Hypoxia-Nitric Oxide Axis and the Associated Damage Molecular Pattern in Cutaneous Melanoma.

Hypoxia was intensively studied in cancer during the last few decades, being considered a characteristic of the tumor microenvironment. The aim of the study was to evaluate the capacity of tumor cells to adapt to the stress generated by limited oxygen tissue in cutaneous melanoma. We developed a case-control prospective study that included 52 patients with cutaneous melanoma and 35 healthy subjects. We focused on identifying and monitoring hypoxia, the dynamic of nitric oxide (NO) serum metabolites and posttranslational metabolic disorders induced by NO signaling according to the clinical, biological and tumoral characteristics of the melanoma patients. Our study showed high levels of hypoxia-inducible factor-1a (HIF-1a) and hypoxia-inducible factor-2a (HIF-2a) in the melanoma patients. Hypoxia-inducible factors (HIFs) control the capacity of tumor cells to adapt to low levels of oxygen. Hypoxia regulated the nitric oxide synthase (NOS) expression and activity. In the cutaneous melanoma patients, disorders in NO metabolism were detected. The serum levels of the NO metabolites were significantly higher in the melanoma patients. NO signaling influenced the tumor microenvironment by modulating tumoral proliferation and sustaining immune suppression. Maintaining NO homeostasis in the hypoxic tumoral microenvironment could be considered a future therapeutic target in cutaneous melanoma.

Metastatic melanoma causing recurrent intussusception and perforation of small bowel: case reports and literature review.

AIM: To present cases of recurred jejuno-jejunal intussusception and jejunal perforation due to melanoma. MATERIALS & METHODS: Case 1: A 43-year-old male under treatment for malignant melanoma was presented with abdominal pain and distention. Ten centimeter intussuscepted jejunum was resected. Second exploration was done due to failure to pass gas and stool. The reintussusception was detected and resection of reintussuscepted jejunum was performed. Case 2: A 63-year-old male was presented with abdominal pain. Abdomen computed tomography showed free air in the abdomen suggesting intestinal perforations. Perforated area at 80 cm in the jejunum sutured. CONCLUSION: We present the seemingly first report of reintussusception of resected segment in a very short time. Surgeons should be aware of both intussusception and perforation in metastatic melanoma.

Nickel oxide nanoparticles exert selective toxicity on skin mitochondria and lysosomes isolated from the mouse model of melanoma.

Nickel oxide nanoparticles (NiO-NPs) are progressively used for an immense number of new applications in modern industries sectors. Nevertheless, the toxic impact of NiO-NPs has not been clearly elucidated on human melanoma cell lines at the cellular and molecular level. Hence, this study was designed to examine the in vitro cytotoxicity potentials of NiO-NPs on malignant cutaneous melanoma (MCM) mitochondria. Results revealed that NiO-NPs significantly increased reactive oxygen species level, lipid peroxidation, and mitochondrial membrane potential and decreased succinate dehydrogenase activity, glutathione level, and ATP content on skin mitochondria isolated from the mouse model of melanoma compared with the non-cancerous mouse skin mitochondria. Our results revealed that NiO-NPs induced lysosomal membrane labialization on mentioned mitochondria. The current study showed that NiO-NPs could significantly induce selective cytotoxicity on MCM mitochondria. Therefore, this compound may be considered as a promising candidate for further in vivo and clinical studies to reach a new anti-MCM drug.

Evaluation of PET/CT in patients with stage III malignant cutaneous melanoma.

In order to evaluate if patients with stage III-IV MCM are eligible for curative treatment PET/CT is performed. Since the diagnostic value of PET/CT is not unambiguously, a retrospective cohort study is performed to tailor optimal indication of PET/CT in patients with stage III MCM. A retrospective cohort study was conducted of all patients with stage III disease in a large oncologic teaching hospital in which PET/CT was performed from 2012 to 2016. The primary tumor- and regional lymph node characteristics were assessed to predict distant metastasis seen on PET/CT. A total of 73 patients were included of which 18% were restaged as stage IV by PET/CT. Twenty percent of the patients with a positive lymph node and 14% of patients with in transit metastasis or satellite lesions were restaged to stage IV. T-classification, ulceration and N-classification did not predict distant metastasis. Localization of the primary tumor significantly differed (P = 0.004). Localization on the head/neck resulted in a 32 greater odds of distant metastasis (P = 0.008). After a median follow-up of 36 months, 13 out of 60 (27%) stage III MCM patients were restaged as stage IV after the first performed PET/CT. This retrospective cohort study resulted in restaging of 18% of the stage III MCM patients by PET/CT, with therapeutic consequences. Patients with stage III MCM on the head/neck seem to have more distant spreading of the tumor than other localizations. Further investigation is needed, with larger sample sizes, to guide optimal indication of PET/CT.

