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.

Estudo do perfil epidemiológico do melanoma cutâneo na cidade de Jaú-SP através do registro de base populacional

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

Metastatic melanoma of the tongue: a case report with immunohistochemical profile

BackgroundMelanoma of the skin is characterised by a high metastatic potential, but reports of metastasis to the tongue are rare. We report a case of skin melanoma with metastasis to the lymph nodes, tongue and brain.ObjectivesThis report highlights the clinical and histological features of oral metastatic melanoma.Case reportA 72-year-old man was seen with a nodule on the tongue. The differential diagnosis included salivary gland tumour, lymphoma and metastatic melanoma. His medical history revealed treatment for melanoma in the periumbilical region and micrometastases in the inguinal lymph nodes. An incisional biopsy was obtained and histological analysis showed the presence of a solid, epithelioid malignant tumour of monotonous appearance infiltrating the skeletal musculature. Immunohistochemistry showed reactivity of neoplastic cells to anti-HMB45, anti-melan A and anti-S100 antibodies and negativity for anti-PAN cytokeratin, confirming the diagnosis of metastatic melanoma.ConclusionThe present findings highlight the importance of a complete medical evaluation of the patient by anamnesis to identify possible oral repercussions of primary diseases in other organs and/or systems.

Pyrostegia venusta heptane extract containing saturated aliphatic hydrocarbons induces apoptosis on B16F10-Nex2 melanoma cells and displays antitumor activity in vivo

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

Antitumor Activity of Kielmeyera Coriacea Leaf Constituents in Experimental Melanoma, Tested in Vitro and in Vivo in Syngeneic Mice

Purpose: The antitumor activity of Kielmeyera coriacea (Clusiaceae), a medicinal plant used in the treatment of parasitic, as well as fungal and bacterial infections by the Brazilian Cerrado population, was investigated. Methods: A chloroform extract (CE) of K. coriacea was tested in the murine melanoma cell line (B16F10-Nex2) and a panel of human tumor cell lines. Tumor cell migration was determined by the wound-healing assay and the in vivo antitumor activity of CE was investigated in a melanoma cell metastatic model. 1H NMR and GC/MS were used to determine CE chemical composition. Results: We found that CE exhibited strong cytotoxic activity against murine melanoma cells and a panel of human tumor cell lines in vitro. CE also inhibited growth of B16F10- Nex2 cells at sub lethal concentrations, inducing cell cycle arrest at S phase, and inhibition of tumor cell migration. Most importantly, administration of CE significantly reduced the number of melanoma metastatic nodules in vivo. Chemical analysis of CE indicated the presence of the long chain fatty compounds, 1-eicosanol, 1-docosanol, and 2-nonadecanone as main constituents. Conclusion: These results indicate that K. coriacea is a promising medicinal plant in cancer therapy exhibiting antitumor activity both in vitro and in vivo against different tumor cell lines.

Epitheliotropic cutaneous T-cell lymphoma associated with melanoma in a dog: case report

Several types of tumors affect dogs' skin. Simultaneously occurring neoplasms with different histological patterns might be rarely present in the same animal. This paper describes the occurrence of epitheliotropic cutaneous T-cell lymphoma and melanoma in a dog. The animal had nodular lesions in the abdominal region and serpiginous plaques on the dorsal region of the trunk. Cytology evidenced malignant fusiform cells from the abdominal lesions as well as few round cells from the dorsal. The histopathological examination of the abdominal lesions showed dermis with polygonal to spindle-shaped neoplastic cells. The lesion of the dorsal region evidenced neoplastic round cells with generally distinct cell borders and a moderate amount of eosinophilic cytoplasm. Abdominal lesions were positive for Melan A. Dorsal and forelimb lesions were positive for CD3. This study reports the occurrence of epitheliotropic cutaneous T-cell lymphoma and malignant melanoma in a crossbred Boxer dog and discusses the importance of performing immunohistochemical profile to confirm the phenotype of the tumor.

Focal invasiveness in complete histological analyses of a large acral lentiginous melanoma

Background: Acral lentiginous melanoma is a melanoma with poor prognosis which is frequently diagnosed at an advanced stage. Since the thickness of tumour is one of the main prognostic factors, this case can exemplify how important complete histological analyses looking for focal invasiveness can be.Case report: A 77 year-old woman with a black spot with slow progressive growth on the left plantar region. She sought medical attention due to the expansion onto the dorsal surface of toes. The lesion had irregular borders and had spread to half the plantar surface. Histopathology confirmed the clinical suspicion of acral lentiginous melanoma Clark level IV and 2.6 mm Breslow thickness. The surgical specimen was entirely processed for histological evaluation, requiring 53 slides. Tumor dermal invasion was detected in only three out of 53 glass slides as the invasiveness was not identified by clinical, dermatoscopy or macroscopy exams.Conclusion: Sectioning through the entire lesion is considered very important to determinate the appropriate stage of the disease and the correct treatment and patient follow-up.

