Clinicopathological Study of Malignant Melanoma at Tertiary Care Centre.

PubMed

Thapa, S; Ghosh, A; Ghartimagar, D; Prasad, T; Narasimhan, R; Talwar, O

2017-01-01

Malignant melanoma, which causes three fourth of all deaths related to skin cancer, is more common in Caucasian population compared to Asian population. There is no reliable information about malignant melanoma in Nepal hence an effort has been made to assess the clinical and pathological features of melanoma patients. This was a retrospective hospital based study done in the department of Pathology. All cases of malignant melanoma diagnosed on biopsy during a period of 13 years were retrieved, reviewed and collated. We had 35 cases with age range from 15 to 84 years with the mean of 51.4 years and M: F of 1.3:1. The predominant site was lower extremities. Most cases were less than 3 cm. Majority of histologic subtypes were nodular melanoma 29 (82.8%) followed by mucosal lentiginous melanoma 3 (8.6%), superficial spreading melanoma 2 (5.7%) and acral lentiginous melanoma 1 (2.9%). Half (50%) of the excisional biopsies were at Clark's level IV and 75% were at high Breslow thickness. The most frequent site in males and females were lower extremities and trunk respectively in contrast to Western studies where it is opposite. Nodular melanoma was the commonest histologic subtype while in other Asian studies and in Western studies majority were acral lentiginous melanoma and superficial spreading melanoma respectively.

Use of Oncept melanoma vaccine in 69 canine oral malignant melanomas in the UK.

PubMed

Verganti, S; Berlato, D; Blackwood, L; Amores-Fuster, I; Polton, G A; Elders, R; Doyle, R; Taylor, A; Murphy, S

2017-01-01

Oral malignant melanomas carry a poor-to-guarded prognosis because of their local invasiveness and high metastatic propensity. The Oncept melanoma vaccine is licensed to treat dogs with stage II or III locally-controlled oral malignant melanoma and this retrospective study aimed to assess survival of affected dogs treated with the vaccine in the UK. Medical records of dogs with histopathologically-confirmed oral malignant melanoma that received the vaccine as part of their treatment were evaluated. Survival analyses for potential prognostic factors were performed. Sixty-nine dogs were included; 56 dogs, staged I to III, and with previous locoregional therapy, had a median survival time of 455 days (95% CI: 324 to 586 days). Based on Kaplan-Meier survival analysis with associated log-rank testing, no significant prognostic factors were identified for this population. Of the 13 patients with macroscopic disease treated with vaccine alone or in combination therapy, eight showed clinical response. Three patients with stage IV oral malignant melanoma survived 171, 178 and 288 days from diagnosis. Patients treated with the melanoma vaccine in our study had survival times similar to their counterparts receiving the vaccine in the USA. There were observed responses in patients with macroscopic disease and so the vaccine could be considered as palliative treatment in dogs with stage IV disease. © 2017 British Small Animal Veterinary Association.

Kruppel-like factor 6 in the progression and prognosis of malignant melanoma.

PubMed

Cai, Daxing; Zhao, Jing; Sun, Qing

2014-02-01

The aims of this study were to investigate the incidence of Krüppel-like factor 6 (KLF6) protein staining in patients with cutaneous malignant melanoma and examine its potential relevance to clinicopathological characteristics and tumour cell proliferation. Clinicopathological data from patients with cutaneous malignant melanoma were analysed retrospectively. Presence of KLF6 and the antigen Ki-67 in malignant melanoma and healthy tissue samples from each patient was detected by immunohistochemistry. The proliferation index was calculated on the basis of Ki-67 expression. The relationship between KLF6 and clinicopathological characteristics was also analysed. KLF6 was detected more frequently in normal healthy skin tissue compared with cutaneous malignant melanoma lesions (n = 40). There was a negative correlation between the presence of KLF6 and the proliferation index. The presence of KLF6 was also significantly correlated with tumour diameter, lymph node metastasis, tumour-node-metastasis stage and 3-year survival rate. KLF6 protein is downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue. KLF6 may be involved in tumour progression and may be a tumour suppressor and prognostic marker for cutaneous malignant melanoma.

Excision versus incision biopsy in the management of malignant melanoma.

PubMed

Sharma, Kavita S; Lim, Philip; Brotherston, Micheal T

2016-01-01

The incidence of melanoma has increased over the last decade. The Breslow thickness is one of the most important histological parameters. The gold standard for histological diagnosis is an excision biopsy. Incisional, punch or shave biopsies are not recommended as they are often incomplete and can result in false negatives. To assess the validity of incision versus excision biopsies in the prediction of Breslow thickness in the histopathological analysis of malignant melanoma. A retrospective review of histopathological records was conducted for all patients undergoing incision biopsy for malignant melanoma. The Breslow thicknesses of the incisional biopsies were matched to the later corresponding excisional biopsies. The demographical data, site of melanoma and histological subtype were also examined. Sixty patients between 1st January 2005 and 31st December 2013 were identified. The most common area biopsied was the upper and lower limbs - 50%. The Breslow thickness and Clark's level were found to be significantly increased in excision versus incision biopsy specimens. Nine patients had differing mitotic rates which were all higher in the excision biopsy samples. Our data supports the UK national guidelines on the management of malignant melanoma in that incisional biopsies are not indicated in the diagnostic pathway of malignant melanoma.

Enhanced Histone Deacetylase Activity in Malignant Melanoma Provokes RAD51 and FANCD2-Triggered Drug Resistance.

PubMed

Krumm, Andrea; Barckhausen, Christina; Kücük, Pelin; Tomaszowski, Karl-Heinz; Loquai, Carmen; Fahrer, Jörg; Krämer, Oliver Holger; Kaina, Bernd; Roos, Wynand Paul

2016-05-15

DNA-damaging anticancer drugs remain a part of metastatic melanoma therapy. Epigenetic reprogramming caused by increased histone deacetylase (HDAC) activity arising during tumor formation may contribute to resistance of melanomas to the alkylating drugs temozolomide, dacarbazine, and fotemustine. Here, we report on the impact of class I HDACs on the response of malignant melanoma cells treated with alkylating agents. The data show that malignant melanomas in situ contain a high level of HDAC1/2 and malignant melanoma cells overexpress HDAC1/2/3 compared with noncancer cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes malignant melanoma cells to apoptosis following exposure to alkylating agents, while not affecting primary melanocytes. Inhibition of HDAC1/2/3 caused sensitization of melanoma cells to temozolomide in vitro and in melanoma xenografts in vivo HDAC1/2/3 inhibition resulted in suppression of DNA double-strand break (DSB) repair by homologous recombination because of downregulation of RAD51 and FANCD2. This sensitized cells to the cytotoxic DNA lesion O(6)-methylguanine and caused a synthetic lethal interaction with the PARP-1 inhibitor olaparib. Furthermore, knockdown experiments identified HDAC2 as being responsible for the regulation of RAD51. The influence of class I HDACs on DSB repair by homologous recombination and the possible clinical implication on malignant melanoma therapy with temozolomide and other alkylating drugs suggests a combination approach where class I HDAC inhibitors such as valproic acid or MS-275 (entinostat) appear to counteract HDAC- and RAD51/FANCD2-mediated melanoma cell resistance. Cancer Res; 76(10); 3067-77. ©2016 AACR. ©2016 American Association for Cancer Research.

Ber-H2 (CD30) immunohistochemical staining in malignant melanoma.

PubMed

Polski, J M; Janney, C G

1999-09-01

Malignant melanoma can be included in the differential diagnosis of Hodgkin's disease, anaplastic large cell lymphoma, or embryonal carcinoma These malignancies express CD30, a marker of diagnostic value. A retrospective immunohistochemical study was undertaken to determine the frequency of immunoreactivity of Ber-H2 (anti-CD30 monoclonal antibody) in malignant melanoma Archival paraffin-embedded tissue from 24 primary and metastatic lesions was used. No Ber-H2 labeling was observed in the majority of the studied cases. Variable weak cytoplasmic staining was present in only one case. The findings are compared with the previous reports claiming frequent CD30 expression in malignant melanoma. We discuss issues pertaining to the interpretation of the Ber-H2 IHC staining in formalin-fixed, paraffin-embedded tissue.

microRNA-625 inhibits tumorigenicity by suppressing proliferation, migration and invasion in malignant melanoma.

PubMed

Fang, Wei; Fan, Yibin; Fa, Zhenzong; Xu, Jinhua; Yu, Hongyu; Li, Pu; Gu, Julin

2017-02-21

Dysregulated microRNA (miR)-625 expression has been observed in several kinds of cancer. MicroRNAs are important factors in the development and progression of malignant melanoma, though the clinical significance and function of miR-625 in human malignant melanoma remain unclear. Levels of miR-625 expression were therefore determined in 36 pairs of malignant melanoma and adjacent non-tumor tissue using qPCR. The effects of miR-625 dysregulation on malignant melanoma cell proliferation, wound healing, migration and invasion in vitro and tumorigenicity in vivo were investigated using CCK-8, transwell assays, and a nude mouse subcutaneous tumor model. Bioinformatics analysis and luciferase reporter system were used to predict and confirm the target gene of miR-625. miR-625 levels were frequently decreased in malignant melanoma. Ectopic expression of miR-625 suppressed proliferation, wound healing, migration, and tumorgenicity in malignant melanoma. Moreover, miR-625 acted, at least in part, by suppressing potential target SOX2. These results show that miR-625 is a tumor suppressor that inhibits the development and progression of malignant melanoma, which suggests miR-625 is potentially a new diagnostic marker and therapeutic target of malignant melanoma.

Limbic encephalitis following immunotherapy against metastatic malignant melanoma

PubMed Central

Salam, Sharfaraz; Lavin, Timothy; Turan, Ayse

2016-01-01

Novel immunotherapies are increasingly being used to treat malignant melanoma. The use of such agents has been associated with triggering autoimmunity. However, there has been a paucity in reports of limbic encephalitis associated with these immunotherapies. Pembrolizumab, a monoclonal antibody against programmed cell death antigen (PD-1), is currently being trialled in the UK to treat malignant melanoma. We report a unique case of antibody-negative limbic encephalitis presenting 1 year after starting pembrolizumab, in the context of malignant melanoma. The patient presented with progressive cognitive decline. MRI of the brain revealed signal change within the limbic structures. Cerebrospinal fluid studies confirmed evidence of inflammation with raised white cell count and protein. We were able to prevent further progression of symptoms by stopping pembrolizumab and treating the patient instead with steroids. We advocate considering autoimmune neuroinflammation as a differential for neurological disorders presenting in patients receiving PD-1 antagonist treatment and immunotherapy in general. PMID:27009198

Effects of Malignant Melanoma Initiating Cells on T-Cell Activation

PubMed Central

Schatton, Tobias; Schütte, Ute; Frank, Markus H.

2016-01-01

Although human malignant melanoma is a highly immunogenic cancer, both the endogenous antitumor immune response and melanoma immunotherapy often fail to control neoplastic progression. Accordingly, characterizing melanoma cell subsets capable of evading antitumor immunity could unravel optimized treatment strategies that might reduce morbidity and mortality from melanoma. By virtue of their preferential capacity to modulate antitumor immune responses and drive inexorable tumor growth and progression, malignant melanoma-initiating cells (MMICs) warrant closer investigation to further elucidate the cellular and molecular mechanisms underlying melanoma immune evasion and immunotherapy resistance. Here we describe methodologies that enable the characterization of immunoregulatory effects of purified MMICs versus melanoma bulk populations in coculture with syngeneic or allogeneic lymphocytes, using [3H] thymidine incorporation, enzyme-linked immunosorbent spot (ELISPOT), or ELISA assays. These assays were traditionally developed to analyze alloimmune processes and we successfully adapted them for the study of tumor-mediated immunomodulatory functions. PMID:26786883

Mucosal Malignant Melanoma of Nasal Cavity Recurring a Year After Radiotherapy.

PubMed

Çomunoğlu, Cem; Kuzey, Gamze Mocan; Inançli, Mete; Baba, Füsun; Özkayalar, Hanife

2017-01-01

Sinonasal mucosal malignant melanoma is a rare entity. In this report we present a nasal mucosal malignant melanoma case with its histopathological and clinical features. An 88-year-old female patient presented with epistaxis a month ago. Examination revealed a polypoid mass lesion of right nasal cavity originating from the middle concha. Her medical history revealed that she had been found to have a mass lesion in the right nasal cavity 15 months ago. She then underwent a punch biopsy from that lesion. A definitive histopathological diagnosis was not made but it was declared that the lesion had been a malignant epithelial tumor. The patient then had radiotherapy and the lesion showed complete regression. One year after completion of radiotherapy, the lesion recurred. Her last PET-CT showed multiple metastatic foci. Endoscopic excisional biopsy was performed for her recurrent lesion. Fragmented tumoral tissues were measured as 3,6x3x0,5 cm. Macroscopically the tumor was brownish in color. Histopathologically the tumor consisted of spindled and epitheloid cells. Immunohistochemically the tumor cells displayed positivity for S-100, HMB-45 and Melan-A. Findings were consistent with malignant melanoma. Mucosal malignant melanomas have a poor prognosis despite chemotherapy and radiotherapy. Five-year survival for sinonasal melanoma is reported to be lower than 35%. Sinonasal melanomas show a high recurrence rate. The immunohistochemical markers showing high specificity for malignant melanoma such as S-100, HMB-45 and Melan-A are used in order to reach a correct diagnosis. In our case the tumor showed recurrence and multiple metastases 1 year after completion of radiotherapy. For this recurrent tumor, chemotherapy and radiotherapy have been planned.

Primary Malignant Melanoma of Pleura: A Case Report and Literature Review.

PubMed

Agarwal, Poojan; Nambiyar, Kaniyyapan; Manju Kaushal; Bhardwaj, Minakshi

2016-07-01

Malignant melanoma is one of the most aggressive and treatment resistant skin cancers. India enjoys a low incidence of melanoma, and age specific incidence rates for cutaneous malignant melanoma (CMM) are being less than 0.5 per 1,000,000. This could be due to under-reporting of melanoma on account of a low index of suspicion by clinicians and pathologists alike. Most common site for origin of primary melanoma is skin, accounting for about 91.2% of all reported primary malignant melanoma cases. Other primary sites are relatively uncommon. Primary pleural melanoma is a very rare tumor and to the best of our knowledge, only seven cases have been reported so far worldwide. We hereby discuss a new case, only second from India. Our patient also had coexistent congenital hairy nevus, an unusual association also noted in two previously reported cases. Excluding primary cutaneous melanoma with pleural metastasis was a diagnostic challenge in this case but multiple cutaneous biopsies together with clinical and findings helped us arrive at this unusual diagnosis. Unfortunately, the patient succumbed to his illness. Diagn. Cytopathol. 2016;44:648-652. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Primary pulmonary malignant melanoma: a clinicopathologic study of two cases.

PubMed

Gong, Li; Liu, Xiao-Yan; Zhang, Wen-Dong; Zhu, Shao-Jun; Yao, Li; Han, Xiu-Juan; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2012-09-19

Malignant melanoma involving the respiratory tract is nearly always metastatic in origin, and primary tumors are very rare. To our knowledge, about 30 cases have been reported in the English literature, one of which involved multiple brain metastases. Here, we report two cases of primary pulmonary malignant melanoma. The first case, which occurred in a 52-year-old Chinese female patient who died 4 months after the initial diagnosis, involved rapid intrapulmonary and intracranial metastases. The second patient, a 65-year-old female, underwent surgical excision, and clinical examination, histopathological characteristics, and immunohistochemical features supported the diagnosis of pulmonary malignant melanoma. No evidence for recurrence and/or metastasis has been found more than one year after the initial surgery. To establish the diagnosis of primary pulmonary malignant melanoma, any extrapulmonary origin must be excluded by detailed examination. Moreover, the tumor should be removed surgically whether it occurs as a single lesion or multiple lesions. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

[Malignant Melanoma - from Classical Histology towards Molecular Genetic Testing].

PubMed

Ryška, A; Horký, O; Berkovcová, J; Tichá, I; Kalinová, M; Matějčková, M; Bóday, Á; Drábek, J; Martínek, P; Šimová, J; Sieglová, K; Vošmiková, H

Malignant melanoma is - in comparison with other skin tumors - a relatively rare malignant neoplasm with highly aggressive biologic behavior and variable prognosis. Recent data in pathology and molecular diagnostics indicate that malignant melanoma is in fact not a single entity but a group of different neoplasms with variable etiopathogenesis, biologic behavior and prognosis. New therapeutic options using targeted treatment blocking MAPK signaling pathway require testing of BRAF gene mutation status. This helps to select patients with highest probability of benefit from this treatment. This article summarizes information on the correlation of morphological findings with genetic changes, discusses the representation of individual genetic types in various morphological subgroups and deals with the newly proposed genetic classification of melanoma and the current possibilities, pitfalls and challenges in BRAF testing of malignant melanoma. It also describes the current testing situation in the Czech Republic - the methods used, the representation of BRAF mutations in the tested population and the future of testing. It also shows the limitations of the BRAF and MEK targeted treatment concept resulting from the heterogeneity of the tumor population. Mechanisms of acquired resistance to MAPK pathway inhibitors, possibilities of their detection, and issues of combination of targeted therapy and immunotherapy are discussed.Key words: malignant melanoma - BRAF - mutation - molecular targeted therapy - tumor microenvironment - tumor heterogeneity This work was supported by projects PROGRES Q40/11, BBMRICZ LM2015089, SVV 260398 and GACR 17-10331S. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 28. 3. 2017Accepted: 16. 5. 2017.

Prognostic significance of thymidylate synthase (TS) expression in cutaneous malignant melanoma.

PubMed

Shimizu, A; Kaira, K; Yasuda, M; Asao, T; Ishikawa, O

2016-01-01

Thymidylate synthase (TS) plays an essential role in the pathogenesis and development of cancer, and TS-targeting agents have been widely used against different types of cancers. However, it remains still unclear whether or not TS is expressed in malignant melanoma. We conducted the clinicopathological study to investigate the prognostic significance of TS expression in cutaneous malignant melanoma. Ninety-nine patients with surgically resected cutaneous malignant melanoma were assessed. Tumor sections were stained by immunohistochemistry for TS, Ki-67, and microvessel density (MVD) determined by CD34. TS was positively expressed in 26% (26 out of 99). The expression of TS was significantly associated with T factor, cell proliferation (Ki-67) and MVD (CD34). By Spearman's rank test, TS expression was significantly correlated with Ki67 and CD34. By univariate analysis, ulceration, disease stage, TS, Ki-67 and CD34 had a significant relationship with survival. Multivariate analysis confirmed that TS was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The positive expression of TS could be a useful marker for predicting poor prognosis in patients with cutaneous malignant melanoma, and TS-targeting agents may be worth trying for the treatment of this dismal disease.

Malignant melanoma misdiagnosed as diabetic foot ulcer: A case report.

PubMed

Gao, Wei; Chen, Dawei; Ran, Xingwu

2017-07-01

Acral lentiginous melanoma (AML) does not exhibit the classic signs of malignant melanoma. ALM is frequently misdiagnosed because of its unusual sites and atypical clinical morphologies, which lead to poor prognosis. A female patient aged 78 years was presented to our center with two ulcers on her right foot. Diabetic foot ulcer was considered as the primary diagnosis. The ulcers failed to improve after 2 weeks' therapy. An incisional biopsy of the lesion revealed malignant melanoma. The patient received wide excision, skin grafting as well as biotherapy. The lesion was healed and no other metastasis has been founded until now. Clinicians must maintain a high level of suspicion in distinguishing malignant melanoma from other more benign skin lesions of the foot. The need for early biopsy of ulcer, even when clinical suspicion is low, can not be overemphasized. Only in this way can we reduce misdiagnosis rate and improve survival rate in patients with foot ulcer.

Single-chain antibody-delivered Livin siRNA inhibits human malignant melanoma growth in vitro and in vivo.

PubMed

Wang, Hao; Yang, Yifei; Wang, Wei; Guan, Bing; Xun, Meng; Zhang, Hai; Wang, Ziling; Zhao, Yong

2017-05-01

Although gene therapy has brought new insights into the treatment of malignant melanoma, targeting delivery of nucleic acid which targets critical oncogene/anti-oncogene in vivo is still a bottleneck in the therapeutic application. Our previous in vitro studies have found that the oncogene Livin could serve as a potential molecular target by small interfering RNA for gene therapy of malignant melanoma. However, how to transport Livin small interfering RNA into malignant melanoma cells specifically and efficiently in vivo needs further investigation. Cumulative evidence has suggested that single-chain antibody-mediated small interfering RNA targeted delivery is an effective way to silence specific genes in human cancer cells. Indeed, this study designed a protamine-single-chain antibody fusion protein, anti-MM scFv-tP, to deliver Livin small interfering RNA into LiBr cells. Further experiments confirmed the induction of cell apoptosis and suppression of cell proliferation by anti-MM scFv-tP in LiBr cells, along with efficient silence of Livin gene both in vitro and in vivo. Altogether, our findings provide a feasible approach to transport Livin small interfering RNA to malignant melanoma cells which would be a new therapeutic strategy for combating malignant melanoma.

Correlation between fertility drugs use and malignant melanoma incidence: the state of the art.

PubMed

Tomao, Federica; Papa, Anselmo; Lo Russo, Giuseppe; Zuber, Sara; Spinelli, Gian Paolo; Rossi, Luigi; Caruso, Davide; Prinzi, Natalie; Stati, Valeria; Benedetti Panici, Pierluigi; Tomao, Silverio

2014-09-01

The relationship between fertility, reproductive hormones, and risk of malignant melanoma has acquired much interest in recent years. Melanocytes are hormonally responsive cells, and some in vitro studies demonstrated that estrogen hormones stimulate the growth of melanocytes. Moreover, estrogen receptors have been identified in melanoma cells, as well as in melanocytic nevi and in normal skin. Some evidences suggest a possible link between fertility treatments and the increased risk of malignant melanoma. This article addresses this association through a scrupulous search of the literature published thus far. The aim of this review is to determine the incidence of malignant melanoma in women treated with fertility drugs and to examine if the exposure to fertility treatments really increases the risk of malignant melanoma. In particular, our analysis focused on the different types of drugs and different treatment schedules used. Finally, this study provides additional insights regarding the long-term relationships between fertility drugs and the risk of malignant melanoma.

Malignant neurocristic hamartoma: a tumor distinct from conventional melanoma and malignant blue nevus.

PubMed

Linskey, Katy R; Dias-Santagata, Dora; Nazarian, Rosalynn M; Le, Long P; Lam, Quynh; Bellucci, Kirsten S W; Robinson-Bostom, Leslie; Mihm, Martin C; Hoang, Mai P

2011-10-01

Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials--the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi.

Increased expression of sex determining region Y-box 11 (SOX11) in cutaneous malignant melanoma.

PubMed

Jian, Jiao; Guoying, Wang; Jing, Zhao

2013-08-01

To observe sex determining region Y-box 11 (SOX11) gene expression in cutaneous malignant melanoma and its effect on tumour cell proliferation. Clinicopathological data and tissue samples from patients with cutaneous malignant melanoma, together with tissue samples from healthy volunteers (controls), were retrospectively reviewed. Protein levels of SOX11 and the antigen identified by monoclonal antibody Ki-67 (Ki-67) in skin lesions were analysed using immunohistochemistry. The correlation between protein levels and clinipathological parameters was investigated. Out of 40 patient samples, 25 (62.5%) were positive for SOX11 protein in malignant melanoma tissue. This was significantly higher than in 40 control tissue samples, in which no SOX11 protein was detected. Presence of SOX11 protein was positively related to the proliferation index of cutaneous malignant melanoma tumour cells. Presence of SOX11 protein in cutaneous malignant melanoma was related to tumour type, tumour location, lymph node metastasis and 5-year survival rate. Human cutaneous malignant melanoma tissues expressed high levels of SOX11 compared with healthy controls, suggesting that SOX11 may be a new prognostic marker for malignant melanoma.

Malignant melanoma of the tongue following low-dose radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.

1985-03-01

A 47-year-old man had a spindly malignant melanoma of the tongue many years after low-dose radiation therapy for lichen planus. To our knowledge, only 12 melanomas of the tongue have been reported previously, and in none of these was radiation documented.

Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue

NASA Astrophysics Data System (ADS)

He, Jinping; Wang, Nan; Tsurui, Hiromichi; Kato, Masashi; Iida, Machiko; Kobayashi, Takayoshi

2016-07-01

Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

Vitamin D status and risk for malignant cutaneous melanoma: recent advances

PubMed Central

Ombra, Maria N.; Doneddu, Valentina; Sini, Maria C.; Colombino, Maria; Rozzo, Carla; Stanganelli, Ignazio; Tanda, Francesco; Cossu, Antonio; Palmieri, Giuseppe

2017-01-01

Cutaneous malignant melanoma, whose incidence is increasing steadily worldwide, is the result of complex interactions between individual genetic factors and environmental risk factors. Ultraviolet radiation represents the most important environmental risk factor for the development of skin cancers, including melanoma. Sun exposure and early sunburn during childhood are the principal causes of cutaneous melanoma insurgence in adults, with double the risk relative to a nonexposed population. Consequently, ultraviolet protection has long been recognized as an important measure to prevent such a malignancy. Biological and epidemiological data suggest that vitamin D status could affect the risk of cancer and play a role in cancer prevention by exerting antiproliferative effects. Solar radiations are critical for vitamin D synthesis in humans; however, uncontrolled and intensive sun exposure is dangerous to skin health and may contribute toward the development of cutaneous malignant melanoma. An optimum balance between sun protection and exposure is thus advocated. Additional research is required to confirm the preventive role of vitamin D in melanoma incidence or a positive influence on patient outcome. PMID:28125434

Primary malignant melanoma of the gallbladder with multiple metastases: A case report.

PubMed

Wang, Jun-Ke; Su, Fei; Ma, Wen-Jie; Hu, Hai-Jie; Yang, Qin; Liu, Fei; Li, Quan-Sheng; Li, Fu-Yu

2017-11-01

Primary malignant melanoma of the gallbladder is an extremely rare tumor, with fewer than 40 cases reported in the literature worldwide. The majority of patients presented as a solitary lesion in the gallbladder. To our knowledge, only one case of primary malignant melanoma of the gallbladder with multiple metastases has been reported, which involved the stomach, duodenum, pancreas, jejunum and a mesenteric lymph node. We report a case of primary malignant melanoma of the gallbladder with metastases to the duodenal bulb, right adrenal and a celiac lymph node. Primary malignant melanoma of the gallbladder with multiple metastases. Gastrojejunostomy, cholecystectomy, and biopsy of the three metastatic lesions were performed. Histopathologic examination revealed melanin pigments were within the tumor cells of the four lesions, however, junctional activity was noted only in the gallbladder, supporting that the gallbladder was the primary site. No pigmented lesions were detected on the skin or eyes. The postoperative recovery was uneventful, and subsequently, chemotherapy with paclitaxel and carboplatin was administered. The patient survived for 16 months due to tumor. progression. The current case was unique due to the adrenal involvement. For patients with multiple metastases of malignant melanoma, gallbladder origin should be considered in the differential diagnosis from cutaneous origin.

Cloudy and starry milia-like cysts: how well do they distinguish seborrheic keratoses from malignant melanomas?

PubMed

Stricklin, S M; Stoecker, W V; Oliviero, M C; Rabinovitz, H S; Mahajan, S K

2011-10-01

Seborrheic keratoses are the most common skin lesions known to contain small white or yellow structures called milia-like cysts (MLCs). Varied appearances can sometimes make it difficult to differentiate benign lesions from malignant lesions such as melanoma, the deadliest form of skin cancer found in humans. The purpose of this study was to determine the statistical occurrence of MLCs in benign vs. malignant lesions. A medical student with 10 months experience in examining approximately 1000 dermoscopy images and a dermoscopy-naïve observer analysed contact non-polarized dermoscopy images of 221 malignant melanomas and 175 seborrheic keratoses for presence of MLCs. The observers found two different types of MLCs present: large ones described as cloudy and smaller ones described as starry. Starry MLCs were found to be prevalent in both seborrheic keratoses and melanomas. Cloudy MLCs, however, were found to have 99.1% specificity for seborrheic keratoses among this group of seborrheic keratoses and melanomas. Cloudy MLCs can be a useful tool for differentiating between seborrheic keratoses and melanomas. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Cloudy and starry milia-like cysts: how well do they distinguish seborrheic keratoses from malignant melanomas?

PubMed Central

Stricklin, S.M.; Stoecker, W.V.; Oliviero, M.C.; Rabinovitz, H.S.; Mahajan, S.K.

2011-01-01

Background Seborrheic keratoses are the most common skin lesions known to contain small white or yellow structures called milia-like cysts (MLCs). Varied appearances can sometimes make it difficult to differentiate benign lesions from malignant lesions such as melanoma, the deadliest form of skin cancer found in humans. Objective The purpose of this study was to determine the statistical occurrence of MLCs in benign vs. malignant lesions. Methods A medical student with 10 months experience in examining approximately 1000 dermoscopy images and a dermoscopy-naïve observer analysed contact non-polarized dermoscopy images of 221 malignant melanomas and 175 seborrheic keratoses for presence of MLCs. Results The observers found two different types of MLCs present: large ones described as cloudy and smaller ones described as starry. Starry MLCs were found to be prevalent in both seborrheic keratoses and melanomas. Cloudy MLCs, however, were found to have 99.1% specificity for seborrheic keratoses among this group of seborrheic keratoses and melanomas. Conclusion Cloudy MLCs can be a useful tool for differentiating between seborrheic keratoses and melanomas. Received: 18 June 2010; Accepted: 27 October 2010 PMID:21923811

A case of primary choroidal malignant melanoma in a cat.

PubMed

Bourguet, Aurélie; Piccicuto, Virginie; Donzel, Elise; Carlus, Marine; Chahory, Sabine

2015-07-01

This report describes the clinical presentation, diagnosis, histological lesions, and prognosis of a primary choroidal malignant melanoma in a 15-year-old cat. The animal was presented for unilateral blindness. On ocular examination, a raised pigmented mass protruding from the posterior pole into the vitreous body was observed by diffuse transillumination and indirect ophthalmoscopy. Ocular ultrasound and computer tomography (CT) scan confirmed localization of the tumor to the posterior segment. The diagnosis of primary choroidal melanoma was confirmed by histopathology after enucleation. To our knowledge, this is the first reported case of a feline malignant melanoma with a primary choroidal localization without iris involvement. © 2014 American College of Veterinary Ophthalmologists.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study.

PubMed

McCourt, C; Coleman, H G; Murray, L J; Cantwell, M M; Dolan, O; Powe, D G; Cardwell, C R

2014-04-01

Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers. To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma. Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case-control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing. Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68-1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56-1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality. Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study. © 2014 British Association of Dermatologists.

miR-137 inhibits glutamine catabolism and growth of malignant melanoma by targeting glutaminase.

PubMed

Luan, Wenkang; Zhou, Zhou; Zhu, Yan; Xia, Yun; Wang, Jinlong; Xu, Bin

2018-01-01

Glutamine catabolism is considered to be an important metabolic pathway for cancer cells. Glutaminase (GLS) is the important rate-limiting enzyme of glutamine catabolism. miR-137 functions as a tumor suppressor in many human malignant tumors. However, the role and molecular mechanism of miR-137 and GLS in malignant melanoma has not been reported. In this study, we showed that miR-137 was decreased in melanoma tissue, and the low miR-137 level and high GLS expression are independent risk factor in melanoma. miR-137 suppressed the proliferation and glutamine catabolism of melanoma cells. GLS is crucial for glutamine catabolism and growth of malignant melanoma. We also demonstrated that miR-137 acts as a tumor suppressor in melanoma by targeting GLS. This result elucidates a new mechanism for miR-137 in melanoma development and provides a survival indicator and potential therapeutic target for melanoma patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Conjunctival amelanotic malignant melanoma arising in primary acquired melanosis sine pigmento.

PubMed

Jay, V; Font, R L

1998-01-01

The authors describe an amelanotic malignant melanoma of the conjunctiva in association with primary acquired melanosis (PAM) sine pigmento, and highlight the clinical and pathologic features of this rare entity. Histopathologic and immunohistochemical studies were performed on a conjunctival tumor in a 54-year-old white woman. Case report. Histopathologic examination revealed an invasive amelanotic melanoma of the conjunctiva, with anterior orbital extension arising from intraepithelial dysplastic melanocytes that lacked melanin pigment (PAM sine pigmento). Both the malignant melanoma cells and the intraepithelial dysplastic melanocytes in the areas of PAM exhibited S-100 and HMB-45 positivity. The patient underwent an orbital exenteration that disclosed tumor within the anterior orbit inferiorly. Amelanotic invasive malignant melanoma can arise in association with PAM sine pigmento, as seen in our patient who had orbital invasion necessitating exenteration. This aggressive form of conjunctival melanoma is often associated with a poor prognosis and risk of metastatic disease. Absence of conjunctival pigmentation in PAM sine pigmento prevents early clinical detection of this variant of PAM. This lack of pigmentation also makes clinical diagnosis virtually impossible, and diagnosis can only be established histopathologically. Awareness of this nonpigmented variety of PAM is crucial for early recognition and appropriate management of the associated melanoma.

Video comparator system for early detection of cutaneous malignant melanoma

NASA Astrophysics Data System (ADS)

Craine, Eric R.; Craine, Brian L.

