Primary malignant melanoma of the esophagus: a rare and aggressive disease

Primary malignant melanoma of the esophagus is an uncommon tumor, with approximately 300 cases having been reported thus far. The purpose of this study was to describe a case of a 60 year-old man with a 10 month history of progressive dysphagia and thoracic pain, the investigations of which led to a diagnosis of primary malignant melanoma of the esophagus. The patient underwent a transhiatal esophagectomy with subcarinal lymphadenectomy, and isoperistaltic gastric tube replacement of the esophagus. Nine months after surgery, he developed ischemic colitis, and metastasis in the mesentery was diagnosed. His disease progressed and he died one year after the esophagectomy. A review of the literature was performed.

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.

Boron uptake in normal melanocytes and melanoma cells and boron biodistribution study in mice bearing B16F10 melanoma for boron neutron capture therapy

Information on B-10 distribution in normal tissues is crucial to any further development of boron neutron capture therapy (BNCT). The goal of this study was to investigate the in vitro and in vivo boron biodistribution in B16F10 murine melanoma and normal tissues as a model for human melanoma treatment by a simple and rapid colorimetric method, which was validated by HR-ICP-MS. The B16F10 melanoma cell line showed higher melanin content than human melanocytes, demonstrating a greater potential for boronophenylalanine uptake. The melanocytes showed a moderate viability decrease in the first few minutes after BNCT application, stabilizing after 75 min, whereas the B16F10 melanoma showed the greatest intracellular boron concentration at 150 min after application, indicating a different boron uptake of melanoma cells compared to normal melanocytes. Moreover, at this time, the increase in boron uptake in melanoma cells was approximately 1.6 times higher than that in normal melanocytes. The B-10 concentration in the blood of mice bearing B16F10 melanoma increased until 90 min after BNCT application and then decreased after 120 min, and remained low until the 240th minute. On the other hand, the B-10 concentration in tumors was increased from 90 min and maximal at 150 min after application, thus confirming the in vitro results. Therefore, the present in vitro and in vivo study of B-10 uptake in normal and tumor cells revealed important data that could enable BNCT to be possibly used as a treatment for melanoma, a chemoresistant cancer associated with high mortality.

In vitro evaluation of combined hyperthermia and photodynamic effects using magnetoliposomes loaded with cucurbit[7]uril zinc phthalocyanine complex on melanoma

The aims of this study were two fold; to develop magnetoliposomes (MLs) loaded with zinc phthalocyanine (ZnPc) complexed with cucurbituril (CB) (CB:ZnPc-MLs) and to evaluate their in vitro photodynamic (PD) and/or hyperthermia (HT) effects while using melanoma cells (B16-F10) as model. The liposomal formulations were characterized by both average diameter and zeta potential. The vesicle average size ranged from 150 to 200 nm and the polydispersity index (PdI) from 0.093 to 0.230. The zeta potential was significantly positive with values between 48 and 57 mV. The cell viability (CV) after PD and HT treatments was assessed by colorimetric MTI method. Melanoma cells were initially treated with the liposome formulation without light and magnetic field application, revealing cell viability not different from the control cells (p > 0.05). Photodynamic and hyperthermia assays were also applied separately, demonstrating that PD is more effective than HT in reducing the CV of the neoplastic cells. Combined application of both PD and HT treatments was even more effective in reducing the CV of B16-F10 cells. At the highest light dose (2 J/cm(2)) and under magnetic field activation the CV was about half than PD applied alone. Therefore, the use of the photosensitizer-loaded magnetoliposome for combined photodynamic therapy (PDT) and magnetohyperthermia (MHT) application can be considered as a potential tool to treat malignant melanoma. (C) 2012 Elsevier B.V. All rights reserved.

Melanoma Staging Where Are We Now?

The seventh version of the American Joint Committee on Cancer (AJCC) Melanoma Staging guidelines, published in 2009, has significant revisions compared with the previous version. The current schema was based on the largest melanoma patient cohort analyzed to date and is the result of a multivariate analysis of 30,946 patients with stages I, II, and III melanoma and 7972 patients with stage IV melanoma. This article summarizes the findings and the new definitions included in the 2009 AJCC Melanoma Staging and Classification. The TNM categories and the stage groupings are defined. Changes in the melanoma staging system are summarized.

