in the molecular epidemiology of cutaneous tumors found in geographical areas with diverse sun exposure and ethnical origins of their populations. Our study proposed to perform molecular analyses of skin tumors on patients living in southeastern Brazil, in areas with high levels of sun exposure. DNA from eight solar keratose (SK), 26 basal cell carcinomas (BCC) and 19 squamous cell carcinomas (SCC) was submitted to PCR-SSCP analysis for codons 12, 13 and 61. Contradicting other authors, we found no mutations in codons 12,13 but detected two BCCs and one SCC with a mutation in codon 61. These findings suggest that the activation of KRAS oncogene may contribute to the pathogenicity of cutaneous lesions in southeastern Brazil.

Catecholamine effects on human melanoma cells evoked by α1-adrenoceptors

The biological effects of catecholamines in mammalian pigment cells are poorly understood. Our previous results showed the presence of α1-adrenoceptors in SK-Mel 23 human melanoma cells. The aims of this work were to (1) characterize catecholamine effects on proliferation, tyrosinase activity and expression, (2) identify the α1- adrenoceptor subtypes, and (3) verify whether chronic norepinephrine (NE) treatment modified the types and/or pharmacological characteristics of adrenoceptors present in SK-Mel 23 human melanoma cells. Cells treated with the aradrenergic agonist, phenylephrine (PHE, 10-5 or 10-4 M), for 24-72 h, exhibited decreased cell proliferation and enhanced tyrosinase activity, but unaltered tyrosinase expression as compared with the control. The proliferation and tyrosinase activity responses were inhibited by the α1-adrenergic antagonist prazosin, suggesting they were evoked by α1-adrenoceptors. The presence of actinomycin D, a transcription inhibitor, did not diminish PHE-induced effects. RT-PCR assays, followed by cloning and sequencing, demonstrated the presence of α1A- and α1B-adrenoceptor subtypes. NE-treated cells (24 or 72 h) were used in competition assays, and showed no significant change in the competition curves of α1-adrenoceptors as compared with control curves. Other adrenoceptor subtypes were not identified in these cells, and NE pretreatment did not induce their expression. In conclusion, the activation of SK-Mel 23 human melanoma α1- radrenoceptors elicit biological effects, such as proliferation decrease and tyrosinase activity increase. Desensitization or expression of other adrenoceptor subtypes after chronic NE treatment were not observed.

Melanoma de coróide: Relato de caso insuspeito

The choroidal melanoma is the most frequent intraocular tumor in elderly, occurring mainly in the 60th. This paper shows a misdiagnosis tumor affecting a female aging 36 years-old, misdiagnosed and initially treated as a toxoplasmic uveitis. The tumor had orbit and neck metastasis. The authors call attention to the necessity of early diagnosis to improve the outcome.

Inhibition of eukaryotic translation initiation factor 5A (eIF5A) hypusination impairs melanoma growth

The eukaryotic translation initiation factor 5A (eIF5A) undergoes a specific post-translational modification called hypusination. This modification is required for the functionality of this protein. The compound N1-guanyl-1,7-diaminoheptane (GC7) is a potent and selective inhibitor of deoxyhypusine synthase, which catalyses the first step of eIF5A hypusination process. In the present study, the effects of GC7 on cell death were investigated using two cell lines: melan-a murine melanocytes and Tm5 marine melanoma. In vitro treatment with GC7 increased by 3-fold the number of cells presenting DNA fragmentation in Tm5 cells. Exposure to GC7 also decreased viability to both cell lines. This study also describes, for the first time, the in vivo antitumour effect of GC7, as indicated by impaired melanoma growth in C57BL/6 mice. Copyright © 2006 John Wiley & Sons, Ltd.

Tumor maligno da bainha de nervo periférico envolvendo raízes nervosas do terceiro segmento medular lombar em um cão