1992-05-01

The recognized incidence of cutaneous malignant melanoma in the United States is now rising faster than any other cancer, increasing by 83% from 1980 to 1987. Recent revelations that depletion of the earth's ozone layer is accelerating at a more rapid rate than previously believed can only exacerbate current projections for the increased incidence of this deadly disease. Because there is no good treatment for metastatic melanoma even small cancers often prove fatal if not detected early. Melanoma allowed to invade the subcutaneous tissue is associated with a five-year survival rate of only 44%. Ironically, few cancers provide a greater opportunity for early discovery and cure. Cutaneous melanoma is not only located where it is readily observed, but typically undergoes a `radial growth' phase prior to metastasis. During this phase the net growth is superficial and circumferential, gradually increasing the area of the lesion and changing its coloration. Screening measures for the early detection of melanoma must concentrate on two primary tasks: (1) detection of lesion changes indicative of the radial growth stage of malignancy and (2) alerting the patient and physician to the existence of a new or changed lesion on the skin. To accomplish these goals we have experimented with the applicability of a microcomputer based video imaging system which stores an image archive of historical reference images for each patient. With the acquisition of new images of the patient, easily registered with the archival images through a technique we have developed we are able to perform a blink comparison of the image pairs. This technique appears to be far more effective than currently used techniques for detecting changed lesions on a comprehensive basis.

A Rare Case of Malignant Melanoma of the Mandible: 
CT and MRI Findings.

PubMed

Ogura, Ichiro; Sasaki, Yoshihiko; Kameta, Ayako; Sue, Mikiko; Oda, Takaaki

Malignant melanoma of the mandibular gingiva is extremely rare. It is a malignant tumour of melanocytes or their precursor cells, and often misinterpreted as a benign pigmented process. A few reports have described computed tomography (CT) and magnetic resonance imaging (MRI) findings of malignant melanoma in the oral cavity. We report a rare case of malignant melanoma of the mandible and the related CT and MRI findings. Soft tissue algorithm contrast-enhanced CT showed an expansile mass and irregular destruction of alveolar bone in the right side of the mandibular molar area. MR images showed an enhancing mass and the tumour had a low to intermediate signal intensity and a high-signal intensity. Soft tissue algorithm contrast-enhanced CT and MR images showed lymphadenopathy involving the submandibular lymph nodes. Histopathological examination confirmed the diagnosis of malignant melanoma.

Prognostic significance of β2-adrenergic receptor expression in malignant melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Mori, Keita; Kato, Madoka; Shimizu, Kimihiro; Yasuda, Masahito; Takahashi, Ayumi; Oyama, Tetsunari; Asao, Takayuki; Ishikawa, Osamu

2016-05-01

Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma.

Modulation of T Cell Activation by Malignant Melanoma Initiating Cells

PubMed Central

Schatton, Tobias; Schütte, Ute; Frank, Natasha Y.; Zhan, Qian; Hoerning, André; Robles, Susanne C.; Zhou, Jun; Hodi, F. Stephen; Spagnoli, Giulio C.; Murphy, George F.; Frank, Markus H.

2010-01-01

Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. This raises the possibility that only a restricted minority of tumorigenic malignant cells might possess the phenotypic and functional characteristics to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis, by demonstrating that tumorigenic ABCB5+ malignant melanoma-initiating cells (MMICs) possess the capacity to preferentially inhibit interleukin (IL)-2-dependent T cell activation and to support, in a B7.2-dependent manner, regulatory T (Treg) cell induction. Compared to melanoma bulk populations, ABCB5+ MMICs expressed lower levels of the major histocompatibility complex (MHC) class I, showed aberrant positivity for MHC class II, and exhibited lower expression levels of the melanoma-associated antigens (MAAs) MART-1, ML-IAP, NY-ESO-1, and MAGE-A. In addition, tumorigenic ABCB5+ subpopulations preferentially expressed the costimulatory molecules B7.2 and PD-1 in both established melanoma xenografts and clinical tumor specimens in vivo. In immune activation assays, ABCB5+ melanoma cells inhibited mitogen-dependent human peripheral blood mononuclear cell (PBMC) proliferation and IL-2 production more efficiently than ABCB5− populations. Moreover, coculture with ABCB5+ MMICs increased, in a B7.2 signalling-dependent manner, CD4+CD25+FoxP3+ Treg cell abundance and IL-10 production by mitogen-activated PBMCs. Consistent with these findings, ABCB5+ melanoma subsets also preferentially inhibited IL-2 production and induced IL-10 secretion by cocultured patient-derived, syngeneic PBMCs. Our findings identify novel T cell-modulatory functions of ABCB5+ melanoma subpopulations and suggest specific roles for MMICs in the evasion of antitumor immunity and in cancer immunotherapeutic resistance. PMID:20068175

Overexpression of adenylate cyclase-associated protein 2 is a novel prognostic marker in malignant melanoma.

PubMed

Masugi, Yohei; Tanese, Keiji; Emoto, Katsura; Yamazaki, Ken; Effendi, Kathryn; Funakoshi, Takeru; Mori, Mariko; Sakamoto, Michiie

2015-12-01

Malignant melanoma is one of the lethal malignant tumors worldwide. Previously we reported that adenylate cyclase-associated protein 2 (CAP2), which is a well-conserved actin regulator, was overexpressed in hepatocellular carcinoma; however, CAP2 expression in other clinical cancers remains unclear. The aim of the current study was to clarify the clinicopathological significance of CAP2 overexpression in malignant melanoma. Immunohistochemical analyses revealed that many melanoma cells exhibited diffuse cytoplasmic expression of CAP2, whereas no normal melanocytes showed detectable immunostaining for CAP2. A high level of CAP2 expression was seen in 14 of 50 melanomas and was significantly correlated with greater tumor thickness and nodular melanoma subtypes. In addition, a high level of CAP2 expression was associated with poor overall survival in univariate and multivariate analyses. For 13 patients, samples of primary and metastatic melanoma tissue were available: four patients exhibited higher levels of CAP2 expression in metastatic tumor compared to the primary site, whereas no patient showed lower levels of CAP2 expression in metastatic melanomas. Our findings show that CAP2 overexpression is a novel prognostic marker in malignant melanoma and that CAP2 expression seems to increase stepwise during tumor progression, suggesting the involvement of CAP2 in the aggressive behavior of malignant melanoma. © 2015 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd.

Expression and clinicopathological significance of microRNA-21 and programmed cell death 4 in malignant melanoma.

PubMed

Jiao, Jian; Fan, Yu; Zhang, Yan

2015-10-01

To measure levels of microRNA (miR)-21 and its target gene, programmed cell death 4 (PDCD4), in samples of human cutaneous malignant melanoma and normal non-malignant control skin. Relative levels of miR-21 and PDCD4 mRNA were measured using a quantitative real-time reverse transcription-polymerase chain reaction. Correlations between the levels of the two molecules and the clinicopathological characteristics of malignant melanoma were analysed. A total of 67 cases of human cutaneous malignant melanoma were analysed and compared with 67 samples of normal nonmalignant control skin. Compared with normal skin samples, the relative level of miR-21 was significantly higher and the relative level of PDCD4 mRNA was significantly lower in the melanoma specimens. A significant negative correlation between PDCD4 mRNA and miR-21 was demonstrated in malignant melanoma (r = -0.602). Elevated miR-21 and reduced PDCD4 mRNA levels were both significantly correlated with increased tumour size, a higher Clark classification level and the presence of lymph node metastases in malignant melanoma. These findings suggest that miR-21 and PDCD4 might be potential biomarkers for malignant melanoma and might provide treatment targets in the future. © The Author(s) 2015.

[Anorectal Malignant Melanoma Is a Very Rare Disease and Has a Poor Prognosis].

PubMed

Yoshida, Yuta; Noura, Shingo; Matsumura, Tae; Hirota, Masaki; Shuto, Takashi; Muratsu, Arisa; Yasuyama, Harunobu; Takata, Akihiro; Koga, Chikato; Kameda, Chizu; Murakami, Masahiro; Kawabata, Ryohei; Shimizu, Junzo; Miwa, Hideaki; Hasegawa, Junichi

2017-11-01

We performed abdomino-perineal-resection(APR)on 2 cases of anorectal malignant melanoma. The first case was a 70- year-old woman suffering from bloody stool. Colonoscopy showed a black tumor in the rectum. Biopsy revealed a malignant melanoma. A CT scan showed multiple lung metastases and liver metastasis. She underwent surgery for the purpose of bleeding control, but died shortly thereafter because her liver and lung metastases had worsened. The second case was a 43- years-old man suffering from bloody stool. He had a black type 3 tumor in the rectum. A biopsy revealed malignant melanoma. A CT scan showed lateral lymph node swelling. He underwent APR with right side-lateral dissection. An established treatment for anorectal malignant melanoma has not been agreed upon and it is controversial. We experienced 2 cases that underwent surgery and we report them along with relevant information from the literature.

Malignant melanoma (non-metastatic): sentinel lymph node biopsy.

PubMed

Pay, Andy

2016-01-19

The incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. The 5-year survival rate ranges from 20% to 95%, depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi. We conducted a systematic overview, aiming to answer the following clinical question: What is the evidence for performing a sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2014 (Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). At this update, searching of electronic databases retrieved 221 studies. After deduplication and removal of conference abstracts, 99 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of 41 full publications. Of the 41 full articles evaluated, one systematic review and three RCTs were added at this update. We performed a GRADE evaluation for two PICO combinations. In this systematic overview, we evaluated the evidence for performing sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes.

Cytologic Features of Malignant Melanoma with Osteoclast-Like Giant Cells.

PubMed

Jiménez-Heffernan, José A; Adrados, Magdalena; Muñoz-Hernández, Patricia; Fernández-Rico, Paloma; Ballesteros-García, Ana I; Fraga, Javier

2018-01-01

Malignant melanoma showing numerous osteoclast-like giant cells (OGCs) is an uncommon morphologic phenomenon, rarely mentioned in the cytologic literature. The few reported cases seem to have an aggressive clinical behavior. Although most findings support monocyte/macrophage differentiation, the exact nature of OGCs is not clear. A 57-year-old woman presented with an inguinal lymphadenopathy. Sixteen years before, cutaneous malignant melanoma of the lower limb had been excised. Needle aspiration revealed abundant neoplastic single cells as well as numerous multinucleated OGCs. Occasional neoplastic giant cells were also present. Nuclei of OGCs were monomorphic with oval morphology and were smaller than those of melanoma cells. The immunophenotype of OGCs (S100-, HMB45-, Melan-A-, SOX10-, Ki67-, CD163-, BRAF-, CD68+, MiTF+, p16+) was the expected for reactive OGCs of monocyte/macrophage origin. The tumor has shown an aggressive behavior with further metastases to the axillary lymph nodes and oral cavity. Numerous OGCs are a rare and relevant finding in malignant melanoma. Their presence should not induce confusion with other tumors rich in osteoclastic cells. Since a relevant number of OGCs in melanoma may mean a more aggressive behavior, and patients may benefit from specific treatments, their presence should be mentioned in the pathologic report. © 2018 S. Karger AG, Basel.

Rare nodular malignant melanoma of the heel in the Caribbean: A case report.

PubMed

Warner, Wayne A; Sookdeo, Vandana Devika; Umakanthan, Srikanth; Sarran, Kevin; Pran, Lemuel; Fortuné, Maurice; Greaves, Wesley; Narinesingh, Sharda; Harnanan, Dave; Maharaj, Ravi

2017-01-01

Malignant melanoma of the heel is a rare melanoma subtype with incidence rates that reflect the complex relationship between sun exposure at certain geographic locations, individual melanin levels and overall melanoma risk. It is oftentimes characterized by poor prognosis because of delays in presentation resulting in longitudinal tumor invasion, lymph node involvement and metastasis. A 59-year-old woman was admitted to the Eric Williams Medical Sciences Complex, Trinidad and Tobago with a 5mm pruritic lesion on her left heel. At presentation, the lesion was asymmetric with border irregularities, color heterogeneity, with dynamics in elevation and overall size. She was subsequently diagnosed with malignant melanoma with left inguinal lymphadenopathy. A single stage wide local excision (WLE) of the left heel lesion with a split-thickness skin graft (STSG) and a left inguinal lymphadenectomy were performed. Dacarbazine (Bayer) was administered post operatively. Globally, the incidence of malignant melanoma is rapidly increasing, particularly, in countries like Trinidad and Tobago with a significant population of non-fair skinned individuals. There is need for strategic initiatives to increase patient adherence in these populations. The rarity of malignant heel melanomas heightens the need for increased patient awareness and greater clinical surveillance to ensure early diagnosis and treatment. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Tanning bed exposure increases the risk of malignant melanoma.

PubMed

Ting, William; Schultz, Kara; Cac, Natalie N; Peterson, Michael; Walling, Hobart W

2007-12-01

Epidemiologic studies have associated tanning bed exposure and cutaneous melanoma. The relationship between the extent of tanning bed exposure and the risk of melanoma has not been elucidated in detail. Surveys assessing the extent of tanning bed exposure and the history of skin cancer, including malignant melanoma, were collected from academic dermatology clinic patients (n = 1518). Of these, 551 (36.3%) completed all components of the survey. The available medical records, including pathology reports (n = 501; 33%), were reviewed to confirm cases of skin cancer. Data on potential confounding factors, including indoor vs. outdoor occupation and leisure activities, Fitzpatrick skin type, history of blistering sunburn, use of sunscreen and sun protective clothing, history of phototherapy, and level of education, were assessed and compared. Of the patients surveyed, 487 (32.1%) reported tanning bed exposure. Women aged 45 years or younger accounted for about 60% of all tanning bed users. Seventy-nine cases of malignant melanoma were reported, 22 in women aged 45 years or younger. In the entire cohort, the "ever-use" of tanning beds was found to be a significant risk factor for the development of melanoma [P < 0.05; odds ratio (OR), 1.64; 95% confidence interval (95% CI), 1.01-2.67]. The risk was greater in women aged 45 years or younger (P < 0.05; OR, 3.22; 95% CI, 1.01-11.46). Patients with a history of melanoma were significantly more likely to report tanning bed sessions exceeding 20 min (P < 0.01; OR, 3.18; 95% CI, 1.48-6.82); this association was even stronger for women aged 45 years or younger (OR, 4.12; 95% CI, 1.41-12.02). The study was subject to recall bias, included only patients at a midwestern academic practice, and had a relatively low response rate. Exposure to tanning beds increases the risk of malignant melanoma, especially in women aged 45 years or younger. These findings reinforce the hazards of tanning bed exposure.

Correlation of histological and ex-vivo confocal tumor thickness in malignant melanoma.

PubMed

Hartmann, Daniela; Krammer, Sebastian; Ruini, Cristel; Ruzicka, Thomas; von Braunmühl, Tanja

2016-07-01

The ex-vivo confocal laser scanning microscopy (ex-vivo CLSM) is a novel diagnostic method for fresh tissue examination, which has already shown promising results in the evaluation of healthy skin and different skin tumors. In malignant melanoma, the histological tumor thickness plays an essential role for further treatment strategies. The immediate perioperative measurement of tumor thickness by means of ex-vivo CLSM might accelerate the decision for further operating procedures in malignant melanoma. Ten histologically confirmed malignant melanomas from various donor sites were blindly examined by two investigators via ex-vivo CLSM and conventional light microscopy. The histopathological tumor thickness (HTT) and confocal tumor thickness (CTT) were measured independently and evaluated using correlation curves, Spearman's correlation coefficient, and Bland-Altman plots. Bland-Altman plots for HTT and reflectance-mode CTT, as well as for fluorescence-mode CTT, showed high correlations. Spearman's correlation coefficient of HTT and CTT was 1.00 in FM and RM. The mean difference of RM-CTT and FM-CTT versus HTT was 0.09 ± 0.30 mm and 0.19 ± 0.35 mm. In one case, the HTT was identical to the CTT in both modes. This pilot study shows high conformity of CTT and HTT measured in malignant melanoma underlining the potential of ex-vivo CLSM for perioperative decisions on safety margin excisions of malignant melanoma in the future.

Citrus Consumption and Risk of Cutaneous Malignant Melanoma

PubMed Central

Wu, Shaowei; Han, Jiali; Feskanich, Diane; Cho, Eunyoung; Stampfer, Meir J.; Willett, Walter C.; Qureshi, Abrar A.

2015-01-01

Purpose Citrus products are widely consumed foods that are rich in psoralens and furocoumarins, a group of naturally occurring chemicals with potential photocarcinogenic properties. We prospectively evaluated the risk of cutaneous malignant melanoma associated with citrus consumption. Methods A total of 63,810 women in the Nurses' Health Study (1984 to 2010) and 41,622 men in the Health Professionals Follow-Up Study (1986 to 2010) were included. Dietary information was repeatedly assessed every 2 to 4 years during follow-up. Incident melanoma cases were identified through self-report and confirmed by pathologic records. Results Over 24 to 26 years of follow-up, we documented 1,840 incident melanomas. After adjustment for other risk factors, the pooled multivariable hazard ratios for melanoma were 1.00 for overall citrus consumption < twice per week (reference), 1.10 (95% CI, 0.94 to 1.30) for two to four times per week, 1.26 (95% CI, 1.08 to 1.47) for five to six times per week, 1.27 (95% CI, 1.09 to 1.49) for once to 1.5 times per day, and 1.36 (95% CI, 1.14 to 1.63) for ≥ 1.6 times per day (Ptrend < .001). Among individual citrus products, grapefruit showed the most apparent association with risk of melanoma, which was independent of other lifestyle and dietary factors. The pooled multivariable hazard ratio for melanoma comparing the extreme consumption categories of grapefruit (≥ three times per week v never) was 1.41 (95% CI, 1.10 to 1.82; Ptrend < .001). Conclusion Citrus consumption was associated with an increased risk of malignant melanoma in two cohorts of women and men. Nevertheless, further investigation is needed to confirm our findings and explore related health implications. PMID:26124488

Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?

PubMed

Kodiatte, Thomas Alex; George, Sam Varghese; Chacko, Raju Titus; Ramakrishna, Banumathi

2017-01-01

Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.

Preparation of nano-hydroxyapatite particles with different morphology and their response to highly malignant melanoma cells in vitro

NASA Astrophysics Data System (ADS)

Li, Bo; Guo, Bo; Fan, Hongsong; Zhang, Xingdong

2008-11-01

To investigate the effects of nano-hydroxyapatite (HA) particles with different morphology on highly malignant melanoma cells, three kinds of HA particles with different morphology were synthesized and co-cultured with highly malignant melanoma cells using phosphate-buffered saline (PBS) as control. A precipitation method with or without citric acid addition as surfactant was used to produce rod-like hydroxyapatite (HA) particles with nano- and micron size, respectively, and a novel oil-in-water emulsion method was employed to prepare ellipse-like nano-HA particles. Particle morphology and size distribution of the as prepared HA powders were characterized by transmission electron microscope (TEM) and dynamic light scattering technique. The nano- and micron HA particles with different morphology were co-cultured with highly malignant melanoma cells. Immunofluorescence analysis and MTT assay were employed to evaluate morphological change of nucleolus and proliferation of tumour cells, respectively. To compare the effects of HA particles on cell response, the PBS without HA particles was used as control. The experiment results indicated that particle nanoscale effect rather than particle morphology of HA was more effective for the inhibition on highly malignant melanoma cells proliferation.

p54nrb is a new regulator of progression of malignant melanoma.

PubMed

Schiffner, Susanne; Zimara, Nicole; Schmid, Rainer; Bosserhoff, Anja-Katrin

2011-08-01

Nuclear RNA-binding protein p54(nrb) 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 p54(nrb). Here, we show that p54(nrb) 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 p54(nrb) promoter activity. Treatment with MIA-specific small interfering RNAs showed an influence of MIA on p54(nrb) expression on both messenger RNA (mRNA) and protein level. Knockdown of p54(nrb) protein in melanoma cell lines led to reduced proliferation rates and to a strong decrease in their migratory potential. In addition, attachment to laminin and poly-l-lysine was significantly increased. We could identify Connexin-43 (Cx-43) as a downstream target molecule of p54(nrb) as knockdown of p54(nrb) resulted in enhanced Cx-43 mRNA and protein levels. As a confirmation of these findings, melanoma cell lines showed very low Cx-43 expression levels compared with melanocytes. Our results demonstrate that p54(nrb) is highly expressed in malignant melanoma and, as a MIA target molecule, it seems to be involved in the development and progression of malignant melanoma.

Malignant melanoma brain metastases. Review of Roswell Park Memorial Institute experience.

PubMed

Madajewicz, S; Karakousis, C; West, C R; Caracandas, J; Avellanosa, A M

1984-06-01

One-hundred twenty five of 700 patients with malignant melanoma treated at Roswell Park Memorial Institute from 1972 to 1978 were found to have brain metastases. Seventy-three percent of the patients had multiple brain metastases. Male to female ratio was 1.9:1. The median survival of the untreated group of patients was 3 weeks as compared with that of 6 weeks for the patients maintained on steroids only, 9 weeks for those who received radiotherapy, 11 weeks for the patients treated with intraarterial chemotherapy, and 26 weeks for the patients who underwent successful surgical excision of a solitary lesion.

CHEK2*1100delC and risk of malignant melanoma: Danish and German studies and meta-analysis.

PubMed

Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E; Eigentler, Thomas; Garbe, Claus; Röcken, Martin; Hölmich, Lisbet Rosenkrantz; Schmidt, Henrik; Klyver, Helle; Bastholt, Lars; Nordestgaard, Børge G

2012-02-01

It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers were 2.01 (95% confidence interval (CI), 1.03-3.91) in Danes, 1.42 (95% CI, 0.46-4.31) in Germans, and 1.79 (95% CI, 1.02-3.17) in Danes and Germans combined. In a meta-analysis, the odds ratio of malignant melanoma for CHEK2*1100delC heterozygotes compared with that for noncarriers was 1.81 (95% CI, 1.07-3.05). Stratifications did not alter these results. CHEK2*1100delC heterozygotes have a twofold risk of malignant melanoma compared with noncarriers.

Malignant melanoma (non-metastatic): sentinel lymph node biopsy

PubMed Central

2016-01-01

Introduction The incidence of malignant melanoma has increased over the past 25 years in the UK, but death rates have remained fairly constant. The 5-year survival rate ranges from 20% to 95%, depending on disease stage. Risks are greater in white populations and in people with higher numbers of skin naevi. Methods and outcomes We conducted a systematic overview, aiming to answer the following clinical question: What is the evidence for performing a sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview). Results At this update, searching of electronic databases retrieved 221 studies. After deduplication and removal of conference abstracts, 99 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 58 studies and the further review of 41 full publications. Of the 41 full articles evaluated, one systematic review and three RCTs were added at this update. We performed a GRADE evaluation for two PICO combinations. Conclusions In this systematic overview, we evaluated the evidence for performing sentinel lymph node biopsy in people with malignant melanoma with clinically uninvolved lymph nodes. PMID:26788739

Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

PubMed

Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

2017-02-01

Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

[Primary malignant melanoma of the central nervous system: A diagnostic challenge].

PubMed

Quillo-Olvera, Javier; Uribe-Olalde, Juan Salvador; Alcántara-Gómez, Leopoldo Alberto; Rejón-Pérez, Jorge Dax; Palomera-Gómez, Héctor Guillermo

2015-01-01

The rare incidence of primary malignant melanoma of the central nervous system and its ability to mimic other melanocytic tumors on images makes it a diagnostic challenge for the neurosurgeon. A 51-year-old patient, with a tumor located in the right forniceal callosum area. Total surgical excision was performed. Histopathological result was consistent with the diagnosis of primary malignant melanoma of the central nervous system, after ruling out extra cranial and extra spinal melanocytic lesions. The primary malignant melanoma of the central nervous system is extremely rare. There are features in magnetic resonance imaging that increase the diagnostic suspicion; nevertheless there are other tumors with more prevalence that share some of these features through image. Since there is not an established therapeutic standard its prognosis is discouraging. Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Microsatellite instability as a predictive factor for immunotherapy in malignant melanoma.

PubMed

Kubecek, Ondrej; Trojanova, Petronela; Molnarova, Veronika; Kopecky, Jindrich

2016-08-01

Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma.

PubMed

Barut, Figen; Udul, Perihan; Kokturk, Furuzan; Kandemir, Nilufer Onak; Keser, Sevinc Hallac; Ozdamar, Sukru Oguz

2016-10-01

The evidence that PITX1 (pituitary homeobox 1) is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100%) normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80%) and was absent in 14 (20%) of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20%) PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma. Copyright © 2016. Published by Elsevier Taiwan.

Apoptosis and injuries of heavy ion beam and x-ray radiation on malignant melanoma cell.

PubMed

Qin, Jin; Li, Sha; Zhang, Chao; Gao, Dong-Wei; Li, Qiang; Zhang, Hong; Jin, Xiao-Dong; Liu, Yang

2017-05-01

This study aims to investigate the influence of high linear energy transfer (LET) heavy ion ( 12 C 6+ ) and low LET X-ray radiation on apoptosis and related proteins of malignant melanoma on tumor-bearing mice under the same physical dosage. C57BL/6 J mice were burdened by tumors and randomized into three groups. These mice received heavy ion ( 12 C 6+ ) and X-ray radiation under the same physical dosage, respectively; their weight and tumor volumes were measured every three days post-radiation. After 30 days, these mice were sacrificed. Then, median survival time was calculated and tumors on mice were proliferated. In addition, immunohistochemistry was carried out for apoptosis-related proteins to reflect the expression level. After tumor-bearing mice were radiated to heavy ion, median survival time improved and tumor volume significantly decreased in conjunction with the upregulated expression of pro-apoptosis factors, Bax and cytochrome C, and the downregulated expression of apoptosis-profilin (Bcl-2, Survivin) and proliferation-related proteins (proliferating cell nuclear antigen). The results indicated that radiation can promote the apoptosis of malignant melanoma cells and inhibit their proliferation. This case was more suitable for heavy ion ( 12 C 6+ ). High LET heavy ion ( 12 C 6+ ) radiation could significantly improve the killing ability for malignant melanoma cells by inducing apoptosis in tumor cells and inhibiting their proliferation. These results demonstrated that heavy ion ( 12 C 6+ ) presented special advantages in terms of treating malignant melanoma. Impact statement Malignant melanoma is a malignant skin tumor derived from melanin cells, which has a high malignant degree and high fatality rate. In this study, proliferating cell nuclear antigen (PCNA) can induce the apoptosis of malignant melanoma cells and inhibit its proliferation, and its induction effect on apoptosis is significantly higher than low LET X-ray; hence, it is expected to

Targeting Histone Deacetylases in Malignant Melanoma: A Future Therapeutic Agent or Just Great Expectations?

PubMed

Garmpis, Nikolaos; Damaskos, Christos; Garmpi, Anna; Dimitroulis, Dimitrios; Spartalis, Eleftherios; Margonis, Georgios-Antonios; Schizas, Dimitrios; Deskou, Irini; Doula, Chrysoula; Magkouti, Eleni; Andreatos, Nikolaos; Antoniou, Efstathios A; Nonni, Afroditi; Kontzoglou, Konstantinos; Mantas, Dimitrios

2017-10-01

Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. HDACI represent a promising agent for targeted therapy. More trials are required. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

[A case of pulmonary malignant melanoma mimicking lung abscess].

PubMed

Mochizuki, Hideaki; Chikui, Emiko; Tokumaru, Aya; Kato, Takayuki; Arai, Tomio; Takahashi, Hideki

2011-06-01

An 84-year-old man was admitted with paresis of the right lower limb. Hemorrhagic lesions were demonstrated in the left frontoparietal lobe and cerebellum by cranial computed tomography (CT) and magnetic resonance imaging (MRI). Chest CT revealed an ill-defined mass measuring 4 x 6 cm in the left lower lobe of the lung, although bronchoscopic examination failed to obtain pathological diagnosis. Clinical diagnosis of primary lung cancer with multiple brain metastases was made, and he underwent whole brain radiotherapy. The pulmonary and cerebral lesions mimicked abscesses during his clinical course, and he died of respiratory failure due to bilateral pneumonia three months after admission. Autopsy revealed that both the pulmonary and brain lesions were malignant melanomas, but no other melanoma lesions could be identified despite meticulous investigation. Although malignant melanoma with an unknown primary site is rare in Japan, careful evaluation of the CT and MRI findings might be the key to correct diagnosis in this case.

Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas

PubMed Central

Chen, Kevin G.; Valencia, Julio C.; Lai, Barry; Zhang, Guofeng; Paterson, Jill K.; Rouzaud, François; Berens, Werner; Wincovitch, Stephen M.; Garfield, Susan H.; Leapman, Richard D.; Hearing, Vincent J.; Gottesman, Michael M.

2006-01-01

Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an ≈8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. PMID:16777967

Melanosomal sequestration of cytotoxic drugs contributes to the intractability of malignant melanomas

NASA Astrophysics Data System (ADS)

Chen, Kevin G.; Valencia, Julio C.; Lai, Barry; Zhang, Guofeng; Paterson, Jill K.; Rouzaud, François; Berens, Werner; Wincovitch, Stephen M.; Garfield, Susan H.; Leapman, Richard D.; Hearing, Vincent J.; Gottesman, Michael M.

2006-06-01

Multidrug resistance mechanisms underlying the intractability of malignant melanomas remain largely unknown. In this study, we demonstrate that the development of multidrug resistance in melanomas involves subcellular sequestration of intracellular cytotoxic drugs such as cis-diaminedichloroplatinum II (cisplatin; CDDP). CDDP is initially sequestered in subcellular organelles such as melanosomes, which significantly reduces its nuclear localization when compared with nonmelanoma/KB-3-1 epidermoid carcinoma cells. The melanosomal accumulation of CDDP remarkably modulates melanogenesis through a pronounced increase in tyrosinase activity. The altered melanogenesis manifested an 8-fold increase in both intracellular pigmentation and extracellular transport of melanosomes containing CDDP. Thus, our experiments provide evidence that melanosomes contribute to the refractory properties of melanoma cells by sequestering cytotoxic drugs and increasing melanosome-mediated drug export. Preventing melanosomal sequestration of cytotoxic drugs by inhibiting the functions of melanosomes may have great potential as an approach to improving the chemosensitivity of melanoma cells. cancer | melanosomes | skin | tumor therapy | multidrug resistance

PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1.

PubMed

Fang, Xian-Ying; Song, Ran; Chen, Wei; Yang, Yuan-Yuan; Gu, Yan-Hong; Shu, Yong-Qian; Wu, Xu-Dong; Wu, Xue-Feng; Sun, Yang; Shen, Yan; Xu, Qiang

2015-09-01

Phosphatase of regenerating liver-3 (PRL-3) has been reported to have a critical role in metastatic progression of cancers. Here, we investigate how PRL-3 increases the malignant degree of melanoma cells. The expression of PRL-3 increased gradually during the malignant progression of melanoma. The phosphorylation of Akt was elevated in highly malignant melanoma cells, which was accompanied by a decrease in nuclear phosphatase and tensin homolog (PTEN). The phosphorylation of NHERF1 in the serine site was regulated by PRL-3 and showed cytoplasmic translocation upon dephosphorylation, which resulted in a decrease in nuclear PTEN. The co-translocation of NHERF1 and PTEN from the nucleus to the cytoplasm was observed during the malignant progression of melanoma cells. Tumor growth was inhibited significantly, and the survival was prolonged upon knockdown of cytoplasmic NHERF1 in B16BL6 cells prior to the inoculation into mice. Taken together, to our knowledge previously unreported, we have identified NHERF1 as a potential substrate of PRL-3. Its phosphorylation status as well as its change in cellular localization and association with PTEN correlated with the malignant progression of melanoma. Our data provide an explanation for how PRL-3 promotes the malignant progression of melanoma, as well as a diagnostic marker or therapeutic target for malignant melanoma.

High ALDH1 expression correlates with better prognosis in tumorigenic malignant melanoma.

PubMed

Taylor, Laura A; Abraham, Ronnie M; Tahirovic, Emin; van Belle, Patricia; Li, Bin; Huang, Linfang; Elder, David E; Gimotty, Phyllis; Xu, Xiaowei

2017-05-01

Aldehyde dehydrogenase 1 (ALDH1) has been proposed as biomarker of stem cells for certain human cancers. ALDH1 expression has been correlated with poor patient outcomes in a variety of malignancies but better patient outcomes in others, and its prognostic significance in malignant melanoma is unclear. Thus, 68 melanoma patients with comprehensive clinical and pathologic follow-up data were used to construct a tissue microarray. A modified histological score (H-score) with a maximum score of 300 was used to quantify immunohistochemical staining for ALDH1. Survival time was defined as the time between diagnosis and melanoma-specific death. Using univariate logistic regression, a low (<80 H-score) ALDH1 score showed 3.7-fold increase in risk for melanoma-specific death within 10 years when compared with high (>80) ALDH1 levels (P=0.017). Odds of MSD were lower by a factor of ~0.9 for each 10-point increase in H-Score. Median survival time was 44.1 months and 180.9 months for patients with low and high ALDH1 expression, respectively. Using multivariate analysis, ALDH1 H-score was found to be an independent prognostic factor. These findings suggest that ALDH1 expression in malignant melanoma has a favorable effect on patient survival. Further study is needed elucidate the function of this enzymatic protein in melanoma progression.

Clinical management of a patient with advanced mucosal malignant melanoma in the sinonasal area.

PubMed

Fusetti, Marco; Eibenstein, Alberto; Lupi, Ettore; Iacomino, Enzo; Pieramici, Tiziana; Fioretti, Alessandra

2014-01-01

We describe a case of mucosal malignant melanoma in the sinonasal area of a 65-year-old woman. She presented with a history of nasal obstruction and epistaxis with subsequent tenderness, facial anesthesia involving cranial nerve V2, red eye, proptosis, diplopia, and conjunctival chemosis. Computed tomography detected a nonspecific solid mass that had involved the left maxillary sinus and surrounding tissues, with extension into the nasal cavity and invasion of the orbital floor and eye muscles. Histopathologic examination of the neoplasm revealed that it was a malignant melanoma. We performed a radical hemimaxillectomy that extended to the orbit, which allowed for radical excision of the tumor. Postoperatively, the patient received adjuvant chemotherapy and radiotherapy. Mucosal melanoma in the head and neck is a rare and highly malignant neoplasm. We suggest that malignant melanoma be suspected when a small-round-cell tumor is found on light microscopy, and we confirm the usefulness of immunohistochemical investigations.

