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OBJECTIVES To evaluate melanoma biopsy specimens for human papilloma virus (HPV) and determine the relation between the presence of HPV, in vitro growth, and clinical progression of melanoma in the patients from whom the biopsy specimens were derived. SUMMARY BACKGROUND DATA Ultraviolet radiation from sun exposure appears to be the primary causal agent in the development of cutaneous melanoma. However, other agents, including HPV, as observed in different epithelial carcinomas, may also play a role in melanoma development and progression. METHODS Twelve melanoma biopsy specimens obtained from 12 patients with AJCC stage III and IV melanoma were stained with antibodies against gp-100 (HMB-45) and S-100 protein to confirm melanoma diagnosis and with a polyclonal HPV antibody. After mechanical dissociation, the melanoma specimen cells ability to grow in vitro was assessed. Patients were evaluated for melanoma progression with physical examination, complete blood count, and liver function tests every 3

In this article, we report the derivation of highly metastatic human melanoma cell lines from poorly metastatic parental lines using an animal metastasis model. We subsequently identified a metastasis aggressiveness gene signature by comparing the gene expression patterns of tumor samples from the highly metastatic derivatives with those from their parental lines. By comparisons with gene expression data from human clinical samples, we found that expression of this metastasis gene signature in human melanoma metastases correlates with poor survival of the corresponding patients. The signature is able to segregate melanoma-bearing patients into three groups, one of which has a significantly lower survival probability. This suggests that the signature provides an indication of aggressiveness of the melanoma metastases rather than of metastasis per se, similar to the lung metastasis signature reported by Minn et al. (10). This result has been confirmed by alternative methods such as GSEA and ...

TY - JOUR. T1 - Primary malignant melanoma of the lung. AU - Bagwell, S. P.. AU - Flynn, S. D.. AU - Cox, P. M.. AU - Davison, J. A.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Primary malignant melanoma of the lung is a rare neoplasm; to date, there have been approximately 20 cases reported in the literature. Extensive clinical and postmortem examinations are necessary to exclude the possibility that the lung tumor does not represent a metastasis from an occult cutaneous or extracutaneous melanoma. We present a case of a 62-yr-old man who appears to have had a primary melanoma of the left upper lobe of the lung. The literature on primary pulmonary melanoma is also reviewed.. AB - Primary malignant melanoma of the lung is a rare neoplasm; to date, there have been approximately 20 cases reported in the literature. Extensive clinical and postmortem examinations are necessary to exclude the possibility that the lung tumor does not represent a metastasis from an occult cutaneous or extracutaneous melanoma. ...

Discussion. Mucosal melanomas are a rare entity and oral cavity melanomas are even rarer, representing 1-2% of all oral malignancies.1 Melanoma of the oral cavity accounts for about 0.2-8% of all malignant melanomas.2 Oral melanomas most frequently involve the maxillary gingiva and palate with the lip being the third most common site.2 Melanoma of the tongue represents less than 2% of all oro-nasal malignant melanomas.2 A review of literature revealed less than 30 cases of primary malignant melanoma of the tongue, with the earliest reference appearing in a survey article by Baxter3 in 1941.. With an equal sex incidence, oral melanomas commonly occur after the 5th decade of life.1 They present as flat, painless, dark brown or black, discolored macules or nodules, sometimes with erythema or ulceration. Less than 10% of oral melanomas are amelanotic. Histologically, oral melanomas are characterized by the presence of atypical melanocytes that are larger than the usual melanocytes with nuclear ...

TY - JOUR. T1 - Adoptive immunotherapy of advanced melanoma patients with interleukin-2 (IL-2) and tumor-infiltrating lymphocytes selected in vitro with low doses of IL-2. AU - Arienti, Flavio. AU - Belli, Filiberto. AU - Rivoltini, Licia. AU - Gambacorti-Passerini, Carlo. AU - Furlan, Luigi. AU - Mascheroni, Luigi. AU - Prada, Augusto. AU - Rizzi, Maurilia. AU - Marchesi, Edoardo. AU - Vaglini, Maurizio. AU - Parmiani, Giorgio. AU - Cascinelli, Natale. PY - 1993/9. Y1 - 1993/9. N2 - Freshly isolated tumor-infiltrating lymphocytes (TIL) from stage IV melanoma patients were cultured for 2 weeks with low doses of interleukin-2 (IL-2; 120 IU/ml), to select potentially for tumor-specific lymphocytes present in the neoplastic lesion, followed by high doses (6000 IU/ml) to achieve lymphocyte expansion. TIL were serially analyzed for their expansion, phenotype and cytotoxic activity against autologous and allogeneic tumor cells. A preferential lysis of autologous melanoma cells was obtained in ...

Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing genes that are characteristic of various cell types including endothelial, neural, and stem cells. Moreover, we have shown that aggressive melanoma cells can participate in neovascularization in vivo and vasculogenic mimicry in vitro, demonstrating that these cells respond to microenvironmental cues and manifest developmental plasticity. To explore this plasticity further, we transplanted human metastatic melanoma cells into zebrafish blastula-stage embryos and monitored their behavior post-transplantation. The data show that human metastatic melanoma cells placed in the zebrafish embryo survive, exhibit motility, and divide. The melanoma cells do not form tumors nor integrate into host organs, but instead become scattered throughout the embryo in interstitial spaces, reflecting the dedifferentiated state of the cancer cells. In contrast to the fate of melanoma cells, human melanocytes transplanted into ...

Endogenously produced interferons can regulate the growth of melanoma cells and are administered exogenously as therapeutic agents to patients with advanced cancer. We investigated the role of negative regulators of interferon signaling known as suppressors of cytokine signaling (SOCS) in mediating interferon-resistance in human melanoma cells. Basal and interferon-alpha (IFN-α) or interferon-gamma (IFN-γ)-induced expression of SOCS1 and SOCS3 proteins was evaluated by immunoblot analysis in a panel of n = 10 metastatic human melanoma cell lines, in human embryonic melanocytes (HEM), and radial or vertical growth phase melanoma cells. Over-expression of SOCS1 and SOCS3 proteins in melanoma cells was achieved using the PINCO retroviral vector, while siRNA were used to inhibit SOCS1 and SOCS3 expression. Tyr701-phosphorylated STAT1 (P-STAT1) was measured by intracellular flow cytometry and IFN-stimulated gene expression was measured by Real Time PCR. SOCS1 and SOCS3 proteins were expressed at basal

Standard chemotherapy drugs have failed in large-scale clinical trials for melanoma. To date, the only Food and Drug Administration-approved drug for melanoma is the alkylating agent dacarbazine (DTIC), which when given as a single agent has a response rate of 5% to 10% (16). Novel approaches to melanoma therapy are therefore urgently needed. Recent work has focused on targeting signaling pathways which are known to be active in melanoma (7). Although many signaling cascades are known to be active in melanoma, most interest has centered on the BRAF/MEK/ERK pathway (2). Questions still remain over whether this pathway would represent a suitable therapeutic target in melanoma and there is still controversy on whether BRAF is a strong enough oncogene to drive melanocytic transformation (17). The finding that there are V600E BRAF mutations in nontumorigenic melanocytic nevi (18) then lacking in early-stage radial growth phase melanomas, only to appear at the later vertical growth phase melanomas ...

Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds? Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years'

Melanoma patients carry a high risk of developing brain metastases, and improvements in survival are still measured in weeks or months. Durable disease control within the brain is impeded by poor drug penetration across the blood-brain barrier, as well as intrinsic and acquired drug resistance. Augmented mitochondrial respiration is a key resistance mechanism in BRAF-mutant melanomas but, as we show in this study, this dependence on mitochondrial respiration may also be exploited therapeutically. We first used high-throughput pharmacogenomic profiling to identify potentially repurposable compounds against BRAF-mutant melanoma brain metastases. One of the compounds identified was β-sitosterol, a well-tolerated and brain-penetrable phytosterol. Here we show that β-sitosterol attenuates melanoma cell growth in vitro and also inhibits brain metastasis formation in vivo. Functional analyses indicated that the therapeutic potential of β-sitosterol was linked to mitochondrial interference. Mechanistically,

23 March 2018. Australian researchers have greater clarity on the best course of treatment for patients with advanced melanoma which has spread to the brain.. Results from a clinical trial, developed and run by investigators at Melanoma Institute Australia and published today in the Lancet Oncology, demonstrate that a combination of immunotherapies are most active in patients with asymptomatic brain metastases who have not previously been treated.. The Phase II trial known as the Anti-PD1 Brain Collaboration (ABC) trial involved advanced melanoma patients being given either a combination of two immunotherapy drugs (nivolumab [Opdivo®] and ipilimumab [Yervoy®]) or single therapy (nivolumab alone).. The results from the trial suggest that patients with asymptomatic brain metastases who have not received any prior targeted therapy (e.g. MEK or BRAF inhibitors) have a high chance of long-term response to treatment. Response rates were less effective in patients who had already been treated with ...