Melanoma Arising in a Melanocytic Nevus. / Melanoma asociado a nevo melanocítico.

The association of melanoma with a preexisting melanocytic nevus varies considerably between series, depending on whether the association is based on histological signs (4%-72%) or a clinically evident lesion (42%-85%). Histological association with a nevus correlates with favorable prognostic factors, whereas a clinical association correlates with unfavorable factors. In this review, we discuss the characteristics of nevus-associated melanoma from different perspectives: Whiteman's divergent pathway hypothesis for the development of cutaneous melanoma; and the factors involved in nevogenicity, including both the genetic and molecular factors involved in the development of the melanoma and its precursor lesions. Finally, a cumulative analysis of the 16 162 cases reported in the literature revealed that 29.8% of melanomas are histologically associated with a melanocytic nevus.

Inflammation and macrophage polarization in cutaneous melanoma: Histopathological and immunohistochemical study.

Tumor-associated macrophages (TAMs) are considered to affect tumor growth and progression. Macrophages can be classified into two states of polarized activation, namely classically activated M1 macrophages and alternatively activated M2 macrophages. The dynamic balance between TAMs and tumor cells has an important impact on tumor homeostasis and progression. The aim of this study was to characterize the phenotype of TAMs present in different subtypes of superficial spreading cutaneous melanoma and their relationship with the lymphocytic infiltrate in order to identify new histopathological tools for melanoma prognosis and suitable targets for melanoma therapy. We selected four groups of patients with malignant melanoma in order to analyze the profile of polarized macrophage activation using immunohistochemical methods. Histopathological analysis showed that the macrophage polarization state appears to be more related to the lymphocytic infiltrate than to the thickness of the lesions. Further studies are necessary to increase understanding of the immunopathological dynamic of melanoma that may be modulated by future targeted immunotherapies.

Actualizaciones en melanoma maligno cutáneo / Updates in malignant cutaneous melanoma

El melanoma maligno cutáneo es una neoplasia que se origina en los melanocitos de la capa basal de la epidermis, y que se caracteriza por su genio biológico agresivo y por su alta mortalidad. El diagnóstico precoz y el tratamiento adecuado y oportuno resultan fundamentales para tratar exitosamente la enfermedad. Durante los últimos años se ha producido un notable aumento en su incidencia, lo que ha llevado a implementar importantes medidas de prevención. Además, se ha desarrollado una serie de recursos que permiten pesquisar y determinar la verdadera extensión de la neoplasia, lo que permite realizar un tratamiento más efectivo y establecer un apropiado pronóstico. En este artículo se analizan aspectos generales del melanoma maligno cutáneo y algunos de los avances más recientes que se han producido en su estudio y manejo.

Melanoma maligno cutáneo: revisión de conceptos actuales en etapificación, manejo y seguimiento / Malignant cutaneous melanoma: staging, management and follow-up

El cáncer de piel aumentó en incidencia en los últimas décadas, y el melanoma maligno cutáneo es su variedad más agresiva. Su diagnóstico tardío determina un mal pronóstico, por lo que se deben dirigir esfuerzos al control de factores de riesgo para prevenir su desarrollo, además de procurar una pesquisa precoz. La biopsia es el estándar de oro para el diagnóstico, a partir del cual se realiza la etapificación, utilizando el sistema TNM de la AJCC (2002). Éste se basa en una serie de factores que han demostrado ser los que mejor se correlacionan con el pronóstico del paciente, como el espesor y ulceración de la lesión, el número de ganglios comprometidos y las metástasis a distancia. Para lo evaluación ganglionar, la biopsia de ganglio centinela es considerada la herramienta más útil y poderosa. El presente artículo tiene como principal objetivo revisar la evidencia actual en cuanto a la etapificación, manejo y seguimiento de los pacientes con melanoma maligno.

Skin cancer has increased in incidence during the last decades, being the malignant cutaneous melanoma its most aggressive type. A late diagnosis determines a bad prognosis, for which is very important to make efforts controlling risk factors to prevent its development, and also to do an early diagnosis. The biopsy is the gold standard for diagnosis after which follows a staging wor-kup, based on the AJCCTNM (2002) system. This includes a series of factors that have been proven as prognostics factors, such as thickness and ulceration of the primary lesion, the number of metastatic lymph nodes and distant metastasis. For the nodal evaluation, the centinel lymph node biopsy is considered the most useful and powerful instrument. Other exams used for the stangig-workup are discussed. The patient’s follow-up should be life, although frequencies of controls are not precisely defined. The present article reviews, the actual evidence in relation with staging workup, management and follow-up of patients with malignant cutaneous melanoma.