Epidemiological and clinical characteristics of malignant melanoma in Southeast Anatolia in Turkey.

PubMed

Sula, Bilal; Uçmak, Feyzullah; Kaplan, Mehmet Ali; Urakçi, Zuhat; Arica, Mustafa; Isikdogan, Abdurrahman

2016-01-01

The present study aimed to establish the epidemiological and clinical characteristics of patients who were histopathologically diagnosed with malignant melanoma (MM). The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM in Dicle University Medical Faculty, Dermatology and Medical Oncology departments between 2005 and 2014. The study included 78 patients in total with 44 (56.4%) male and 34 (43.6%) female. Median age of the patients was 62.50 years (range: 27 - 84 years). Of the patients, 78.2% (n = 61) had cutaneous melanoma, 8.9% had solid organ melanoma, and 2.5% had ocular and mucosal melanoma. The most common tumor localization among the patients was the lower extremities with 29.4% (n = 23). The most common histopathological type was nodular malignant melanoma with 35.8% (n = 28). Based on TNM, Clark and Breslow classifications, 26.9% (n = 21) of the patients were stage 4, 26.9% (n = 21) were Clark stage 4, and 37.1% (n = 29) were Breslow stage 4. Median overall survival in all patients was 14.9 months (95% CI 10.9 - 18.8 months). In the multivariate Cox analysis, only stage statistically significantly affecting survival [odds ratio (OR): 0.54; (95% CI 0.16-1.82, p = 0.02)]. Malignant melanoma data are also important for the optimal utilization of effective methods and healthcare resources to prevent the disease. In order to minimize MM mortality and morbidity, not only the society but also physicians from primary and secondary care hospitals should become familiar with melanoma.

The proliferation of malignant melanoma cells could be inhibited by ranibizumab via antagonizing VEGF through VEGFR1.

PubMed

Li, Jiao; Cui, Yan; Wang, Qin; Guo, Dadong; Pan, Xuemei; Wang, Xingrong; Bi, Hongsheng; Chen, Wei; Liu, Zhengfeng; Zhao, Shengya

2014-01-01

Angiogenesis is an important mediator in tumor progression. Vascular endothelial growth factor (VEGF) is one of the major cytokines that can influence angiogenesis. However, the potential mechanism of tumor growth inhibition through anti-VEGF agents is still unclear. This study was performed to examine whether ranibizumab could inhibit malignant melanoma growth in vitro and to determine the safety of ranibizumab on human adult retinal pigment epithelium cell line (ARPE-19 cells). Malignant melanoma cells obtained from a clinic were cultured in vitro. VEGF concentrations secreted by malignant melanoma cells and the ARPE-19 cells were examined by enzyme-linked immunosorbent assay (ELISA). The two kinds of cells were both treated with VEGF and its antagonist, ranibizumab. The dynamic changes of the two types of cells were monitored by real-time cell electronic sensing (RT-CES) assay. The effect of ranibizumab on both types of cells was verified by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of VEGF receptor 1 (VEGFR1) RNA in uveal melanoma was further investigated through the PCR technique. The levels of VEGF secreted by malignant melanoma cells were much higher than those of ARPE-19 cells, and were markedly decreased in the action of 0.1 mg/ml ranibizumab. However, there was no obvious reduction of VEGF in the presence of ranibizumab for ARPE-19 (p>0.05). Meanwhile, RT-CES showed that the viability of malignant melanoma cells increased greatly in the presence of VEGF. When VEGF was 20 ng/ml, viability of the malignant melanoma cells increased by 40% compared with the negative control. There was no evident effect on proliferation of ARPE-19 (p>0.05). Furthermore, the growth of malignant melanoma cells was obviously inhibited after ranibizumab intervention. When ranibizumab was administered at 0.25 mg/ml, the survival rate of the malignant melanoma cells decreased to 57.5%. Nevertheless, low-dose exposure to ranibizumab had only a slight

Clinicopathological findings of primary esophageal malignant melanoma: report of six cases and review of literature.

PubMed

Zheng, Jinfeng; Mo, Haiying; Ma, Shufang; Wang, Zhenzheng

2014-01-01

We studied images and histopathological features of primary esophageal malignant melanoma to explore the clinical pathological features, diagnosis, differential diagnoses, and treatment. Immunolabelling was conducted on six cases of esophageal malignant melanoma using histological and immunohistochemical techniques. Combined with the related literature, the clinical manifestations, imaging, histopathological and immunohistochemical features, treatment, and prognosis of primary esophageal malignant melanoma were observed and analyzed. The six patients with primary esophageal malignant melanoma were all male with an average age of 63.4 years. Poor food intake was observed in all patients, and the symptoms showed progressive aggravation. Endoscopic feed tube revealed dark brown and black nodular and polypoid lesions, 1/4-1/2 loop cavity. Tumor histopathology revealed the following characteristics: tumor cells arranged in nests, sheets and cords, round or polygonal, abundant and red-stained cytoplasm, melanin granules in the cytoplasm, heterogeneous nucleus sizes, centered or deviated nuclei, clearly identifiable nucleoli, and apparent pathological mitosis. The immune phenotype was as follows: tumor cells had diffuse expression of HMB45, Melan A, and S100. The cells were CK negative, and the Ki67-positive cell number was 40%-45%. Primary esophageal malignant melanoma is rare with high malignancy and poor prognosis. Immunohistochemical staining is helpful for diagnosing this tumor. The differential diagnosis includes low differentiated carcinoma, primitive neuroectodermal tumor, esophageal sarcomatoid carcinoma, esophageal lymphoma, and other tumors.

Primary malignant melanoma of the female urethra: Report of a rare neoplasm of the urinary tract.

PubMed

Bhutani, Namita; Kajal, Pradeep; Pawar, Devendra

2017-01-01

Melanoma is a malignant tumor that can affect any area of the anatomical economy. Its occurance in the female urethra is extremely rare. We report a case of primary malignant urethral melanoma developed in an elderly female patient. A 70 years old female presented with dysuria, poor stream, gross haematuria, intermittent blood spots, and a painful mass. On physical examination, there were no suspicious lesions on the skin. On external genital examination, a lesion at the level of the urethral meatus was observed. The mass was removed by wide local excision under spinal anaesthesia. The pathological diagnosis was malignant melanoma of the urethra. The common presentations include bleeding and/or discharge per urethra, voiding dysfunction and the presence of tumor mass. Survival depends on the stage, location and size of the neoplasm at the time of diagnosis. Despite major surgery, radiotherapy or immunotherapy; malignant melanoma usually has a poor prognosis. Melanoma of the female urethra is an extremely uncommon pathology leading to paucity of literature and any definite recommendations regarding management. The histological and immunohistochemical findings can be helpful in making an early and accurate diagnosis of malignant melanoma in the urogenital region. Copyright © 2017. Published by Elsevier Ltd.

Tumor initiation in human malignant melanoma and potential cancer therapies.

PubMed

Ma, Jie; Frank, Markus H

2010-02-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment.

Tumor Initiation in Human Malignant Melanoma and Potential Cancer Therapies

PubMed Central

Ma, Jie; Frank, Markus H.

2010-01-01

Cancer stem cells (CSCs), also known as tumor-initiating cells, have been identified in several human malignancies, including human malignant melanoma. The frequency of malignant melanoma-initiating cells (MMICs), which are identified by their expression of ATP-binding cassette (ABC) family member ABCB5, correlates with disease progression in human patients. Furthermore, targeted MMIC ablation through ABCB5 inhibits tumor initiation and growth in preclinical xenotransplantation models, pointing to potential therapeutic promise of the CSC concept. Recent advances also show that CSCs can exert pro-angiogenic roles in tumor growth and serve immunomodulatory functions related to the evasion of host anti-tumor immunity. Thus, MMICs might initiate and sustain tumorigenic growth not only as a result of CSC-intrinsic self-renewal, differentiation and proliferative capacity, but also based on pro-tumorigenic interactions with the host environment. PMID:20184545

Coffee consumption and the risk of malignant melanoma in the Norwegian Women and Cancer (NOWAC) Study.

PubMed

Lukic, Marko; Jareid, Mie; Weiderpass, Elisabete; Braaten, Tonje

2016-07-29

Coffee contains biologically-active substances that suppress carcinogenesis in vivo, and coffee consumption has been associated with a lower risk of malignant melanoma. We studied the impact of total coffee consumption and of different brewing methods on the incidence of malignant melanoma in a prospective cohort of Norwegian women. We had baseline information on total coffee consumption and consumption of filtered, instant, and boiled coffee from self-administered questionnaires for 104,080 women in the Norwegian Women and Cancer (NOWAC) Study. We also had follow-up information collected 6-8 years after baseline. Multiple imputation was used to deal with missing data, and multivariable Cox regression models were used to calculate hazard ratios (HR) for malignant melanoma by consumption category of total, filtered, instant, and boiled coffee. During 1.7 million person-years of follow-up, 762 cases of malignant melanoma were diagnosed. Compared to light consumers of filtered coffee (≤1 cup/day), we found a statistically significant inverse association with low-moderate consumption (>1-3 cups/day, HR = 0.80; 95 % confidence interval [CI] 0.66-0.98) and high-moderate consumption of filtered coffee (>3-5 cups/day, HR = 0.77; 95 % CI 0.61-0.97) and melanoma risk (p trend = 0.02). We did not find a statistically significant association between total, instant, or boiled coffee consumption and the risk of malignant melanoma in any of the consumption categories. The data from the NOWAC Study indicate that a moderate intake of filtered coffee could reduce the risk of malignant melanoma.

Malignant melanoma risk after exposure to fertility drugs: results from a large Danish cohort study.

PubMed

Hannibal, Charlotte Gerd; Jensen, Allan; Sharif, Heidi; Kjaer, Susanne Krüger

2008-09-01

The aim was to examine the effects of fertility drugs on malignant melanoma risk using data from the largest cohort of infertile women to date. A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established. A detailed data collection including information about type and amount of treatment was conducted. Using case-cohort techniques, we calculated rate ratios (RRs) of malignant melanoma associated with different fertility drugs after adjustment for parity status. 112 malignant melanomas were identified during follow-up through 2000. Use of clomiphene, gonadotrophins, hCG or GnRH did not affect risk of malignant melanoma significantly. When stratifying for parity, however, use of gonadotrophins (RR = 2.29; CI: 1.16-4.52) or GnRH (RR = 3.26; 95% CI: 1.50-7.09) among parous women was associated with a significant increased risk. For all groups of fertility drugs, we found no association with number of cycles of use or years since first use (latency). Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use of gonadotrophins or GnRH might increase risk in parous women. Longer follow-up is needed to confirm our findings.

Malignant uveal melanoma and similar lesions studied by computed tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mafee, M.F.; Peyman, G.A.; McKusick, M.A.

1985-08-01

Forty-four patients with intraocular disease were studied by computed tomography (CT); in 19 cases malignant uveal melanoma was considered the likely diagnosis. CT proved to be accurate in determining the location and size of uveal melanomas, demonstrating scleral invasion, and differentiating melanoma from choroidal detachment or angioma, toxocariasis, and senile macular degeneration. On CT, uveal melanomas appeared as hyperdense lesions with slight to moderate contrast enhancement. Tumors thinner than 2 mm could not be seen. Using dynamic CT, the authors noted moderate peak amplitude, normal or delayed tissue transit time, and persistently elevated washout phase (downslope), indicating increased permeability asmore » the result of an impaired tumor blood barrier. Histological types of uveal melanoma could not be differentiated on the basis of circulatory patterns. Dynamic CT may be useful in distinguishing uveal melanoma from choroidal hemangioma or hematoma.« less

Another duel in the sun: weighing the balances between sun protection, tanning beds, and malignant melanoma.

PubMed

Roberts, Daniel J; Hornung, Carlton A; Polk, Hiram C

2009-07-01

The purpose of this report is to put the dueling factors of risk and prevention for melanoma in perspective for the thoughtful pediatric specialist to facilitate preteen preventive health counseling. We examined the rate of malignant melanoma among Kentucky residents and compared this rate with indicators of tanning bed prevalence in a large metropolitan area and sunscreen sales from a major distributor. We obtained malignant melanoma annual incidence data from the Kentucky Cancer Registry, which recorded Kentucky population incidence rates over the years 1995 to 2004. The rates reflected 2 malignant melanoma classifications: pre-invasive cancer only, or both invasive and noninvasive cancers combined. The age-adjusted incidence rate per hundred thousand for combined invasive and pre-invasive malignant melanoma swelled from 21.9 in 1995 to 31.3 in 2004. The respective invasive-only malignant melanoma incidence rates increased less dramatically, from 17.3 to 20.7, during this same 10-year time period. Since 1983, the number of separate tanning bed businesses increased from 1 in 1983 to 119 by the mid-1990s, and then declined to about 74 separate businesses by 2003. Sunscreen sales data is uneven between states and is currently inconclusive. Although current data cannot draw a precise link between melanoma and the use of tanning beds, the associated risk is implicit, as the ultraviolet A (UVA) and ultraviolet B (UVB) radiation in tanning bed usage is a well-established melanoma risk factor. In advising patients, the pediatric specialist should consider that melanoma rates are poised as a balance of some known risk factors and a few potential preventive factors.

Proton irradiation of malignant melanoma of the ciliary body.

PubMed Central

Gragoudas, E S; Goitein, M; Koehler, A; Wagner, M S; Verhey, L; Tepper, J; Suit, H D; Schneider, R J; Johnson, K N

1979-01-01

This is our first case of malignant melanoma of the ciliary body treated with proton beam irradiation, a technique that we developed for irradiating choroidal melanomas. After 21 months of follow-up no growth of the tumour has been observed, and shrinkage of the tumour was noted on the follow-up photographs and by ultrasonography. The 32P uptake test, which was positive before treatment, turned negative 14 months after irradiation. The described technique of proton beam irradiation might offer an alternative for the treatment of ciliary body melanomas when the present techniques of iridocyclectomy cannot be applied because of the size of the lesion. Images PMID:106873

Bone marrow metastasis of malignant melanoma in childhood arising within a congenital melanocytic nevus.

PubMed

Volejnikova, Jana; Bajciova, Viera; Sulovska, Lucie; Geierova, Marie; Buriankova, Eva; Jarosova, Marie; Hajduch, Marian; Sterba, Jaroslav; Mihal, Vladimir

2016-09-01

Malignant melanoma in childhood is infrequent and can arise within congenital melanocytic nevi. Spread of malignant melanoma to the bone marrow, especially in children, is extremely rare. Reported is a case of a 5-year-old boy with a congenital large melanocytic nevus of the head and neck who presented with a short history of low back and leg pain, fever and cervical lymphadenopathy. Despite regular follow-up by a dermatologist and plastic surgeon and repeatedly negative histology of previous partial excisions, diffuse bone marrow infiltration with malignant melanoma was diagnosed. The primary site was identified in the post-excision area. The disease progressed rapidly on ipilimumab immunotherapy and led to death at four months from the diagnosis. Surveillance is indispensable in children with a predisposition to melanoma and nonspecific symptoms such as bone pain, gait impairment or cytopenia, should always be taken into account.

Autologous cytokine-induced killer cell immunotherapy may improve overall survival in advanced malignant melanoma patients.

PubMed

Zhang, Yong; Zhu, Yu'nan; Zhao, Erjiang; He, Xiaolei; Zhao, Lingdi; Wang, Zibing; Fu, Xiaomin; Qi, Yalong; Ma, Baozhen; Song, Yongping; Gao, Quanli

2017-11-01

Our study was conducted to explore the efficacy of autologous cytokine-induced killer (CIK) cells in patients with advanced malignant melanoma. Materials & Methods: Here we reviewed 113 stage IV malignant melanoma patients among which 68 patients received CIK cell immunotherapy alone, while 45 patients accepted CIK cell therapy combined with chemotherapy. Results: We found that the median survival time in CIK cell group was longer than the combined therapy group (21 vs 15 months, p = 0.07). In addition, serum hemoglobin level as well as monocyte proportion and lymphocyte count were associated with patients' survival time. These indicated that CIK cell immunotherapy might extend survival time in advanced malignant melanoma patients. Furthermore, serum hemoglobin level, monocyte proportion and lymphocyte count could be prognostic indicators for melanoma.

Decreased expression of class III β-tubulin is associated with unfavourable prognosis in patients with malignant melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu

2016-02-01

Class III β-tubulin (TUBB3) has been recognized as being associated with resistance to taxane-based regimens in several cancers. However, little is known about the clinicopathological significance of TUBB3 expression in patients with cutaneous malignant melanoma. The aim of this study was to examine the prognostic significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106 patients with surgically resected cutaneous malignant melanoma were assessed. Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of patients. No statistically significant relationship was observed between the high expression of TUBB3 and any variables. On univariate analysis, ulceration, disease stage, TUBB3 and CD34 revealed a significant relationship with overall survival and progression-free survival. Multivariate analysis confirmed that a low TUBB3 expression was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The decreased expression of TUBB3 could be a significant marker for predicting unfavourable prognosis in patients with cutaneous malignant melanoma.

A report of amelanotic malignant melanoma of the esophagus diagnosed appropriately with novel markers: A case report.

PubMed

Kobayashi, Junya; Fujimoto, Daisuke; Murakami, Makoto; Hirono, Yasuo; Goi, Takanori

2018-06-01

The present case study reported of amelanotic malignant melanoma of the esophagus. A 68-year-old man underwent laparoscopic distal gastrectomy for early gastric cancer diagnosis. After gastrectomy, endoscopic examination revealed a protruded lesion lying adjacent to the melanosis area of the esophagus. Histology of the biopsy specimen suggested malignancy, but the diagnosis could not be made. The patient underwent trans-thoraco-abdominal curative subtotal esophagectomy. Immunohistochemical examination of the resected specimen was negative for HBM-45 and Melan-A. However, immunohistochemical examinations of SOX10 (Sry-related HMg-Box gene 10) and KBA.62, which are not associated with melanosome, were strongly positive, and tyrosinase was notably positive. A diagnosis primary of amelanotic malignant melanoma of the esophagus that consisted of only premelanosomes was made. The present findings suggest that, in the diagnosis of malignant melanoma, SOX10 and KBA.62 may be useful, particularly in diagnosing amelanotic malignant melanoma.

Sensitization of recombinant human tumor necrosis factor-related apoptosis-inducing ligand-resistant malignant melanomas by quercetin.

PubMed

Turner, Katherine A; Manouchehri, Jasmine M; Kalafatis, Michael

2018-03-28

Malignant melanoma is the most commonly diagnosed skin cancer associated with a high rate of metastasis. Low-stage melanoma is easily treated, but metastatic malignant melanoma is an extremely treatment-resistant malignancy with low survival rates. The application of recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) for the treatment of metastatic malignant melanoma holds considerable promise because of its selective proapoptotic activity towards cancer cells and not nontransformed cells. Unfortunately, the clinical utilization of rhTRAIL has been terminated due to the resistance of many cancer cells to undergo apoptosis in response to rhTRAIL. However, rhTRAIL-resistance can be abrogated through the cotreatment with compounds derived from 'Mother Nature' such as quercetin that can modulate cellular components responsible for rhTRAIL-resistance. Here, we show that rhTRAIL-resistant malignant melanomas are sensitized by quercetin. Quercetin action is manifested by the upregulation of rhTRAIL-binding receptors DR4 and DR5 on the surface of cancer cells and by increased rate of the proteasome-mediated degradation of the antiapoptotic protein FLIP. Our data provide for a new efficient and nontoxic treatment of malignant melanoma.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0/.

Establishing a Southern Swedish Malignant Melanoma OMICS and biobank clinical capability

PubMed Central

2013-01-01

Background The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM) are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. The SSMM research team is a truly cross-functional group with members from oncology, surgery, bioinformatics, proteomics, and genomics initiatives. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. Methods Clinical materials from patients before, during and after treatments with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. Standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community are used. The patient biobank archives are fully automated with novel ultralow temperature biobank storage units and used as clinical resources. Results An IT-infrastructure using a laboratory information management system (LIMS) has been established, that is the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund forms the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are associated with the biobank materials, including pathology reports on disease diagnosis on the malignant melanoma (MM) patients. Conclusions We provide data on the developments of protein profiling and targeted protein assays on isolated

Establishing a Southern Swedish Malignant Melanoma OMICS and biobank clinical capability.

PubMed

Welinder, Charlotte; Jönsson, Göran; Ingvar, Christian; Lundgren, Lotta; Olsson, Håkan; Breslin, Thomas; Végvári, Akos; Laurell, Thomas; Rezeli, Melinda; Jansson, Bo; Baldetorp, Bo; Marko-Varga, György

2013-02-27

The objectives and goals of the Southern Swedish Malignant Melanoma (SSMM) are to develop, build and utilize cutting edge biobanks and OMICS platforms to better understand disease pathology and drug mechanisms. The SSMM research team is a truly cross-functional group with members from oncology, surgery, bioinformatics, proteomics, and genomics initiatives. Within the research team there are members who daily diagnose patients with suspect melanomas, do follow-ups on malignant melanoma patients and remove primary or metastatic lesions by surgery. This inter-disciplinary clinical patient care ensures a competence build as well as a best practice procedure where the patient benefits. Clinical materials from patients before, during and after treatments with clinical end points are being collected. Tissue samples as well as bio-fluid samples such as blood fractions, plasma, serum and whole blood will be archived in 384-high density sample tube formats. Standardized approaches for patient selections, patient sampling, sample-processing and analysis platforms with dedicated protein assays and genomics platforms that will hold value for the research community are used. The patient biobank archives are fully automated with novel ultralow temperature biobank storage units and used as clinical resources. An IT-infrastructure using a laboratory information management system (LIMS) has been established, that is the key interface for the research teams in order to share and explore data generated within the project. The cross-site data repository in Lund forms the basis for sample processing, together with biological samples in southern Sweden, including blood fractions and tumor tissues. Clinical registries are associated with the biobank materials, including pathology reports on disease diagnosis on the malignant melanoma (MM) patients. We provide data on the developments of protein profiling and targeted protein assays on isolated melanoma tumors, as well as reference blood

[Malignant Choroidal Melanoma in T4 Orbital Stage; Prosthesis of the Orbit].

PubMed

Furdová, A; Ferková, A; Krásnik, V; Krčová, I; Horkovičová, K

2015-06-01

Diagnosis and treatment of tumors of the eye is extremely difficul; surgical treatment in advanced stages, when the tumor grows in the orbit, leads to extensive radical surgery of the face. The extent and nature of surgical procedures depends on the nature of the tumor process, in advanced stages is indicated mutilating surgery--exenteration of the orbit. Exenteration of the orbit due to the extrascleral extension of malignant melanoma of the uvea is very rare, unfortunately, even today in certain cases it is necessary to make such a mutilating surgery. Case report--65 year old female patient, sent to our Departement in 2008 with the finding of the pigment deposits on the posterior pole of the left eye. Ultrasound study found elevations of up to 3 mm, she was asked to come for further control in three months interval. She did not coma, furthermore she sporadically attended another eye clinic. In 2011 she was treated for secondary glaucoma--cyclocryopexia. Due to pain another surgery--tarzoraphia was indicated. In 2012 she underwent surgery at St. Elisabeth Cancer Institute in Bratislava--Nefrectomia transperitoneally l. dx., excision hepatis. Histological examination in addition to the primary papillary renal carcinoma--mucinous tubular T1 Nx Mx type, found the metastasis of malignant melanoma to the liver and right kidney. She underwent the diagnostic procedure to find the origo of the melanoma. The patient was subsequently admitted to our clinic with blind painfull eye for enucleation. During the surgery the was found retrobulbar tumor ingrowth. Histopatholigical findings confirmed malignant melanoma. Indicated was exenteration of the orbit due to malignant melanoma T4 N0 M2 stage in June 2012. After healing of the cavity she was recommended to design an individual prosthesis. After completing several courses of palliative chemotherapy during a recent review in January 2015 the patient is without recurrence of the melanoma in the orbit Histological examination

Primary Sinonasal Malignant Melanoma: Effect of Clinical and Histopathologic Prognostic Factors on Survival.

PubMed

Göde, Sercan; Turhal, Göksel; Tarhan, Ceyda; Yaman, Banu; Kandiloğlu, Gülşen; Öztürk, Kerem; Kaya, İsa; Midilli, Raşit; Karcı, Bülent

2017-05-05

Mucosal melanoma is a rare malignancy arising from melanocytes of the mucosal surfaces. The pattern and frequency of oncogenic mutations and histopathological biomarkers have a role on distinct tumour behaviour and survival. To assess the rate of C-KIT positivity and its effect on survival of surgically treated sinonasal malignant melanoma patients with other histopathological biomarkers and clinical features. Retrospective cross-sectional study. Seventeen sinonasal malignant melanoma patients with a mean age of 65.41 (39-86) years were included. Overall survival and disease-specific survival rates were calculated. The impact of age, gender, stage and extent of the disease, type of surgery, and adjuvant therapies were also taken into consideration. The effect of mitotic index, pigmentation, S100, HMB-45, Melan-A and C-KIT on survival were evaluated. Median tumour size was 20 mm (interquartile range=27.5 mm). Pigmentation was present in 7 (41.2%) cases. Median number of mitoses per millimetre squared was 11 (interquartile range=13). Melan A was positive in 7 (41.2%) patients, ulceration was present in 6 cases (35.3%), and necrosis was present in (47.1%) 8 cases. Six patients (35.3%) were positive for S100, 14 (82.4%) specimens stained positive for HMB-45 and C-KIT (CD117) was positive in 9 cases (52.9%). Three patients (16.7%) developed distant metastasis. Five year overall and disease free survival rates were 61.4% and 43.8%, respectively. Although C-KIT positive sinonasal malignant melanoma patients (52.9%) can be candidates for targeted tumour therapies, the studied clinical or histopathological features along with C-KIT seem to have no significant effect on survival in a small group of patients with sinonasal malignant melanoma.

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011.

PubMed

Schoffer, Olaf; Schülein, Stefanie; Arand, Gerlinde; Arnholdt, Hans; Baaske, Dieter; Bargou, Ralf C; Becker, Nikolaus; Beckmann, Matthias W; Bodack, Yves; Böhme, Beatrix; Bozkurt, Tayfun; Breitsprecher, Regine; Buchali, Andre; Burger, Elke; Burger, Ulrike; Dommisch, Klaus; Elsner, Gudrun; Fernschild, Karin; Flintzer, Ulrike; Funke, Uwe; Gerken, Michael; Göbel, Hubert; Grobe, Norbert; Gumpp, Vera; Heinzerling, Lucie; Kempfer, Lana Raffaela; Kiani, Alexander; Klinkhammer-Schalke, Monika; Klöcking, Sabine; Kreibich, Ute; Knabner, Katrin; Kuhn, Peter; Lutze, Stine; Mäder, Uwe; Maisel, Tanja; Maschke, Jan; Middeke, Martin; Neubauer, Andreas; Niedostatek, Antje; Opazo-Saez, Anabelle; Peters, Christoph; Schell, Beatrice; Schenkirsch, Gerhard; Schmalenberg, Harald; Schmidt, Peter; Schneider, Constanze; Schubotz, Birgit; Seide, Anika; Strecker, Paul; Taubenheim, Sabine; Wackes, Matthias; Weiß, Steffen; Welke, Claudia; Werner, Carmen; Wittekind, Christian; Wulff, Jörg; Zettl, Heike; Klug, Stefanie J

2016-12-05

Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97-0.97), sex (OR 1.18, 95% CI 1.11-1.25), date of diagnosis (OR 1.05, 95% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95% CI 2.50-4.19) and place of residence (OR 1.23, 95% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8-83.9%). No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008.

Genetic progression of malignant melanoma.

PubMed

Tímár, J; Vizkeleti, L; Doma, V; Barbai, T; Rásó, E

2016-03-01

Malignant melanoma of the skin is the most aggressive human cancer given that a primary tumor a few millimeters in diameter frequently has full metastatic competence. In view of that, revealing the genetic background of this potential may also help to better understand tumor dissemination in general. Genomic analyses have established the molecular classification of melanoma based on the most frequent driver oncogenic mutations (BRAF, NRAS, KIT) and have also revealed a long list of rare events, including mutations and amplifications as well as genetic microheterogeneity. At the moment, it is unclear whether any of these rare events have role in the metastasis initiation process since the major drivers do not have such a role. During lymphatic and hematogenous dissemination, the clonal selection process is evidently reflected by differences in oncogenic drivers in the metastases versus the primary tumor. Clonal selection is also evident during lymphatic progression, though the genetic background of this immunoselection is less clear. Genomic analyses of metastases identified further genetic alterations, some of which may correspond to metastasis maintenance genes. The natural genetic progression of melanoma can be modified by targeted (BRAF or MEK inhibitor) or immunotherapies. Some of the rare events in primary tumors may result in primary resistance, while further new genetic lesions develop during the acquired resistance to both targeted and immunotherapies. Only a few genetic lesions of the primary tumor are constant during natural or therapy-modulated progression. EGFR4 and NMDAR2 mutations, MITF and MET amplifications and PTEN loss can be considered as metastasis drivers. Furthermore, BRAF and MITF amplifications as well as PTEN loss are also responsible for resistance to targeted therapies, whereas NRAS mutation is the only founder genetic lesion showing any association with sensitivity to immunotherapies. Unfortunately, there are hardly any data on the

Loco-Regional Control With Complete Resection and Tongue Reconstruction on the Malignant Melanoma in the Tongue.

PubMed

Alkaff, Tuqa; Jeong, Woo Shik; Nam, Soon Yuhl; Choi, Jong Woo

2017-07-01

Primary malignant melanoma in the tongue is very uncommon disease that is considered low in comparison to cutaneous melanoma. In this report, the authors described a case of the hemitongue reconstruction with fasciocutaneous free flap on the patient who suffered from the malignant melanoma primarily originating from the base of the tongue that was treated with surgery and radiotherapy but developed a lung metastasis. A 76-year-old man was referred to the otorhinolaryngology clinic after complaining of a painful mass present for 3 months on the right side of the tongue. A punch biopsy was revealed atypical cells with pigmentation that is consistent with malignant melanoma. After wide excision and bilateral neck dissection performed, hemipartial tongue reconstruction was done using a radial forearm free flap. The patient had an uneventful recovery and received a course of radiotherapy along with follow-up examinations for 3 years. The authors report this rare patient for providing the other surgeons with the useful information regarding the management of the malignant melanoma on the tongue with free flap reconstruction which turned out to be successful in loco-regional control.

RAGE-aptamer Attenuates the Growth and Liver Metastasis of Malignant Melanoma in Nude Mice

PubMed Central

Nakamara, Nobutaka; Matsui, Takanori; Ishibashi, Yuji; Sotokawauchi, Ami; Fukami, Kei; Higashimoto, Yuichiro; Yamagishi, Sho-ichi

2017-01-01

Epidemiological studies have suggested a link between cumulative diabetic exposure and cancer. The interaction of advanced glycation end products (AGEs) with their receptor (RAGE) may contribute to the phenomenon. We examined the effects of DNA aptamer raised against RAGE (RAGE-aptamer) on growth and liver metastasis of G361 melanoma in nude mice. Malignant melanoma cells were intradermally injected into the upper flank region of nude mice, which received continuous administration of RAGE-aptamer (38.4 pmol/day/g body weight) or vehicle intraperitoneally by an osmotic pump up to 42 d. RAGE-aptamer significantly reduced levels of 8-hydroxy-2’-deoxy-guanosine, AGEs, RAGE, proliferating nuclear antigen, cyclin D1, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), and CD31 and Mac-3, respective markers of endothelial cells and macrophages in tumors of nude mice, and suppressed proliferation and liver metastasis of malignant melanoma. Furthermore, RAGE-aptamer attenuated AGE-induced oxidative stress generation, proliferation, and VEGF and MCP-1 gene expression in both G361 melanoma cells and endothelial cells. The present findings suggest that RAGE-aptamer could attenuate melanoma growth and liver metastasis in nude mice by suppressing tumor angiogenesis and macrophage infiltration via inhibition of the AGE-RAGE system. RAGE-aptamer may be a novel therapeutic tool for the treatment of malignant melanoma. PMID:29387865

Unexpected pulmonary hypertensive crisis after surgery for ocular malignant melanoma.

PubMed

Sato, Kaori; Saji, Tsutomu; Kaneko, Taku; Takahashi, Kei; Sugi, Kaoru

2014-11-24

To report a case of unexpected pulmonary hypertensive crisis caused by endothelin release from melanoma cells after surgery for choroidal melanoma. A 56-year-old man suddenly developed dyspnea after resection of choroidal melanoma. Worsening hypoxia required intensive treatment, including percutaneous cardiopulmonary support, after which a series of tests were immediately performed. The tentative diagnosis was idiopathic pulmonary arterial hypertension. Previous studies noted a significant association between melanoma and endothelin (ET)-1. We hypothesized that a substantial amount of ET-1 had been released from malignant melanoma cells during resection, thus triggering the pulmonary hypertensive crisis in our patient. The patient fully recovered after intensive treatment and administration of the endothelin receptor antagonist bosentan. The success of bosentan treatment, along with the extremely high level of ET-1 on pathologic analysis, confirmed our hypothesis regarding the increase in plasma ET-1 level. Copyright © 2014 Elsevier Inc. All rights reserved.

Relation of phosphodiesterase type 5 inhibitors and malignant melanoma: a meta-analysis and systematic review.

PubMed

Wang, Jie; Shen, Yigen; Wang, Jiaoni; Xue, Yangjing; Liao, Lianming; Thapa, Saroj; Ji, Kangting

2017-07-11

Data on the association between using PDE5 inhibitors and malignant melanoma are conflicting. To estimate the relation of using PDE5 inhibitors with risk of malignant melanoma, Medline (Ovid) and Embase (Ovid) databases were searched up to February 2017, and a random effects model was used to calculate the summary risk estimates. Five observational studies were included. Five studies reports encompassed a total of 15,979 melanoma cases occurring among 1, 188,414 participants. The pooled multivariable-adjusted RR of melanoma in patients with using PDE5 inhibitors was 1.12 (95% CI: 1.03-1.21, I2 = 0.48). Findings from this systematic review support that PDE5 inhibitor use is associated with increased risk of melanoma in ED patients, the result remains inclusive and warrants further study in the future.