Despite stricter criteria and important changes for stage III melanoma criteria, the new American Joint Committee on Cancer (AJCC) 8th Edition Melanoma Staging System compares well overall to the older 7th Edition in terms of prognostic and discriminatory ability for predicting patients melanoma-specific survival, according to findings from a prospective database analysis of AJCC stage III melanoma patients (abstract 9500) presented at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1-5 in Chicago.. However, there are new complexities to bear in mind, cautioned lead study coauthor Max F. Madu, MD, of the Netherlands Cancer Institute.. The 8th Edition holds up during external validation, Madu reported. There is similar prognostic accuracy in the 7th and 8th editions, and survival differentiation is comparable-though slightly worse in the 8th edition for stage IIIA vs IIIB.. The AJCC is the most widely used and validated melanoma staging system.. The ...

BACKGROUND: Checkpoint inhibitors have changed overall survival for patients with advanced melanoma. However, there is a lack of data on health-related quality of life (HRQoL) of long-term advanced melanoma survivors, years after treatment. Therefore, we evaluated HRQoL in long-term advanced melanoma survivors and compared the study outcomes with matched controls without cancer.. MATERIAL AND METHODS: Ipilimumab-treated advanced melanoma survivors without evidence of disease and without subsequent systemic therapy for a minimum of two years following last administration of ipilimumab were eligible for this study. The European Organization for Research and Treatment of Cancer quality of life questionnaire Core 30 (EORTC QLQ-C30), the Multidimensional Fatigue Inventory (MFI), the Hospital Anxiety and Depression Scale (HADS), and the Functional Assessment of Cancer Therapy-Melanoma questionnaire (FACT-M) were administered. Controls were individually matched for age, gender, and educational status. ...

TY - JOUR. T1 - Three-year follow-up of advanced melanoma patients who received ipilimumab plus fotemustine in the Italian network for tumor biotherapy (NIBIT)-M1 phase II study. AU - Di Giacomo, A. M.. AU - Ascierto, P. A.. AU - Queirolo, P.. AU - Pilla, L.. AU - Ridolfi, R.. AU - Santinami, M.. AU - Testori, A.. AU - Simeone, E.. AU - Guidoboni, M.. AU - Maurichi, A.. AU - Orgiano, L.. AU - Spadola, G.. AU - Del Vecchio, M.. AU - Danielli, R.. AU - Calabrò, L.. AU - Annesi, D.. AU - Giannarelli, D.. AU - Maccalli, Cristina. AU - Fonsatti, E.. AU - Parmiani, G.. AU - Maio, Michele. PY - 2015/4/1. Y1 - 2015/4/1. N2 - Background: In the NIBIT-M1 study, we reported a promising activity of ipilimumab combined with fotemustine in metastatic melanoma (MM) patients with or without brain metastases. To corroborate these initial findings, we now investigated the long-term efficacy of this combination. Patients and methods: This analysis captured the 3-year outcome of MM patients who received ipilimumab ...

TY - JOUR. T1 - IDH1R132 mutation identified in one human melanoma metastasis, but not correlated with metastases to the brain. AU - Lopez, Giselle Y.. AU - Reitman, Zachary J.. AU - Solomon, David. AU - Waldman, Todd. AU - Bigner, Darell D.. AU - McLendon, Roger E.. AU - Rosenberg, Steven A.. AU - Samuels, Yardena. AU - Yan, Hai. PY - 2010/7/1. Y1 - 2010/7/1. N2 - Isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) are enzymes which convert isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP. +. to NADPH). IDH1/2 were recently identified as mutated in a large percentage of progressive gliomas. These mutations occur at IDH1R132 or the homologous IDH2R172. Melanomas share some genetic features with IDH1/2-mutated gliomas, such as frequent TP53 mutation. We sought to test whether melanoma is associated with IDH1/2 mutations. Seventy-eight human melanoma samples were analyzed for IDH1R132 and IDH2R172 mutation status. A somatic, ...

Clinical trial for Pathologic Stage IIIB Cutaneous Melanoma AJCC v8 | Mucosal Melanoma | Acral Lentiginous Melanoma | Pathologic Stage IIIC Cutaneous Melanoma AJCC v8 | Pathologic Stage IV Cutaneous Melanoma AJCC v8 | Pathologic Stage III Cutaneous Melanoma AJCC v8 | Pathologic Stage IIID Cutaneous Melanoma AJCC v8 | Pathologic Stage IIIA Cutaneous Melanoma AJCC v8 | Clinical Stage IV Cutaneous Melanoma AJCC v8 | Clinical Stage III Cutaneous Melanoma AJCC v8 , Pembrolizumab in Treating Patients With Stage III-IV High-Risk Melanoma Before and After Surgery

Conditions: Clinical Stage 0 Cutaneous Melanoma AJCC v8; Clinical Stage I Cutaneous Melanoma AJCC v8; Clinical Stage IA Cutaneous Melanoma AJCC v8; Clinical Stage IB Cutaneous Melanoma AJCC v8; Clinical Stage II Cutaneous Melanoma AJCC v8; Clinical Stage IIA Cutaneous Melanoma AJCC v8; Clinical Stage IIB Cutaneous Melanoma AJCC v8; Clinical Stage IIC Cutaneous Melanoma AJCC v8; Clinical Stage III Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8; Colitis; Diarrhea; Malignant Genitourinary System Neoplasm; Pathologic Stage 0 Cutaneous Melanoma AJCC v8; Pathologic Stage I Cutaneous Melanoma AJCC v8; Pathologic Stage IA Cutaneous Melanoma AJCC v8; Pathologic Stage IB Cutaneous Melanoma AJCC v8; Pathologic Stage II Cutaneous Melanoma AJCC v8; Pathologic Stage IIA Cutaneous Melanoma AJCC v8; Pathologic Stage IIB Cutaneous Melanoma AJCC v8; Pathologic Stage IIC Cutaneous Melanoma AJCC v8; Pathologic Stage III Cutaneous Melanoma AJCC v8; Pathologic Stage IIIA Cutaneous Melanoma ...

Pets get melanoma too! But unlike people, it is not usually a result of too many hours lying on the beach. Canine melanoma on the skin presents as a pigmented or non-pigmented skin mass most commonly on the face, trunk, feet or scrotum. Feline melanoma on the skin presents on the head or ears. Oral melanoma grows inside the mouth.. Up to half of skin melanomas and most oral melanomas are malignant. Diagnosis can often be made with a fine needle aspirate biopsy, but sometimes a surgical biopsy is required. Surgery is the first step for treatment of pet melanoma. Skin melanomas require removal with surrounding margins of healthy tissue. Oral melanomas also require excision with margins, and this often entails removal of a part of the jaw to ensure that adequate margins are removed. Malignant melanomas can spread, and the first sites of spread are the local lymph nodes and the lungs. The vet will probably stage the disease by checking local lymph nodes and taking chest X-rays prior to any major ...

Recent progress in the structural identification of human melanoma antigens recognized by autologous cytotoxic T cells has led to the recognition of a new melanocyte differentiation antigen, Melan-A(MART-1). To determine the properties of the Melan-A gene product, Melan-A recombinant protein was produced in Escherichia coli and used to generate mouse monoclonal antibodies (mAbs). Two prototype mAbs, A103 and A355, were selected for detailed study. Immunoblotting results with A103 showed a 20-22-kDa doublet In Melan-A mRNA positive melanoma cell lines and no reactivity with Melan-A mRNA-negative cell lines. A355, in addition to the 20-22-kDa doublet, recognized several other protein species in Melan-A mRNA-positive cell lines. Immunocytochemical assays on cultured melanoma cells showed specific and uniform cytoplasmic staining in Melan-A mRNA-positive cell lines. Immunohistochemical analysis of normal human tissues with both mAbs showed staining of adult melanocytes and no reactivity with the ...

Clinical trial for Stage III Cutaneous Melanoma AJCC v7 | Unresectable Cutaneous Melanoma | Mucosal Melanoma | Stage IV Cutaneous Melanoma AJCC v6 and v7 | Stage IIIA Cutaneous Melanoma AJCC v7 | Advanced Melanoma | Melanoma of Unknown Primary | Stage IIIB Cutaneous Melanoma AJCC v7 | Stage IIIC Cutaneous Melanoma AJCC v7 | Unresectable Melanoma | Refractory Melanoma , Testing Treatment With Ipilimumab and Nivolumab Compared to Treatment With Ipilimumab Alone in Advanced Melanoma

TY - JOUR. T1 - Exon 15 BRAF mutations are uncommon in canine oral malignant melanomas. AU - Shelly, Suzanne. AU - Chien, May B.. AU - Yip, Becky. AU - Kent, Michael S. AU - Theon, Alain P. AU - McCallan, Jennifer L.. AU - London, Cheryl A.. PY - 2005/3. Y1 - 2005/3. N2 - An activating mutation in codon 599 of BRAF has been identified in approximately 60% of human cutaneous nevi and melanomas, but not melanomas of mucosal origin. The purpose of this study was to determine if BRAF mutations occur in canine oral malignant melanomas. The canine BRAF gene was first cloned from normal canine testicular cDNA, and a novel previously unreported splice variant involving exon 5 was identified during this process. To screen canine melanoma samples for BRAF mutation in codon 599, cDNA and genomic DNA were isolated from canine malignant melanoma cell lines and primary tumor samples respectively, all from cases seen at the Veterinary Medical Teaching Hospital at the University of California, Davis. Polymerase ...