Transmission of clear cell tumor in a graft liver from cadaveric donor: Case report

Neoplasms in children after organ transplantation are related to the type and intensity of immunosuppression and the donorrecipient serostatus, especially in relation to the EpsteinBarr virus. The patient was a two-yr-old female child with biliary atresia who underwent a liver transplantation from a female cadaver donor. Two adults received kidney transplants from the same donor. Nine months after transplantation, one of the adult recipients developed an urothelial tumor in the kidney graft. Imaging tests were repeated monthly in the liver-transplanted child and revealed no abnormalities. However, one yr and two months after the transplantation, the patient developed episodes of fever. At that time, imaging and liver biopsy showed a clear cell tumor of urothelial origin in the graft and the disease was limited to the liver. The patient underwent liver retransplantation, and she is currently free of tumor recurrence. Although rare, the occurrence of tumors in the post-transplant period from cadaver donors, without previously diagnosed tumors, is one of the many problems encountered in the complex world of organ transplantation.

Fotoproteção tópica na infância e na adolescência

OBJETIVO: A exposição à luz solar na infância ocorre, frequentemente, de forma mais intensa do que em muitos adultos. Dados da literatura comprovam de maneira inequívoca a associação desse comportamento social com o risco de desenvolvimento do melanoma maligno e do câncer cutâneo não melanoma mesmo na vida adulta. Além disso, o fotoenvelhecimento cutâneo é semeado já na infância com a exposição solar inadequada. Esta revisão tem como objetivo orientar os pediatras nas medidas adequadas de fotoproteção tópica nas crianças e adolescentes, o que irá alterar de maneira positiva o futuro desses pacientes. FONTES DOS DADOS: Realizou-se uma revisão da literatura indexada na base de dados MEDLINE/PubMed entre os anos de 1999 e 2012 sobre fotoproteção na infância, selecionando-se como fonte os artigos de revisão mais relevantes, do ponto de vista de abrangência do tema fotoproteção em crianças e adolescentes, fotoproteção e vitamina D, fototerapia na neonatologia e impacto no câncer cutâneo, bronzeamento artificial e câncer cutâneo. SÍNTESE DOS DADOS: Crianças e adolescentes devem adotar medidas adequadas de fotoproteção para diminuir o risco de câncer cutâneo melanoma e não melanoma. CONCLUSÕES: Há dados na literatura que suportam a associação de hábitos de exposição solar segura e uso de fotoprotetores tópicos em crianças e adolescentes com a redução da ocorrência do câncer cutâneo.

Discrimination of Basal Cell Carcinoma and Melanoma from Normal Skin Biopsies in Vitro Through Raman Spectroscopy and Principal Component Analysis

Objective: Raman spectroscopy has been employed to discriminate between malignant (basal cell carcinoma [BCC] and melanoma [MEL]) and normal (N) skin tissues in vitro, aimed at developing a method for cancer diagnosis. Background data: Raman spectroscopy is an analytical tool that could be used to diagnose skin cancer rapidly and noninvasively. Methods: Skin biopsy fragments of similar to 2 mm(2) from excisional surgeries were scanned through a Raman spectrometer (830 nm excitation wavelength, 50 to 200 mW of power, and 20 sec exposure time) coupled to a fiber optic Raman probe. Principal component analysis (PCA) and Euclidean distance were employed to develop a discrimination model to classify samples according to histopathology. In this model, we used a set of 145 spectra from N (30 spectra), BCC (96 spectra), and MEL (19 spectra) skin tissues. Results: We demonstrated that principal components (PCs) 1 to 4 accounted for 95.4% of all spectral variation. These PCs have been spectrally correlated to the biochemicals present in tissues, such as proteins, lipids, and melanin. The scores of PC2 and PC3 revealed statistically significant differences among N, BCC, and MEL (ANOVA, p < 0.05) and were used in the discrimination model. A total of 28 out of 30 spectra were correctly diagnosed as N, 93 out of 96 as BCC, and 13 out of 19 as MEL, with an overall accuracy of 92.4%. Conclusions: This discrimination model based on PCA and Euclidean distance could differentiate N from malignant (BCC and MEL) with high sensitivity and specificity.