DNA methylation and histone acetylation regulate the expression of MGMT and chemosensitivity to temozolomide in malignant melanoma cell lines.

PubMed

Chen, Ya-Ping; Hou, Xiao-Yang; Yang, Chun-Sheng; Jiang, Xiao-Xiao; Yang, Ming; Xu, Xi-Feng; Feng, Shou-Xin; Liu, Yan-Qun; Jiang, Guan

2016-08-01

Malignant melanoma is an aggressive, highly lethal dermatological malignancy. Chemoresistance and rapid metastasis limit the curative effect of multimodal therapies like surgery or chemotherapy. The suicide enzyme O6-methylguanine-DNA methyltransferase (MGMT) removes adducts from the O6-position of guanine to repair DNA damage. High MGMT expression is associated with resistance to therapy in melanoma. However, it is unknown if MGMT is regulated by DNA methylation or histone acetylation in melanoma. We examined the effects of the DNA methylation inhibitor 5-Aza-2'-deoxycytidine and histone deacetylase inhibitor Trichostatin A alone or in combination on MGMT expression and promoter methylation and histone acetylation in A375, MV3, and M14 melanoma cells. This study demonstrates that MGMT expression, CpG island methylation, and histone acetylation vary between melanoma cell lines. Combined treatment with 5-Aza-2'-deoxycytidine and Trichostatin A led to reexpression of MGMT, indicating that DNA methylation and histone deacetylation are associated with silencing of MGMT in melanoma. This study provides information on the role of epigenetic modifications in malignant melanoma that may enable the development of new strategies for treating malignant melanoma.

DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria

PubMed Central

Antony, Jayesh; Saikia, Minakshi; V, Vinod.; Nath, Lekshmi. R.; Katiki, Mohana Rao; Murty, M.S.R.; Paul, Anju; A, Shabna; Chandran, Harsha; Joseph, Sophia Margaret; S, Nishanth Kumar.; Panakkal, Elizabeth Jayex; V, Sriramya I.; V, Sridivya I.; Ran, Sophia; S, Sankar; Rajan, Easwary; Anto, Ruby John

2015-01-01

Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma. PMID:26061820

The activation of human endogenous retrovirus K (HERV-K) is implicated in melanoma cell malignant transformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Serafino, A.; Balestrieri, E.; Pierimarchi, P.

2009-03-10

Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derivedmore » non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression.« less

[A case report of anorectal malignant melanoma showing a complete response after DTIC/ACNU/VCR therapy].

PubMed

Sasaki, Shin; Kojima, Tetsu; Hidemura, Akio; Hatanaka, Kazuhito; Uekusa, Toshimasa; Ishimaru, Masahiro

2010-10-01

We report herein the case of a 64-year-old male who presented with hematochezia. The patient was diagnosed with malignant melanoma of the anorectum using colonoscopy. Preoperative studies revealed no distant metastases, and he underwent Miles operation. Pathological exams revealed that the tumor had invaded the submucosa with lymphatic and venous invasion. Cancer cells were found in regional lymph nodes. Post-operative CT scan demonstrated multiple metastases in the liver, and he received two courses of combined chemotherapy, DAV regimen (dacarbazine: DTIC 100 mg iv days 1-5, nimustine hydrochloride: ACNU 100 mg iv day 1, vincristine sulfate: VCR 1 mg iv day 1), leading to a complete response. However, malignant melanoma cells were found in hernia contents at the operation for left inguinal hernia, which led to a diagnosis of recurrent malignant melanoma. The patient has subsequently been well without any sign of recurrence including liver metastases. To our knowledge, this is the first report of a complete response in a patient with multiple liver metastases of anorectal malignant melanoma after DAV regimen.

The magic of numbers: malignant melanoma between science and pseudoscience.

PubMed

Weyers, Wolfgang

2011-06-01

In 2009, a new system for staging and classification of malignant melanoma has been proposed by the American Joint Committee on Cancer (AJCC). The AJCC recommends that staging of primary melanoma be based on 3 criteria, namely, thickness, ulceration, and mitotic rate, the latter substituting Clark levels in the previous classification. In melanomas measuring ≤1 mm in thickness, ulceration or finding of single mitotic figure in the dermis defines stage T1b. According to the AJCC, sentinel lymph node dissection should be considered for those melanomas because of a significantly impaired prognosis. As with other prognostic parameters, however, assessment of mitotic rate, with one mitotic figure being the cutoff point, is highly unreliable, and statistics based on such data lack validity. Despite the large database being employed, they may be pseudoscience rather than science.

Computer-Aided Diagnosis of Micro-Malignant Melanoma Lesions Applying Support Vector Machines.

PubMed

Jaworek-Korjakowska, Joanna

2016-01-01

Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions.

[Clinopahological analysis of sinonasal mucosal malignant melanoma].

PubMed

Gu, Qingjia; He, Gang; Li, Jingxian; Fan, Jiagang; Li, Debing; Zhao, Libing; Song, Linhong

2014-10-01

To investigate the clinopathological characteristics, differential diagnosis, therapy and prognosis of sinonasal mucosal malignant melanoma. Clinopathological data of 18 cases which were diagnosed by pathology and immmunohistochemistry were analyzed retrospectively. All cases were proved by pathology and immmunohistochemistry. All cases were performed operations. 5 underwent single surgery. 4 underwent surgery plus adjuvant radiotherapy. 4 underwent surgery plus adjuvant radiotherapy chemotherapy. 5 underwent surgery plus adjuvant chemoradiation. All cases were followed up for a period of 1 to 7 years after operation. Twelve patients died of tumor until the last follow-up, meanwhile 6 patients stayed alive. In Six cases recurrence occurred. In five casescervical lymph node metastasis occurred, of which 3 cases received neck dissection and 2 cases received chemotherapy and radiotherapy due to no surgical indications. In three cases distant metastasis oc- curred. Sinonasal mucosal malignant melanoma is rare and highly heterogenous. Current diagnosis depends on clinical characteristics and immunohistochemical examination. It still should be differentially diagnosed from other tumors. CT and MRI image examination can provide some helpful information to understand the extent and nature of lesions. The treatment of nasal endoscopic or the surgery under endoscopy has become to be a safe, viable and reasonable alternative to open resection. Appropriate indication must be carefully selected for these lesions.

MicroRNA-365 inhibits growth, invasion and metastasis of malignant melanoma by targeting NRP1 expression.

PubMed

Bai, Juanjuan; Zhang, Zhongling; Li, Xing; Liu, Huifan

2015-01-01

The role of miR-365 in cancer cells seemed controversial in previous studies. We thereby in this article aimed to define the role of miR-365 in malignant melanoma (MM) pathogenesis. We detected miR-365 expression in malignant melanoma cell lines and then investigated the effects of miR-365 on the metastasis and malignancy of melanoma cells. The correlation between miR-365 level and NRP1 (neuropilin1) was further investigated in clinical malignant melanoma specimens. MiR-365 was strongly down-regulated in malignant melanoma (MM) tissues and cell lines, and its expression levels were associated with lymph node metastasis and clinical stage, as well as overall survival and replase-free survival of MM. We also found that ectopic expression of miR-365 inhibited MM cell proliferation and MM metastasis in vitro and in vivo. We further identified a novel mechanism of miR-365 to suppress MM growth and metastasis. NRP1 was proved to be a direct target of miR-365, using luciferase assay and western blot. NRP1 over-expression in miR-365 expressing cells could rescue invasion and growth defects of miR-365. In addition, miR-365 expression inversely correlated with NRP1 protein levels in MM. Our data suggest that miR-365 functions as a tumor suppressor in MM development and progression, and holds promise as a prognostic biomarker and potential therapeutic target for MM.

c-RET Molecule in Malignant Melanoma from Oncogenic RET-Carrying Transgenic Mice and Human Cell Lines

PubMed Central

Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

2010-01-01

Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma. PMID:20422010

c-RET molecule in malignant melanoma from oncogenic RET-carrying transgenic mice and human cell lines.

PubMed

Ohshima, Yuichiro; Yajima, Ichiro; Takeda, Kozue; Iida, Machiko; Kumasaka, Mayuko; Matsumoto, Yoshinari; Kato, Masashi

2010-04-21

Malignant melanoma is one of the most aggressive cancers and its incidence worldwide has been increasing at a greater rate than that of any other cancer. We previously reported that constitutively activated RFP-RET-carrying transgenic mice (RET-mice) spontaneously develop malignant melanoma. In this study, we showed that expression levels of intrinsic c-Ret, glial cell line-derived neurotrophic factor (Gdnf) and Gdnf receptor alpha 1 (Gfra1) transcripts in malignant melanomas from RET-transgenic mice were significantly upregulated compared with those in benign melanocytic tumors. These results suggest that not only introduced oncogenic RET but also intrinsic c-Ret/Gdnf are involved in murine melanomagenesis in RET-mice. We then showed that c-RET and GDNF transcript expression levels in human malignant melanoma cell lines (HM3KO and MNT-1) were higher than those in primary cultured normal human epithelial melanocytes (NHEM), while GFRa1 transcript expression levels were comparable among NHEM, HM3KO and MNT-1. We next showed c-RET and GFRa1 protein expression in HM3KO cells and GDNF-mediated increased levels of their phosphorylated c-RET tyrosine kinase and signal transduction molecules (ERK and AKT) sited potentially downstream of c-RET. Taken together with the finding of augmented proliferation of HM3KO cells after GDNF stimulation, our results suggest that GDNF-mediated c-RET kinase activation is associated with the pathogenesis of malignant melanoma.

Malignant melanoma of the choroid in a naevus of Ota.

PubMed

Singh, M; Kaur, B; Annuar, N M

1988-02-01

A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye.

Is cutaneous malignant melanoma associated with the use of antibacterial soaps?

PubMed

Arbesman, H

1999-07-01

Since 1960, the incidence of melanoma has increased dramatically in Caucasians worldwide, and during the past decade has risen at a rate of 6% a year in the USA. A hypothesis regarding this increased incidence suggests that the prevalent use of antibacterial soaps that contain photosensitizing compounds may be a risk factor for the development of cutaneous malignant melanoma. These antibacterial soaps were introduced in the 1960s and compounds with photosensitizing properties are still present in various soaps throughout the industrialized world. The use of these antibacterial soaps, in combination with sun exposure, leads to free radical production in the skin. These free radicals are hypothesized to cause damage to melanocytes, leading to the development of melanoma. Various epidemiological findings regarding melanoma are consistent with this hypothesis. A significant reduction in the number of new cases of melanoma could be achieved if this hypothesis is correct.

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A.

PubMed

Chang, Xiao; Zhang, Haiping; Lian, Shi; Zhu, Wei

2016-07-01

As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation and colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. Copyright © 2016 Elsevier Inc. All rights reserved.

Malignant melanoma associated with lichen sclerosus in the vulva of a 10-year-old.

PubMed

Hassanein, Ashraf M; Mrstik, Megan E; Hardt, Nancy S; Morgan, Linda A; Wilkinson, Edward J

2004-01-01

Malignant melanoma of the vulva in childhood is a rare neoplasm. Lichen sclerosus of the vulva in childhood is also a rare disease. The association of these two rare lesions in the vulva of young girls is extremely rare. We present a 10-year-old white girl with malignant melanoma associated with lichen sclerosus of the vulva. She had dark pigmentation of both the labia minora and posterior fourchette. The inner labia majora and fourchette showed whitish, glistening areas of skin. Histologic examination found mostly an in situ lentiginous/mucosal melanoma with focal invasion to a depth of 0.44 mm in the left upper labium majus. All specimens showed evidence of lichen sclerosus. Partial vulvectomy was performed, and no metastases were detected at the time of treatment. The patient has been disease free for the 12 months after treatment. It is critical for physicians to realize that melanoma can occur in children, and although rare, can occur in the vulva. We feel that lichen sclerosus in this instance may represent a pattern of host immune response to melanoma.

Malignant melanoma of the skin: long-term follow-up and time to first recurrence.

PubMed

Hohnheiser, Annika M; Gefeller, Olaf; Göhl, Jonas; Schuler, Gerold; Hohenberger, Werner; Merkel, Susanne

2011-03-01

Surgical excision can cure most patients with malignant melanoma of the skin. However, the risk of recurrence remains for years. The aim of our study was to identify factors that influence time to recurrence and survival after the first recurrence with a special interest in late recurrences. Data from 2487 patients with malignant melanoma and primary treatment between 1978 and 1997 at the Department of Surgery or the Department of Dermatology, University Hospital Erlangen, Germany, were prospectively collected in the Melanoma Registry of the University Hospital Erlangen. After a median follow-up period of 13 years, overall survival, the time to first recurrence and survival after the first relapse were examined in univariate and multivariate analyses. Overall survival was found to be significantly worse in older patients, men, melanoma of the head or trunk, and melanoma with high pT and pN categories. In 523 patients, relapse from malignant melanoma was observed after a median of 24 months. Among patients with recurrences, young age and low pT and pN categories proved to be independent factors that prolonged the disease-free interval. Advanced age at the time of the recurrence diagnosis, male sex, high pN category, and distant metastases as the first manifestation of recurrence were associated with a poor prognosis after the first recurrence. Although thin lesions have a favorable prognosis, among a cohort with recurrences they showed a relatively high rate of late recurrences. These late recurrences have an extremely poor prognosis when they present with distant metastases.

Dietary polychlorinated biphenyls, long-chain n-3 polyunsaturated fatty acids and incidence of malignant melanoma.

PubMed

Donat-Vargas, Carolina; Berglund, Marika; Glynn, Anders; Wolk, Alicja; Åkesson, Agneta

2017-02-01

For malignant melanoma, other risk factors aside from sun exposure have been hardly explored. Polychlorinated biphenyls (PCBs)-mainly from fatty fish- may affect melanogenesis and promote melanoma progression, while long-chain n-3 polyunsaturated fatty acids seem to exert antineoplastic actions in melanoma cells. We aimed to assess the association of validated estimates of dietary PCB exposure as well as the intake of eicosapentaenoic acid and docosahexaenoic acid (EPA-DHA), accounting for sun habits and skin type, with the risk of malignant melanoma in middle-aged and elderly women. We included 20,785 women at baseline in 2009 from the prospective population-based Swedish Mammography Cohort. Validated estimates of dietary PCB exposure and EPA-DHA intake were obtained via a food frequency questionnaire. Incident melanoma cases were ascertained through register-linkage. During 4.5 years of follow-up, we ascertained 67 incident cases of melanoma. After multivariable adjustments, exposure to dietary PCBs was associated with four-fold increased risk of malignant melanoma (hazard ratio [HR], 4.0 [95% confidence interval {CI}, 1.2-13; P for trend = 0.02]), while EPA-DHA intake was associated with 80% lower risk (HR, 0.2 [95% CI, 0.1-0.8; P for trend = 0.03]), comparing the highest exposure tertiles with the lowest. While we found a direct association between dietary PCB exposure and risk of melanoma, EPA-DHA intake showed to have a substantial protective association. Question of benefits and risk from fish consumption is very relevant and further prospective studies in the general population verifying these findings are warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

Surgical outcomes in patients with cutaneous malignant melanoma in Europe - a systematic literature review.

PubMed

Costa Svedman, F; Spanopoulos, D; Taylor, A; Amelio, J; Hansson, J

2017-04-01

There is limited comparative evidence of the outcomes of different types of surgical management in patients with malignant melanoma in Europe. To address that gap we conducted a systematic literature review to summarize studies reporting outcomes of surgical procedures in patients with malignant melanoma in Europe. Medline was searched for European studies published in English, between 2004 and 2014 reporting surgical outcomes in adults with cutaneous malignant melanoma. We identified 23 studies that evaluated 18 332 patients treated surgically between 1979 and 2009 from 11 European countries. Most of the studies (21/23) were observational; the two remaining studies were randomized controlled trials (RCTs). Studies compared the effect of a range of surgical interventions on a range of clinical outcomes, more commonly overall survival (OS) and disease-free survival (DFS)/recurrence-free survival (RFS). Wider excisions were not associated with improved survival in patients with melanoma thickness ≥2 mm in both studies (RCTs), however, recent results based on long-term follow-up data associate 3 cm excision margins (vs. 1 cm) with favourable survival outcomes. There was some evidence that complete lymph node dissection after positive sentinel lymph node offers survival benefits over therapeutic lymph node dissection. Sentinel lymph node biopsy was not shown to be associated with significant OS benefits, however, it was overly related with higher rates of DFS/RFS. This review highlights the difficulties of making comparisons between different types of surgical procedures for malignant melanoma. As surgery remains the main treatment, this is an important field, and further evidence, particularly from RCTs, is needed. © 2016 European Academy of Dermatology and Venereology.

IgG1-iS18 impedes the adhesive and invasive potential of early and late stage malignant melanoma cells.

PubMed

Munien, Carmelle; Rebelo, Thalia M; Ferreira, Eloise; Weiss, Stefan F T

2017-02-15

The 37kDa/67kDa laminin receptor (LRP/LR) is a non-integrin laminin receptor which is overexpressed in tumorigenic cells and supports progression of cancer via promoting metastasis, angiogenesis and telomerase activity and impediment of apoptosis. The present study investigates the role of LRP/LR on the metastatic potential of early (A375) and late (A375SM) stage malignant melanoma cells. Flow cytometry revealed that both early and late stage malignant melanoma cells display high levels of LRP/LR on their cell surface. Flow cytometry and western blot analysis showed that late stage malignant melanoma cells display significantly higher total and cell surface LRP/LR levels in comparison to early stage malignant melanoma cells and the poorly invasive breast cancer (MCF-7) control cell line. Targeting LRP/LR using the LRP/LR specific antibody IgG1-iS18 resulted in a significant reduction of the adhesive potential to laminin-1 and the invasive potential through the 'ECM-simulating' Matrigel™ of both early and late stage malignant melanoma cells. Furthermore, Pearson's correlation coefficient confirmed that increased LRP levels correlate with the increased invasive and adhesive potential in early and late stage melanoma cells. Thus, blocking LRP/LR using the IgG1-iS18 antibody may therefore be a promising therapeutic strategy for early and late stage malignant melanoma treatment. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of tumor microenvironment in development and progression of malignant melanomas - a systematic review.

PubMed

Gurzu, Simona; Beleaua, Marius Alexandru; Jung, Ioan

2018-01-01

To reveal the particular aspects of the tumor microenvironment of malignant melanomas, a systematic review including 34 representative papers was performed. The review took into account the aspects related the Wnt/β-catenin pathway-related epithelial-mesenchymal transition (EMT) versus mesenchymal-epithelial transition (MET) of keratinocytes, fibroblasts and melanoma cells, as possible tools for understanding genesis and evolution of malignant melanoma. The possible reversible features of EMT and the role of tumor microenvironment in the metastatic process were also analyzed. A particular issue was related on the cancer stem cells that include melanocyte stem cells (McSCs) and multipotent mesenchymal stem/stromal cells (MSCs). As the McSCs embryological development in mouse is not similar to human development, the role of stem cells in genesis and development of human melanoma should be proved in human melanoma cells only. For further development of targeted therapy, a better understanding of melanomagenesis pathways and its microenvironment particularities is necessary.

A Retrospective Study, an Initial Lesion of Primary Malignant Melanoma of the Esophagus Revealed by Endoscopy.

PubMed

Fukuda, Sho; Ito, Hirotaka; Ohba, Reina; Sato, Yuichirou; Ohyauchi, Motoki; Igarashi, Takehiko; Obana, Nobuya; Iijima, Katsunori

2017-08-15

A 66-year-old man presented to his previous physician with epigastric discomfort in 2014. He was then referred to our hospital due to suspected primary malignant melanoma of the esophagus (PMME). A biopsy showed atypical cells containing melanin granules. A diagnosis of PMME was thus made. We investigated the endoscopic findings of the previous physician, which revealed a black point-like pigmentation at the same site since 2009. In 2010, black pigmentation was also observed at the same site. Although esophageal melanosis was suspected, no biopsy was performed. This case demonstrates the process by which esophageal melanomas develop into malignant melanomas.

Malignant melanoma of the choroid in a naevus of Ota.

PubMed Central

Singh, M.; Kaur, B.; Annuar, N. M.

1988-01-01

A rare case of choroidal malignant melanoma in a naevus of Ota is described. This is the first reported case from Asia outside the Japanese population. This case illustrates the need for close observation of all pigmented lesions of the eye. Images PMID:3349013

miR-137 suppresses tumor growth of malignant melanoma by targeting aurora kinase A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Xiao; Zhang, Haiping; Lian, Shi

2016-07-01

As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3′ untranslated region (3′UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation andmore » colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. -- Highlights: •First reported overexpression of AURKA in melanoma. •Targeting AURKA inhibits melanoma growth in vitro and in vivo. •Further found miR-137 suppressed cell growth by binding to AURKA 3′UTR. •Re-expression of AURKA rescued miR-137-mediated suppression. •miR-137-AURKA axis may be potential therapeutic targets of melanoma.« less

Synthesis and evaluation of ¹²³/¹³¹I-Iochlonicotinamide as a novel SPECT probe for malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell

2015-05-01

Malignant melanoma expresses a highly aggressive metastasis. Early diagnosis of malignant melanoma is important for patient survival. Radiolabeled benzamides and nicotinamides have been reported to be attractive candidates for malignant melanoma diagnosis as they bind to melanin, a characteristic substance that displays in malignant melanoma, and show high tumor accumulation and retention. Herein, we designed and synthesized a novel (123/131)I-labeled nicotinamide derivative that specifically binds to melanin. (123/131)I-Iochlonicotinamide was prepared with good radiochemical yield (50-70%, decay corrected) and high specific radioactivity (50-80 GBq/μmol). (131)I-Iochlonicotinamide exhibited good in vitro stability (radiochemical purity >95% after a 24-h incubation) in human serum. High uptake of (123/131)I-Iochlonicotinamide in B16F0 melanoma cells compared to that in A375 amelanotic cells demonstrated its selective binding to melanin. Intravenous administration of (123/131)I-Iochlonicotinamide in a melanoma-bearing mouse model revealed high uptake in melanotic melanoma and high tumor-to-muscle ratio. MicroSPECT scan of (123/131)I-Iochlonicotinamide injected mice also displayed high contrast tumor imaging as compared with normal organs. The radiation-absorbed dose projection for the administration of (131)I-Iochlonicotinamide to human was based on the results of biodistribution study. The effective dose appears to be approximately 0.44 mSv/MBq(-1). The specific binding of (123/131)I-Iochlonicotinamide to melanin along with a prolonged tumor retention and acceptable projected human dosimetry suggest that it may be a promising theranostic agent for treating malignant melanoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patterns of regional head and neck lymph node metastasis in primary conjunctival malignant melanoma

PubMed Central

Lim, M; Tatla, T; Hersh, D; Hungerford, J

2006-01-01

Objective To correlate patterns of regional lymph node metastasis with the site of origin in primary conjunctival malignant melanoma. Design Retrospective analysis (1990–2003) of clinical data. Setting Two London tertiary referral centres. Participants 12 patients presenting with regional metastases after failed local treatment for conjunctival malignant melanoma. Results 6 cases predominantly involving the temporal conjunctiva metastasised to the pre‐auricular lymph nodes. Two cases predominantly involving the nasal conjunctiva metastasised to the submandibular nodes. Of the two cases with purely multifocal disease, one metastasised to the pre‐auricular nodes and another to both submandibular and parotid nodes. One primary conjunctival malignant melanoma had its origin in temporal conjunctiva but metastasised to submandibular nodes, and another case originating from nasal conjunctiva metastasised to pre‐auricular nodes. Conclusions Temporal conjunctival melanotic lesions tend to metastasise clinically to pre‐auricular lymph nodes and nasal conjunctival melanotic lesions metastasise to the submandibular lymph nodes. Patterns appear consistent with laboratory‐based anatomically mapped lymphatic drainage basins of the conjunctiva. PMID:16928703

Histone variant H2A.Z.2 mediates proliferation and drug sensitivity of malignant melanoma

PubMed Central

Vardabasso, Chiara; Gaspar-Maia, Alexandre; Hasson, Dan; Pünzeler, Sebastian; Valle-Garcia, David; Straub, Tobias; Keilhauer, Eva C.; Strub, Thomas; Dong, Joanna; Panda, Taniya; Chung, Chi-Yeh; Yao, Jonathan L.; Singh, Rajendra; Segura, Miguel F.; Fontanals-Cirera, Barbara; Verma, Amit; Mann, Matthias; Hernando, Eva; Hake, Sandra B.; Bernstein, Emily

2015-01-01

SUMMARY Histone variants are emerging as key regulatory molecules in cancer. Here we report a novel role for the H2A.Z isoform H2A.Z.2 as a driver of malignant melanoma. H2A.Z.2 is highly expressed in metastatic melanoma, correlates with decreased patient survival, and is required for cellular proliferation. Our integrated genomic analyses reveal that H2A.Z.2 controls the transcriptional output of E2F target genes in melanoma cells. These genes are highly expressed and display a distinct signature of H2A.Z occupancy. We identify BRD2 as an H2A.Z interacting protein, whose levels are also elevated in melanoma. We further demonstrate that H2A.Z.2 regulated genes are bound by BRD2 and E2F1 in a H2A.Z.2-dependent manner. Importantly, H2A.Z.2 deficiency sensitizes melanoma cells to chemotherapy and targeted therapies. Collectively, our findings implicate H2A.Z.2 as a mediator of cell proliferation and drug sensitivity in malignant melanoma, holding translational potential for novel therapeutic strategies. PMID:26051178

WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

PubMed

Sasse, Andre D; Sasse, Emma C; Clark, Luciana Go; Clark, Otavio Augusto Camara

2018-02-06

Malignant melanoma, one of the most aggressive of all skin cancers, is increasing in incidence throughout the world. Surgery remains the cornerstone of curative treatment in earlier stages. Metastatic disease is incurable in most affected people, because melanoma does not respond to most systemic treatments. A number of novel approaches are under evaluation and have shown promising results, but they are usually associated with increased toxicity and cost. The combination of chemotherapy and immunotherapy has been reported to improve treatment results, but it is still unclear whether evidence exists to support this choice, compared with chemotherapy alone. No language restrictions were imposed. To compare the effects of therapy with chemotherapy and immunotherapy (chemoimmunotherapy) versus chemotherapy alone in people with metastatic malignant melanoma. We searched the Cochrane Skin Group Specialised Register (14 February 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2005), MEDLINE (2003 to 30 January 2006 ), EMBASE (2003 to 20 July 2005) and LILACS (1982 to 20 February 2006). References, conference proceedings, and databases of ongoing trials were also used to locate trials. All randomised controlled trials that compared the use of chemotherapy versus chemoimmunotherapy on people of any age, diagnosed with metastatic melanoma. Two authors independently assessed each study to determine whether it met the pre-defined selection criteria, with differences being resolved through discussion with the review team. Two authors independently extracted the data from the articles using data extraction forms. Quality assessment included an evaluation of various components associated with biased estimates of treatment effect. Whenever possible, a meta-analysis was performed on the extracted data, in order to calculate a weighed treatment effect across trials. Eighteen studies met our criteria and were included in the meta

A clinicopathological analysis of primary mucosal malignant melanoma.

PubMed

Izumi, Daisuke; Ishimoto, Takatsugu; Yoshida, Naoya; Nakamura, Kenichi; Kosumi, Keisuke; Tokunaga, Ryuma; Sugihara, Hidetaka; Sawayama, Hiroshi; Karashima, Ryuichi; Imamura, Yu; Ida, Satoshi; Hiyoshi, Yukiharu; Iwagami, Shiro; Baba, Yoshifumi; Sakamoto, Yasuo; Miyamoto, Yuji; Watanabe, Masayuki; Baba, Hideo

2015-07-01

Primary mucosal malignant melanoma (PMMM) is a rare and highly lethal neoplasm associated with a poor prognosis. CXC chemokine receptor 4 (CXCR4) is expressed on various tumor cells, including malignant melanoma. Recent data indicate that CXCL12 and CXCR4 play a critical role in the behavior of cancer cells and in the survival of cancer patients. However, there has been no study that has addressed the expression and function of CXCR4/CXCL12 signaling in PMMM. Immunohistochemical staining for CXCL12 and Ki67 in biopsy tissues from 10 cases of PMMM was performed. We analyzed the correlations between the clinicopathological features and expression levels of CXCL12 and Ki67. Six cases showed a high level of CXCL12 expression, while four cases had a low level of expression. High expression of CXCL12 correlated with a poor prognosis, although statistical significance was not reached (p = 0.054). Ki67 was highly expressed in five cases, while the expression in the other five cases was low. There was no correlation between the Ki67 expression and prognosis. The findings of this study suggest that CXCL12 expression may play an important role in the biological behavior of PMMM and may be associated with a poor prognosis of PMMM patients.

MiR-135 post-transcriptionally regulates FOXO1 expression and promotes cell proliferation in human malignant melanoma cells.

PubMed

Ren, Jian-Wen; Li, Zhang-Jun; Tu, Chen

2015-01-01

Malignant melanoma is the deadliest form of all skin cancers. Recently, microRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. Our study showed that miR-135a is upregulated in malignant melanoma tissues and cell lines by using Real-time PCR assay. Enforced expression of miR-135a in malignant melanoma cells promotes cell proliferation, tumorigenicity, and cell cycle progression, whereas inhibition of miR-135a reverses the function. Additionally, we demonstrated FOXO1 is a direct target of miR-135a and transcriptionally down-regulated by miR-135a. Ectopic expression of miR-135a led to downregulation of the FOXO1 protein, resulting in upregulation of Cyclin D1, and downregulation of P21(Cip1) and P27(Kip1) through AKT pathway. Our findings suggested that miR-135a represents a potential onco-miRNA and plays an important role in malignant melanoma progression by suppressing FOXO1 expression.

Relationship of cutaneous malignant melanoma to individual sunlight-exposure habits.

PubMed

Holman, C D; Armstrong, B K; Heenan, P J

1986-03-01

The relationships of different histologic types of cutaneous malignant melanoma to occupational and recreational sunlight exposure, habits of clothing, sunburn histories, and use of sunscreening agents were examined in a case-control study of 507 patients and 507 matched controls in Western Australia. Variations in relationships according to the primary site of melanoma were also examined. An increased incidence rate of superficial spreading melanoma was associated with low total outdoor exposure in early adulthood and frequent participation in boating and fishing. Superficial spreading melanoma of the trunk was also related to frequency of sunbathing at ages 15-24 years and of exposure of the trunk while working outdoors. In women the rate ratio for all types of melanoma occurring on the trunk was estimated at 13.0 (95% confidence interval, 2.0-83.9) in those who wore a bikini or bathed nude at ages 15-24 years compared with those wearing a conservative one-piece bathing suit. There was little evidence that sunbathing or wearing a bikini within 10 years of case diagnosis were risk factors for melanoma of the trunk. After control of confounding due to constitutional factors, only Hutchinson's melanotic freckle melanoma showed a relationship to severe sunburn. For nodular melanoma, sunburn appeared to be protective. Although many of the results supported the hypothesis that melanomas other than the Hutchinson's melanotic freckle type are related to occasional bursts of recreational sun exposure during a susceptible period in early adult life, little support for the hypothesis was obtained when recreational sun exposure was expressed as a proportion of total outdoor exposure, which had been considered a priori to be an index of intermittent sunlight exposure.

Exophytic Tumor Growth After Incomplete Removal of Polypoid Malignant Melanoma of the Maxillary Gingiva: A Case Report and Review of the Literature.

PubMed

Taga, Tomoharu; Nonaka, Taichiro; Manabe, Toshiaki; Bessho, Kazuhisa

2016-11-01

Polypoid malignant melanoma of the oral cavity is extremely rare. This report describes the case of the 3-time occurrence of a polypoid malignant melanoma of the maxillary gingiva in an 84-year-old woman who had removed the primary tumor by herself. The second polypoid malignant melanoma was a black 7-cm pedunculated mass surrounded by pigmented mucosa. Histologically, the tumor exhibited an ulcerated surface lined by squamous cells and contained polygonal cells with brown-and-black pigmentation. The third polypoid malignant melanoma was observed at the same location 7 months after surgery; it was a black hemorrhagic mass approximately 1.5 cm. Histologic analysis showed morphologic findings that were similar to those observed in the second polypoid melanoma. The patient died of lung metastasis 28 months after the second surgery. This report also reviews the 5 previously reported cases of polypoid malignant melanoma of the oral cavity, all of which occurred in the upper jaw. In 2 cases, initial exophytic growth of the tumor before invasion of the submucosa and relatively early detection resulted in a good prognosis. However, in 1 case, amelanotic melanoma located in the periodontal tissues was clinically misdiagnosed as epulis. Therefore, immunostaining for S-100 and HMB-45 should be considered for nonpigmented epulis-like lesions, and wide surgical resection of primary polypoid malignant melanomas at an early stage should result in a favorable prognosis. Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

The importance of consumption of the epidermis in malignant melanoma and correlation with clinicopathological prognostic parameters.