Malignant peripheral nerve sheath tumors (MPNST) involving spinal nerve roots are uncommon in dogs. A nine-year old, intact, mixed-breed dog, demonstrated clinical signs of incoordination in the pelvic limbs and micturition for approximately one week. Clinical examination revealed proprioceptive deficits and bilateral patellar hyperreflexia. During exploratory celiotomy a mass was observed adhered to the lumbar vertebral segments. Medical therapy was initiated, but neurological signs were progressive, and the owner opted for euthanasia. Gross examination showed that the mass in the abdominal cavity was attached to the lumbar segments L3 and L4, causing bone lysis in L3, but showed no tumor invasion into the spinal canal. Microscopic features were characterized by prominent proliferation of ovoid and fusiform cells with poorly defined cytoplasm arranged in interlacing bundles and concentric whorls. The cells were embedded in a delicate to moderate collagenous stroma and moderate anisokariose and high mitotic activity were noted. The immunohistochemical assay showed positive staining for GFAP, S-100 protein and vimentin, and negative staining for factor VIII, α-actin and citokeratine. The definitive diagnosis of malignant peripheral nerve sheath tumor was made on the basis of the histological and immunohistochemical findings.

A biópsia de linfonodo sentinela não deve ser recomendada para pacientes portadores de melanoma espesso

Objective: To ascertain whether there is any relationship between the state of the sentinel lymph node histopathology, recurrence and mortality from thick melanoma in patients undergoing SLNB over a long follow-up. Methods: Eighty-six patients with thick melanoma undergoing SLNB were selected from a prospective database. Lymphoscintigraphy, lymphatic mapping and intraoperative gamma probe detection were performed in all patients. The sentinel lymph node (SLN) was analyzed by HE and immunohistochemistry. Complete lymphadenectomy was indicated for patients with positive sentinel node. The histopathological SLN status was related to the rate of recurrence and mortality from melanoma. Results: One hundred and sixty-six SLNs were taken from the 86 patients. Ages ranged from 18 to 73 years. There were 47 women and 39 men. Micrometastases were found in 44 patients. Forty-two patients underwent complete lymphadenectomy. Seven other patients had positive lymph node. Among the 44 patients with positive sentinel node, there were 20 recurrences and 15 deaths. There were 18 recurrences and 12 deaths in the group with negative SLN. The Breslow thickness was not correlated with the histopathological SLN status. The histopathological SLN status did not affect the rates of recurrence and mortality (Fisher test, p = 1.00). The median follow-up was 69 months. Conclusion: Considering the lack of evidence of benefit, SLNB should not be indicated for patients with thick melanoma outside of clinical studies.

Tonsilar metastases of melanoma in an older person

We presented a rare case of metastasis of melanoma in palatine tonsils alerting healthcare professionals to this diagnose in black oral lesions. © The Author 2013. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

Técnicas de imagem para triagem de melanoma

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Fatores de crescimento e citocinas envolvidos na angiogênese de melanoma em animais selecionados pela intensidade da resposta inflamatória aguda

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Padrão histológico, perfil imunoistoquímico e potencial pré-maligno das lesões diaplásicas da próstata canina

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Desenvolvimento de melanoma em animais selecionados pela intensidade de resposta inflamatória aguda (Airmax/Airmin): caracterização das células Natural Killer, NKT, Treg e perfil de citocinas

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito da própolis sobre a produção de citocinas por camundongos submetidos a estresse crônico e desafiados com melanoma

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Caracterização do infiltrado inflamatório e avaliação dos marcadores de prognóstico Ki-67, p53, receptor de estrógeno e progesterona no tumor mamário maligno de cadelas

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

Antiproliferative effect of Pterogyne nitens on melanoma cells

As part of our program of bioprospecting for novel antitumor drug prototypes, twenty extracts and fractions obtained from Pterogyne nitens Tul. (Fabaceae, Caesalpinioideae) were screened for antiproliferative activity against B16F10 murine melanoma cells, by the MTT colorimetric assay. The strongest activity was found in EtOAc fractions from the flowers (IC50 = 0.35 µg/mL), fruits (IC50 = 0.34 µg/mL), leaves (IC50 = 0.33 µg/mL) and stems (IC50 = 0.29 µg/mL). Analysis by TLC and HPLC-DAD showed the presence of guanidine alkaloids, flavones and flavonols in the bioactive samples. Additionally, a phytochemical study of the EtOAc fraction of the stems afforded quercetin (1) and isoquercitrin (2), two flavonols with antiproliferative activity previously described in the literature. On the basis of these results, it can be concluded that P. nitens inhibits the growth of melanoma cells in vitro. Further investigations will be needed to assess the usefulness of the samples under study for the treatment of neoplasms and to characterize other bioactive compounds. Keywords: antiproliferative; Pterogyne nitens; Caesalpinioideae; melanoma; flavonoids; Fabaceae.