Clinico-genetic aspects of a pediatric non-neurofibromatosis type 1 malignant triton tumor with loss of chromosome X

Malignant triton tumor (MTT) is an aggressive peripheral nerve sheath tumor with rhabdomyoblastic differentiation. Less than 100 cases have been described, being mostly male children with type 1 neurofibromatosis. We report a 6-year-old female with MTT and no diagnostic criteria for neurofibromatosis type 1. Cytogenetic analysis showed a 46,X,-X[4]/46,XX[16] karyotype. She underwent a transfemoral amputation and chemotherapy and is free of disease 15 months after diagnosis. The few cytogenetic studies of MTT described in the literature have been inconclusive. Further cytogenetic analyses are needed to understand the role of chromosome X monosomy in the pathogenesis of this rare tumor. Pediatr Blood Cancer 2012; 59: 13201323. (C) 2012 Wiley Periodicals, Inc.

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.

Duodenal stenting for malignant gastric outlet obstruction: Prospective study

AIM: To evaluate the results of duodenal stenting for palliation of gastroduodenal malignant obstruction by using a gastric outlet obstruction score (GOOS). METHODS: A prospective, non-randomized study was performed at a tertiary center between August 2005 and April 2010. Patients were eligible if they had malignant gastric outlet obstruction (GOO) and were not candidates for surgical treatment. Medical history and patient demographics were collected at baseline. Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180 d later or unscheduled as necessary. RESULTS: Fifteen patients (6 male, 9 female; median age 61 years) with GOO who had undergone duodenal stenting were evaluated. Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral intake (93.33%), including 7 patients who were using a feeding tube. Laboratory data showed biliary obstruction in eight cases (53.33%); all were submitted to biliary drainage. Two patients developed obstructive symptoms due to tumor ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of stent migration occurred. A good response to treatment was observed, with a mean time of approximately 1 d (19 h) until toleration of a liquid diet and slightly more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h). The mean time to first failure to maintain liquid intake (GODS >= 1) was 93 d. During follow-up, the mean time to first failure to maintain the previously achieved GODS of 2-3 (solid/semi-solid food), considered technical failure, was 71 d. On the basis of oral intake a GODS is defined: 0 for no oral intake; 1 for liquids only; 2 for soft solids only; 3 for low-residue or full diet. CONCLUSION: Enteral stenting to alleviate gastroduodenal malignant obstruction improves quality of life in patients with limited life expectancy, which can be evaluated by using a GOO scoring system. (C) 2012 Baishideng. All rights reserved.

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. (C) 2012 International Society for Advancement of Cytometry

Molecular confirmation of ovine herpesvirus 2-induced malignant catarrhal fever lesions in cattle from Rio Grande do Norte, Brazil

Molecular findings that confirmed the participation of ovine herpesvirus 2 (OVH-2) in the lesions that were consistent with those observed in malignant catarrhal fever of cattle are described. Three mixed-breed cattle from Rio Grande do Norte state demonstrated clinical manifestations that included mucopurulent nasal discharge, corneal opacity and motor incoordination. Routine necropsy examination demonstrated ulcerations and hemorrhage of the oral cavity, corneal opacity, and lymph node enlargement. Significant histopathological findings included widespread necrotizing vasculitis, non-suppurative meningoencephalitis, lymphocytic interstitial nephritis and hepatitis, and thrombosis. PCR assay performed on DNA extracted from kidney and mesenteric lymph node of one animal amplified a product of 423 base pairs corresponding to a target sequence within the ovine herpesvirus 2 (OVH-2) tegument protein gene. Direct sequencing of the PCR products, from extracted DNA of the kidney and mesenteric lymph node of one cow, amplified the partial nucleotide sequences (423 base pairs) of OVH-2 tegument protein gene. Blast analysis confirmed that these sequences have 98-100% identity with similar OVH-2 sequences deposited in GenBank. Phylogenetic analyses, based on the deduced amino acid sequences, demonstrated that the strain of OVH-2 circulating in ruminants from the Brazilian states of Rio Grande do Norte and Minas Gerais are similar to that identified in other geographical locations. These findings confirmed the active participation of OVH-2 in the classical manifestations of sheep associated malignant catarrhal fever.

Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma

Background Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer-testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE-A4 (melanoma antigen) and MAGE-C1 are expressed in carcinoma of the oral cavity and are related with survival. Methods This study involved immunohistochemical analysis of 23 patients with oral squamous cell carcinoma (SCC) and was carried out using antibodies for MAGE-A4 and MAGE-C1. Fisher's exact test and log-rank test were used to evaluate the results. Results The expression of the MAGE-A4 and MAGE-C1 were 56.5% and 47.8% without statistical difference in studied variables and survival. Conclusion The expression of at least 1 CTA was present in 78.3% of the patients, however, without correlation with clinicopathologic variables and survival. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2012

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.