TY - JOUR. T1 - Fluorescence image-guided surgery and repetitive Photodynamic Therapy in brain metastatic malignant melanoma. AU - Zilidis, G.. AU - Aziz, F.. AU - Telara, S.. AU - Eljamel, M. Sam. PY - 2008/12. Y1 - 2008/12. N2 - Metastatic brain melanoma occurs in about 3.5% of patients suffering from malignant melanoma. It has disabling effects on cognition, memory, language and mobility. We studied the use of fluorescence image-guided resection and repetitive Photodynamic Therapy in six consecutive metastatic brain melanomas. Three were males and the mean age of the group was 52.8 years. Results: All six patients (100%) remained free of brain disease till death, 50% died of malignant melanoma elsewhere, and 50% died of unrelated causes. Conclusion: Adjuvant fluorescence image-guided resection and repetitive Photodynamic Therapy offers an excellent local control of metastatic brain melanoma. © 2009 Elsevier B.V. All rights reserved.. AB - Metastatic brain melanoma occurs in about 3.5% of ...

1059 Certain aggressive melanoma cell lines exhibit a dedifferentiated phenotype, expressing multiple molecular markers that are specific for various cell types including endothelial, neural, and even stem cells. These cells are able to participate in vasculogenic mimicry in vitro and respond to ischemic microenvironmental cues by participating in neovascularization in vivo. We examined the potential plasticity of human metastatic melanoma cells by exposing them to a developmental microenvironment in zebrafish embryos. The data reveal that the zebrafish embryos make a powerful model system in which to investigate tumor-microenvironment interactions and tumor cell plasticity. We show here that fluorescently labeled human metastatic melanoma cells transplanted into zebrafish embryos survive for up to two weeks, exhibit motility, seem to proliferate and most importantly, are no longer tumorigenic. The data also show that normal human melanocytes and fibroblasts transplanted into the zebrafish ...

Melanoma skin cancer (as opposed to non-melanoma skin cancer) is less common, but more serious than other types of skin cancer. Early detection is key to successfully treating melanoma skin cancers. Turley Hansen represents a number of 9/11 responders and survivors with melanoma skin cancer.. Melanoma cancer is sometimes called malignant melanoma and cutaneous melanoma. Most melanoma tumors are brown or black, but some melanomas can appear pink, tan, or even white. Melanomas can develop anywhere on the skin, but they are more likely to start on the chest and back in men and on the legs in women. The neck and face are other common sites. Melanoma cancer can also appear in the eye.. Based on the stage of the cancer, treatment options may include:. ...

A study published in The New England Journal of Medicine defines the succession of genetic alterations during melanoma progression, showing distinct evolutionary trajectories for different melanoma subtypes. It identified an intermediate category of melanocytic neoplasia, characterised by the presen

We used the chick embryo transplant model to study the reprogramming of human metastatic melanoma cells towards a benign cell type. We had previously reported that human patient-derived C8161 metastatic melanoma cells upregulated a marker of melanin synthesis, Mart-1, after exposure to unknown signals in the embryonic neural crest microenvironment (Kulesa et al., 2006). The goal of this study was to identify and examine the function of the microenvironmental signal(s) underlying the reprogramming process. To enable the dynamic readout of one of the changes in metastatic melanoma cell state, we generated a lentiviral Mart-1:GFP reporter and methodically determined the age, tissue type and ultimately the factor that induced re-expression of Mart-1. We learned that the neurotrophin NGF induced Mart-1 re-expression and changes in cell behavior and gene expression of human C8161 metastatic melanoma cells. We confirmed Mart-1:GFP re-expression in C8161 cells after NGF exposure using Mart-1 antibody ...

Fig. 1. Cytokine-ELISA of culture supernatants from malignant melanoma cell lines and melanocyte cultures. The melanoma cell lines MV3, BLM (highly metastatic, marked by **) and IF6, 530 (low metastatic potential, marked by ∗) were kept for 24 h under hypoxia, followed by an additional 24 h of reoxygenation. Parallel cultures kept under normoxia for 24 and 48 h were used as control. A, ANG; B, VEGF; and C, Gro-α, cytokine production was determined by solid phase ELISA; bars, SD. D, ANG, VEGF, and Gro-α production in two melanocyte cultures, which were kept under the same conditions. Values (pg/106 cells) are given as means of three independent experiments for each cytokine; bars, SD. Differences concerning ANG induction levels between highly aggressive and low aggressive cell lines were statistically significant (P ≤ 0.05), whereas differences between baseline levels were not statistically significant.. ...

Plasma cells within the infiltrate of primary cutaneous malignant melanoma have been reported as a valuable criterion for the prediction of lymph node metastases. In order to evaluate plasma cells, their prognostic significance and their relationship

Clinical management of primary cutaneous melanomas is based on histopathological staging of the tumour. The aim of this study was to investigate, in a non-selected population in clinical practice, the agreement rate between general pathologists and pathologists experienced in melanoma in terms of the evaluation of histopathological prognostic parameters in cutaneous malignant melanomas, and to what extent the putative variability affected clinical management. A total of 234 cases of invasive cutaneous malignant melanoma were included in the study from the Stockholm-Gotland Healthcare Region in Sweden. Overall interobserver variability between a general pathologist and an expert review was 68.8-84.8%. Approximately 15.5% of melanomas ,= 1 mm were re-classified either as melanoma in situ or melanomas ,1 mm after review. In conclusion, review by a pathologist experienced in melanoma resulted in a change in recommendations about surgical excision margins and/or sentinel node biopsy in subgroups of ...

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The analysis of the protein complement expressed by a cell in a given moment or condition gathers information on the real potential expressed by the genome. In fact, gene expression analysis, although offering the advantage of a wider coverage, is biased by the vast plethora of variables that come into play after gene transcription, such as the different half lives of transcripts, their transcriptional efficiency, as well as the different half lives of proteins within the cell. By directly measuring protein abundances, differential proteomics has the advantage of providing a more realistic picture of the cell response to a given stimulus, although the number of proteins that can be evaluated is often lower than the one obtained in a transcriptomic study. In a recent paper, we described the changes induced by D6 treatments in the gene expression profile of LB24Dagi MM cells [10]. In order to integrate and validate those findings, a differential proteomics study was carried out, and it is ...

Incidence rates for cutaneous malignant melanoma are increasing worldwide. Estimates of the future number of melanoma cases are important for strategic planning of the care pathway. The aim of this study was to use system dynamics modelling to evaluate the long;term effects of changes in incidence, population growth and preventive interventions. Historical data on invasive melanoma cases in Western Sweden from 1990 to 2006 were obtained. Using computer simulation software, a model estimating the accumulated number of melanoma cases for 2014 to 2023 was developed. Five future scena; rios were designed: stable incidence, business;as;usual, 25% reduced patients delay, 50% reduced doctors de; lay, and a combination of the last two, called improved overall secondary prevention. After 10 years, improved overall secondary prevention would have resulted in a 42% decrease in melanomas | 4 mm and a 10% increase in melanomas

If you have a question about this talk, please contact Kate Davenport.. Cutaneous melanoma is a highly aggressive skin cancer and one of the most challenging cancers in its therapeutic management. Emerging studies demonstrate that cancer is a result of a concerted action of genetic and epigenetic alterations. Our understanding of the epigenetic landscape of melanoma remains poorly understood. We have shown a critical role for histone variants of the H2A family in regulating melanoma pathogenesis. For example, macroH2A acts as a barrier to melanoma growth and metastasis (Kapoor et al., Nature 2010), and H2A .Z.2 promotes melanoma growth by positively regulating transcription of E2F target genes (Vardabasso et al., Molecular Cell 2015). Studies will be presented of our ongoing efforts to identify key epigenetic players in melanoma progression and drug resistance, and to decipher the melanoma epigenome by comparing normal melanocytes with malignant melanoma cells.. This talk is part of the Cancer ...