PubMed

Seçkin, Selda; Ozgũn, Elmas

2011-01-01

The aim of the study was to investigate the importance of consumption of the epidermis as an additional diagnostic criteria for malignant melanoma and to evaluate its relationship to clinicopathological findings. The age, gender, localization of the lesion and the histopathological parameters such as tumor type, Breslow thickness, ulceration, Clark's level, mitosis/mm2, lymphocytic infiltration were noted in 40 malignant melanoma cases. Consumption of the epidermis was evaluated in tumor sections. Consumption of the epidermis (COE) due to thinning of the epidermis and loss of rete ridges was noted as (+) or (-). Furthermore, COE was compared with clinical and histopathological parameters. The Shapiro Wilk and Logistic Regression tests were used for statistical analysis. The results were accepted as significant if the p value was < 0.05. COE was detected in 60% (24/40) of malignant melanoma cases. A positive correlation was present between COE and head and neck localization (p = 0,698), superficial spreading melanoma (p = 0,341), ulceration (p = 0,097) and brisk lymphocytic infiltration (p = 0,200) but the results were not statistically significant. COE was frequently detected in males but the difference was not statistically significant (p = 0.796). There was no correlation or significant statistical association between COE and age, Breslow thickness, Clark's level or the mitotic index. The detection of COE in most of the patients suggests that COE could be a histopathological criterion in the diagnosis of malignant melanoma. The frequent association between COE and the presence of ulceration could also direct attention to COE as regards prognostic importance.

Patients' Characteristics, Histopathological Findings, and Tumor Stage in Different Types of Malignant Melanoma: A Retrospective Multicenter Study.

PubMed

Farahmand, Ali-Mohammad; Ehsani, Amir-Hoshang; Mirzaei, Mojtaba; Mohsenian, Maryam; Ghanadan, Alireza

2017-05-01

Cutaneous malignant melanoma (CMM) is currently the most fatal of skin cancers accounting for 50000 deaths annually. Five distinct melanomas are described histopathologically: superficial spreading, lentigo maligna, nodular, acral lentiginous and mucosal melanoma. The aim of this study was to investigate the characteristics of patients with various types of malignant melanoma and evaluate histopathological findings. In this retrospective study, we obtained our data from the records of 111 patients with melanoma. Biopsied specimens were collected and re-evaluated. Demographic information and histopathological findings were noted. SPSS 16 was used for analyzing data. Chi-square and one-way ANOVA was conducted for comparing categorical and numerical variables respectively. The mean age of patients was 59.33±14.68 years old. Most common melanoma type was acral lentiginous (40.5%), followed by nodular (35.1%) and mucosal (10.8%). The highest tumor thickness was viewed in nodular melanoma followed by mucosal melanoma. The highest rate of metastasis, microsatellitosis, perineural invasion and Clark level of the invasion were reported in nodular and acral lentiginous respectively. The most frequent rate of ulceration and vascular invasion was reported in mucosal melanoma. Distribution of melanoma types varies largely in different regions. Lack of classic presentations in some types necessitate specific public education about warning signs. Histopathological and pathological characteristics in melanoma can aid in better staging and management of the tumor.

[A case of small-cell malignant melanoma in a pregnant patient].

PubMed

Calderón Garcidueñas, Anna Laura; Dragustinovis Valdez, Irma Yadira; Castelán Maldonado, Edmundo Erbey; Zavala, Pompa Angel

2005-01-01

Malignant melanoma (MM) is an aggressive neoplasm that may affect pregnant women. Malignant melanoma with small-cell morphology (MMSCM) is a rare variant of MM that can cause confusion in its diagnosis. To report a fatal case of MMSCM in a pregnant woman, highlighting immunohistochemistry (IHC) as a very useful tool in the final diagnosis. A 22-year-old pregnant female presented with a 5-cm cutaneous tumor in her right leg. The lesion was excised but the patient refused any further therapy. The natural outcome of this neoplasm occurred with local recurrence and multiple metastases to the lungs, liver, and kidneys. MM should be included in the differential diagnosis of small-cell cutaneous tumor, and IHC is mandatory for diagnosis confirmation. The recommended suggested screening includes, as a minimum, one sensitive marker (S-100 protein) and one specific (HMB45) marker for melanogenesis.

Adrenal malignant melanoma masquerading as a pheochromocytoma in a patient with a history of a multifocal papillary and medullary thyroid carcinoma.

PubMed

Barmpari, Maria E; Savvidis, Christos; Dede, Anastasia D; Markogiannakis, Haridimos; Dikoglou, Christina; Xekouki, Paraskevi; Stratakis, Constantine A; Manouras, Andreas; Malaktari-Skarantavou, Sofia

2016-04-01

Adrenal masses usually represent benign and nonfunctional adrenal adenomas; however, primary or metastatic malignancy should also be considered. Discovery of an adrenal mass needs further evaluation in order to exclude malignancy and hormonal secretion. We present a rare case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. A 61-year-old male farmer was referred for evaluation of a mass in the right supraclavicular region and a left adrenal lesion. The patient had a history of a multifocal papillary and medullary thyroid carcinoma. Laboratory tests revealed increased 24hour urinary dopamine and also increased serum calcitonin and neuron specific enolase. A pathology report of the resected right supraclavicular mass and left adrenal showed a malignant melanoma. This is a case of a possibly primary adrenal malignant melanoma with imaging and biochemical features of a pheochromocytoma. Although this case is very rare and there are rigid diagnostic criteria for the diagnosis of primary adrenal melanoma, it underlines the fact that the differential diagnosis of a dopamine secreting adrenal mass should include primary or metastatic malignant melanoma in order to determine the best diagnostic approach for the patient and select the most appropriate surgical management.

[Primary malignant melanoma of the vagina and treatment options: a case report].

PubMed

Tsvetkov, Ch; Gorchev, G; Tomov, S; Hinkova, N; Nikolova, M; Veselinova, T

2014-01-01

To present and analyze the clinical characteristics, treatment, and treatment options for a patient with primary malignant melanoma of the vagina and review of literature. A 71-year-old patient with a history of vaginal bleeding caused by four tumor growths located in the vagina is presented. The size of each formation was about 2 cm. Three of them were located in the proximal two-thirds of the anterior wall of the vagina and one in the distal third. Excisional biopsy was performed of the lesion located near the entrance of the vagina. Histopathological examination revealed that it was a malignant melanoma of the vagina, which was confirmed immunohistochemically. After ruling out a tumor of an unknown primary site, the patient underwent radical hysterectomy type IV total vaginectomy and pelvic lymph node dissection. Hystological examination proved a clinically asymptomatic melanoma lesion of the uterine cervix. After surgery, the patient was given chemotherapy with Dacarbasine and monthly immunotherapy with BCG vaccine. The patient survived 21 months after surgery without developing a local relapse and died of distant metastases in the spine. Radical surgery for primary melanoma of the vagina is a secure way of achieving locoregional control of multifocal disease. The wide local excision can be used in unifocal lesions with security in achieving clean surgical margins.

The quinone methide aurin is a heat shock response inducer that causes proteotoxic stress and Noxa-dependent apoptosis in malignant melanoma cells.

PubMed

Davis, Angela L; Qiao, Shuxi; Lesson, Jessica L; Rojo de la Vega, Montserrat; Park, Sophia L; Seanez, Carol M; Gokhale, Vijay; Cabello, Christopher M; Wondrak, Georg T

2015-01-16

Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinder(TM) PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. © 2015 by The

The Quinone Methide Aurin Is a Heat Shock Response Inducer That Causes Proteotoxic Stress and Noxa-dependent Apoptosis in Malignant Melanoma Cells*

PubMed Central

Davis, Angela L.; Qiao, Shuxi; Lesson, Jessica L.; Rojo de la Vega, Montserrat; Park, Sophia L.; Seanez, Carol M.; Gokhale, Vijay; Cabello, Christopher M.; Wondrak, Georg T.

2015-01-01

Pharmacological induction of proteotoxic stress is rapidly emerging as a promising strategy for cancer cell-directed chemotherapeutic intervention. Here, we describe the identification of a novel drug-like heat shock response inducer for the therapeutic induction of proteotoxic stress targeting malignant human melanoma cells. Screening a focused library of compounds containing redox-directed electrophilic pharmacophores employing the Stress & Toxicity PathwayFinderTM PCR Array technology as a discovery tool, a drug-like triphenylmethane-derivative (aurin; 4-[bis(p-hydroxyphenyl)methylene]-2,5-cyclohexadien-1-one) was identified as an experimental cell stress modulator that causes (i) heat shock factor transcriptional activation, (ii) up-regulation of heat shock response gene expression (HSPA6, HSPA1A, DNAJB4, HMOX1), (iii) early unfolded protein response signaling (phospho-PERK, phospho-eIF2α, CHOP (CCAAT/enhancer-binding protein homologous protein)), (iv) proteasome impairment with increased protein-ubiquitination, and (v) oxidative stress with glutathione depletion. Fluorescence polarization-based experiments revealed that aurin displays activity as a geldanamycin-competitive Hsp90α-antagonist, a finding further substantiated by molecular docking and ATPase inhibition analysis. Aurin exposure caused caspase-dependent cell death in a panel of human malignant melanoma cells (A375, G361, LOX-IMVI) but not in non-malignant human skin cells (Hs27 fibroblasts, HaCaT keratinocytes, primary melanocytes) undergoing the aurin-induced heat shock response without impairment of viability. Aurin-induced melanoma cell apoptosis depends on Noxa up-regulation as confirmed by siRNA rescue experiments demonstrating that siPMAIP1-based target down-regulation suppresses aurin-induced cell death. Taken together, our data suggest feasibility of apoptotic elimination of malignant melanoma cells using the quinone methide-derived heat shock response inducer aurin. PMID:25477506

Downregulation of miR-125b in metastatic cutaneous malignant melanoma.

PubMed

Glud, Martin; Rossing, Maria; Hother, Christoffer; Holst, Line; Hastrup, Nina; Nielsen, Finn C; Gniadecki, Robert; Drzewiecki, Krzysztof T

2010-12-01

This study aimed to identify microRNA species involved in the earliest metastatic event in cutaneous malignant melanoma (MM). Samples from 28 patients with MM [stage T2 (tumor), M0 (distant metastasis)] were grouped by the presence of micrometastasis in the sentinel lymph nodes (N0/N1). Melanoma cells were harvested from primary, cutaneous MM tumors by laser-capture microdissection, and microRNA expression profiles were obtained by the microarray technique. Results were validated by quantitative reverse transcription PCR. We found that miR-125b was downregulated in the primary cutaneous melanomas that produced early metastases (T2, N1, M0) compared with the sentinel lymph node-negative (T2, N0, M0) melanomas. MiR-125b has earlier been found to be downregulated in other tumor types and in atypic naevi compared with the common acquired naevi. In conclusion, miR-125b may be involved in an early progression of cutaneous MM.

[Malignant melanoma of the skin in Denmark--epidemiology, diagnosis and treatment].

PubMed

von der Maase, H; Osterlind, A; Drzewiecki, K T; Dahlstrøm, K K; Geertsen, P F; Gjedde, S B; Hastrup, N C; Holmberg, S B; Krag, C; Lock-Andersen, J

1992-07-06

About 700 new cases of malignant melanoma of the skin are registered annually in Denmark. The incidence is increasing rapidly and the number of new cases increases by more than 5% per annum. The most important phenotypical risk factors are the number of acquired pigmented naevi and exposure to sunlight is the most important risk factor in the external environment so that severe sunburn in children and intermittent intense exposure to sunlight increase the risk of melanoma. The thickness of the tumour at the time of the diagnosis is the most important prognostic factor. The prognosis deteriorates with increasing thickness. Treatment is primarily surgical. In cases of inoperable local melanoma and regional recurrences, irradiation may be administered. Chemotherapy and/or immunotherapy are of experimental character. In the light of the rapidly increasing incidence, it is important that knowledge of risk factors for development of the disease and the clinical characteristics of early melanoma is spread to not only the medical profession but also to the general public.

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial.

PubMed

De Smedt, J; Van Kelst, S; Boecxstaens, V; Stas, M; Bogaerts, K; Vanderschueren, D; Aura, C; Vandenberghe, K; Lambrechts, D; Wolter, P; Bechter, O; Nikkels, A; Strobbe, T; Emri, G; Marasigan, V; Garmyn, M

2017-08-23

Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor. This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80 years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6 month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees. If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease. Clinical Trial.gov, NCT01748448 , 05/12/2012.

Diagnosis and treatment of concurrent dermal malignant melanoma and melanocytomas in a pygmy hippopotamus (Choeropsis liberiensis).

PubMed

Saunders, Richard A; Killick, Rowena S; Barrows, Michelle G; Bowlt, Kelly A; Denk, Daniella

2017-10-01

Dermal melanocytic neoplasms are common in some even-toed ungulates (Artiodactyla), yet this entity has not been reported in the pygmy hippopotamus to date. Concurrent occurrence of multiple benign and malignant melanocytic neoplasms is unusual. Malignant transformation occurs in a small percentage of benign melanocytic tumours in people but this phenomenon has not been well documented in animals. To report the diagnosis and treatment of concurrent dermal melanocytomas and malignant melanomas in a pygmy hippopotamus. A 36-year-old intact male pygmy hippopotamus, part of a zoological collection, housed with a 10-year-old female of the same species, presented with multiple raised and pigmented skin masses. Initial impression smears of one ulcerated lesion were consistent with inflammation; subsequent histopathological findings from a skin biopsy revealed an underlying malignant melanoma. The animal was anaesthetised, ultrasonographic imaging of the local lymph nodes indicated no local involvement and all skin lesions were removed. Recovery from anaesthesia was unremarkable, skin healing was within normal limits for the species. There was no sign of recurrence 34 months post-surgery. A diagnosis of malignant melanomas and concurrent melanocytomas was made on histopathological evaluation. To the best of the authors' knowledge, this is the first reported case of melanocytic neoplasia in the pygmy hippopotamus. The occurrence of both benign and malignant melanocytic skin tumours should be considered in this species. © 2017 ESVD and ACVD.

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma.

PubMed

Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J; Qureshi, Abrar A

2015-11-01

Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. We evaluated the association among caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. The analysis used data from 89,220 women in the Nurses' Health Study II (1991-2009), 74,666 women in the Nurses' Health Study (1980-2008), and 39,424 men in the Health Professionals Follow-up Study (1986-2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CIs) of melanoma associated with dietary intakes. We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/day vs. <60 mg/day: HR = 0.78, 95% CI = 0.64, 0.96; Ptrend = 0.048). The association was more apparent in women (≥393 mg/day vs. <60 mg/day: HR = 0.70, 95% CI = 0.58, 0.85; Ptrend = 0.001) than in men (HR = 0.94, 95% CI = 0.75, 1.2; Ptrend = 0.81), and more apparent for melanomas occurring on body sites with higher continuous sun exposure (head, neck, and extremities; ≥393 mg/day vs. <60 mg/day: HR = 0.71, 95% CI = 0.59, 0.86; Ptrend = 0.001) than for melanomas occurring on body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen, and chest; HR = 0.90, 95% CI = 0.70, 1.2; Ptrend = 0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Increasing caffeine intake and caffeinated coffee consumption is associated with decreased risk of cutaneous malignant melanomas.

Anorectal melanoma: experience from a tertiary cancer care centre in South India.

PubMed

Ranjith, S; Muralee, M; Sajeed, A; Arun, P M; Cherian, K; Nair, C K; Augustine, P; Ahamed, I

2018-03-01

Introduction Mucosal malignant melanoma of the anorectum is a rare and aggressive disease, in which early diagnosis is difficult. The prognosis remains extremely poor, irrespective of the treatment. We share our experience in treating this malignancy at our centre in South India. Methods This study describes a retrospective analysis of 31 cases of anorectal melanoma presented to our centre between January 2001 and December 2013. Results Twenty-two patients (71%) presented with metastasis and had a median overall survival of nine months. None of the 22 patients survived for two years. Nine patients (29%) had curative surgery, in the form of abdominoperineal resection (six patients), abdominoperineal resection with bilateral inguinal node dissection (one patient), abdominoperineal resection with liver resection (one patient) and posterior exenteration (one patient). In patients who underwent curative surgery, the median overall survival was 15 months and disease-free survival was nine months, with a two-year overall survival of 22%. Conclusions Anorectal melanoma is an aggressive disease with a poor prognosis. The majority of patients present with distant metastases. Prognosis depends on stage at presentation. Early diagnosis and surgical resection may improve the overall outcome. Newer modalities such as immunotherapy and targeted therapies such as anti-CTLA4 monoclonal antibody and anti-programmed cell death protein 1 monoclonal antibodies have radically changed the management of mucosal melanoma and may, in the future, improve the overall prognosis of anorectal melanoma.

Synergistic inhibition of malignant melanoma proliferation by melphalan combined with ultrasound and microbubbles.

PubMed

Matsuo, Miki; Yamaguchi, Kazuki; Feril, Loreto B; Endo, Hitomi; Ogawa, Koichi; Tachibana, Katsuro; Nakayama, Juichiro

2011-09-01

The cavitational effects of ultrasound (US) exposure induce transient pores on the cell membrane (sonoporation). Sonoporation have been applied in the field of cancer therapy by promoting delivery of extracellular molecules such as drugs and genes into cytoplasm. In addition, it is known that using US together with microbubbles (MB) elevates permeability of these agents. In this study, by applying the US-MB strategy for melanoma chemotherapy, we evaluated the antitumor effect of melphalan combined with US-MB on a melanoma cell line (C32) in vitro and in vivo. The in vitro cytotoxic effect of the melphalan with US-MB was greater than that of melphalan alone or melphalan in combination with US. In vivo experiments using xenografts, intratumoral injection of melphalan and MB with US exposure led to a greater degree of tumor regression than did the intratumoral injection of the melphalan alone or melphalan in combination with US. These results suggest that US-MB promotes the antitumor effect of melphalan by increasing delivery of molecules into cells and that this strategy may become an effective method of adjuvant therapy against malignant melanoma. Copyright © 2011 Elsevier B.V. All rights reserved.

Survival of cutaneous malignant melanoma patients at University of Iowa Hospitals: 1950--1974.

PubMed

Griffel, M

1981-01-01

Survival of 387 patients treated for cutaneous malignant melanoma at University of Iowa Hospitals during the period 1950--1974 was analyzed. For the entire period, the observed five-year survivals were 57% for women and 33% for men; the corresponding ten-year survivals were 43 and 23%. For both men and women, there was an impressive improvement in outcome between the earliest and the latest periods, so that for 1970--1974, the five-year observed survival was 68% for women and 49% for men. Data are presented on mean age at diagnosis, distribution by stage, site, and sex, and survival by site and sex. The question is raised whether the biologic nature of malignant melanoma is variable, so that increased incidence is associated with better prognosis.

Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules

PubMed Central

Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom

2017-01-01

Objectives Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Design Systematic review. Data sources A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Study selection and data extraction Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. Results From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. Conclusions At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. PMID:28264830

Patient with giant upper limb melanoma presenting to a UK plastic surgery unit: differentials and experience of management.

PubMed

Honeyman, Calum Sinclair; Wilson, Paul

2016-02-02

A 57-year-old woman was referred to our regional sarcoma unit following a 2-year history of a progressively enlarging mass on her right forearm. At 14 × 7 × 12 cm, this mass turned out to be one of the largest upper limb cutaneous malignant melanomas ever described, and, to the best of our knowledge, the first documented in the UK. Remarkably, despite having a T4 malignant tumour with a Breslow thickness of 70 mm, this patient is still alive over 4 years later with no locoregional or distant metastatic spread. We present our experience in the management of this giant malignant melanoma of the upper limb and consider important differentials. 2016 BMJ Publishing Group Ltd.

Malignant Melanoma of the Anus Found during Routine Colonoscopy in Ulcerative Colitis.

PubMed

Seo, Kwang Il; Moon, Won; Kim, Sung Eun; Park, Moo In; Park, Seun Ja

2017-06-25

Inflammatory bowel disease (IBD) is characterized by recurrent or chronic inflammation of the gastrointestinal tract, which results in increased risk of developing cancer. Anorectal malignant melanoma is often misdiagnosed as either hemorrhoids or benign anorectal conditions in inflammatory bowel disease. Therefore, the overall prognosis and survival of IBD are poor. To date, the best treatment strategy remains controversial. Only early diagnosis and complete excision yield survival benefit. Here, we report a 64-year-old woman with ulcerative colitis, who was found to have anal malignant melanoma on routine colonoscopy. The lesion was confined to the mucosa with no distant metastasis. She underwent complete trans-anal excision. There was no recurrence at the four-year follow-up. Physicians should be aware of increased risk of cancer development in IBD patients and remember the importance of meticulous inspection of the anal canal.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity.

PubMed

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma.

Anti-DR5 monoclonal antibody-mediated DTIC-loaded nanoparticles combining chemotherapy and immunotherapy for malignant melanoma: target formulation development and in vitro anticancer activity

PubMed Central

Ding, Baoyue; Wu, Xin; Fan, Wei; Wu, Zhaoyong; Gao, Jing; Zhang, Wei; Ma, Lulu; Xiang, Wang; Zhu, Quangang; Liu, Jiyong; Ding, Xueying; Gao, Shen

2011-01-01

Background The increased incidence of malignant melanoma in recent decades, along with its high mortality rate and pronounced resistance to therapy pose an enormous challenge. Novel therapeutic strategies, such as immunotherapy and targeted therapy, are urgently needed for melanoma. In this study, a new active targeting drug delivery system was constructed to combine chemotherapy and active specific immunotherapy. Methods The chemotherapeutic drug, dacarbazine (DTIC), that induces apoptosis through the intrinsic pathway which typically responds to severe DNA damage, was used as a model drug to prepare DTIC-loaded polylactic acid (PLA) nanoparticles (DTIC-NPs), which were covalently conjugated to a highly specific targeting functional TRAIL-receptor 2 (DR5) monoclonal antibody (mAb) that can contribute directly to cancer cell apoptosis or growth inhibition through the extrinsic pathway. Results Our in vitro experiments demonstrated that DTIC-PLA-DR5 mAb nanoparticles (DTIC-NPs-DR5 mAb) are an active targeting drug delivery system which can specifically target DR5-overexpressing malignant melanoma cells and become efficiently internalized. Most strikingly, compared with conventional DTIC-NPs, DTIC-NPs-DR5 mAb showed significantly enhanced cytotoxicity and increased cell apoptosis in DR5-positive malignant melanoma cells. Conclusion The DTIC-NPs-DR5 mAb described in this paper might be a potential formulation for targeting chemotherapy and immunotherapy to DR5-overexpressing metastatic melanoma. PMID:21976975

Tanning beds, sunlamps, and risk of cutaneous malignant melanoma.

PubMed

Gallagher, Richard P; Spinelli, John J; Lee, Tim K

2005-03-01

A number of studies have been conducted evaluating the risk of cutaneous malignant melanoma after exposure to sunlamps and/or sunbeds. The proportion of subjects in the individual studies who have reported exposure has, in general, been modest, and the resulting risk estimates for melanoma have been unstable with wide 95% confidence intervals (95% CI). The inconclusive results seen in individual studies have resulted in confusion as to the carcinogenicity of these devices. We conducted a systematic review and meta-analysis of these studies. A review of the literature from Jan 1, 1984 to April 2004 using MEDLINE identified 12 case-control studies and 1 cohort study which quantitatively evaluated the use of sunlamps and/or sunbeds and subsequent melanoma. After applying exclusion/inclusion criteria, 9 case-control and 1 cohort study provided data for the analysis. Summary odds ratios (OR) and 95% CIs for sunlamp/sunbed use and subsequent melanoma were calculated using a random-effect model. Ten studies provided data for assessment of melanoma risk among subjects who reported "ever" being exposed compared with those "never" exposed. A positive association was found between exposure and risk (summary OR, 1.25; 95% CI, 1.05-1.49). Significant heterogeneity between studies was present. Evaluation of the metrics "first exposure as a young adult" (5 studies) and "longest duration or highest frequency of exposure" (6 studies) also yielded significantly elevated risk estimates (summary OR, 1.69; 95% CI, 1.32-2.18, and 1.61; 95% CI, 1.21-2.12, respectively, with no heterogeneity in either analysis). Results indicate a significantly increased risk of cutaneous melanoma subsequent to sunbed/sunlamp exposure.

Regulation of cell cycle checkpoint kinase WEE1 by miR-195 in malignant melanoma.

PubMed

Bhattacharya, A; Schmitz, U; Wolkenhauer, O; Schönherr, M; Raatz, Y; Kunz, M

2013-06-27

WEE1 kinase has been described as a major gate keeper at the G2 cell cycle checkpoint and to be involved in tumour progression in different malignant tumours. Here we analysed the expression levels of WEE1 in a series of melanoma patient samples and melanoma cell lines using immunoblotting, quantitative real-time PCR and immunohistochemistry. WEE1 expression was significantly downregulated in patient samples of metastatic origin as compared with primary melanomas and in melanoma cell lines of high aggressiveness as compared with cell lines of low aggressiveness. Moreover, there was an inverse correlation between the expression of WEE1 and WEE1-targeting microRNA miR-195. Further analyses showed that transfection of melanoma cell lines with miR-195 indeed reduced WEE1 mRNA and protein expression in these cells. Reporter gene analysis confirmed direct targeting of the WEE1 3' untranslated region (3'UTR) by miR-195. Overexpression of miR-195 in SK-Mel-28 melanoma cells was accompanied by WEE1 reduction and significantly reduced stress-induced G2-M cell cycle arrest, which could be restored by stable overexpression of WEE1. Moreover, miR-195 overexpression and WEE1 knockdown, respectively, increased melanoma cell proliferation. miR-195 overexpression also enhanced migration and invasiveness of melanoma cells. Taken together, the present study shows that WEE1 expression in malignant melanoma is directly regulated by miR-195. miR-195-mediated downregulation of WEE1 in metastatic lesions may help to overcome cell cycle arrest under stress conditions in the local tissue microenvironment to allow unrestricted growth of tumour cells.

Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry.

PubMed

Gassenmaier, Maximilian; Eigentler, Thomas Kurt; Keim, Ulrike; Goebeler, Matthias; Fiedler, Eckhard; Schuler, Gerold; Leiter, Ulrike; Weide, Benjamin; Grischke, Eva-Maria; Martus, Peter; Garbe, Claus

2017-12-01

For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry. A multivariate binary logistic regression model was used to identify risk factors for the initial metastatic pathway. Distant metastasis-free survival (hazard ratio = 1.02; 95% confidence interval = 0.91-1.14; P = 0.76) and overall survival (HR = 1.09; 95% CI = 0.96-1.23; P = 0.177) did not differ between stage IV patients with primary hematogenous or primary lymphatic metastasis. Melanoma localization was the only significant risk factor for the initial metastatic pathway. These findings indicate that regional and distant metastases originate from the primary tumor itself in a rather parallel than serial fashion and could explain the lack of survival benefit associated with immediate complete lymph node dissection in sentinel lymph node-positive melanoma patients. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma.

PubMed

Yang, Chunhua; Cao, Hang; Liu, Ning; Xu, Kai; Ding, Meng; Mao, Li-Jun

2016-01-01

Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy.

Oncolytic adenovirus expressing interleukin-18 improves antitumor activity of dacarbazine for malignant melanoma

PubMed Central

Yang, Chunhua; Cao, Hang; Liu, Ning; Xu, Kai; Ding, Meng; Mao, Li-jun

2016-01-01

Conditionally replicating adenoviruses have emerged as novel therapeutic agents for cancer. This study aimed to evaluate synergistic antitumor activity of replication-competent adenovirus armed with interleukin (IL)-18 (ZD55-IL-18) and dacarbazine (DTIC) against melanoma. Melanoma A375 cells or nude mouse tumor xenografts were treated with ZD55-IL-18 alone or together with DTIC. The results showed that ZD55-IL-18 competently replicated in A375 cells and expressed IL-18, and these were not affected by DTIC. ZD55-IL-18 enhanced the cytotoxicity of DTIC accompanied by increased apoptosis. Moreover, ZD55-IL-18 and DTIC synergistically inhibited the growth but promoted the apoptosis of A375 xenografts and inhibited vascular endothelial growth factor expression and lung metastasis in xenografts of nude mice. In conclusion, this is the first study to show synergistic anticancer activity of ZD55-IL-18 and DTIC for malignant melanoma. Our results provide evidence that chemo-gene-viro therapeutic approach has greater potential for malignant cancers than conventional chemotherapy or gene therapy. PMID:27895465

Aberrant intermediate filament and synaptophysin expression is a frequent event in malignant melanoma: an immunohistochemical study of 73 cases.

PubMed

Romano, Ryan C; Carter, Jodi M; Folpe, Andrew L

2015-08-01

Malignant melanomas are known to express vimentin, among other intermediate filaments. Though anomalous keratin expression by malignant melanoma has been reported, its frequency is not well-established and this phenomenon is not well-known. We have seen in consultation a number of malignant melanomas with anomalous expression of keratin, other intermediate filaments, or synaptophysin, and therefore studied a large group of primary and metastatic melanomas to determine the frequency of these events. About 73 cases of malignant melanoma (22 primaries and 51 metastases) from 71 patients (51 male, 20 female; mean 59 years, range 17-87 years) were retrieved from our archives. Prior diagnoses were confirmed by re-review of hematoxylin and eosin sections and relevant (e.g., S100 protein, HMB45, Melan-A, and tyrosinase) immunohistochemical studies. Available sections were immunostained for keratin (OSCAR and AE1/AE3 antibodies), desmin, neurofilament protein, glial fibrillary acidic protein, synaptophysin, and chromogranin A. Not all cases could be tested for all markers. Cases were predominantly epithelioid (48/73, 66%) or spindle cell/desmoplastic (25/73, 34%). S100 protein, Melan-A, HMB45, and tyrosinase were positive in 60/65 (92%), 34/64 (53%), 30/60 (50%), 25/48 (52%) of cases, respectively. All five S100-protein-negative cases expressed at least one of the other melanocytic markers: Melan-A (two of four, 50%), HMB45 (two of three, 67%), and tyrosinase (one of two, 50%). All cases expressed at least one melanocytic marker. Cases were positive for keratin (OSCAR, 17/61, 28%; AE1/AE3, 16/40, 40%), desmin (11/47, 24%), neurofilament protein (5/31, 16%), glial fibrillary acidic protein (3/32, 9%), and synaptophysin (10/34, 29%), typically only in a minority of cells. Chromogranin was negative (0/32, 0%). Altogether 9/73 cases (12%) showed expression of >1 intermediate filament. All S100-protein-negative melanomas showed anomalous intermediate filament expression (keratin

Malignant melanoma and Charcot-Marie-Tooth disease: A further case

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manoukian, S.; Briscioli, V.; Lalatta, F.

1997-01-20

In a previous issue of this journal, Greene et al. described 2 patients with Charcot-Marie-Tooth (CMT) disease who later developed cutaneous malignant melanoma. Although the development of the two diseases in the same patient may have occurred by chance, the authors raised the possibility of a shared neural crest defect or a genetic linkage. Among the patients reported by Greene et al., one had a dominant form of CMT. The patient`s mother and brother were similarly affected. A paternal aunt died of melanoma. The second patient had a neuronal type of CMT. His brother showed the same disease, but themore » parents were not examined. 7 refs.« less

Breast metastasis from cutaneous malignant melanoma mimicking a breast cancer.

PubMed

Maniglio, Marina; Capalbo, Emanuela; Viganò, Sara; Trecate, Giovanna; Scaperrotta, Gianfranco Paride; Panizza, Pietro

2015-06-25

Breast metastases are very uncommon, either from solid tumors or malignant melanoma. We present the case of a 42-year-old woman with a history of cutaneous melanoma of the shoulder excised 21 years ago. She presented with a palpable lump in the upper outer quadrant of the right breast. Ultrasound demonstrated a solid mass within a cystic lesion. A core biopsy was taken and first histology reported a poorly differentiated primary breast cancer suspected to be triple negative. MRI detected a satellite lesion in the same breast, a focus of suspected enhancement in the other breast, and the extramammary finding of an enhancing pulmonary lesion. Staging computed tomography detected widespread metastases to the lungs, brain, subcutaneous left shoulder, liver, pancreas, and hepatorenal recess. A core biopsy was taken from the left breast lesion and the previous slides were reviewed; histopathology and immunohistochemistry were in keeping with metastasis from melanoma. The possibility of a metastatic lesion to the breast should be taken into account in any patient presenting with a breast lump and a previous history of melanoma. Breast involvement cannot be considered an isolated finding, as it might be the first manifestation of widespread disease.

Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma.

PubMed

Lazova, Rossitza; Yang, Zhe; El Habr, Constantin; Lim, Young; Choate, Keith Adam; Seeley, Erin H; Caprioli, Richard M; Yangqun, Li

2017-09-01

Histopathological interpretation of proliferative nodules occurring in association with congenital melanocytic nevi can be very challenging due to their similarities with congenital malignant melanoma and malignant melanoma arising in association with congenital nevi. We hereby report a diagnostically challenging case of congenital melanocytic nevus with proliferative nodules and ulcerations, which was originally misdiagnosed as congenital malignant melanoma. Subsequent histopathological examination in consultation by one of the authors (R.L.) and mass spectrometry imaging analysis rendered a diagnosis of congenital melanocytic nevus with proliferative nodules. In this case, mass spectrometry imaging, a novel method capable of distinguishing benign from malignant melanocytic lesions on a proteomic level, was instrumental in making the diagnosis of a benign nevus. We emphasize the importance of this method as an ancillary tool in the diagnosis of difficult melanocytic lesions.

Bone Metabolism of the Patient with a Malignant Melanoma during the Entry Examination and the Check-up of Whole-body Bone Scintigraphy.

PubMed

Weissensteiner, Jaroslav; Babušíková, Eva

Malignant melanoma is a malignancy located predominantly in the skin and the incidence of melanoma increases. We compared the markers of bone metabolism - osteocalcin (OC), beta-carboxyterminal cross-linked telopeptide of type I collagen (β-CrossLaps, β-CTx) and tumour marker - human epididymis protein 4 (HE4) in the serum with finding during the entry examination and the check-up of whole-body bone scintigraphy of the patient with a malignant melanoma. Serum concentrations of OC, β-CTx, HE4 were determined in 1 patient (female, age 64 years) with malignant melanoma and correlated with the presence of equivocal bone metastases detected by whole-body bone scintigraphy (the entry examination and check-up after 6 months). Concentrations of bone metabolism markers decreased during six months and we observed progress in bone metastases. The change of the markers levels during the entry examination and the check-up of the whole-body bone scintigraphy with equivocal finding of bone metastases could be a sign of a possible initiating progression of malignant melanoma despite a clinically negative finding that does not prove the progression of the disease.