Nanotechnology-based drug delivery systems for melanoma antitumoral therapy: a review

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Vacina de DNA: uma alternativa para o tratamento do melanoma canino: revisão de literatura

O melanoma é considerado um dos tumores cutâneos de maior importância em cães devido ao seu caráter agressivo, à capacidade de produzir metástases em estágios precoces e à baixa resposta aos tratamentos não cirúrgicos. Recentemente, as vacinas de DNA apresentam-se promissoras na terapêutica do melanoma canino. O objetivo deste trabalho é apresentar uma revisão bibliográfica sobre o assunto. As vacinas de DNA são baseadas em plasmídeos que contêm o gene codificante para o antígeno alvo, expressando-o na célula do hospedeiro e apresentando, assim, vantagens em relação às vacinas tradicionais, como: facilidade de produção, estabilidade térmica, baixo custo e estimulação da resposta imune celular (linfócitos T CD8+). Devido ao sucesso limitado das terapias padrões, o estabelecimento de uma vacina de DNA efetiva aumenta a possibilidade de uma terapia promissora para o melanoma canino, podendo trazer novas expectativas aos animais portadores dessa neoplasia.

Melanoma subungueal in situ tratado com cirurgia funcional

Melanoma subungueal in situ tratado com cirurgia funcionalHamilton Ometto StolfI, Hélio Amante MiotI, Nilton de Ávila ReisIIDepartamento de Dermatologia e Radioterapia, Universidade Estadual Paulista (Unesp)INTRODUÇÃOO melanoma subungueal representa aproximadamente 2% a 3% dos melanomas cutâneos em pacientes caucasianos1 e 20% em pacientes negros2 ou asiáticos.3A exposição solar, tida com principal fator de risco para o melanoma cutâneo,4 parece desempenhar papel secundário no desenvolvimento da variante subungueal,5 uma vez que a radiação ultravioleta dificilmente penetra no leito ungueal. Além disso, nevos subungueais como lesões precursoras são extremamente raros.6Os polegares e háluces são os mais acometidos, sendo o polegar responsável por 56% dos casos entre todos os dedos e o hálux por 86% dos dedos dos pés.7A confirmação do diagnóstico é feita a partir do exame anatomopatológico da lesão, geralmente localizada na matriz ou leito ungueal. A verificação histológica do melanoma subungueal é frequentemente postergada por conta do atraso no diagnóstico clínico,8-10 gerando piora do prognóstico.O prognóstico geralmente é ruim: as taxas de sobrevida real de cinco anos variam entre 16% a 20%, podendo atingir até 80% se consideradas taxas de sobrevida estimada.2,3,11-18RELATO DE CASOPaciente de 44 anos, do sexo feminino, professora, com queixa de aparecimento de mancha na unha do hálux direito há cinco anos. Relata aumento progressivo lento na largura da faixa. Ao exame dermatológico, apresentava faixa de melanoníquia extensa, irregular, bordas mal definidas e estria de pigmentação mais acentuada em uma das margens do leito ungueal do hálux direito (Figura 1). Exame dermatoscópico (aparelho Dermalite II Pro, aumento de 10 vezes) confirmou faixas irregulares e cores variadas de hiperpigmentação.Foi realizada a avulsão parcial da lâmina ungueal e incisão na prega ungueal lateral para visualização do local da origem da pigmentação no leito ungueal,

Ethnicity and Cutaneous Melanoma in the City of Sao Paulo, Brazil: A Case-Control Study