Genetic alterations in the INK4a/ARF (or CDKN2A) locus have been reported in many cancer types, including melanoma; head and neck squamous cell carcinomas; lung, breast, and pancreatic cancers. In melanoma, loss of function CDKN2A alterations have been identified in approximately 50% of primary melanomas, in over 75% of metastatic melanomas, and in the germline of 40% of families with a predisposition to cutaneous melanoma. The CDKN2A locus encodes two critical tumor suppressor proteins, the cyclin-dependent kinase inhibitor p16INK4a and the p53 regulator p14ARF. The majority of CDKN2A alterations in melanoma selectively target p16INK4a or affect the coding sequence of both p16INK4a and p14ARF. There is also a subset of less common somatic and germline INK4a/ARF alterations that affect p14ARF, while not altering the syntenic p16INK4a coding regions. In this review, we describe the frequency and types of somatic alterations affecting the CDKN2A locus in melanoma and germline CDKN2A alterations in

Cutaneous melanoma is an aggressive neoplasm refractory to traditional therapies, especially at the metastatic stage. Furthermore, its incidence is continuously increasing during the last decade (1). Melanomas develop through a multistep process that from normal melanocytes proceeds to nevi and to radial and vertical growth phase tumors (2). During this process, melanomas are characterized by certain well-defined genetic alterations as well as frequent chromosomal aberrations associated with tumor progression (3). However, the molecular mechanisms involved in the carcinogenesis and progression of melanoma are complex and not entirely clear (4). Because of the intractability of metastatic melanomas with only 14% of the patients survive for 5 years and no effective treatments (2), understanding the underlying molecular mechanisms involved in melanoma and identifying molecular markers may lead to improvements in therapeutic approaches for metastatic melanomas.. Mal de Meleda (MDM; OMIM 248300) is a ...

TY - JOUR. T1 - Store-operated Ca2+ entry (SOCE) regulates melanoma proliferation and cell migration. AU - Umemura, Masanari. AU - Baljinnyam, Erdene. AU - Feske, Stefan. AU - De Lorenzo, Mariana S.. AU - Xie, Lai Hua. AU - Feng, Xianfeng. AU - Oda, Kayoko. AU - Makino, Ayako. AU - Fujita, Takayuki. AU - Yokoyama, Utako. AU - Iwatsubo, Mizuka. AU - Chen, Suzie. AU - Goydos, James S.. AU - Ishikawa, Yoshihiro. AU - Iwatsubo, Kousaku. PY - 2014/2/21. Y1 - 2014/2/21. N2 - Store-operated Ca2+ entry (SOCE) is a major mechanism of Ca 2+ import from extracellular to intracellular space, involving detection of Ca2+ store depletion in endoplasmic reticulum (ER) by stromal interaction molecule (STIM) proteins, which then translocate to plasma membrane and activate Orai Ca2+ channels there. We found that STIM1 and Orai1 isoforms were abundantly expressed in human melanoma tissues and multiple melanoma/melanocyte cell lines. We confirmed that these cell lines exhibited SOCE, which was inhibited by knockdown ...

Target-specific inhibition of the BRAFV600E mutant protein has been a major breakthrough in the treatment of metastatic cutaneous melanoma. However, the success of therapies is significantly overshadowed by the development of resistance. Understanding the molecular mechanisms associated with acquired resistance is an important step to increase the effectiveness of melanoma treatment. Our aim was to elucidate the molecular differences underlying the development of drug resistance using a mutant BRAF protein inhibitor (vemurafenib analogue: PLX4720) in BRAFV600E mutant melanoma cell lines. We developed four BRAF inhibitor-resistant cell lines and examined the effect of BRAF inhibitor withdrawal on cell division. ArrayCGH was used to define genetic, and Affymetrix HumanGene 1.0 microarray to monitor gene expression alterations between the sensitive and resistant cell lines. Protein expression was determined using Proteome Profiler Human XL Oncology Array. We found that withdrawal of the inhibitor ...

Malignant melanoma arises from melanocytic cells in the skin and mucosal membranes. Malignant melanomas predominantly develop in areas that are exposed to sunlight including the face, back, or extremities. Because melanoma predominantly occurs in the skin and mucous membranes, malignant melanoma of the breast is particularly rare. The incidence of primary melanoma of the breast is | 5% of all melanomas[1]. Furthermore, secondary tumors of the breast from metastatic malignancies are quite uncommon. Of metastatic malignancies to the breast, melanoma is, however, among the most common[2]. Therefore, metastasis to the breast must be considered in any patient with a known primary malignant tumor history who presents with a breast mass. A full diagnostic work up with observation of the clinical pathological features, immunohistochemical staining methods and tissue origin are required to distinguish primary malignant melanoma of the breast from possible metastatic melanoma.

Click here for Mucosal Melanoma guidelines.. Introduction. Mucosal melanomas are rare, representing only about 1-2% of all melanomas. 55% of all primary mucosal melanomas occur in the head and neck region, with the nose and paranasal sinuses being the most common sites. Surgery at all stages frequently involves complex decisions about risk and benefit, and the value of adjuvant treatment - drug therapy or radiotherapy - is unclear. Medical treatment of advanced melanoma is evolving rapidly and its relevance to this group of patients requires clarification. There is no agreement about diagnostic imaging techniques or follow-up protocols. There is therefore a need for clinical guidance in this area.. As the principal UK melanoma charity, Melanoma Focus leads in the development of clinical guidelines for rare forms of melanoma. The initiative to produce the head & neck mucosal melanoma and ano-uro-genital mucosal guidelines follows the charitys development of the Uveal Melanoma Guideline.. The AUG ...

Cell lines and culture conditions. The human fibroblast cells FF2441 and metastatic melanoma cell lines UACC 903 and 1205 Lu were maintained in Dulbeccos modified eagles medium (DMEM; Invitrogen), supplemented with 10% fetal bovine serum (FBS; Hyclone) at 37°C with 5% CO2 atmosphere in a humidified incubator. Vertical growth phase melanoma cell line WM115 was maintained in Tu2% medium as described previously (6).. Western blot analysis. For Western blot analysis, floating and adherent cells treated with compounds or control vehicle (DMSO) were harvested by addition of lyses buffer containing 50 mmol/L HEPES (pH 7.5), 150 mmol/L NaCl, 10 mmol/L EDTA, 10% glycerol, 1% Triton X-100, 1 mmol/L sodium orthovanadate, 0.1 mmol/L sodium molybdate, 1 mmol/L phenylmethylsulfonyl fluoride, 20 μg/mL aprotinin, and 5 μg/mL leupeptin. Whole cell lysates were centrifuged (≥10,000 × g) for 10 min at 4°C to remove cell debris. Protein concentrations were quantitated using the BCA assay from Pierce, and ...

Melanoma is the deadliest form of skin cancer. Amgen has been working on an experimental vaccine used for treating melanoma. This vaccine from Amgen proved effective, and gave hope, in a late-stage study for melanoma cancer.. When someone who has not been impacted by melanoma before hears of melanoma, he or she might think it is a simple skin cancer. It is not. One person will die from melanoma every hour of every day. Once melanoma has metastasized, meaning once it has spread to other areas of the body, it becomes extremely difficult to treat. In later stages of metastatic melanoma, cancer typically spreads to the liver, bones, lungs, and brain. The five-year survival rate for stage IV melanoma is roughly 15 to 20 percent, with the 10-year survival rate dropping to 10 to 15 percent.. The most common form of cancer for young adults who are ages 25 to 29 is melanoma. Someone in the U.S. receives a diagnosis of melanoma every eight minutes. Roughly 63,000 people in America were diagnosed with ...

Margins of excision for cutaneous melanoma of the eyelid skin: the Collaborative Eyelid Skin Melanoma Group Report. Journal Articles ...

TY - CHAP. T1 - Superficial spreading melanoma. AU - Longo, Caterina. AU - Casari, Alice. AU - Pellacani, Giovanni. PY - 2012/1/1. Y1 - 2012/1/1. N2 - Superficial spreading melanoma (SSM) is the most common type of melanoma in Caucasian, accounting for about 70% of all diagnosed melanoma cases [1]. This type of melanoma can strike at any age and occurs slightly more often in females than males. SSM has two growth phases: the radial growth phase and the vertical ones [2]. The radial phase involves expansion of the lesion through the epidermis (upper skin layer). In the early radial phase, the lesion is thin, and it can remain in this phase for months or years. This is the less life threatening of the two phases because once the melanoma enters into the vertical growth stage, the prognosis worsens.. AB - Superficial spreading melanoma (SSM) is the most common type of melanoma in Caucasian, accounting for about 70% of all diagnosed melanoma cases [1]. This type of melanoma can strike at any age and ...

Primary malignant melanoma of the vagina is rare but aggressive. Various treatment options include surgery and adjuvant therapy has been advocated but the outcome remained unpredictable. Standard treatment protocol is yet to be established. We report a case of 54-year-old, Para 4+1, with malignant melanoma of the vagina. She underwent wide local excision but the surgical margin was not clear of malignant cells, hence adjuvant radiotherapy was given. Combination chemotherapy was initiated subsequently as her disease disseminated. She succumbed later due to septicaemic shock. The treatment options for vaginal melanoma were reviewed. ...