Primary mucosal malignant melanoma of the cervix: case report and review of the literature.

PubMed

Cetinkaya, Kadir; Benzer, Emine; Dervisoglu, Haluk

2015-09-09

The incidence of primary mucosal malignant melanoma (PMMM) is 1.3% among all malignant melanomas (MM). Cervical involvement is very rare; the number of cases of cervical PMMM reported so far is around 80. In our patient, a dark color, 2-cm diameter, nonulcerated tumor formation was observed upon examination of the cervix. Tumoral tissue consisted of atypical melanocytic cells containing numerous mitotic figures. In immunochemical studies, S-100, Melan-A, and HMB-45 positivity were observed. The tumor was 20 mm in invasion depth, Breslow IV, and FIGO stage IB1. Radical surgery was followed by adjuvant radiotherapy, and subsequently interferon treatment was applied. Examination and scans 20 months after surgery were free from tumor.

HSP-70, C-myc and HLA-DR expression in patients with cutaneous malignant melanoma metastatic in lymph nodes.

PubMed

Kalogeraki, A; Garbagnati, F; Darivianaki, K; Delides, G S; Santinami, M; Stathopoulos, E N; Zoras, O

2006-01-01

HSP-70, C-myc and HLA-DR were examined in patients with cutaneous malignant melanoma metastatic to lymph nodes. Lymph-nodal fine-needle aspiration biopsies (FNABs) were analyzed and the results were correlated to other variables, such as the gender of the patients, Clark level and Breslow thickness of the primary tumor. Thirty cases of metastatic melanoma in lymph nodes from 30 patients with cutaneous malignant melanoma were studied. All patients (100%) had microscopic regional nodal metastasis and a recurrence of the lesion during the first two years. The HSP-70, C-myc and HLA-DR expressions were investigated immunocytologically, using the APAAP (alkaline phosphatase) method on the FNAB samples. The immunocytochemical expressions of HSP-70 protein, C-myc oncogene, and HLA-DR antigen were found in 18 cases (60%), in 14 cases (43.3%) and in 12 cases (40%), respectively. Clark levels were significantly associated with HSP-70 protein (< 0.01), C-myc oncogene expression (< 0.05) and HLA-DR antigen (< 0.01) expression. The HLA-DR antigen was also found to be related (< 0.05) to higher Breslow thickness (> 1.5 mm). The clinical course of malignant cutaneous melanoma is related to the expression of these indices, which seem to play a significant role in the metastasis and prognosis of this aggressive tumor. The immunocytochemical expression of HSP-70 in the malignant melanoma tumor could be of particular value in the identification of patients with poor prognosis.

HMB-45 and Melan-A are useful in the differential diagnosis between granular cell tumor and malignant melanoma.

PubMed

Gleason, Briana C; Nascimento, Alessandra F

2007-02-01

Granular cell tumors (GCTs), especially if atypical or malignant, may share cytomorphologic and architectural features with malignant melanoma, when the latter shows granular cell change. In many cases, these neoplasms can be differentiated from each other on histologic grounds, but distinction may sometimes be challenging. By immunohistochemistry, both tumors are strongly positive for S-100 protein and frequently express other nonspecific markers such as CD68, NSE, and NKIC3. In the current study, we reviewed 60 cases of conventional cutaneous, mucosal, and visceral GCT and studied the use of immunoperoxidase staining for the differential diagnosis between malignant melanoma and GCT. Immunohistochemical stains for S-100 protein, A, HMB-45, and microphthalmia transcription factor (MITF) were performed in all cases. All of the tumors were positive for S-100 protein. MITF immunostaining was diffusely positive in 53 (88%) cases, focally positive in three (5%) cases, and negative in four (7%). Fifty-seven (95%) tumors were negative for Melan-A, one case was focally positive, and two cases showed rare positive tumor cells. None of the tumors expressed HMB-45. In conclusion, GCT and malignant melanoma can be reliably differentiated on the basis of immunohistochemical stains in the majority of cases. Although not always positive in malignant melanoma, in this context, HMB-45 expression seems to be 100% specific for the diagnosis of melanoma. Melan-A is slightly less specific, with rare cases of GCT showing focal positivity. MITF is not useful in this differential-93% of the GCTs in our series showed nuclear reactivity for this marker. The latter finding highlights the limited specificity of this antibody in the diagnosis of melanocytic tumors.

Clinical and Pathological Significance of ER Stress Marker (BiP/GRP78 and PERK) Expression in Malignant Melanoma.

PubMed

Shimizu, Akira; Kaira, Kyoichi; Yasuda, Masahito; Asao, Takayuki; Ishikawa, Osamu

2017-01-01

Glucose-regulated protein of 78 kD (GRP78) also referred to as immunoglobulin heavy chain binding protein (BiP/GRP78) plays an important role in the endoplasmic reticulum (ER) stress. The level of BiP/GRP78 is highly elevated in various human cancers. The purpose of this study is to examine the prognostic significance of BiP/GRP78 expression in patients with malignant melanoma. A total of 133 malignant melanoma patients were analyzed, and tumor specimens were stained by immunohistochemistry for BiP/GRP78, PKR-like endoplasmic reticulum kinase (PERK), Ki-67, p53 and microvessel density (MVD) determined by CD34. BiP/GRP78 and PERK were highly expressed in 40 % (53/133) and 78 % (104/133), respectively. BiP/GRP78 disclosed a significant relationship with PERK expression, thickness, T factor, N factor, disease staging, cell proliferation (Ki-67) and MVD (CD34). By multivariate analysis, the high expression of BiP/GRP78 was identified as an independent prognostic factor for predicting poor survival against malignant melanoma. The increased BiP/GRP78 expression was clarified as an independent prognostic marker for predicting worse outcome. ER stress marker, BiP/GRP78 could be a powerful molecular target for the treatment of malignant melanoma.

Malignant anal sac melanoma in dogs: eleven cases (2000 to 2015).

PubMed

Vinayak, A; Frank, C B; Gardiner, D W; Thieman-Mankin, K M; Worley, D R

2017-04-01

To report the signalment, clinical presentation, treatments pursued and outcomes of dogs with malignant anal sac melanoma. Medical records from five institutions from January 2000 through December 2015 were reviewed and dogs with cytologically- or histologically-confirmed malignant anal sac melanoma were identified. Signalment, clinical signs, staging, cytology, histopathologic analysis, surgical and non-surgical treatments were extracted from the medical records. The referring veterinarians and owners were contacted for follow-up data. Eleven dogs were included and survival data was available for all. The most common clinical signs were bloody anal sac discharge and perianal licking. Initial treatments pursued included surgery (n=8), chemotherapy (n=1), and palliative treatment with pain medications and stool softeners (n=2). In an adjuvant setting, melanoma vaccine was pursued following surgery in three dogs and chemotherapy in one dog. Regardless of treatment, progression-free survival (mean 92 · 5 days) and overall survival times (median 107 days) were short. Dogs in this case series had a guarded to poor prognosis regardless of treatment. Ten of 11 dogs were euthanased due to local or distant disease progression. Only 1 of 11 dogs was alive one year after diagnosis. An understanding of tumour behaviour in this location could lead to improved survival times with earlier diagnosis and treatment. © 2017 British Small Animal Veterinary Association.

Serum sialyltransferase and liver catalase activity in cachectic nude mice bearing a human malignant melanoma.

PubMed

Kondo, Y; Sato, K; Ueyama, Y; Ohsawa, N

1981-07-01

Cachexia is rare in nude mice bearing human malignant tumors even when the transplanted tumors become as large as the body size of the host. In our series on heterotransplantation of a variety of human malignant tumors into nude mice, a malignant melanoma (SEKI) was found to induce severe body weight loss in the host at the early stage of transplantation. There was no electrolyte disturbance, hyper- or hypoadrenocorticism, hyperthyroidism, or destruction of cells of vital organs to account for the weight loss. Moreover, no evidence was obtained for concomitant infection with bacteria, Mycoplasma or fungi. These cachectic mice revealed remarkably increased levels of serum sialyltransferase and decreased liver catalase activity. The removal of tumor tissues from these mice resulted in prompt recovery of body weight, serum sialyltransferase, and liver catalase activity within 1 to 2 weeks. On the basis of the results obtained, the SEKI melanoma was thought to have produced a pathophysiological state in host nude mice which was very similar to that of cachexia in cancer patients. Nude mice bearing transplants of SEKI melanoma may provide a useful system for the study of cancer cachexia in humans.

Caffeine Intake, Coffee Consumption, and Risk of Cutaneous Malignant Melanoma

PubMed Central

Wu, Shaowei; Han, Jiali; Song, Fengju; Cho, Eunyoung; Gao, Xiang; Hunter, David J.; Qureshi, Abrar A.

2015-01-01

Background Caffeine has been shown to prevent ultraviolet radiation-induced carcinogenesis and to inhibit growth of melanoma cells in experimental studies. Objectives We evaluated the association between caffeine intake, coffee consumption, and melanoma risk among three large cohort studies. Methods The analysis used data from 163,886 women in the Nurses’ Health Study II (NHS II, 1991–2009) and Nurses’ Health Study (NHS, 1980–2008) and 39,424 men in the Health Professionals Follow-up Study (HPFS, 1986–2008). We used Cox proportional hazards models to estimate the hazard ratios (HR) with 95% confidence intervals (CI) of melanoma associated with dietary intakes. Results We documented 2,254 melanoma cases over 4 million person-years of follow-up. After adjustment for other risk factors, higher total caffeine intake was associated with a lower risk of melanoma (≥393 mg/d vs. <60 mg/d: HR=0.78, 95% CI=0.64–0.96, Ptrend=0.048). The association was more apparent in women (≥393 mg/d vs. <60 mg/d: HR=0.70, 95% CI=0.58–0.85, Ptrend=0.001) than in men (HR=0.94, 95% CI=0.75–1.18, Ptrend=0.81), and more apparent for melanomas occurred on the body sites with higher continuous sun exposure (head, neck and extremities) (≥393 mg/d vs. <60 mg/d: HR=0.71, 95% CI=0.59–0.86, Ptrend=0.001) than for melanomas occurred on the body sites with lower continuous sun exposure (trunk including shoulder, back, hip, abdomen and chest) (HR=0.90, 95% CI=0.70–1.16, Ptrend=0.60). This pattern of association was similar to that for caffeinated coffee consumption, whereas no association was found for decaffeinated coffee consumption and melanoma risk. Conclusions Increasing caffeine intake and caffeinated coffee consumption may be protective against cutaneous malignant melanomas. PMID:26172864

An independent validation of a gene expression signature to differentiate malignant melanoma from benign melanocytic nevi.

PubMed

Clarke, Loren E; Flake, Darl D; Busam, Klaus; Cockerell, Clay; Helm, Klaus; McNiff, Jennifer; Reed, Jon; Tschen, Jaime; Kim, Jinah; Barnhill, Raymond; Elenitsas, Rosalie; Prieto, Victor G; Nelson, Jonathan; Kimbrell, Hillary; Kolquist, Kathryn A; Brown, Krystal L; Warf, M Bryan; Roa, Benjamin B; Wenstrup, Richard J

2017-02-15

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. A set of 1400 melanocytic lesions was selected from samples prospectively submitted for gene expression testing at a clinical laboratory. Each sample was tested and subjected to an independent histopathologic evaluation by 3 experienced dermatopathologists. A primary diagnosis (benign or malignant) was assigned to each sample, and diagnostic concordance among the 3 dermatopathologists was required for inclusion in analyses. The sensitivity and specificity of the score in differentiating benign and malignant melanocytic lesions were calculated to assess the association between the score and the pathologic diagnosis. The gene expression signature differentiated benign nevi from malignant melanoma with a sensitivity of 91.5% and a specificity of 92.5%. These results reflect the performance of the gene signature in a diverse array of samples encountered in routine clinical practice. Cancer 2017;123:617-628. © 2016 American Cancer Society. © 2016 Myriad Genetics, Inc. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

VEGFR-1 expressed by malignant melanoma-initiating cells is required for tumor growth.

PubMed

Frank, Natasha Y; Schatton, Tobias; Kim, Soo; Zhan, Qian; Wilson, Brian J; Ma, Jie; Saab, Karim R; Osherov, Veronika; Widlund, Hans R; Gasser, Martin; Waaga-Gasser, Ana-Maria; Kupper, Thomas S; Murphy, George F; Frank, Markus H

2011-02-15

Melanoma growth is driven by malignant melanoma-initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member ABCB5. ABCB5(+) melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE1 and are associated with CD31(-) vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5(+) MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5(+) tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced the expression of CD144 in ABCB5(+) subpopulations that constitutively expressed VEGFR-1 but not in ABCB5(-) bulk populations that were predominantly VEGFR-1(-). In vivo, melanoma-specific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5(+) VM morphology and inhibited ABCB5(+) VM-associated production of the secreted melanoma mitogen laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by > 90%). Our results show that VEGFR-1 function in MMIC regulates VM and associated laminin production and show that this function represents one mechanism through which MMICs promote tumor growth. ©2011 AACR.

Radiation Therapy Field Extent for Adjuvant Treatment of Axillary Metastases From Malignant Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beadle, Beth M.; Guadagnolo, B. Ashleigh; Ballo, Matthew T.

2009-04-01

Purpose: To compare treatment-related outcomes and toxicity for patients with axillary lymph node metastases from malignant melanoma treated with postoperative radiation therapy (RT) to either the axilla only or both the axilla and supraclavicular fossa (extended field [EF]). Methods and Materials: The medical records of 200 consecutive patients treated with postoperative RT for axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients received postoperative hypofractionated RT for high-risk features; 95 patients (48%) received RT to the axilla only and 105 patients (52%) to the EF. Results: At a median follow-up of 59 months, 111 patients (56%) hadmore » sustained relapse, and 99 patients (50%) had died. The 5-year overall survival, disease-free survival, and distant metastasis-free survival rates were 51%, 43%, and 46%, respectively. The 5-year axillary control rate was 88%. There was no difference in axillary control rates on the basis of the treated field (89% for axilla only vs. 86% for EF; p = 0.4). Forty-seven patients (24%) developed treatment-related complications. On both univariate and multivariate analyses, only treatment with EF irradiation was significantly associated with increased treatment-related complications. Conclusions: Adjuvant hypofractionated RT to the axilla only for metastatic malignant melanoma with high-risk features is an effective method to control axillary disease. Limiting the radiation field to the axilla only produced equivalent axillary control rates to EF and resulted in lower treatment-related complication rates.« less

Significance of /sup 99m/Tc-sulfur colloid splenic image in malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berjian, R.A.; Parthasarathy, K.L.; Didolkar, M.S.

To evaluate the clinical significance of /sup 99m/Tc-sulfur-colloid (TcSC) spleen scan findings in patients with malignant melanoma, a retrospective study was undertaken. Eighty-one patients with histologically proven malignant melanoma who received treatment in Roswell Park during a five-year period were included in this study. The scans were analyzed for spleen size, differential uptake of the tracer in liver and spleen, and for the presence of metastases in these two organs. These data were compared with stage of disease, survival, and autopsy findings. Significant correlation was found between the splenic size as measured on the scintiscan and at autopsy examination. Themore » spleen size was found to be normal in 92% of the patients in early melanoma. The median survival of patients who had a normal-sized spleen by scan criteria was found to be longer than those who had splenomegaly. No significant difference in survival was noted between the patients with and without augmented splenic uptake of TcSC. Only a small number (17.7%) of patients with augmented splenic uptake had splenic metastases; hence, the possible role of immunological factors was considered.« less

Diagnosing malignant melanoma in ambulatory care: a systematic review of clinical prediction rules.

PubMed

Harrington, Emma; Clyne, Barbara; Wesseling, Nieneke; Sandhu, Harkiran; Armstrong, Laura; Bennett, Holly; Fahey, Tom

2017-03-06

Malignant melanoma has high morbidity and mortality rates. Early diagnosis improves prognosis. Clinical prediction rules (CPRs) can be used to stratify patients with symptoms of suspected malignant melanoma to improve early diagnosis. We conducted a systematic review of CPRs for melanoma diagnosis in ambulatory care. Systematic review. A comprehensive search of PubMed, EMBASE, PROSPERO, CINAHL, the Cochrane Library and SCOPUS was conducted in May 2015, using combinations of keywords and medical subject headings (MeSH) terms. Studies deriving and validating, validating or assessing the impact of a CPR for predicting melanoma diagnosis in ambulatory care were included. Data extraction and methodological quality assessment were guided by the CHARMS checklist. From 16 334 studies reviewed, 51 were included, validating the performance of 24 unique CPRs. Three impact analysis studies were identified. Five studies were set in primary care. The most commonly evaluated CPRs were the ABCD, more than one or uneven distribution of Colour, or a large (greater than 6 mm) Diameter (ABCD) dermoscopy rule (at a cut-point of >4.75; 8 studies; pooled sensitivity 0.85, 95% CI 0.73 to 0.93, specificity 0.72, 95% CI 0.65 to 0.78) and the 7-point dermoscopy checklist (at a cut-point of ≥1 recommending ruling in melanoma; 11 studies; pooled sensitivity 0.77, 95% CI 0.61 to 0.88, specificity 0.80, 95% CI 0.59 to 0.92). The methodological quality of studies varied. At their recommended cut-points, the ABCD dermoscopy rule is more useful for ruling out melanoma than the 7-point dermoscopy checklist. A focus on impact analysis will help translate melanoma risk prediction rules into useful tools for clinical practice. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Upregulation of miR-124 by physcion 8-O-β-glucopyranoside inhibits proliferation and invasion of malignant melanoma cells via repressing RLIP76.

PubMed

Zhang, Di; Han, Yantao; Xu, Luo

2016-12-01

Melanoma is the most malignant type of skin cancer. In recent years, mounting studies have evidenced the involvement of miRNAs in melanoma. One of these miRNAs, miR-124 has been found aberrantly downregulated in a variety of human malignancies. In this study, our results showed that the expression of miR-124 was significantly lower in malignant melanoma tissues and cell lines and miR-124 functioned as a tumor suppressor in melanoma. Moreover, our findings showed that miR-124 exerted anti-tumor effect by directly targeting RLIP76, a stress-inducible non-ABC transporter that plays a crucial role in the development of melanoma. Furthermore, our study also showed that physcion 8-O-β-glucopyranoside, a natural compound from medicinal plant, could inhibit the proliferation and invasion of melanoma cells by targeting miR-124/RLIP76 signaling. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mining Gene Expression Signature for the Detection of Pre-Malignant Melanocytes and Early Melanomas with Risk for Metastasis

PubMed Central

de Souza, Camila Ferreira; Xander, Patrícia; Monteiro, Ana Carolina; Silva, Amanda Gonçalves dos Santos; da Silva, Débora Castanheira Pereira; Mai, Sabine; Bernardo, Viviane; Lopes, José Daniel; Jasiulionis, Miriam Galvonas

2012-01-01

Background Metastatic melanoma is a highly aggressive skin cancer and currently resistant to systemic therapy. Melanomas may involve genetic, epigenetic and metabolic abnormalities. Evidence is emerging that epigenetic changes might play a significant role in tumor cell plasticity and metastatic phenotype of melanoma cells. Principal findings In this study, we developed a systematic approach to identify genes implicated in melanoma progression. To do this, we used the Affymetrix GeneChip Arrays to screen 34,000 mouse transcripts in melan-a melanocytes, 4C pre-malignant melanocytes, 4C11− non-metastatic and 4C11+ metastatic melanoma cell lines. The genome-wide association studies revealed pathways commonly over-represented in the transition from immortalized to pre-malignant stage, and under-represented in the transition from non-metastatic to metastatic stage. Additionally, the treatment of cells with 10 µM 5-aza-2′-deoxycytidine (5AzaCdR) for 48 hours allowed us to identify genes differentially re-expressed at specific stages of melan-a malignant transformation. Treatment of human primary melanocytes with the demethylating agent 5AzaCdR in combination to the histone deacetylase inhibitor Trichostatin A (TSA) revealed changes on melanocyte morphology and gene expression which could be an indicator of epigenetic flexibility in normal melanocytes. Moreover, changes on gene expression recognized by affecting the melanocyte biology (NDRG2 and VDR), phenotype of metastatic melanoma cells (HSPB1 and SERPINE1) and response to cancer therapy (CTCF, NSD1 and SRC) were found when Mel-2 and/or Mel-3-derived patient metastases were exposed to 5AzaCdR plus TSA treatment. Hierarchical clustering and network analyses in a panel of five patient-derived metastatic melanoma cells showed gene interactions that have never been described in melanomas. Significance Despite the heterogeneity observed in melanomas, this study demonstrates the utility of our murine melanoma

Monocytes and macrophages in malignant melanoma. III. Reduction of nitroblue tetrazolium by peripheral blood monocytes.

PubMed Central

Hedley, D. W.; Currie, G. A.

1978-01-01

Peripheral-blood monocytes from normal individuals and from patients with malignant melanoma reduce nitroblue tetrazolium (NBT). A quantitative assay for dye reduction was applied to 25 healthy donors and 31 patients with malignant melanoma. NBT reduction expressed as dye reduction per monocyte was significantly impaired in patients with disseminated disease, and they responded poorly to a phagocytic stimulus. Monocytes from patients with micrometastatic disease, however, showed normal resting NBT reduction but, following exposure to a suspension of latex-polystyrene, showed significantly greater NBT reduction than those from normal individuals. Since NBT reduction is an indirect measure of intracellular hexose-monophosphate-shunt activity we conclude that the monocytes from patients with minimal disease are in some way activated. PMID:656304

Incidence, Survival, and Mortality of Malignant Cutaneous Melanoma in Wisconsin, 1995-2011.

PubMed

Peterson, Molly; Albertini, Mark R; Remington, Patrick

2015-10-01

To assess trends in malignant melanoma incidence, survival, and mortality in Wisconsin. Incidence data for Wisconsin were obtained from the Wisconsin Cancer Reporting System Bureau of Health Information using Wisconsin Interactive Statistics on Health, while incidence data for the United States were obtained from the Surveillance, Epidemiology, and End Results system (SEER). The mortality to incidence ratio [1 - (mortality/incidence)] was used as a proxy to estimate relative 5-year survival in Wisconsin, while observed 5-year survival rates for the United States were obtained from SEER. Mortality data for both Wisconsin and the United States were extracted using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. During the past decade, malignant melanoma incidence rates increased 57% in Wisconsin (from 12.1 to 19.0 cases per 100,000) versus a 33% increase (from 20.9 to 27.7 cases per 100,000) in the United States during the same time period. The greatest Wisconsin increase in incidence was among women ages 45-64 years and among men ages 65 years and older. Overall relative percent difference in 5-year survival in Wisconsin rose 10% (from 77% to 85%) and was unchanged (82%) for the United States. Wisconsin overall mortality rates were unchanged at 2.8 deaths per 100,000, compared to a 10% increase in the United States (from 3.1 to 3.4 deaths per 100,000). Wisconsin mortality rates improved for women ages 45-64 and for men ages 25-44. Despite improvements in malignant melanoma survival rates, increases in incidence represent a major public health challenge for physicians and policymakers.

Malignant melanoma slide review project: Patients from non-Kaiser hospitals in the San Francisco Bay Area. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reynolds, P.

This project was initiated, in response to concerns that the observed excess of malignant melanoma among employees of Lawrence Livermore National Laboratory (LLNL) might reflect the incidence of disease diagnostically different than that observed in the general population. LLNL sponsored a slide review project, inviting leading dermatopathology experts to independently evaluate pathology slides from LLNL employees diagnosed with melanoma and those from a matched sample of Bay Area melanoma patients who did not work at the LLNL. The study objectives were to: Identify all 1969--1984 newly diagnosed cases of malignant melanoma among LLNL employees resident in the San Francisco-Oakland Metropolitanmore » Statistical Area, and diagnosed at facilities other than Kaiser Permanente; identify a comparison series of melanoma cases also diagnosed between 1969--1984 in non-Kaiser facilities, and matched as closely as possible to the LLNL case series by gender, race, age at diagnosis, year of diagnosis, and hospital of diagnosis; obtain pathology slides for the identified (LLNL) case and (non-LLNL) comparison patients for review by the LLNL-invited panel of dermatopathology experts; and to compare the pathologic characteristics of the case and comparison melanoma patients, as recorded by the dermatopathology panel.« less

Malignant anterior uveal melanoma with diffuse metastasis in a dog.

PubMed

Minami, T; Patnaik, A K

1992-12-15

Enucleation was performed in 10-year-old sexually intact female mixed-breed German Shepherd Dog. Histologic examination revealed that the dog had an uveal amelanotic melanoma of the eye. The tumor consisted of anaplastic cells with a high mitotic index, indicating malignancy. On examination 3 months after enucleation, the dog had difficulty breathing and nasal discharge. Radiography revealed pulmonary metastasis. The dog was euthanatized. Necropsy revealed diffuse metastasis involving various organs.

Cutaneous amelanotic signet-ring cell malignant melanoma with interspersed myofibroblastic differentiation in a young cat.

PubMed

Hirz, Manuela; Herden, Christiane

2016-07-01

The diagnosis of malignant melanoma can be difficult because these tumors can be amelanotic and may contain diverse variants and divergent differentiations, of which the signet-ring cell subtype is very rare and has only been described in humans, dogs, cats, and a hamster. We describe herein histopathologic and immunohistochemical approaches taken to diagnose a case of signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. A tumor within the abdominal skin of a 2-year-old cat was composed of signet-ring cells and irregularly interwoven streams of spindle cells. Both neoplastic cell types were periodic-acid-Schiff, Fontana, and Sudan black B negative. Signet-ring cells strongly expressed vimentin and S100 protein. Spindle cells strongly expressed vimentin and smooth muscle actin; some cells expressed S100, moderately neuron-specific enolase, and others variably actin and desmin. A few round cells expressed melan A, and a few plump spindle cells expressed melan A and PNL2, confirming the diagnosis of amelanotic signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. Differential diagnoses were excluded, including signet-ring cell forms of adenocarcinomas, lymphomas, liposarcomas, leiomyosarcomas, squamous cell carcinomas, basal cell carcinomas, and adnexal tumors. © 2016 The Author(s).

Miliary pattern of brain metastases - a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging.

PubMed

Reiter, Florian P; Giessen-Jung, Clemens; Dorostkar, Mario M; Ertl-Wagner, Birgit; Denk, Gerald U; Heck, Suzette; Rieger, Christina T; Pfister, Hans W; op den Winkel, Mark

2015-07-19

Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days. We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology. This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma.

VEGFR-1 Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Growth

PubMed Central

Frank, Natasha Y.; Schatton, Tobias; Kim, Soo; Zhan, Qian; Wilson, Brian J.; Ma, Jie; Saab, Karim R.; Osherov, Veronika; Widlund, Hans R.; Gasser, Martin; Waaga-Gasser, Ana-Maria; Kupper, Thomas S.; Murphy, George F.; Frank, Markus H.

2011-01-01

Melanoma growth is driven by malignant melanoma-initiating cells (MMIC) identified by expression of the ATP-binding cassette (ABC) member ABCB5. ABCB5+ melanoma subpopulations have been shown to overexpress the vasculogenic differentiation markers CD144 (VE-cadherin) and TIE1 and are associated with CD31− vasculogenic mimicry (VM), an established biomarker associated with increased patient mortality. Here we identify a critical role for VEGFR-1 signaling in ABCB5+ MMIC-dependent VM and tumor growth. Global gene expression analyses, validated by mRNA and protein determinations, revealed preferential expression of VEGFR-1 on ABCB5+ tumor cells purified from clinical melanomas and established melanoma lines. In vitro, VEGF induced the expression of CD144 in ABCB5+ subpopulations that constitutively expressed VEGFR-1 but not in ABCB5− bulk populations that were predominantly VEGFR-1−. In vivo, melanoma-specific shRNA-mediated knockdown of VEGFR-1 blocked the development of ABCB5+ VM morphology and inhibited ABCB5+ VM-associated production of the secreted melanoma mitogen laminin. Moreover, melanoma-specific VEGFR-1 knockdown markedly inhibited tumor growth (by >90%). Our results show that VEGFR-1 function in MMIC regulates VM and associated laminin production and show that this function represents one mechanism through which MMICs promote tumor growth. PMID:21212411

Dual-energy computed tomography in patients with cutaneous malignant melanoma: Comparison of noise-optimized and traditional virtual monoenergetic imaging.

PubMed

Martin, Simon S; Wichmann, Julian L; Weyer, Hendrik; Albrecht, Moritz H; D'Angelo, Tommaso; Leithner, Doris; Lenga, Lukas; Booz, Christian; Scholtz, Jan-Erik; Bodelle, Boris; Vogl, Thomas J; Hammerstingl, Renate

2017-10-01

The aim of this study was to investigate the impact of noise-optimized virtual monoenergetic imaging (VMI+) reconstructions on quantitative and qualitative image parameters in patients with cutaneous malignant melanoma at thoracoabdominal dual-energy computed tomography (DECT). Seventy-six patients (48 men; 66.6±13.8years) with metastatic cutaneous malignant melanoma underwent DECT of the thorax and abdomen. Images were post-processed with standard linear blending (M_0.6), traditional virtual monoenergetic (VMI), and VMI+ technique. VMI and VMI+ images were reconstructed in 10-keV intervals from 40 to 100keV. Attenuation measurements were performed in cutaneous melanoma lesions, as well as in regional lymph node, subcutaneous and in-transit metastases to calculate objective signal-to-noise (SNR) and contrast-to-noise (CNR) ratios. Five-point scales were used to evaluate overall image quality and lesion delineation by three radiologists with different levels of experience. Objective indices SNR and CNR were highest at 40-keV VMI+ series (5.6±2.6 and 12.4±3.4), significantly superior to all other reconstructions (all P<0.001). Qualitative image parameters showed highest values for 50-keV and 60-keV VMI+ reconstructions (median 5, respectively; P≤0.019) regarding overall image quality. Moreover, qualitative assessment of lesion delineation peaked in 40-keV VMI+ (median 5) and 50-keV VMI+ (median 4; P=0.055), significantly superior to all other reconstructions (all P<0.001). Low-keV noise-optimized VMI+ reconstructions substantially increase quantitative and qualitative image parameters, as well as subjective lesion delineation compared to standard image reconstruction and traditional VMI in patients with cutaneous malignant melanoma at thoracoabdominal DECT. Copyright © 2017 Elsevier B.V. All rights reserved.

Conjunctival malignant melanoma: A rare variant and review of important diagnostic and therapeutic considerations

PubMed Central

Albreiki, Danah H.; Gilberg, Steven M.; Farmer, James P.

2012-01-01

Malignant melanoma of the conjunctiva is a relatively infrequent neoplasm that can be associated with significant morbidity and cause diagnostic difficulty to both the ophthalmologist and pathologist. We herein describe the first reported case in North American and European databases of a rare variant-signet ring cell melanoma – arising in the background of primary acquired melanosis (PAM) and use this case as a review of important diagnostic and therapeutic considerations when faced with this condition. PMID:23960986

Severe sunburn and subsequent risk of primary cutaneous malignant melanoma in scotland.

PubMed Central

MacKie, R. M.; Aitchison, T.

1982-01-01

A case-control study of occupational and recreational sun exposure, Mediterranean and other sun-exposed holidays, tanning history and history of isolated episodes of severe sunburn has been carried out on 113 patients with cutaneous malignant melanoma and 113 age- and sex-matched controls. Social class and skin type were also considered in the analysis of the data which involved the use of conditional multiple logistic regression. A highly significant increase in the history of severe sunburn was recorded in melanoma patients of both sexes in the 5-year period preceding presentation with their tumour. Higher social class and negative history of recreational sun exposure were also significantly increased in patients by comparison with controls. In the male group severe sunburn, lack of occupational sun exposure and higher social class were significant factors while in the female group only severe sunburn was significantly increased in the melanoma patients. This study thus provides evidence to suggest that short intense episodes of UV exposure resulting in burning may be one of the aetiological factors involved in subsequent development of melanoma. PMID:7150488

Mucosal Malignant Melanoma of the Head and Neck Treated by Carbon Ion Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yanagi, Takeshi; Mizoe, Jun-etsu; Hasegawa, Azusa

2009-05-01

Purpose: To evaluate the efficacy of carbon ion radiotherapy for mucosal malignant melanoma of the head and neck. Methods and Materials: Between 1994 and 2004, 72 patients with mucosal malignant melanoma of the head and neck were treated with carbon ion beams in three prospective studies. Total dose ranged from 52.8 GyE to 64 GyE given in 16 fixed fractions over 4 weeks. Clinical parameters including gender, age, Karnofsky index, tumor site, tumor volume, tumor status, total dose, fraction size, and treatment time were evaluated in relation to local control and overall survival. Results: The median follow-up period was 49.2more » months (range, 16.8-108.5 months). Treatment toxicity was within acceptable limits, and no patients showed Grade 3 or higher toxicity in the late phase. The 5-year local control rate was 84.1%. In relation to local control, there were no significant differences in any parameters evaluated. The 5-year overall and cause-specific survival rates were 27.0% and 39.6%, respectively. For overall survival, however, tumor volume ({>=}100 mL) was found to be the most significant prognostic parameter. Of the patients who developed distant metastasis, 85% were free from local recurrence. Conclusion: Carbon ion radiotherapy is a safe and effective treatment for mucosal malignant melanoma of the head and neck in terms of high local control and acceptable toxicities. Overall survival rate was better than in those treated with conventional radiotherapy and was comparable to that with surgery.« less

AZD2171 in Treating Patients With Recurrent or Stage IV Melanoma

ClinicalTrials.gov

2015-06-01

Acral Lentiginous Malignant Melanoma; Ciliary Body and Choroid Melanoma, Medium/Large Size; Ciliary Body and Choroid Melanoma, Small Size; Extraocular Extension Melanoma; Intraocular Melanoma; Iris Melanoma; Lentigo Maligna Malignant Melanoma; Recurrent Melanoma; Stage, Intraocular Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

Colonisation of basal cell carcinoma and actinic keratosis by malignant melanoma in situ in a patient with xeroderma pigmentosum variant

PubMed Central

Smith, Louise J.; Husain, Ehab A.