Background: Over the last century the incidence of cutaneous melanoma has increased worldwide, a trend that has also been observed in Brazil. The identified risk factors for melanoma include the pattern of sun exposure, family history, and certain phenotypic features. In addition, the incidence of melanoma might be influenced by ethnicity. Like many countries, Brazil has high immigration rates and consequently a heterogenous population. However, Brazil is unique among such countries in that the ethnic heterogeneity of its population is primarily attributable to admixture. This study aimed to evaluate the contribution of European ethnicity to the risk of cutaneous melanoma in Brazil. Methodology/Principal Findings: We carried out a hospital-based case-control study in the metropolitan area of Sao Paulo, Brazil. We evaluated 424 hospitalized patients (202 melanoma patients and 222 control patients) regarding phenotypic features, sun exposure, and number of grandparents born in Europe. Through multivariate logistic regression analysis, we found the following variables to be independently associated with melanoma: grandparents born in Europe-Spain (OR = 3.01, 95% CI: 1.03-8.77), Italy (OR = 3.47, 95% CI: 1.41-8.57), a Germanic/Slavic country (OR = 3.06, 95% CI: 1.05-8.93), or >= 2 European countries (OR = 2.82, 95% CI: 1.06-7.47); eye color-light brown (OR = 1.99, 95% CI: 1.14-3.84) and green/blue (OR = 4.62; 95% CI 2.22-9.58); pigmented lesion removal (OR = 3.78; 95% CI: 2.21-6.49); no lifetime sunscreen use (OR = 3.08; 95% CI: 1.03-9.22); and lifetime severe sunburn (OR = 1.81; 95% CI: 1.03-3.19). Conclusions: Our results indicate that European ancestry is a risk factor for cutaneous melanoma. Such risk appears to be related not only to skin type, eye color, and tanning capacity but also to others specific characteristics of European populations introduced in the New World by European immigrants.

Proteasome inhibition and ROS generation by 4-nerolidylcatechol induces melanoma cell death

Induction of apoptotic cell death in response to chemotherapy and other external stimuli has proved extremely difficult in melanoma, leading to tumor progression, metastasis formation and resistance to therapy. A promising approach for cancer chemotherapy is the inhibition of proteasomal activity, as the half-life of the majority of cellular proteins is under proteasomal control and inhibitors have been shown to induce cell death programs in a wide variety of tumor cell types. 4-Nerolidylcatechol (4-NC) is a potent antioxidant whose cytotoxic potential has already been demonstrated in melanoma tumor cell lines. Furthermore, 4-NC was able to induce the accumulation of ubiquitinated proteins, including classic targets of this process such as Mcl-1. As shown for other proteasomal inhibitors in melanoma, the cytotoxic action of 4-NC is time-dependent upon the pro-apoptotic protein Noxa, which is able to bind and neutralize Mcl-1. We demonstrate the role of 4-NC as a potent inducer of ROS and p53. The use of an artificial skin model containing melanoma also provided evidence that 4-NC prevented melanoma proliferation in a 3D model that more closely resembles normal human skin.

In Vitro PLK1 Inhibition by BI 2536 Decreases Proliferation and Induces Cell-Cycle Arrest in Melanoma Cells

Melanoma is one of the most treatment-resistant malignancies and regardless of new therapeutic tactics the outcome remains dismal. Polo-like kinase 1 (PLK1) has been shown to be over-expressed in a variety of tumors, becoming an attractive target for cancer management. In the present study we tested the in vitro antitumor activities of BI 2536, a selective inhibitor of PLK1, against two melanoma cell lines. Our results showed that nanomolar concentrations (10-150 nmol/L) of the drug significantly decreased cell proliferation and clonogenicity, promoting cell cycle arrest in G2/M. Targeting the cell cycle offers an attractive potential cancer-treatment option. Herein we show that PLK1 inhibition may be a feasible approach for the impairment of tumor progression and dissemination. This in vitro profile of melanoma cell growth inhibition by PLK1 modulation may be an interesting model to be tested in association with first-line antineoplasic agents in melanomas.

Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas.

Apoptotic Cells Contribute to Melanoma Progression and This Effect is Partially Mediated by the Platelet-Activating Factor Receptor

There is evidence that the platelet-activating factor receptor (PAFR) is involved in the clearance of apoptotic cells by macrophages, and that this is associated with anti-inflammatory phenotype. Our group has previously shown that coinjection of a large number of apoptotic cells can promote tumor growth from a subtumorigenic dose of melanoma cells. Here, we studied the involvement of the PAFR in the tumor growth promoting effect of apoptotic cells. A sub-tumorigenic dose of melanoma cells (Tm1) was coinjected with apoptotic Tm1 cells, subcutaneously in the flank of C57Bl/6 mice, and the volume was monitored for 30 days. Animals received the PAFR antagonists, WEB2170 or PCA4248 (5 mg/kg body weight) or vehicle, by peritumoral daily injection for 5 days. Results showed that PAFR antagonists significantly inhibited the tumor growth induced by the coinjection of a subtumorigenic dose of melanoma cells together with apoptotic cells. This was accompanied by inhibition of early neutrophil and macrophage infiltration. Addition of (platelet-activating factor) to this system has no significant effect. PAFR antagonists did not affect the promoting effect of carrageenan. We suggest that the recognition of apoptotic cells by phagocytes leads to activation of PAFR pathways, resulting in a microenvironment response favorable to melanoma growth.