Exportin 1 (XPO1, also known as CRM1), is a chaperone protein responsible for the export of over 200 target proteins out of the nucleus. The expression and activity of XPO1 is upregulated in several human cancers and its expression is also linked to the development of chemotherapy resistance. Recent studies using both human and murine cancer cell lines have demonstrated that XPO1 is a relevant target for therapeutic intervention. The present study sought to characterize the biologic activity of an orally bioavailable selective inhibitor of nuclear export (SINE), KPT-335, against canine melanoma cell lines as a prelude to future clinical trials in dogs with melanoma. We evaluated the effects of KPT-335 on 4 canine malignant melanoma cell lines and found that KPT-335 inhibited proliferation, blocked colony formation, and induced apoptosis of treated cells at biologically relevant concentrations of drug. Additionally, KPT-335 downregulated XPO1 protein while inducing a concomitant increase in XPO1

Study information from Be Involved at Wake Forest Baptist Medical Center for: A study comparing the outcome of advanced skin Melanoma cancer treated with a test drug given locally into the affected area versus standard of care treatments.

One of the major challenges in cancer therapy is to overcome drug resistance. Melanoma cells are an illustrative example for this notion, as metastasized melanoma is almost universally resistant against chemotherapy. The NF-κB signaling pathway is constitutively active and plays a crucial role for drug resistance in melanoma cells. This work starts from the observation that doxorubicin leads to profound activation of NF-κB in two different melanoma cell lines, while several other chemotherapeutics with different modes of action did not activate this pathway. Likewise, NF-κB dependent transcription of mediators, which are thought to be involved in tumor progression, was increased by doxorubicin. Notably, the strongest NF-κB activation was detected at a concentration of 1 ...

21 January 2020. Australian researchers have played a critical role in the discovery of a potential new test to predict which early stage melanoma patients are at high risk of their disease recurring and progressing.. A joint study led by researchers from Melanoma Institute Australia, The University of Sydney, Harvard Medical School, Sydney Local Health District and Adaptive Biotechnology analysed immune cells (known as T-cells) in primary melanoma samples taken from 209 patients, 164 of whom came from MIA.. The study, published today in Nature Cancer, found that patients with a T-cell fraction (TCFr) of less than 20% in their primary melanoma were two-and-a-half times more likely to have disease progression than those with more than 20% TCFr.. The study was jointly led by Dr James Wilmott and Co-Medical Director Professor Richard Scolyer from Melanoma Institute Australia and researchers from Harvard Medical School.. These findings suggest analysing TCFr in primary melanomas is a valuable tool ...

Looking for online definition of radial growth phase melanoma in the Medical Dictionary? radial growth phase melanoma explanation free. What is radial growth phase melanoma? Meaning of radial growth phase melanoma medical term. What does radial growth phase melanoma mean?

Even though the ideal method of diagnosis of melanoma should be complete excisional biopsy,[14] the location of the melanoma may require alternatives. Dermatoscopy of acral pigmented lesions is very difficult but can be accomplished with diligent attention. Initial confirmation of the suspicion can be done with a small wedge biopsy or small punch biopsy.[4] Thin deep wedge biopsies can heal very well on acral skin, and small punch biopsies can give enough clue to the malignant nature of the lesion. Once this confirmatory biopsy is done, a second complete excisional skin biopsy can be performed with a narrow surgical margin (1 mm). This second biopsy will determine the depth and invasiveness of the melanoma,[15] and will help to define what the final treatment will be. If the melanoma involves the nail fold and the nail bed, complete excision of the nail unit might be required. Final treatment might require wider excision (margins of 0.5 cm or more), digital amputation, lymphangiogram with lymph ...

Purpose : The effects of zeaxanthin on uveal melanoma in experimental animal models remain unknown. We found that zeaxanthin inhibited the growth and induced apoptosis of human uveal melanoma cells in vitro. We hypothesize that zeaxanthin may also have effects on uveal melanoma in vivo. The present study investigated the in vivo effects of zeaxanthin on human uveal melanoma in a nude mouse model. Methods : Cultured human uveal melanoma cells from an immortal cell line were inoculated into the choroid of nude mice. Mice were randomly divided into control group (without treatment of zeaxanthin), zeaxanthin low group and zeaxanthin high group (treated with intra-choroidal injection of zeaxanthin at 0.171 mg and 0.684 mg, respectively). After 21 days, mice were sacrificed and the eyes enucleated. Gross appearances and tumor mass was determined. Histopathological analysis was performed in hematoxylin and eosin stained frozen sections. Melanoma developed rapidly in the control group. Results : ...

PurposeUveal melanoma is the most common primary intraocular malignancy in adults with no effective systemic treatment option in the metastatic setting. Selumetinib (AZD6244, ARRY-142886) is an oral, potent, and selective MEK1/2 inhibitor with a short half-life, which demonstrated single-agent activity in patients with metastatic uveal melanoma in a randomized phase II trial.Methods: The Selumetinib (AZD6244: ARRY-142886) (Hyd-Sulfate) in Metastatic Uveal Melanoma (SUMIT) study was a phase III, double-blind trial (ClinicalTrial.gov identifier: NCT01974752) in which patients with metastatic uveal melanoma and no prior systemic therapy were randomly assigned (3:1) to selumetinib (75 mg twice daily) plus dacarbazine (1,000 mg/m(2) intravenously on day 1 of every 21-day cycle) or placebo plus dacarbazine. The primary end point was progression-free survival (PFS) by blinded independent central radiologic review. Secondary end points included overall survival and objective response rate.Results: A ...

Central nervous system imaging is needed during programmed death 1 (PD-1) inhibitor therapy to monitor incidence, patterns of progression, and outcomes of melanoma brain metastases, according to research presented at the 2017 ASCO Annual Meeting (June 2-6, 2017; Chicago, IL).. -----. Related Content. Ipilimumab Combination Significantly Improves Melanoma Outcomes. Skip whole-brain radiation in patients with limited brain metastases. -----. Metastases in the brain is a common occurrence for patients with metastatic melanoma. Currently available therapies are often unable to treat metastatic melanoma tumors in the brain. Limited data exists concerning the incidence, patterns of progression, and outcomes of patients with melanoma brain metastasis treated with PD-1 inhibitors, particularly in conjunction with central nervous system-focused therapy.. Gustavo Schvartsman, MD, MD Anderson Cancer Center (Houston, TX), and colleagues retrospectively reviewed the survival outcomes of patients with ...

Histologically, the tumour has a radial growth phase and is characterized by lentiginous and some nesting proliferation of large atypical melanocytes. Focally, pagetoid spread is present, however this is not as prominent as in superficial spreading melanoma. The melanocytes may be surrounded by a halo giving a lacunar appearance.. Some of the melanocytes may have dendritic processes. The invasive dermal component may be composed of spindle or epithelioid cells or nevus like cells. Diagnosis of Acral lentiginous melanoma during the radial growth phase is often difficult, and it may not be recognized initially, but treatment in this phase offers an excellent prognosis. There is a high incidence of regressive changes and desmoplasia in Acral lentiginous melanoma.. These changes, together with the anatomic peculiarities of nail beds, palms, and soles as compared with other skin areas, make it difficult to determine the Clarks level and to measure the depth of invasion. ...

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D. Synonyms and Keywords: Malignant melanoma; Acral lentiginous melanoma; Lentiginous melanoma; Lentigo maligna melanoma; Nodular melanoma; Amelanotic melanoma; Familial melanoma; Non-pigmented melanoma; MM; Metastatic melanoma; Metastatic malignant melanoma; Cutaneous melanoma; Actinic melanosis; Solar melanoma; Melanose; Malignant nevus; Melanocyte malignancy; Melanotic cancer ...

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D.; Serge Korjian M.D.Sabawoon Mirwais, M.B.B.S, M.D.[2] Synonyms and Keywords: Malignant melanoma; Acral lentiginous melanoma; Lentiginous melanoma; Lentigo maligna melanoma; Nodular melanoma; Amelanotic melanoma; Familial melanoma; Non-pigmented melanoma; MM; Metastatic melanoma; Metastatic malignant melanoma; Cutaneous melanoma; Actinic melanosis; Solar melanoma; Melanose; Malignant nevus; Melanocyte malignancy; Melanotic cancer ...