2012-01-01

Although malignant melanoma (MM) and both basal cell carcinoma (BCC) and actinic keratosis (AK) are sun-induced lesions, the coexistence of these entities at the same anatomical site (collision tumour) is exceedingly rare. We report the case of a 54-year-old woman with a known history of xeroderma pigmentosum variant (XPV) who presented with 2 separate skin lesions over the middle and upper right forearm, respectively. The clinical impression was that of BCCs or squamous cell lesions. On histological examination, both specimens showed features of melanoma in situ (MIS). In the first lesion, MIS merged with and colonised a superficial and focally invasive BCC. In the second lesion, MIS merged with an AK. No separate invasive nests of malignant melanoma were seen in either specimen. The atypical melanocytes were highlighted by Melan-A and HMB-45 immunostaining, whereas the epithelial cells in both the BCC and AK stained with the pancytokeratin MNF-116. The patient had a previous history of multiple MMs and non-melanomatous skin cancers and finally developed widespread metastatic malignant melanoma, which proved fatal. The rare and interesting phenomenon of collision tumours may pose diagnostic difficulties. To our knowledge, this is the first reported simultaneous presentation of cytologically malignant collision tumours in a patient with XPV. PMID:24765446

Expression of VEGF(xxx)b, the inhibitory isoforms of VEGF, in malignant melanoma.

PubMed

Pritchard-Jones, R O; Dunn, D B A; Qiu, Y; Varey, A H R; Orlando, A; Rigby, H; Harper, S J; Bates, D O

2007-07-16

Malignant melanoma is the most lethal of the skin cancers and the UK incidence is rising faster than that of any other cancer. Angiogenesis - the growth of new vessels from preexisting vasculature - is an absolute requirement for tumour survival and progression beyond a few hundred microns in diameter. We previously described a class of anti-angiogenic isoforms of VEGF, VEGF(xxx)b, that inhibit tumour growth in animal models, and are downregulated in some cancers, but have not been investigated in melanoma. To determine whether VEGF(xxx)b expression was altered in melanoma, PCR and immunohistochemistry of archived human tumour samples were used. In normal epidermis and in a proportion of melanoma samples, VEGF(xxx)b staining was seen. Some melanomas had much weaker staining. Subsequent examination revealed that expression was significantly reduced in primary melanoma samples (both horizontal and vertical growth phases) from patients who subsequently developed tumour metastasis compared with those who did not (analysis of variance (ANOVA) P<0.001 metastatic vs nonmetastatic), irrespective of tumour thickness, while the surrounding epidermis showed no difference in expression. Staining for total VEGF expression showed staining in metastatic and nonmetastatic melanomas, and normal epidermis. An absence of VEGF(xxx)b expression appears to predict metastatic spread in patients with primary melanoma. These results suggest that there is a switch in splicing as part of the metastatic process, from anti-angiogenic to pro-angiogenic VEGF isoforms. This may form part of a wider metastatic splicing phenotype.

[Cutaneous malignant melanomas in New Caledonia. Study of the Cancer Registry (1977-1987)].

PubMed

Di Schino, M; Merouze, F; Huerre, M; Grimaldi, F; Lorthioir, J M; Breda, Y; Merrien, Y

1989-01-01

Investigation of cancer registration files in New Caledonia over a period of 11 years (1977-1987) draws the following conclusions: --The uncorrected incidence rate of cutaneous malignant melanoma is 3.63/100,000 inhabitants/year, for all ethnic groups together. --The incidence rate in the "non-European" population is 0.6/100,000 inhabitants/year. This low incidence and the anatomo-clinical manifestations observed (lentiginous melanoma of extremities) are common in coloured people. --The incidence rate in the "European" population is 8.75/100,000 inhabitants/year is noticeably higher than the incidence in the metropolitan population. Such conclusions are in accordance with the admitted data regarding epidemiology of cutaneous melanoma in high insolation countries. Cumulated incidence rate and topography of lesions are similar in this series whatever the sex.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China

PubMed Central

Yong, Zhong; Song, Zewen; Zhou, Yongmao; Liu, Tong; Zhang, Zizhu; Zhao, Yanzhong; Chen, Yang; Jin, Congjun; Chen, Xiang; Lu, Jianyun; Han, Rui; Li, Pengzhou; Sun, Xulong; Wang, Guohui; Shi, Guangqing; Zhu, Shaihong

2016-01-01

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world’s first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals. PMID:28174492

Melanocytoma-like melanoma may be the missing link between benign and malignant uveal melanocytic lesions in humans and dogs: a comparative study.

PubMed

Zoroquiain, Pablo; Mayo-Goldberg, Erin; Alghamdi, Sarah; Alhumaid, Sulaiman; Perlmann, Eduardo; Barros, Paulo; Mayo, Nancy; Burnier, Miguel N

2016-12-01

The cutoff presented in the current classification of canine melanocytic lesions by Wilcock and Pfeiffer is based on the clinical outcome rather than morphological concepts. Classification of tumors based on morphology or molecular signatures is the key to identifying new therapies or prognostic factors. Therefore, the aim of this study was to analyze morphological findings in canine melanocytic lesions based on classic malignant morphologic principles of neoplasia and to compare these features with human uveal melanoma (HUM) samples. In total, 64 canine and 111 human morphologically malignant melanocytic lesions were classified into two groups (melanocytoma-like or classic melanoma) based on the presence or absence of M cells, respectively. Histopathological characteristics were compared between the two groups using the χ-test, t-test, and multivariate discriminant analysis. Among the 64 canine tumors, 28 (43.7%) were classic and 36 (56.3%) were melanocytoma-like melanomas. Smaller tumor size, a higher degree of pigmentation, and lower mitotic activity distinguished melanocytoma-like from classic tumors with an accuracy of 100% for melanocytoma-like lesions. From the human series, only one case showed melanocytoma-like features and had a low risk for metastasis characteristics. Canine uveal melanoma showed a morphological spectrum with features similar to the HUM counterpart (classic melanoma) and overlapped features between uveal melanoma and melanocytoma (melanocytoma-like melanoma). Recognition that the subgroup of melanocytoma-like melanoma may represent the missing link between benign and malignant lesions could help explain the progression of uveal melanoma in dogs; these findings can potentially be translated to HUM.

Cutaneous malignant melanoma in children and adolescents treated in pediatric oncology units.

PubMed

Réguerre, Yves; Vittaz, Marie; Orbach, Daniel; Robert, Caroline; Bodemer, Christine; Mateus, Christina; Plantaz, Dominique; Plouvier, Emmanuel; Lutz, Patrick; Rakotonjanahary, Josue; Fraitag, Sylvie; Martin, Ludovic

2016-11-01

Recent progress in the understanding of tumor biology and new targeted therapies has led to improved survival in adults with malignant melanoma (MM). MM is rare in children, especially before puberty. We report here our experience with pediatric patients with MM, describe the clinical presentation, treatment and evolution, and compare prepubescent and postpubescent disease. A retrospective, descriptive, national multicenter study was undertaken of 52 cases of MM in children and adolescents. Demographic, histopathology, treatment evolution data, and survival distributions are described. Median age was 15 years (5-18). The tumors were often amelanotic (45%) and raised (83%), and Breslow thickness was greater than 4 mm in 35% of cases. Histological examination showed superficial spreading (n = 16) or spitzoid (n = 16) or nodular (n = 9) pattern. Twelve children (23%) were less than 10 years of age. The spitzoid histotype was more frequent in prepubescent children (seven of 12). Seventeen patients relapsed, of whom four had skin lesions initially diagnosed as benign. Ten patients died after relapse. Five-year event-free survival and overall survival were 62.7% (95% confidence interval [CI]: 45.3-76) and 75.5% (95% CI: 56.8-87.1), respectively. MM appears to be different in prepubescent children, of whom most had a spitzoid histotype. Diagnosis can be difficult, leading to delay in treatment. New biological tools to identify targets for treatment in MM and to differentiate spitzoid melanomas from Spitz nevi now exist. As effective targeted therapies are now available, we recommend requesting biological examination of all melanocyte-derived skin lesions in children that could be malignant. © 2016 Wiley Periodicals, Inc.

18F-FDG PET/CT in the detection of asymptomatic malignant melanoma recurrence.

PubMed

Lawal, Ismaheel; Lengana, Thabo; Ololade, Kehinde; Boshomane, Tebatso; Reyneke, Florette; Modiselle, Moshe; Vorster, Mariza; Sathekge, Mike

2017-06-12

To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed-up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.

Raspberry pulp polysaccharides inhibit tumor growth via immunopotentiation and enhance docetaxel chemotherapy against malignant melanoma in vivo.

PubMed

Yang, Yong-Jing; Xu, Han-Mei; Suo, You-Rui

2015-09-01

It has been reported previously that the systemic efficacy of chemotherapeutic agents is substantially restricted for some cancer types, including malignant melanoma. Therefore, the development of more effective treatment modalities remains a critical, albeit elusive, goal in anticancer therapy. The study presented here evaluates the antitumor activity of raspberry pulp polysaccharides (RPPs) against malignant melanoma using a murine tumor-bearing model. Furthermore, the underlying mechanism of this antitumor activity has also been investigated. The results show that while RPP exhibits no direct cytotoxic effect on HT-29, MGC-803, HeLa, Bel-7402, L02 and B16F10 cells in vitro, it does demonstrate a dose-dependent growth inhibition of melanoma in vivo with an inhibition ratio of 59.95% at a dose of 400 mg kg(-1). Besides this, the body weight and spleen index in tumor-bearing mice have also been improved in RPP-treated groups. RPP is also found to induce splenocyte proliferation and is able to upregulate the activity of immune-related enzymes, including acid phosphatase (ACP), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and superoxide dismutase (SOD) in the spleen of tumor-bearing mice. The levels of tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) and interleukin 2 (IL-2) in the serum of tumor-bearing mice show to be effectively increased upon RPP treatment. Histopathological analyses show that RPP induces tumor tissue necrosis by increasing inflammatory cell infiltration and causes no lesions to liver and kidney tissues. Remarkably, RPP further enhances the antitumor effect of the chemotherapeutic drug docetaxel and alleviates docetaxel-induced liver and kidney lesions in tumor-bearing mice. These findings indicate that RPP exhibits antitumor activity in vivo against malignant melanoma, partly by enhancing the cellular immune response of the host organism. In summary, RPP features critical properties to potentially find use as an

Thiourea derivatives, methods of their preparation and their use in neutron capture therapy of malignant melanoma

DOEpatents

Gabel, D.

1991-06-04

The present invention pertains to boron containing thiouracil derivatives, their method of preparations, and their use in the therapy of malignant melanoma using boron neutron capture therapy. No Drawings

A natural product-like JAK2/STAT3 inhibitor induces apoptosis of malignant melanoma cells

PubMed Central

Zhong, Hai-Jing; Dong, Zhen-Zhen; Vellaisamy, Kasipandi; Lu, Jin-Jian; Chen, Xiu-Ping; Chiu, Pauline; Kwong, Daniel W. J.; Han, Quan-Bin; Ma, Dik-Lung

2017-01-01

The JAK2/STAT3 signaling pathway plays a critical role in tumorigenesis, and has been suggested as a potential molecular target for anti-melanoma therapeutics. However, few JAK2 inhibitors were being tested for melanoma therapy. In this study, eight amentoflavone analogues were evaluated for their activity against human malignant melanoma cells. The most potent analogue, compound 1, inhibited the phosphorylation of JAK2 and STAT3 in human melanoma cells, but had no discernible effect on total JAK2 and STAT3 levels. A cellular thermal shift assay was performed to identify that JAK2 is engaged by 1 in cell lysates. Moreover, compound 1 showed higher antiproliferative activity against human melanoma A375 cells compared to a panel of cancer and normal cell lines. Compound 1 also activated caspase-3 and cleaved PARP, which are markers of apoptosis, and suppressed the anti-apoptotic Bcl-2 level. Finally, compound 1 induced apoptosis in 80% of treated melanoma cells. To our knowledge, compound 1 is the first amentoflavone-based JAK2 inhibitor to be investigated for use as an anti-melanoma agent. PMID:28570563

The helicase HAGE expressed by malignant melanoma-initiating cells is required for tumor cell proliferation in vivo.

PubMed

Linley, Adam J; Mathieu, Morgan G; Miles, Amanda K; Rees, Robert C; McArdle, Stephanie E B; Regad, Tarik

2012-04-20

Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells responsible for melanoma tumor growth and progression. They are defined by the expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here, we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+ MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits melanoma tumor growth mediated by this tumor-initiating population. Knockdown of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in activation of the AKT and ERK signaling pathways implicated to play an important role in melanoma progression. To confirm that the reduction in NRAS (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we showed that NRAS, effectively silenced by siRNA, could be rescued by reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor transplantation in Non-obese diabetic/severe combined immunodeficiency mice that the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant decrease in tumor growth and compared with the control. Our results suggest that the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeting HAGE helicase may have broad applications for treating malignant melanoma and potentially other cancer types.

The Helicase HAGE Expressed by Malignant Melanoma-Initiating Cells Is Required for Tumor Cell Proliferation in Vivo*

PubMed Central

Linley, Adam J.; Mathieu, Morgan G.; Miles, Amanda K.; Rees, Robert C.; McArdle, Stephanie E. B.; Regad, Tarik

2012-01-01

Malignant melanoma-initiating cells (MMIC) are a subpopulation of cells responsible for melanoma tumor growth and progression. They are defined by the expression of the ATP-binding cassette (ABC) subfamily B member 5 (ABCB5). Here, we identified a critical role for the DEAD-box helicase antigen (HAGE) in ABCB5+ MMIC-dependent tumorigenesis and show that HAGE-specific inactivation inhibits melanoma tumor growth mediated by this tumor-initiating population. Knockdown of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in activation of the AKT and ERK signaling pathways implicated to play an important role in melanoma progression. To confirm that the reduction in NRAS (Neuroblastoma RAS) expression was dependent on the HAGE helicase activity, we showed that NRAS, effectively silenced by siRNA, could be rescued by reintroduction of HAGE in cells lacking HAGE. Furthermore, we provide a mechanism by which HAGE promotes NRAS unwinding in vitro. We also observed using tumor transplantation in Non-obese diabetic/severe combined immunodeficiency mice that the HAGE knockdown in a ABCB5+ melanoma cell line displayed a significant decrease in tumor growth and compared with the control. Our results suggest that the helicase HAGE is required for ABCB5+ MMIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeting HAGE helicase may have broad applications for treating malignant melanoma and potentially other cancer types. PMID:22393060

[Molecular and immunohistochemical diagnostics in melanoma].

PubMed

Schilling, B; Griewank, K G

2016-07-01

To provide appropriate therapy and follow-up to patients with malignant melanoma, proper diagnostics are of critical importance. Targeted therapy of advanced melanoma is based on the molecular genetic analyses of tumor tissue. In addition, sequencing of genes and other genetic approaches can provide insight into the origin of melanocytic tumors and can aid in distinguishing benign from malignant lesions. In this regard, spizoid neoplasms remain a challenging entity. Aside from genetic analyses of tumor tissue, immunohistochemistry remains an essential tool in melanoma diagnostics and TNM classification. With new immunotherapies being approved for advanced melanoma, immunohistochemistry to determine PD-L1 expression has gained clinical interest. While PD-L1 expression is associated with response to PD-1 blockade, a substantial number of patients without PD-L1 expression can still experience tumor remission upon treatment. In this review, current and future developments in melanoma diagnostics with regard to molecular genetics and immunohistochemistry are summarized. The utilization of such analyses in clinical decision making is also discussed.

Sentinel lymph node biopsy in thick malignant melanoma: A 16-year single unit experience.

PubMed

Hunger, Robert E; Michel, Aude; Seyed Jafari, S Morteza; Shafighi, Maziar

2015-01-01

The role of sentinel lymph node biopsy (SLNB) and its benefits in patients with thick melanoma is still controversial. We evaluated the clinical effect of SLNB in patients with thick melanoma. We performed a retrospective cohort review (1996-2012) of thick melanomas. Collected data included the patient and tumour characteristics. Locoregional recurrence, distant metastases, disease free and overall survival were compared between the patients with positive and negative SLNB. 126 thick melanomas with a mean age of 64.09 years were included in the study. Positive SLNB were found in 47 (37.3%) patients. Significantly more locoregional recurrence (P = 0.002) and distant metastases (P = 0.030) were detected in the patients with positive SLNB. Furthermore, the patients with negative SLNB showed significantly better disease free survival (P = 0.021). Positive SLNB might be prognostic factor in thick melanoma and aggravates the outcome of thick melanomas.

The tumour suppressor, miR-137, inhibits malignant melanoma migration by targetting the TBX3 transcription factor.

PubMed

Peres, Jade; Kwesi-Maliepaard, Eliza M; Rambow, Florian; Larue, Lionel; Prince, Sharon

2017-10-01

The transcription factor, TBX3, is a key driver of malignant melanoma and any drug that impacts its expression is likely to have an impact on the treatment of this highly aggressive and treatment resistant cancer. Replacement of miRNAs that target oncogenes has gained much attention as a therapy because it is anticipated to be effective with little side-effects since miRNAs are naturally occurring and often target large set of genes in the same oncogenic pathway. Here we show that miR-137 levels correlate inversely with TBX3 mRNA levels in a panel of melanoma cell lines and in a cohort of patients with primary melanoma. Low levels of miR-137 and high levels of TBX3 are shown to be associated with poor patient survival. We show that miR-137 binds a conserved site in the TBX3 3' untranslated region and that a miR-137 mimic significantly reduces endogenous levels of TBX3 and inhibits anchorage independent growth and migration of malignant melanoma cells. Novel data are provided that the miR-137/TBX3/E-cadherin axis plays an important role in melanomagenesis and that miR-137 replacement is a potential therapeutic approach for treating melanomas. Copyright © 2017 Elsevier B.V. All rights reserved.

Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Stage IV Melanoma

ClinicalTrials.gov

2016-05-06

Acral Lentiginous Malignant Melanoma; Lentigo Maligna Malignant Melanoma; Nodular Malignant Melanoma; Recurrent Melanoma; Solar Radiation-related Skin Melanoma; Stage IV Melanoma; Superficial Spreading Malignant Melanoma

Effects of low-dose cyclophosphamide with piroxicam on tumour neovascularization in a canine oral malignant melanoma-xenografted mouse model.

PubMed

Choisunirachon, N; Jaroensong, T; Yoshida, K; Saeki, K; Mochizuki, M; Nishimura, R; Sasaki, N; Nakagawa, T

2015-12-01

Low-dose cyclophosphamide (CyLD) has shown promise in the treatment of several cancers; however, the effect of CyLD on canine oral malignant melanoma has never been explored. In this study, we investigated the effects of CyLD with or without piroxicam (Px) on tumour neovascularization and vascular normalization in a canine oral malignant melanoma-xenografted mice model. After treatment with CyLD, Px or a combination of both (CyPx), the growth of the tumour in the treatment groups was significantly suppressed compared to the control group at 30 days of treatment. Proliferation index was also significantly reduced by all treatments, only CyPx significantly lowered microvessel density and vascular endothelial growth factor (VEGF) levels. Additionally, CyLD significantly reduced the proportion of normal vessels and caused an imbalance between VEGF and thrombospondin-1. These results suggested that CyPx has potent anti-angiogenic effects in terms of both the number and quality of blood vessels in xenografted canine oral malignant melanoma. © 2013 John Wiley & Sons Ltd.

Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma.

PubMed

Stryker, W S; Stampfer, M J; Stein, E A; Kaplan, L; Louis, T A; Sober, A; Willett, W C

1990-04-01

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β

PubMed Central

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion. PMID:24707255

A Case of Malignant Melanoma with In-Transit Metastasis That Responded to Intravenous Infusion of Interferon-β.

PubMed

Arima, Masaru; Iwata, Youhei; Morita, Yusuke; Kobayashi, Tsukane; Sasaki, Ryousuke; Suzuki, Kayoko; Matsunaga, Kayoko

2014-01-01

A 77-year-old man with a history of surgical resection of malignant melanoma involving the fifth toe of his left foot 14 years ago presented at the Kariya Toyota General Hospital with a 3-month history of skin ulcer at the same site and red nodules on the lower left leg. Malignant melanoma was suspected, and the patient was referred to our department. On examination, a skin ulcer measuring 25 × 20 mm was observed at the amputation site on the left foot. In addition, multiple red nodules were observed on the lower left leg. Skin biopsies of the ulcer and nodules revealed recurrent malignant melanoma with in-transit metastasis. Two weeks later, he developed acute myocardial infarction and was hospitalized at the Kariya Toyota General Hospital. One month later, the myocardial infarction ameliorated, and he was transferred to our department. As the myocardial infarction had decreased the patient's tolerance to surgery, interferon-β was administered by intravenous infusion. The skin ulcer and red nodules on the lower left leg disappeared 26 weeks after infusion had been initiated. The patient's progress has been satisfactory, with no evidence of recurrence or metastasis at 1 year and 9 months after the initiation of intravenous infusion.

Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22.

PubMed

Luan, Wenkang; Li, Lubo; Shi, Yan; Bu, Xuefeng; Xia, Yun; Wang, Jinlong; Djangmah, Henry Siaw; Liu, Xiaohui; You, Yongping; Xu, Bin

2016-09-27

Long non-coding RNAs (lncRNAs) are involved in tumorigenesis. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), an lncRNAs, is associated with the growth and metastasis of many human tumors, but its biological roles in malignant melanoma remain unclear. In this study, the aberrant up-regulation of MALAT1 was detected in melanoma. We determined that MALAT1 promotes melanoma cells proliferation, invasion and migration by sponging miR-22. MiR-22 was decreased and acted as a tumor suppressor in melanoma, and MMP14 and Snail were the functional targets of miR-22. Furthermore, MALAT1 could modulate MMP14 and Snail by operating as a competing endogenous RNA (ceRNA) for miR-22. The effects of MALAT1 in malignant melanoma is verified using a xenograft model. This finding elucidates a new mechanism for MALAT1 in melanoma development and provides a potential target for melanoma therapeutic intervention.

Sporadic naturally occurring melanoma in dogs as a preclinical model for human melanoma

PubMed Central

Simpson, R Mark; Bastian, Boris C; Michael, Helen T; Webster, Joshua D; Prasad, Manju L; Conway, Catherine M; Prieto, Victor M; Gary, Joy M; Goldschmidt, Michael H; Esplin, D Glen; Smedley, Rebecca C; Piris, Adriano; Meuten, Donald J; Kiupel, Matti; Lee, Chyi-Chia R; Ward, Jerrold M; Dwyer, Jennifer E; Davis, Barbara J; Anver, Miriam R; Molinolo, Alfredo A; Hoover, Shelley B; Rodriguez-Canales, Jaime; Hewitt, Stephen M

2014-01-01

Melanoma represents a significant malignancy in humans and dogs. Different from genetically engineered models, sporadic canine melanocytic neoplasms share several characteristics with human disease that could make dogs a more relevant preclinical model. Canine melanomas rarely arise in sun-exposed sites. Most occur in the oral cavity, with a subset having intra-epithelial malignant melanocytes mimicking the in situ component of human mucosal melanoma. The spectrum of canine melanocytic neoplasia includes benign lesions with some analogy to nevi, as well as invasive primary melanoma, and widespread metastasis. Growing evidence of distinct subtypes in humans, differing in somatic and predisposing germ-line genetic alterations, cell of origin, epidemiology, relationship to ultraviolet radiation and progression from benign to malignant tumors, may also exist in dogs. Canine and human mucosal melanomas appear to harbor BRAF, NRAS, and c-kit mutations uncommonly, compared with human cutaneous melanomas, although both species share AKT and MAPK signaling activation. We conclude that there is significant overlap in the clinical and histopathological features of canine and human mucosal melanomas. This represents opportunity to explore canine oral cavity melanoma as a preclinical model. PMID:24128326

Melanoma Diagnosis

NASA Astrophysics Data System (ADS)

Horsch, Alexander

The chapter deals with the diagnosis of the malignant melanoma of the skin. This aggressive type of cancer with steadily growing incidence in white populations can hundred percent be cured if it is detected in an early stage. Imaging techniques, in particular dermoscopy, have contributed significantly to improvement of diagnostic accuracy in clinical settings, achieving sensitivities for melanoma experts of beyond 95% at specificities of 90% and more. Automatic computer analysis of dermoscopy images has, in preliminary studies, achieved classification rates comparable to those of experts. However, the diagnosis of melanoma requires a lot of training and experience, and at the time being, average numbers of lesions excised per histology-proven melanoma are around 30, a number which clearly is too high. Further improvements in computer dermoscopy systems and their competent use in clinical settings certainly have the potential to support efforts of improving this situation. In the chapter, medical basics, current state of melanoma diagnosis, image analysis methods, commercial dermoscopy systems, evaluation of systems, and methods and future directions are presented.

Malignant melanoma in 63 dogs (2001-2011): the effect of carboplatin chemotherapy on survival.

PubMed

Brockley, L K; Cooper, M A; Bennett, P F

2013-01-01

The aim of the study was to compare the effect of carboplatin chemotherapy on the survival of canine patients diagnosed with malignant melanoma after loco-regional control or as a sole therapy. A retrospective study of 63 dogs with oral, digital or cutaneous malignant melanoma treated with surgery and/or chemotherapy was undertaken. Dogs were grouped based on the anatomical site of melanoma development. For oral melanoma, dogs were subclassified into two groups: loco-regional control and gross disease. All patients in the digital and cutaneous groups had achieved loco-regional control with surgery. Comparisons between survival data for each group at each anatomical site were then made. Within the loco-regional control groups survival time was compared between those treated with and without chemotherapy post surgery. For the oral melanoma patients with gross disease survival was compared between those treated with chemotherapy and palliative therapy. The toxicity of carboplatin chemotherapy was evaluated overall. The overall median survival times for patients with oral, digital and cutaneous melanoma were 389, 1,350 days and not reached (with a median follow-up of 776 days) respectively. Median survival time was defined as "not reached" when less than 50% of the subjects died of the disease at the end of the follow-up period, or at the time they were lost to follow-up. The addition of chemotherapy to surgery did not confer a survival benefit in the loco-regional control setting when assessing survival for each anatomical site. For oral melanoma patients with gross disease there was no difference between survival of patients treated with chemotherapy and palliative intent therapy. There was however an improvement in survival in the three dogs that responded to chemotherapy (978 days; p=0.039) compared to the eight non-responders (147 days). On univariate and multivariate analysis, anatomic location was the only variable that was significantly related to survival (p=0

PD-L1 Promotes Self-Renewal and Tumorigenicity of Malignant Melanoma Initiating Cells

PubMed Central

Dang, Jianzhong; Zha, Hui; Zhang, Bingyu; Lin, Ming

2017-01-01

Recent studies have indicated that therapeutic antibodies targeting PD-L1 show remarkable efficacy in clinical trials in multiple tumors and that a melanoma cell-intrinsic PD-1: PD-L1 axis promotes tumor growth. However, few studies have shown tumor-intrinsic PD-L1 effects in malignant melanoma initiating cells (MMICs). Here, we aim to determine the possible regulatory effects of PD-L1 on MMICs. The ALDEFLUOR kit was used to identify ALDH+ MMICs. Flow cytometry was used to examine the expression of PD-L1 on ALDH+ MMICs. To determine the role of PD-L1 in MMICs self-renewal, we cultured melanoma cells with anti-PD-L1 and measured tumorsphere formation and apoptosis. In addition, the effects of anti-PD-L1 on tumorigenicity and residual ALDH+ MMICs in tumors were evaluated in vivo. We demonstrated that melanoma cell-intrinsic PD-L1 was expressed in ALDH+ MMICs. Blocking PD-L1 in melanoma cell lines impaired tumorsphere formation and induced the apoptosis of sphere cells. In addition, blocking PD-L1 inhibited tumor growth in vivo. We observed residual ALDH+ MMICs within the tumor. The results showed that blocking PD-L1 also significantly decreased the residual ALDH+ MMICs in the tumors. In conclusion, these results suggest a new mechanism underlying melanoma progression and PD-L1-targeted therapy, which is distinct from the immunomodulatory actions of PD-L1. PMID:29250533

Comparing initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care: A study of Irish National data.

PubMed

Doherty, Sarah M; Jackman, Louise M; Kirwan, John F; Dunne, Deirdre; O'Connor, Kieran G; Rouse, John M

2016-12-01

The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].

[Construction of recombinant lentiviral vector of Tie2-RNAi and its influence on malignant melanoma cells in vitro].

PubMed

Shan, Xiu-ying; Liu, Zhao-liang; Wang, Biao; Guo, Guo-xiang; Wang, Mei-shui; Zhuang, Fu-lian; Cai, Chuan-shu; Zhang, Ming-feng; Zhang, Yan-ding

2011-07-01

To construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells. Recombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency. The recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi. Lentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.

Combinatorial Discovery of Defined Substrates That Promote a Stem Cell State in Malignant Melanoma

PubMed Central

2017-01-01

The tumor microenvironment is implicated in orchestrating cancer cell transformation and metastasis. However, specific cell–ligand interactions between cancer cells and the extracellular matrix are difficult to decipher due to a dynamic and multivariate presentation of many signaling molecules. Here we report a versatile peptide microarray platform that is capable of screening for cancer cell phenotypic changes in response to ligand–receptor interactions. Using a screen of 78 peptide combinations derived from proteins present in the melanoma microenvironment, we identify a proteoglycan binding and bone morphogenic protein 7 (BMP7) derived sequence that selectively promotes the expression of several putative melanoma initiating cell markers. We characterize signaling associated with each of these peptides in the activation of melanoma pro-tumorigenic signaling and reveal a role for proteoglycan mediated adhesion and signaling through Smad 2/3. A defined substratum that controls the state of malignant melanoma may prove useful in spatially normalizing a heterogeneous population of tumor cells for discovery of therapeutics that target a specific state and for identifying new drug targets and reagents for intervention. PMID:28573199

Enhanced targeting of triple-negative breast carcinoma and malignant melanoma by photochemical internalization of CSPG4-targeting immunotoxins.

PubMed

Eng, M S; Kaur, J; Prasmickaite, L; Engesæter, B Ø; Weyergang, A; Skarpen, E; Berg, K; Rosenblum, M G; Mælandsmo, G M; Høgset, A; Ferrone, S; Selbo, P K

2018-05-16

Triple-negative breast cancer (TNBC) and malignant melanoma are highly aggressive cancers that widely express the cell surface chondroitin sulfate proteoglycan 4 (CSPG4/NG2). CSPG4 plays an important role in tumor cell growth and survival and promotes chemo- and radiotherapy resistance, suggesting that CSPG4 is an attractive target in cancer therapy. In the present work, we applied the drug delivery technology photochemical internalization (PCI) in combination with the novel CSPG4-targeting immunotoxin 225.28-saporin as an efficient and specific strategy to kill aggressive TNBC and amelanotic melanoma cells. Light-activation of the clinically relevant photosensitizer TPCS2a (fimaporfin) and 225.28-saporin was found to act in a synergistic manner, and was superior to both PCI of saporin and PCI-no-drug (TPCS2a + light only) in three TNBC cell lines (MDA-MB-231, MDA-MB-435 and SUM149) and two BRAFV600E mutated malignant melanoma cell lines (Melmet 1 and Melmet 5). The cytotoxic effect was highly dependent on the light dose and expression of CSPG4 since no enhanced cytotoxicity of PCI of 225.28-saporin compared to PCI of saporin was observed in the CSPG4-negative MCF-7 cells. The PCI of a smaller, and clinically relevant CSPG4-targeting toxin (scFvMEL-rGel) validated the CSPG4-targeting concept in vitro and induced a strong inhibition of tumor growth in the amelanotic melanoma xenograft A-375 model. In conclusion, the combination of the drug delivery technology PCI and CSPG4-targeting immunotoxins is an efficient, specific and light-controlled strategy for the elimination of aggressive cells of TNBC and malignant melanoma origin. This study lays the foundation for further preclinical evaluation of PCI in combination with CSPG4-targeting.

Ultrasonographic detection of regional lymph node metastases in patients with intermediate or thick malignant melanoma.

PubMed

Brountzos, Elias N; Panagiotou, Irene E; Bafaloukos, Dimitrios I; Kelekis, Dimitrios A

2003-01-01

Careful monitoring of regional lymph nodes and early detection of metastases in malignant melanoma patients has an impact on their survival, since it may permit beneficial surgical therapy. Palpation is routinely used in clinical practice. The value of ultrasonography for routine follow-up of melanoma patients, still, is not generally accepted. The aim of our study was to assess the sensitivity and specificity of ultrasound and clinical examination respectively, in the detection of melanoma regional node metastases. Additionally, we evaluated whether early detection of metastases improved overall survival. One hundred and forty-eight melanoma patients with an intermediate or thick primary lesion were followed between January 1997 and May 2001. Clinical examination and concomitant regional lymph node ultrasonography were performed, every 3-4 months. If suspicious findings were identified, regional lymph node dissection was undertaken. Forty-four from the initial 148 patients relapsed with regional lymph nodal metastases. In 11 patients (25%) palpation failed to reveal the disease and metastases were depicted only by ultrasonography. In only 1 patient ultrasonography was false-negative. The sensitivity and specificity of palpation were 72.7 and 97% respectively, while those of ultrasonography were 97.7 (p<0.001) and 98% respectively. Ultrasonography was more sensitive in detecting lymph node metastases in the axilla (100%) and the groin (93.3%). When overall survival of patients presenting with local-regional recurrence was calculated--depending on the number of involved lymph nodes--a survival benefit (p<0.05) was found for patients with only one lymph node metastasis. In conclusion, ultrasonography is superior to clinical examination in the early detection of regional lymph node metastases from an intermediate or thick malignant melanoma and should be a part of those patients' surveillance.