Previous reports showed that the Steroidal Glycoalkaloid Solamargine inhibited proliferation of non-melanoma skin cancer cells. However, Solamargine was not tested systematically on different types of melanoma cells and was not simultaneously tested on normal cells either. In this study we aimed to investigate the effect of Solamargine and the mechanism involved in inhibiting the growth of different types of melanoma cells. Solamargine effect was tested on normal cells and on another three melanoma cell lines. Vertical growth phase metastatic and primary melanoma cell lines WM239 and WM115, respectively and the radial growth phase benign melanoma cells WM35 were used. The half inhibitory concentration IC50 of Solamargine was determined using Alamarblue assay. The cellular and subcellular changes were assessed using light and Transmission Electron Microscope, respectively. The percentage of cells undergoing apoptosis and necrosis were measured using Flow cytometry. The different protein expression was

Primary pigmented tumors of the CNS are unusual; they include melanotic schwannoma, meningeal melanocytoma, blue nevus of the CNS, and primary melanoma (3-6). Among these lesions, primary malignant melanoma of CNS is rare and accounts for about 1% of all melanomas. Primary malignant melanoma of the spinal cord is a very rare entity, occuring most often in the middle or lower thoracic cord (1-8). Among the 27 cases of CNS malignant melanoma that Hayward (1) reported, only four lesions were in the spinal cord. Hirschberg (9) first reported primary spinal cord melanoma in 1906. Since then, a few cases have been reported in the literature; these involve intra- or extramedullary, leptomeningeal, and extradural lesions (1-3, 5, 7, 8).. A malignant melanoma can occur in any organ in which melanin-containing cells are present. Two theories have been proposed for the origin of the rare cases of CNS melanoma. Primary melanoma in the CNS may originate from melanoblasts accompanying the pial sheaths of ...

Uveal melanoma is the most common primary intra-ocular malignancy in adults with an incidence of 0.6 - 0.7 per 100,000 per year.. Prognosis of metastatic uveal melanoma is poor. In retrospective analyses a median survival time after detection of metastases of 5 months (Flaherty et al, 1998) and 7 months (Kath et al, 1993) was reported. For patients receiving no treatment reported median survival was 2.0 months compared with 5.2 months for those receiving treatment for metastases (Gragoudas et al, 1991).. Up to now there is no established treatment of metastatic uveal melanoma. Some therapeutic approaches with locoregional treatment or systemic chemotherapy have been undertaken:. In case of metastatic disease which is confined to the liver in about 85% of patients with uveal melanoma surgical resection led to a median survival of 14 months (Mariani et al, 2009) or 19 months and a 5-year survival rate of 22% in a selected patient population (Adam et al, 2006).. As locoregional treatment option ...

Here, we identified a correlation between sensitivity to MAPK inhibition and suppression of TORC1 in BRAF-mutant melanoma. Several additional factors have previously been suggested to predict resistance to MAPK pathway inhibition in BRAF-mutant melanoma cells, including loss of PTEN, increased basal levels of P-AKT, or induction of P-AKT levels after MAPK inhibition (16, 17). Although a tendency toward resistance was observed for some melanoma cell lines bearing these markers, we failed to detect a significant correlation for most markers across our BRAF-mutant melanoma cell line panel after treatment with either vemurafenib or selumetinib. Although each of these mechanisms may play a role in resistance to MAPK inhibition, the interaction of these mechanisms and others that influence sensitivity may be sufficiently complex that evaluation of any of these alone may be inadequate to predict responsiveness. Indeed, a multitude of resistance mechanisms to RAF and MEK inhibitors has been identified ...

Uveal melanoma is a cancer (melanoma) of the eye involving the iris, ciliary body, or choroid (collectively referred to as the uvea). Tumors arise from the pigment cells (melanocytes) that reside within the uvea giving color to the eye. These melanocytes are distinct from the retinal pigment epithelium cells underlying the retina that do not form melanomas. Uveal melanoma was first described in the literature in 1809-1812 by two Scottish surgeons, Allan Burns and James Wardrop. Uveal melanomas are the most common primary intraocular tumor in adults. The incidence has remained stable for several years. The cause of uveal melanoma is unclear. Uveal nevi are common (5% of Caucasians), but rarely progress to melanoma. Uveal melanomas, often referred to by the media and in the general population as ocular melanomas, may arise from any of the three parts of the uvea, and are sometimes referred to by their location, as choroidal melanoma, ciliary body melanoma, or iris melanoma. Large tumors often ...

Purpose: : AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase, which senses cellular energy change, and helps regulate cellular metabolism. 5-Aminoimidazole-4-carboxamide riboside (AICAR) is taken up by cells, converted to ZMP (an analog of AMP) and is used as a pharmacologic activator of AMPK. It has recently been shown that AICAR can cause growth arrest in various cancer cell lines. We chose to investigate the effect and mechanism of action of AICAR on the growth of primary and metastatic uveal melanoma cell lines. Methods: : Growth Inhibition Assay: Primary and metastatic uveal melanoma cell lines were cultured in the presence of 1, 2 and 4mM AICAR for 3-5 days. In separate experiments, cells were pretreated with 0.1 uM Iodotubericin (inhibits conversion of AICAR to ZMP) or 2 uM dipyridamole (inhibits the entry of AICAR into the cells). At the end of the incubation, cell growth was assessed with the MTT assay. Flow cytometry for cell cyle analysis: Uveal melanoma cells ...

TY - JOUR. T1 - An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi. AU - Clarke, Loren E.. AU - Flake, Darl D.. AU - Busam, Klaus. AU - Cockerell, Clay. AU - Helm, Klaus. AU - Mcniff, Jennifer. AU - Reed, Jon. AU - Tschen, Jaime. AU - Kim, Jinah. AU - Barnhill, Raymond. AU - Elenitsas, Rosalie. AU - Prieto, Victor G.. AU - Nelson, Jonathan. AU - Kimbrell, Hillary. AU - Kolquist, Kathryn A.. AU - Brown, Krystal L.. AU - Warf, M. Bryan. AU - Roa, Benjamin B.. AU - Wenstrup, Richard J.. PY - 2016. Y1 - 2016. N2 - BACKGROUND: Recently, a 23-gene signature was developed to produce a melanoma diagnostic score capable of differentiating malignant and benign melanocytic lesions. The primary objective of this study was to independently assess the ability of the gene signature to differentiate melanoma from benign nevi in clinically relevant lesions. METHODS: A set of 1400 melanocytic lesions was selected from samples prospectively ...

Human melanoma cells (M21) actively attach and spread on a fibronectin substrate. Indirect immunofluorescence assays with specific monoclonal antibodies directed to the disialoganglioside GD2, the major ganglioside expressed on M21 melanoma cells, indicate that during the cell attachment process this molecule redistributes into microprocesses that make direct contact with the fibronectin substrate. Scanning and transmission immunoelectron microscopic studies with anti-GD2 monoclonal antibodies and immuno-gold staining demonstrate that GD2 preferentially localizes into substrate-associated microprocesses that emanate from the plasma membrane of the M21 cells. Staining with monoclonal antibodies directed to other melanoma surface antigens fails to demonstrate a similar distribution pattern on these cells. Direct evidence is provided that GD2 is involved in M21 cell attachment to fibronectin, since treatment of these cells with anti-GD2 monoclonal antibodies causes cell rounding and detachment from ...

TY - JOUR. T1 - Pembrolizumab as first-line treatment for metastatic uveal melanoma. AU - Rindi, Guido. AU - Zollino, Marcella. AU - Blasi, Maria Antonietta. AU - Cassano, Alessandra. AU - Bria, Emilio. AU - Tortora, Giampaolo. AU - Rossi, Ernesto. AU - Pagliara, Monica Maria. AU - Caputo, Carmela Grazia. AU - Petrone, Gianluigi. AU - Schinzari, Giovanni. PY - 2019. Y1 - 2019. N2 - Background: No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. Patients and methods: In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. Results: Seventeen patients were enrolled. A median of 8 cycles were ...

In normal human epidermis, expression of HLA-DR antigen is restricted to Langerhans cells (LC) and acrosyringial epithelium. However, in diseases such as lichen planus and graft-vs.-host, HLA-DR antigen appears to be expressed by keratinocytes, although the exact source of the HLA-DR is unclear. Two possibilities are that (1) the HLA-DR is shed by neighboring immunocompetent cells, or (2) that the keratinocytes are synthesizing the antigen themselves. Recently, gamma interferon has been shown to induce HLA-DR biosynthesis and expression on human malignant melanoma cells lines and on normal vascular endothelium. We report here that pure recombinant human gamma interferon (100 units/ml) induces HLA-DR expression on 60-70% of cultured human adult keratinocytes depleted of LC within 2-4 days of culture as determined by fluorescence-activated cell sorter (FACS) analysis using monoclonal antibodies. No residual LC or lymphocytes could be detected in these cultures. This is the first demonstration of HLA-DR

TY - JOUR. T1 - Phase II study of 5′-deoxy-5-fluorouridine (doxifluridine) in advanced malignant melanoma. AU - Alberto, P.. AU - Rozencweig, M.. AU - Clavel, M.. AU - Siegenthaler, P.. AU - Cavalli, F.. AU - Gundersen, S.. AU - Bruntsch, U.. AU - Renard, J.. AU - Pinedo, H.. PY - 1986/1. Y1 - 1986/1. N2 - Forty-two patients with malignant melanoma were treated with doxifluridine, 4000 mg/m2 daily ×5, repeated every 3 weeks. The daily dose was reduced to 3000 mg/m2 in patients who had experienced severe myelosuppression with prior chemotherapy. A total of 35 patients were evaluable for response, and 25 of these received two or more courses. Two responses were observed. Toxicity mainly took the form of nausea, vomiting, stomatitis, dizziness, ataxia, and fatigue. Mild leukopenia was frequent (43%). Nadir counts 9/l leukocytes or 50×109/l platelets were seen in 7% and 2% of the courses respectively. Doxifluridine has no useful activity against malignant melanoma.. AB - Forty-two patients with ...

To manage acral lentiginous melanoma daily, its important to follow treatment advice from your doctors. Usually, treatment will involve the immediate

We report a case of metastatic malignant melanoma that presented with macroscopic hematuria and lower urinary tract symptoms. Effective palliation of urinary tract symptoms was achieved with transurethral resection of metastatic lesions in the bladder, However, the patient was lost due to widespread disease despite systemic therapy. Solitary or multiple dark blue-black nodular or vegetating lesions encountered during cystoscopy should raise the suspicion of metastasis of malignant melanoma and be investigated accordingly. Copyright (C) 2000 S. Karger AG, Basel. ...

More than one-third of patients with metastatic uveal melanoma had objective tumor regression when treated with adoptive transfer of autologous tumor-infiltrating lymphocytes.

Between September 2012 and December 2017, 112 consecutive patients ≥18 years old receiving combined SRS and ipilimumab or nivolumab for one to ten melanoma brain metastases were retrospectively evaluated. In general, patients with lesions up to 2.5 cm in size were treated with single-fraction SRS, while larger lesions located near or in eloquent areas (i.e., motor, somatosensory, speech, visual cortices, basal ganglia, thalamus, and the brainstem) received multi-fraction SRS to minimize potential increased risk of late radiation-induced brain necrosis (RN).. All radiographic, surgical, and pathological information were drawn from a prospectively maintained database of patients with brain tumors treated at Sant Andrea Hospital and UPMC Hillman Cancer Center San Pietro Hospital. Thirty-two patients were excluded due to insufficient clinical information, previous use of anti-PD-1/PD-L1, brain surgery or radiation. Previous adjuvant therapies, including ipilimumab or BRAF/MEK inhibitors, were ...

Primary malignant melanoma of the lung (PMML) is an uncommon tumor with very few cases reported in the literature that satisfy the required criteria to establish a primary bronchial origin. We report a case of a 44-year-old man with acute abdominal distress and a right pulmonary roentgenographic opacity. A cranial-thoracic-abdominal CT scan confirmed the presence of a pulmonary nodule with bilateral cerebral metastases and marked dilatation of intestinal loops. At laparotomy an ileal intussusception was noted and an ileal resection was done. The resected intestinal segment contained three endoluminal polypoidal formations. Histological and immunohistochemical analyses showed the presence of multiple sites of melanoma. These lesions as well as the brain lesions clearly appeared metastatic. The patient underwent further evaluation to identify a primary site of melanoma; bronchoscopy was performed with biopsy of the pulmonary nodule. Pathology revealed a neoplastic process of fusiform cells, with ...

There are many options available, but the melanoma treatment you receive depends on the type of melanoma you have and the stage of the disease. Surgery to remove the melanoma is the most common treatment for early stages of the disease. Mohs surgery, in which skin cancer is removed layer by layer, may also be a treatment option for some patients with melanoma.. Surgery is also an option for advanced stages of the disease. Deeper excisions of the tumor or removal of the lymph nodes may be needed for advanced melanoma. If melanoma has spread to the lymph nodes or other parts of the body, immunotherapy can be a treatment option. Immunotherapy triggers the immune systems ability to attack cancer cells.. Chemotherapy is another treatment option used to destroy melanoma cancer cells. Radiation therapy kills cancer cells with high-energy X-ray beams, and its also used to reduce the chance of recurrence after melanoma has been removed. With targeted therapy, drugs and other medications target the ...

TY - JOUR. T1 - A perfusion system developed for 31p NMR study of melanoma cells at tissue‐like density. AU - Minichiello, Margaret M.. AU - Albert, Daniel M.. AU - Kolodny, Nancy H.. AU - Lee, Moon‐Soo ‐S. AU - Craft, Joseph L.. PY - 1989/4. Y1 - 1989/4. N2 - A perfusion culture system has been developed for 31P NMR study of human uveal melanoma metabolism by adapting the Vitafiber I cartridge system (Amicon). 31P NMR spectra collected weekly during periods of up to 10 weeks demonstrated increasing levels of phosphorus metabolites as the anchorage‐dependent cells grew to tissue‐like density. © 1989 Academic Press, Inc.. AB - A perfusion culture system has been developed for 31P NMR study of human uveal melanoma metabolism by adapting the Vitafiber I cartridge system (Amicon). 31P NMR spectra collected weekly during periods of up to 10 weeks demonstrated increasing levels of phosphorus metabolites as the anchorage‐dependent cells grew to tissue‐like density. © 1989 Academic ...

A wide variety of high-throughput microarray platforms have been used to identify molecular targets associated with biological and clinical tumor phenotypes by comparing samples representing distinct pathological states. The gene expression profiles of human cutaneous melanomas were determined by cDNA microarray analysis. Next, a robust analysis to determine functional classifications and make predictions based on data-oriented hypotheses was performed. Relevant networks that may be implicated in melanoma progression were also considered. In this study we aimed to analyze coordinated gene expression changes to find molecular pathways involved in melanoma progression. To achieve this goal, ontologically-linked modules with coordinated expression changes in melanoma samples were identified. With this approach, we detected several gene networks related to different modules that were induced or repressed during melanoma progression. Among them we observed high coordinated expression levels of genes involved

The sentinel node biopsy (SNB) procedure is a multidisciplinary technique, invented to gain prognostic information in different malignant tumors. The aim of the present study was to study the cohort of patients with malignant melanoma, operated with SNB, from the introduction of the technique in Sweden, concerning the prognostic information retrieved and the outcome of the procedures. In Sweden all patients with malignant melanoma are registered at regional Oncological Centers. From these databases ten centers were identified, treating malignant melanoma and performing sentinel node biopsy. Consecutive data concerning tumor characteristics, outcome of the procedure and disease related events during the follow-up time were collected from these ten centers. All cases from the very first in each centre were included. The SNB procedure was performed in 422 patients with a sentinel node (SN) detection rate of 97%, the mean Breslow thickness of the primary tumors was 3.2 mm (median 2.4 mm) and the ...

TY - JOUR. T1 - Multi-Modality Analysis Improves Survival Prediction in Enucleated Uveal Melanoma Patients. AU - Drabarek, Wojtek. AU - Yavuzyigitoglu, Serdar. AU - Obulkasim, Askar. AU - van Riet, Job. AU - Smit, Kyra N. AU - van Poppelen, Natasha M. AU - Vaarwater, Jolanda. AU - Brands, Tom. AU - Eussen, Bert. AU - Verdijk, Robert M. AU - Naus, Nicole C. AU - Mensink, Hanneke W. AU - Paridaens, Dion. AU - Boersma, Eric. AU - van de Werken, Harmen J G. AU - Kilic, Emine. AU - de Klein, Annelies. AU - Rotterdam Ocular Melanoma Study Group. PY - 2019/8/1. Y1 - 2019/8/1. N2 - Purpose: Uveal melanoma (UM) is characterized by multiple chromosomal rearrangements and recurrent mutated genes. The aim of this study was to investigate if copy number variations (CNV) alone and in combination with other genetic and clinico-histopathological variables can be used to stratify for disease-free survival (DFS) in enucleated patients with UM.Methods: We analyzed single nucleotide polymorphisms (SNP) array data ...

Background Melanoma incidence and mortality rates are increasing worldwide within the white population. Clinical and histological factors have been usually used for the prognosis and assessment of the risk for melanoma.. Objectives The aim of the study was to describe the clinical and histopathological features of the cutaneous melanoma (CM) in the Latvian population, to test the association between melanoma features and patient survival, and to assess the time trends for melanoma incidence.. Methods We undertook a descriptive, retrospective analysis of archive data of 984 melanoma patients treated at the largest oncological hospital of Latvia, Riga East University Hospital Latvian Oncology Centre (LOC), between 1998 and 2008. Cox proportional hazards model was used to analyse patient survival and autoregressive models were applied to detect trends in melanoma incidence over time for various categories of melanoma.. Results The study showed a significant ascending trend in melanoma incidence in ...

The effects of irradiation with gamma rays and protons on HTB140 human melanoma cell morphology and viability were analyzed. Exponentially growing cells were irradiated close to the Bragg peak maximum of the 62-MeV proton beam, as well as with (60)Co gamma rays, with doses ranging from 8 to 24 Gy. The overall cell morphology was unchanged 6 and 48 h after gamma irradiation, also showing a relatively weak cell-inactivation level. After exposure to proton beam, considerable changes in cell morphology followed by stronger cell inactivation were achieved. Proliferation capacity of irradiated cells significantly decreased in both experimental set-ups. Higher ionization level of protons with respect to gamma rays, representing the main physical difference between these two types of radiation, was also revealed on the cell membrane level through larger pro-apoptotic capacity of protons ...

The anaphase-promoting complex or cyclosome with the subunit Cdh1 (APC/CCdh1) is an E3 ubiquitin ligase involved in the control of the cell cycle. Here, we identified sporadic mutations occurring in the genes encoding APC components, including Cdh1, in human melanoma samples and found that loss of APC/CCdh1 may promote melanoma development and progression, but not by affecting cell cycle regulatory targets of APC/C. Most of the mutations we found in CDH1 were those associated with ultraviolet light (UV)-induced melanomagenesis. Compared with normal human skin tissue and human or mouse melanocytes, the abundance of Cdh1 was decreased and that of the transcription factor PAX3 was increased in human melanoma tissue and human or mouse melanoma cell lines, respectively; Cdh1 abundance was further decreased with advanced stages of human melanoma. PAX3 was a substrate of APC/CCdh1 in melanocytes, and APC/CCdh1-mediated ubiquitylation marked PAX3 for proteolytic degradation in a manner dependent on the ...

Case: The authors describe a patient with a primary malignant melanoma of the urethra 5.4 cm in diameter presenting as postmenopausal vaginal bleeding and treated with anterior pelvic exenteration. No adjuvant therapy was administered. The patient died of pneumonia shortly after discharge ...

Background: Melanoma is a deadly form of malignancy. Early diagnosis might pave the way to cure but its aggressive nature leads to rapid dissemination and colonization of distant organs. Dietary herbs may play a significant role in prevention of cancer. In this study, we tested anti-tumor efficacy of the Crocus sativus derived active constituent crocin, it is well established to have anti-cancer properties in different cancer models by our group and other groups. Notably, crocin is reported to exert anti-proliferative effect on melanoma cells (B16F10) in vitro. However, roles of crocin on in vivo melanoma tumor remission have not yet been reported to our knowledge. Materials and Methods: Melanoma tumor model was established by transplanting B16F10 (5 X 105) cells into C57BL/6 mice, which were then observed for tumor development and once the tumor volume reached 6 mm, mice were divided into (Group I: tumor-bearing animals treated with normal saline and Group II: counterparts treated with crocin at 2 mg

Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma Academic Article ...

Nuclear RNA-binding protein p54nrb and its murine homolog NonO are known to be involved in a variety of nuclear processes including transcription and RNA processing. Melanoma inhibitory activity (MIA) has been shown to play an essential role in the progression of malignant melanoma and to influence melanoma-associated molecules and pathways in the early tumor formation steps. Interestingly, recent studies suggest that MIA is a regulator of p54nrb. Here, we show that p54nrb is strongly expressed and localized in the nucleus of both melanoma cell lines and melanoma tissue samples compared with normal human melanocytes or normal skin, respectively. Furthermore, all tested melanoma cell lines revealed strong p54nrb promoter activity. Treatment with MIA-specific small interfering RNAs showed an influence of MIA on p54nrb expression on both messenger RNA (mRNA) and protein level. Knockdown of p54nrb protein in melanoma cell lines led to reduced proliferation rates and to a strong decrease in their ...

Aminopeptidase N (APN)/CD13 as ubiquitously expressed membrane peptidase exerts important functions in diverse cellular processes, such as proliferation, migration and differentiation. Previously, a role of APN in the invasiveness of melanoma cells has been demonstrated, but the underlying molecular mechanisms controlling APN expression are not understood. The present study demonstrates that lack of APN expression in primary and established melanoma cells was directly associated with a high-grade DNA methylation status of the myeloid APN promoter. Demethylation by 5-aza-2-desoxycytidine not only induced constitutive and cytokine-regulated APN protein expression but also resulted in an increased APN-dependent migration of melanoma cells. Furthermore, its heterogeneous expression was inversely correlated to the expression of melanocytic marker proteins in established as well as in short-term cultured human melanoma cells. Staining of tissue microarrays generated from a large series of melanoma ...

Dive into the research topics of Modulation by Interferons of HLA Antigen, High-Molecular-Weight Melanoma-associated Antigen, and Intercellular Adhesion Molecule 1 Expression by Cultured Melanoma Cells with Different Metastatic Potential. Together they form a unique fingerprint. ...

Once established in the liver organ, uveal melanomas respond extremely to therapy choices available badly, including targeted therapies, chemotherapies and immunotherapies [8]. Theres been some recommendation that the fairly low mutational burden of uveal melanoma weighed against cutaneous melanoma C producing a lower appearance of tumor neoantigens C may underlie having less efficacy observed in immunotherapy. To time, most function in the targeted therapy area has focused upon the inhibition of kinases downstream of GNAQ/GNA11. The major focus so far has been upon MEK, for which several US FDA-approved small molecule MEK inhibitors exist. There is preclinical evidence that targeting MEK has some efficacy against uveal melanoma cells and in uveal melanoma xenograft models [18]. Multiple isoforms of HDACs exist, and it is not yet obvious which HDAC or combination of HDACs regulate the BAP1 loss phenotype. Some recent evidence from both and human uveal melanoma cell collection models have ...

Background: Uveal Melanoma is a rare and aggressive subtype of melanoma, with singular characteristics that separate it from the most famous, the cutaneous melanoma. This uncommon condition becomes even rarer if we look to young population. Traditional chemotherapy doesn´t work with this aggressive disease in its metastatic scenario, and the new armament like targeted and immunotherapies are still looking for more robust evidence. Case Presentation: We report a rare case of uveal melanoma in a patient below 20 years of age, with abdominal pain as his initial complaint. He couldn´t present with the traditional visual symptoms of the primary site because of an auto-accident suffered 4 months before the presentation, letting him blind of the eye affected by the tumor development.Conclusion: There is always a possibility of the diagnosis of uveal melanoma in cases with associated isolated hepatic metastases, even in a young population, where this hypothesis is often rejected by the epidemiological

Background/Purpose Surfing is one of the most popular outdoor aquatic activities in Australia with an estimated 2.7 million recreational surfers; however, Australia has long been recognized as having the highest incidence of melanoma in the world, and it is the most common type of cancer in young Australians. The aim of this study was to investigate the lifetime prevalence of non-melanoma [basal cell carcinoma (BCC), squamous cell carcinoma (SCC)] and melanoma skin cancers in Australian recreational and competitive surfers. Methods Australian surfers were invited to complete an online surveillance survey to determine the lifetime prevalence of non-melanoma and melanoma skin cancers. Results A total of 1348 surfers (56.9% recreational) participated in this study, of which 184 surfers reported a skin cancer (competitive n = 96, recreational n = 87). Of non-melanoma and melanoma cancers reported, BCC was the most common (6.8%), followed by melanoma (1.4%) and SCC (0.6%). The relative risk was higher (P

Although a deadly form of skin cancer, melanoma is treatable if detected early. Existing approaches in melanoma detection training employ a rule-based method where lesions are assessed by their Asymmetry, Border, Color, Diameter and Evolvement in appearance (i.e., the ABCDE rule). However, the rule-based training practices in melanoma detection were not effective. In the current study, we assessed an innovative way to train melanoma detection using the principles of perceptual expertise training. All participants first reviewed the ABCDE rules pamphlet, and were then given the Melanoma Detection Test (MDT) as the pre-test where they categorized a set of skin lesion images as either melanoma or benign. Participants in the perceptual expertise training group received four training sessions where they were taught to categorize melanoma and benign lesions to 95% accuracy. Participants in the control group received no training. After training, all participants were retested with the same items on ...

TY - JOUR. T1 - The impact of biopsy technique on upstaging, residual disease, and outcome in cutaneous melanoma. AU - Egnatios, Genevive L.. AU - Dueck, Amylou C.. AU - MacDonald, James B.. AU - Laman, Susan D.. AU - Warschaw, Karen E.. AU - Dicaudo, David J.. AU - Nemeth, Shari A.. AU - Sekulic, Aleksandar. AU - Gray, Richard J.. AU - Wasif, Nabil. AU - Pockaj, Barbara A.. N1 - Copyright: Copyright 2012 Elsevier B.V., All rights reserved.. PY - 2011/12. Y1 - 2011/12. N2 - Background: After skin biopsy of malignant melanoma, the findings in the subsequent wide local excision (WLE) sometimes result in upgrading of the T-category. Herein, we examine the influence of biopsy technique on residual disease in melanoma WLE specimens and on upstaging. Methods: We performed a retrospective review of data from malignant melanoma patients who underwent sentinel lymph node biopsy between 1997 and 2010. Results: A total of 609 patients were biopsied by shave (51%), punch (19%), and excision (30%). Residual ...