Malignant melanoma with a rhabdoid phenotype: histologic, immunohistochemical, and ultrastructural study of a case and review of the literature.

PubMed

Abbott, Jared J; Amirkhan, Robin H; Hoang, Mai P

2004-06-01

Malignant melanoma is known to display tremendous histologic diversity. One rare variant is the rhabdoid phenotype, so called because of the appearance of cells resembling rhabdomyoblasts seen in malignant rhabdoid tumors of the kidney. We present the histologic, immunohistochemical, and ultrastructural features of a malignant melanoma composed entirely of rhabdoid cells. A 62-year-old man presented with a 6.5-cm lung mass. Although presumed to be a metastatic lesion, extensive workup failed to reveal a primary tumor site. Histologic sections showed a mass composed entirely of polygonal neoplastic cells with prominent nucleoli and large hyaline cytoplasmic inclusions. The tumor cells were strongly immunoreactive with S100 protein, vimentin, and CD56, and were focally reactive with Mart-1. Tumor cells were negative for Melan-A, tyrosinase, HMB-45, AE1/AE3, cytokeratin (CK) 7, CK8/ 18, CK20, CK903, CAM 5.2, epithelial membrane antigen, smooth muscle actin, desmin, leukocyte common antigen, Bcl-2, CD3, CD20, CD30, CD138, kappa and lambda light chains, CD68, CD34, factor VIII, synaptophysin, and glial fibrillary acidic protein. Electron microscopy showed cytoplasmic whorls of intermediate filaments containing entrapped rough endoplasmic reticulum, mitochondria, and lipid. Recognition of this rare variant of malignant melanoma is important in the evaluation of tumors with rhabdoid morphology.

Towards new therapeutic approaches for malignant melanoma.

PubMed

Pacheco, Ivan; Buzea, Cristina; Tron, Victor

2011-11-01

Recent progress in understanding the molecular mechanisms of the initiation and progression of melanoma has created new opportunities for developing novel therapeutic modalities to manage this potentially lethal disease. Although at first glance, melanoma carcinogenesis appears to be a chaotic system, it is indeed, arguably, a deterministic multistep process involving sequential alterations of proto-oncogenes, tumour suppressors and miRNA genes. The scope of this article is to discuss the most recent and significant advances in melanoma molecular therapeutics. It is apparent that using single agents targeting solely individual melanoma pathways might be insufficient for long-term survival. However, the outstanding results on melanoma survival observed with novel selective inhibitors of B-RAF, such as PLX4032 give hope that melanoma can be cured. The fact that melanoma develops acquired resistance to PLX4032 emphasises the importance of simultaneously targeting several pathways. Because the most striking feature of melanoma is its unsurpassed ability to metastasise, it is important to implement newer systems for drug delivery adapted from research on stem cells and nanotechnology.

Topical CpG enhances the response of murine malignant melanoma to dacarbazine.

PubMed

Najar, Hossain M; Dutz, Jan P

2008-09-01

Malignant melanoma is a potentially fatal skin cancer that is increasing in incidence. Standard chemoimmunotherapy consisting of dacarbazine (DTIC) given with IFN-alpha has had disappointing results. We describe a chemoimmunotherapy protocol for cutaneous melanoma that combines the administration of DTIC with the topical application of CpG oligodinucleotide (ODN). Subcutaneous B16 melanoma tumors in C57BL/6 mice were treated with intraperitoneal injections of DTIC followed by the topical application of CpG-ODN over the tumors. This therapeutic approach abrogated the growth of established tumors and significantly enhanced survival. Topical CpG application was more effective than intratumoral CpG. Cell depletion studies indicated that the antitumor effect was dependent on both CD4(+) and CD8(+) cells but not on natural killer (NK) cells. Tumor-specific cytotoxic T-lymphocyte activity was generated in treated animals and was highest in topically treated animals. Immunohistochemical analysis revealed that DTIC, but not CpG, enhanced tumor cell apoptosis. Further, topical CpG induced an expansion of a B220(+)CD8(+) subset of dendritic cells and a subset of NK1.1(+) CD11c(+) cells within the tumors. By enhancing both tumor cell death and local immune activation, DTIC/topical CpG chemoimmunotherapy induced an effective T-cell-dependent host-immune response against melanoma.

Increased levels of circulating microparticles are associated with increased procoagulant activity in patients with cutaneous malignant melanoma.

PubMed

Laresche, Claire; Pelletier, Fabien; Garnache-Ottou, Francine; Lihoreau, Thomas; Biichlé, Sabeha; Mourey, Guillaume; Saas, Philippe; Humbert, Philippe; Seilles, Estelle; Aubin, François

2014-01-01

Microparticles (MPs) are known to be increased in various malignancies and are involved in tumor invasion, angiogenesis, coagulation, and metastasis. We investigated the plasma levels of annexin-V MPs (AV(+)MPs), platelet-derived MPs (PMPs), and endothelial-derived MPs (EMPs) in patients with melanoma (n=129) and in healthy controls (n=49). A functional coagulation test STA Procoag-PPL measuring the clotting time was performed on samples containing MPs to evaluate their procoagulant potential. The plasma levels of PMPs, EMPs, and AV(+)MPs were significantly higher, and the clotting time-PPL was significantly lower in melanoma patients than in healthy controls. The plasma levels of PMPs, EMPs, and AV(+)MPs were higher in stage IV than in the other stages of melanoma, but with no significant difference. In addition, we observed an inverse correlation between PMPs, AV(+)MPs, and clotting times. Our data suggest that MPs are involved in the progression of melanoma and may be associated to melanoma-associated thrombogenesis.

Lymphoscintigraphy mapping of truncal malignant melanoma: A study of 212 patients at the Christie NHS Foundation Trust.

PubMed

El Muntasar, Ahmed; Oudit, Deems

2017-01-01

Malignant melanoma (MM) on the trunk, because of its anatomical location, has multiple potential lymphatic basins to which to drain. The aim of this study is to map the location of the sentinel lymph node (SLN) on the basis of the anatomical location of the primary malignant melanoma on the trunk. Patients diagnosed with MM on the trunk who had undergone a SLN biopsy from January 2006 to March 2015 were identified in the Christie NHS Foundation Trust through a computer database search. The anterior and posterior surfaces of the trunk were divided into four sections each. A total of 212 patients were evaluated. MM was more common on the posterior trunk, accounting for 73% of cases, and 57% of melanomas were on the right side of the trunk. The axillary basins were involved in drainage in 91.5% of all truncal melanomas. Drainage was to a single lymphatic basin in 68.3% of cases. The incidence of drainage to multiple lymphatic basins was not uniform for the anterior and posterior surfaces of the trunks. One-third of MM on the posterior surface of the trunk will drain to multiple basins. Around 50% of the melanomas of the upper back drain to a contralateral basin. Independent of the location of the MM, the axillary basins were the most common location of drainage, with a total of 91% of the cohort. Therefore, the location of the SLN could be predicted, depending on the location of the MM on the trunk. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Vitamin C at high concentrations induces cytotoxicity in malignant melanoma but promotes tumor growth at low concentrations.

PubMed

Yang, Guang; Yan, Yao; Ma, Younan; Yang, Yixin

2017-08-01

Vitamin C has been used in complementary and alternative medicine for cancers regardless of its ineffectiveness in clinical trials and the paradoxical effects antioxidants have on cancer. Vitamin C was found to induce cytotoxicity against cancers. However, the mechanisms of action have not been fully elucidated, and the effects of vitamin C on human malignant melanoma have not been examined. This study revealed that vitamin C at millimolar concentrations significantly reduced the cell viability as well as invasiveness, and induced apoptosis in human malignant melanoma cells. Vitamin C displayed stronger cytotoxicity against the Vemurafenib-resistance cell line A2058 compared with SK-MEL-28. In contrast, vitamin C at micromolar concentrations promoted cell growth, migration and cell cycle progression, and protected against mitochondrial stress. Vemurafenib paradoxically activated the RAS-RAF-MEK-ERK signaling pathway in the Vemurafenib-resistant A2058, however, vitamin C abolished the activations. Vitamin C displayed synergistic cytotoxicity with Vemurafenib against the Vemurafenib-resistant A2058. In vivo assay suggested that lower dosage (equivalent to 0.5 g/70 kg) of vitamin C administered orally increased the melanoma growth. Therefore, vitamin C may exert pro- or anti-melanoma effect depending on concentration. The combination of vitamin C at high dosage and Vemurafenib is promising in overcoming the action of drug resistance. © 2017 Wiley Periodicals, Inc.

Efficacy and side effects of dacarbazine in comparison with temozolomide in the treatment of malignant melanoma: a meta-analysis consisting of 1314 patients.

PubMed

Teimouri, Fatemeh; Nikfar, Shekoufeh; Abdollahi, Mohammad

2013-10-01

The widespread prevalence of melanoma, one of the most malignant forms of skin cancer, is increasing rapidly. Two chemotherapeutic regimens are commonly used for the palliative treatment of malignant melanoma: intravenous administration of single-agent dacarbazine or oral administration of temozolomide. The aim of this study was to compare the effectiveness and side effects of dacarbazine with those of temozolomide through a meta-analysis. A thorough literature bibliography search was conducted up to 2012 to gather and review all randomized clinical trials comparing the use of dacarbazine with that of temozolomide in the treatment of malignant melanoma. Three head-to-head randomized clinical trials comprising 1314 patients met the criteria and were included. Comparison of temozolomide with dacarbazine yielded a nonsignificant relative risk (RR) of 0.83 [95% confidence interval (CI) = 0.26-2.64, P = 0.76] for complete response, a nonsignificant RR of 1.05 (95% CI = 0.85-1.3, P = 0.65) for stable disease, and a nonsignificant RR of 2.64 (95% CI = 0.97-1.36, P = 0.11) for disease control rate. The RR for nonhematologic side effects and hematologic side effects, such as anemia, neutropenia, and thrombocytopenia, of temozolomide compared with dacarbazine in patients with malignant melanoma was nonsignificant in all cases, but the RR for lymphopenia of temozolomide compared with dacarbazine was 3.79 (95% CI = 1.38-10.39, P = 0.01), which was significant. Although it is easier to administer oral medication, according to the results, there is no significant difference in the efficacy and side effects of these two drugs. Owing to the higher cost of treatment with temozolomide and the increased prevalence of lymphopenia on using temozolomide, use of dacarbazine as the first choice treatment for malignant melanoma is suggested.

Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma.

PubMed

Yano, Seiichi; Ashida, Kenji; Nagata, Hiromi; Ohe, Kenji; Wada, Naoko; Takeichi, Yukina; Hanada, Yuki; Ibayashi, Yuta; Wang, Lixiang; Sakamoto, Shohei; Sakamoto, Ryuichi; Uchi, Hiroshi; Shiratsuchi, Motoaki; Furue, Masutaka; Nomura, Masatoshi; Ogawa, Yoshihiro

2018-06-08

Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85 years; 54% female) were retrospectively analyzed. Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P < 0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

Time trends and latitude dependence of uveal and cutaneous malignant melanoma induced by solar radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moan, J.; Setlow, R.; Cicarma, E.

2010-01-01

In order to evaluate the role of solar radiation in uveal melanoma etiology, the time and latitude dependency of the incidence rates of this melanoma type were studied in comparison with those of cutaneous malignant melanoma (CMM). Norway and several other countries with Caucasian populations were included. There is a marked north - south gradient of the incidence rates of CMM in Norway, with three times higher rates in the south than in the north. No such gradient is found for uveal melanoma. Similar findings have been published for CMM in other Caucasian populations, with the exception of Europe asmore » a whole. In most populations the ratios of uveal melanoma incidence rates to those of CMM tend to decrease with increasing CMM rates. This is also true for Europe, in spite of the fact that in this region there is an inverse latitude gradient of CMM, with higher rates in the north than in the south. In Norway the incidence rates of CMM have increased until about 1990 but have been constant, or even decreased (for young people) after that time, indicating constant or decreasing sun exposure. The uveal melanoma rates have been increasing after 1990. In most other populations the incidence rates of CMM have been increasing until recently while those of uveal melanoma have been decreasing. These data generally support the assumption that uveal melanomas are not generated by ultraviolet (UV) radiation and that solar UV, via its role in vitamin D photosynthesis, may have a protective effect.« less

Associations of non-melanoma skin cancer and melanoma, extra-cutaneous cancers and smoking in adults: a US population-based study.

PubMed

Silverberg, J I; Ratner, D

2015-07-01

Non-melanoma skin cancer (NMSC) and melanoma are common malignancies in the US and may be associated with other types of cancer. We sought to determine whether NMSC and melanoma are associated with extra-cutaneous cancers and identify modifiable risk factors for such an association. We analysed data from 447,801 adult participants in the 1997-2011 National Health Interview Surveys. Survey logistic regression models were constructed that accounted for the complex sample weights. History of NMSC, melanoma and 27 primary extra-cutaneous cancers was assessed. NMSC was associated with increased odds of one (multinomial survey logistic regression, unadjusted odds ratio [95% CI]: 2.43 [2.20-2.68]) or multiple (2.94 [2.21-3.92]) extra-cutaneous malignancies. Melanoma was also associated with increased odds of one (3.25 [2.70-3.90]) or multiple (6.11 [4.34-8.61]) extra-cutaneous malignancies. Extra-cutaneous cancers were more common in younger patients (ages 18-39 and 40-49 years) and Caucasians with NMSC or melanoma (P < 0.0001). Smokers with a history of NMSC or melanoma had even higher odds of extra-cutaneous malignancy at ages 18-39 and 40-49 years compared to smokers without NMSC or melanoma (P < 0.0001). History of NMSC was associated with higher odds of malignancies of the bladder, brain, breast, colon, oesophagus, kidney, lung, lymphoma, melanoma, prostate, soft tissue, throat/pharynx, thyroid and uterus. Melanoma was associated with malignancies of the bladder, breast, colon, kidney, lung, pancreas, prostate, soft tissue, throat/pharynx, thyroid and uterus. The prevalence of extra-cutaneous cancers increased between 1997 and 2011 in all subjects (4.51% and 5.73%, P < 0.0001), with even higher rates of increase in those with history of NMSC or melanoma. Patients with history of NMSC and melanoma have increased odds of developing extra-cutaneous cancers, especially those with younger age and smoking history. © 2014 European Academy of Dermatology and Venereology.

Withania somnifera Root Extract Has Potent Cytotoxic Effect against Human Malignant Melanoma Cells

PubMed Central

Halder, Babli; Singh, Shruti; Thakur, Suman S.

2015-01-01

In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells. PMID:26334881

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis

PubMed Central

Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B.; da Motta, Leonardo L.; Klamt, Fabio; Ibañez, Irene L.; Durán, Hebe

2016-01-01

Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy. PMID:27206672

Reprogramming human A375 amelanotic melanoma cells by catalase overexpression: Reversion or promotion of malignancy by inducing melanogenesis or metastasis.

PubMed

Bracalente, Candelaria; Salguero, Noelia; Notcovich, Cintia; Müller, Carolina B; da Motta, Leonardo L; Klamt, Fabio; Ibañez, Irene L; Durán, Hebe

2016-07-05

Advanced melanoma is the most aggressive form of skin cancer. It is highly metastatic and dysfunctional in melanogenesis; two processes that are induced by H2O2. This work presents a melanoma cell model with low levels of H2O2 induced by catalase overexpression to study differentiation/dedifferentiation processes. Three clones (A7, C10 and G10) of human A375 amelanotic melanoma cells with quite distinct phenotypes were obtained. These clones faced H2O2 scavenging by two main strategies. One developed by clone G10 where ROS increased. This resulted in G10 migration and metastasis associated with the increased of cofilin-1 and CAP1. The other strategy was observed in clone A7 and C10, where ROS levels were maintained reversing malignant features. Particularly, C10 was not tumorigenic, while A7 reversed the amelanotic phenotype by increasing melanin content and melanocytic differentiation markers. These clones allowed the study of potential differentiation and migration markers and its association with ROS levels in vitro and in vivo, providing a new melanoma model with different degree of malignancy.

Malignant melanoma in the penguin: characterization of the clinical, histologic, and immunohistochemical features of malignant melanoma in 10 individuals from three species of penguin.

PubMed

Duncan, Ann E; Smedley, Rebecca; Anthony, Simon; Garner, Michael M

2014-09-01

Malignant melanomas are aggressive neoplasms that are relatively common in penguins compared to other avian species. In this study, the clinical and pathologic characteristics of melanocytic neoplasms in five macaroni (Eudyptes chrysolophus), three rock hopper (Eudyptes chrysocome), and two Humboldt (Spheniscus humboldti) penguins are described. Tumors most commonly occurred in the skin of the foot or hock, and were seen in the subcutaneous muscle, especially near the beak/oral cavity. Gross lesions were usually heavily pigmented, becoming raised and ulcerated over time. Humboldt penguins had a unique presentation, forming variably pigmented, cornified lesions in the inguinal area. Original case materials were obtained from all but two cases, and were assessed to define the characteristics of malignancy, evaluate four immunohistochemical markers for melanoma, and look for factors useful to informing prognosis and clinical decisions. Diagnosis was made histologically, based on morphologic features and pigmentation. Though not necessary for diagnosis, PNL-2 was found to be a useful immunohistochemical marker. HMB-45 showed unreliable positive labelling and S-100, Melan-A and Ki67 were not useful. Several factors were associated with prognosis, including gross surface dimension, mitotic index, depth of neoplastic cell invasion, and degree of surface ulceration. Metastatic spread occurred to the liver, lung, adrenal gland, brain, and bone; all lesions showed positive labelling to PNL-2. The average survival after diagnosis was 7 mo, though complete surgical excision of tumors less than 2.0 cm was curative in two cases and radiation therapy prolonged survival in one penguin. The underlying pathogenesis associated with the high prevalence of melanocytic neoplasms in captive penguins could not be identified. Three different molecular methods were performed to look for viral particles and results were negative. Advanced age is the most probable associated risk factor

Clinical Characteristics of Malignant Melanoma in Southwest China: A Single-Center Series of 82 Consecutive Cases and a Meta-Analysis of 958 Reported Cases

PubMed Central

Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui

2016-01-01

Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not

Giant melanocytic nevus with malignant melanoma: a rare disorder in a black African child.

PubMed

Katibi, Oludolapo Sherifat; Ogunbiyi, Adebola; Brown, Biobele Jotham; Adeyemi, Oyedeji Oladele

2014-10-01

Giant congenital melanocytic nevus (GCMN) is rare in babies of African descent. Unfortunately, it has an increased potential for malignant transformation. A 3-year-old female child presented with a 6-month history of multiple nodules on an existing giant congenital melanocytic nevus and swelling in the right axilla of four weeks duration. Skin biopsy of the nodular skin lesions was in keeping with a metastatic malignant melanoma (Clark stage 4). She completed a full course of chemotherapy but subsequently died four months after presentation. Patients with large GCMN should be counseled and followed up appropriately to improve and prolong life. © 2014 The International Society of Dermatology.

[Malignant melanoma of the skin: does screening for cancer influence the incidence and mortality?].

PubMed

Schubert, A

2012-03-01

The increase in incidence of malignant melanoma, early diagnosis activities increasingly reaching ever larger population groups and mortality remaining at a constant level in trend comprise the background of the study. We aimed at answering the question whether the early diagnosis can have an influence on the increase in incidence and how one can one judge the effect on the reduction of the mortality. The study is based on data from official tumour registries of the regions Saarland, Schleswig-Holstein, the administrative district Münster, the former GDR and the New Dfederal states (Berlin, Brandenburg, Mecklenburg-Vorpommern, Sachsen, Sachsen-Anhalt, Thüringen), as well as that of Queensland (Australia). Parallel to the increasing incidence, there is also an increase in the number of melanomas detected at early stages. Hence, it is obvious to assume that this increase in incidence is due to a large extent to screening programmes. In a non-determinable number of cases, overdiagnostics could have contributed to the increase in incidence. In the period of observation mortality remained constant in the regions described in this study. It can be assumed the mortality risk is influenced by tumours with a high degree of malignancy whose share in the number of melanomas remains roughly constant. The early diagnosis of cancer, the inclusion of increasingly larger groups of the populations in the regions described, and constant mortality rates for men and women during the period of observation all relate the use of early diagnosis. If the efficiency of population screening is measured against the outcome reduction of the mortality rate, it appears to be sufficient to continue cancer early detection according to SGB V § 25. A preventive check-up is indicated for risk groups, e. g., those with a positive familiar history or if potentially malignant skin alterations have been diagnosed. © Georg Thieme Verlag KG Stuttgart · New York.

CPA melanoma: diagnosis and management.

PubMed

Brackmann, Derald E; Doherty, Joni K

2007-06-01

Melanoma rarely invades the cerebellopontine angle (CPA) and can evade accurate diagnosis, which may alter management decisions. Diagnosis may be facilitated via careful history, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) analysis. Retrospective case review. Tertiary referral center. Thirteen internal auditory canal/CPA lesions in eight patients who presented with CPA syndrome and who had a pathological diagnosis consistent with malignant melanoma. There were four bilateral and four unilateral lesions. Six of eight patients had a history of melanoma. One was apparently primary CPA lesion, whereas all others were metastatic. T1- and T2-weighted precontrast and postcontrast gadolinium-enhanced MRI were obtained, including fat suppression and fluid-attenuated inversion recovery sequence images in two patients; lumbar puncture with CSF centrifugation and cytological analysis confirmed the diagnosis in two patients. Translabyrinthine craniotomy was performed for tumor extirpation in five patients. Symptoms at presentation, MRI findings, presence of malignant cells in CSF, tumor progression, intraoperative findings, response to treatment, time interval from initial diagnosis of melanoma elsewhere, and survival. Seven of eight patients had history and/or MRI findings suggestive of malignancy in the internal auditory canal and/or CPA, and diagnosis was confirmed via CSF analysis in two patients. In one patient, diagnosis was made at surgery. Internal auditory canal melanoma portends a grim prognosis, can occur up to 17 years after initial melanoma diagnosis/treatment, and can be detected with appropriate MRI sequences, especially enhanced fluid-attenuated inversion recovery images. In disseminated cases, diagnosis can be confirmed with lumbar puncture demonstrating malignant cells. Management includes tumor resection when melanoma seems to be solitary and malignant cells are not present in CSF. Intrathecal chemotherapy and radiation are

Comparing disciplines: outcomes of non melanoma cutaneous malignant lesions in oral and maxillofacial surgery and dermatology.

PubMed

Thavarajah, M; Szamocki, S; Komath, D; Cascarini, L; Heliotis, M

2015-01-01

300 cases of non-melanoma cutaneous lesion procedures carried out by the Oral and Maxillofacial Surgery and Dermatology departments in a North West London hospital over a 6 month period between September 2011 and February 2012 were included in a retrospective case control study. The results from each speciality were compared. The mean age of the OMFS group was 75.8 years compared to 69.9 years in the dermatology group. There was no statistically significant difference in gender between the 2 groups. The OMFS group treated a higher proportion of atypical (17%) and malignant (64.9%) cases compared to the dermatology group (11.3% and 50.5% respectively). This could also account for the fact that the OMFS group carried out a higher number of full excisions compared to dermatology. Both groups had a similar number of false positives (a benign lesion initially diagnosed as malignant) and a similar proportion of false negatives (a malignant lesion initially diagnosed as benign). Overall, the results show that both specialities had similar outcomes when managing non-melanoma cutaneous lesions. Both groups adhere to the guidelines set out by the British Association of Dermatologists and the National Institute of Clinical Excellence when managing such lesions. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Trends in the presentation of cutaneous malignant melanoma over three decades at King's College Hospital, London.

PubMed

Harman, K E; Fuller, L C; Salisbury, J R; Higgins, E M; du Vivier, A W P

2004-09-01

The aim of this study was to examine trends in the presentation of cutaneous malignant melanoma at King's College Hospital (KCH) over the last three decades (1970-2000). KCH was one of seven centres that participated in the 1987 Cancer Research Campaign (CRC) publicity campaign aimed at promoting earlier self-recognition of melanoma. Data included patient age at presentation, sex, tumour site, Breslow thickness and histological subtype. The late 1980s saw a threefold increase in the annual number of melanomas and an eightfold increase in thin melanomas compared to the 1970s. The increase occurred in both sexes and was particularly marked after the CRC campaign but numbers had already begun to increase prior to this. The increase has predominantly been thin (Breslow < 1.5 mm) tumours of the superficial spreading variety with a resultant fall in mean Breslow thickness. There has been a decline in the annual number of melanomas since the peak in 1992 which is not explained by increased proportion of in situ tumours. The CRC campaign may have contributed to the documented increase in thin tumours but this trend had begun prior to 1987 suggesting factors other than public awareness and earlier presentation are important. It is encouraging that the number of melanomas has declined over the last 5 years at KCH but it is yet to be seen whether this reflects a real decrease in the incidence of melanoma.

[Evaluation of inflammatory cells (tumor infiltrating lymphocytes - TIL) in malignant melanoma].

PubMed

Dundr, Pavel; Němejcová, Kristýna; Bártů, Michaela; Tichá, Ivana; Jakša, Radek

2018-01-01

The evaluation of inflammatory infiltrate (tumor infiltrating lymphocytes - TIL) should be a standard part of biopsy examination for malignant melanoma. Currently, the most commonly used assessment method according to Clark is not optimal and there have been attempts to find an alternative system. Here we present an overview of possible approaches involving five different evaluation methods based on hematoxylin-eosin staining, including the recent suggestion of unified TIL evaluation method for all solid tumors. The issue of methodology, prognostic and predictive significance of TIL determination as well as the importance of immunohistochemical subtyping of inflammatory infiltrate is discussed.

A mathematical analysis of the ABCD criteria for diagnosing malignant melanoma

NASA Astrophysics Data System (ADS)

Lee, Hyunju; Kwon, Kiwoon

2017-03-01

The medical community currently employs the ABCD (asymmetry, border irregularity, color variegation, and diameter of the lesion) criteria in the early diagnosis of a malignant melanoma. Although many image segmentation and classification methods are used to analyze the ABCD criteria, it is rare to see a study containing mathematical justification of the parameters that are used to quantify the ABCD criteria. In this paper, we suggest new parameters to assess asymmetry, border irregularity, and color variegation, and explain the mathematical meaning of the parameters. The suggested parameters are then tested with 24 skin samples. The parameters suggested for the 24 skin samples are displayed in three-dimensional coordinates and are compared to those presented in other studies (Ercal et al 1994 IEEE Trans. Biomed. Eng. 41 837-45, Cheerla and Frazier 2014 Int. J. Innovative Res. Sci., Eng. Technol. 3 9164-83) in terms of Pearson correlation coefficient and classification accuracy in determining the malignancy of the lesions.

Repressing CD147 is a novel therapeutic strategy for malignant melanoma

PubMed Central

Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

2017-01-01

CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM. PMID:28445958

Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

PubMed

Hu, Xing; Su, Juan; Zhou, Youyou; Xie, Xiaoyun; Peng, Cong; Yuan, Zhimin; Chen, Xiang

2017-04-11

CD147/basigin, a transmembrane protein, is a member of the immunoglobulin super family. Accumulating evidence has revealed the role of CD147 in the development and progression of various cancers, including malignant melanoma (MM). MM is a malignancy of pigment-producing cells that causes the greatest number of skin cancer-related deaths worldwide. CD147 is overexpressed in MM and plays an important role in cell viability, apoptosis, proliferation, invasion, and metastasis, probably by mediating vascular endothelial growth factor (VEGF) production, glycolysis, and multi-drug resistance (MDR). As a matrix metalloproteinase (MMP) inducer, CD147 could also promote surrounding fibroblasts to secrete abundant MMPs to further stimulate tumor cell invasion. Targeting CD147 has been shown to suppress MM in vitro and in vivo, highlighting the therapeutic potential of CD147 silencing in MM treatment. In this review article, we discuss CD147 and its biological roles, regulatory mechanisms, and potential application as a molecular target for MM.

Genetics of metastasis: melanoma and other cancers.

PubMed

Turner, Noel; Ware, Olivia; Bosenberg, Marcus

2018-05-02

Melanoma is a malignant neoplasm of melanocytes that accounts for the majority of skin cancer deaths despite comprising less than 5% of all cutaneous malignancies. Its incidence has increased faster than that of any other cancer over the past half-century and the annual costs of treatment in the United States alone have risen rapidly. Although the majority of primary melanomas are cured with local excision, metastatic melanoma historically carries a grim prognosis, with a median survival of 9 months and a long-term survival rate of 10%. Given the urgent need to develop treatment strategies for metastatic melanoma and the explosion of genetic technologies over the past 20 years, there has been extensive research into the genetic alterations that cause melanocytes to become malignant. More recently, efforts have focused on the genetic changes that drive melanoma metastasis. This review aims to summarize the current knowledge of the genetics of primary cutaneous and ocular melanoma, the genetic changes associated with metastasis in melanoma and other cancer types, and non-genetic factors that may contribute to metastasis.

Congenital nevi versus metastatic melanoma in a newborn to a mother with malignant melanoma - diagnosis supported by sex chromosome analysis and Imaging Mass Spectrometry.

PubMed

Alomari, Ahmed K; Glusac, Earl J; Choi, Jennifer; Hui, Pei; Seeley, Erin H; Caprioli, Richard M; Watsky, Kalman L; Urban, Jennifer; Lazova, Rossitza

2015-10-01

A 37-year-old pregnant woman presented with a 2-cm irregular reddish nodule on her left upper arm during pregnancy. A biopsy from the lesion showed a 2.2-mm thick malignant melanoma with intravascular invasion, 25 mitosis/mm(2) and no ulceration. Following induction of labor, the patient underwent re-excision with sentinel lymph node biopsy. This showed no residual melanoma and no lymph node metastasis. The newborn boy had multiple pigmented lesions on the trunk, some of which were large and irregular. Two were biopsied and histologic examination showed dense dermal proliferation of medium sized melanocytes with multiple mitotic figures and no maturation with their descent into the dermis, raising suspicion of transplacental metastases. Examination of the placenta failed to show metastatic lesions. Multiplex polymerase chain reaction (PCR)-based genotyping, including testing for amelogenin locus for sex chromosome determination, demonstrated the presence of Y chromosome material in the melanocytes of the newborn's lesions excluding maternal origin. A diagnosis of congenital nevi was rendered. Subsequently, Imaging Mass Spectrometric analysis of the mother's lesion showed proteomic signature expression indicative of malignant melanoma, whereas the two lesions in the newborn showed changes indicative of nevi. This case demonstrates the utility of genotyping and Mass Spectrometry analysis in this challenging clinical scenario. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The ''hot spleen'' phenomenon in metastatic malignant melanoma: its incidence and relationship with the immune system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wagstaff, J.; Phadke, K.; Adam, N.

1982-02-01

Of patients with Stage II and III malignant melanoma, 34.7% display reversal of the liver-spleen ratio on technetium-99m-sulfhur colloid isotope scans. Such an occurrence does not suggest a greater likelihood of relapse or a worse survival. The phenomenom is more common in female patients and there is a significant relationship between the presence of a ''hot spleen'' and a high IgM level. Patients with Stage II disease and high IgM levels have relapses more quickly than do those with normal IgM levels. Lymphopenia is common in patients with Stage II and III disease and the survival of these patients ismore » worse than that of those with normal lymphocyte counts. In this report, the data are discussed together with results from other investigations, and a unifying hypothesis is presented which explains the phenomenon and relates it to increased activity of macrophages as a result of the presence of the tumor. The usefulness of isotope liver scanning in stage III malignant melanoma is also discussed.« less

Riluzole and Sorafenib Tosylate in Treating Patients With Advanced Solid Tumors or Melanoma

ClinicalTrials.gov

2018-05-15

Advanced Malignant Solid Neoplasm; Recurrent Melanoma; Refractory Malignant Solid Neoplasm; Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7

Mechanisms of Tanshinone II a inhibits malignant melanoma development through blocking autophagy signal transduction in A375 cell.

PubMed

Li, Xiaojing; Li, Zhifeng; Li, Xianping; Liu, Baoguo; Liu, Zhijun

2017-05-22

Malignant melanoma (MM) is one of the high degree of malignancy and early prone to blood and lymph node metastasis. There is not cured for MM. Tan II A has been reported to reduce cancer cell proliferation. But the mechanism by which Tan II A inhibited melanoma growth are not well characterized. We sought to explore the possible mechanism by which Tan II A regulated cell proliferation through autophagy signaling pathway in A375 cells. We tested the effects of Tan II A on melanoma A375, MV3, M14, and other human cell lines including Hacat and HUVEC cells in cell culture model. Cell proliferation was assessed by using methyl thiazol tetrazolium (MTT) assay. Cell migration ability melanoma A375 was monitored by using cell scratch assay. Transwell chamber experimental was performed to assess the effect of Tan II A on A375 melanoma cell invasion ability. The autophagy body was examined by using flow cytometry. The expression of autophagy-associated protein beclin-1 and microtubule-associated protein 1 light chain 3(LC3)-II, as well as phosphatidylinositol 3-kinase(PI3K)、protein kinase B (Akt)、mammalian target of rapamycin (mTOR)、p70S6K1 signaling pathways were detected by using Western blotting. The effects of Tan II A on tumor progression was also examined in melanoma A375 induced tumor in mouse model. We found that Tan IIA inhibited melanoma A375, MV3, and M14 cell proliferation in dose and time dependent manner. Tan II A reduced CXCL12-induced A375 cell invasive ability and migration in a dose dependent manner. Tan IIA promoted autophagic body production and increased autophagy-associated protein beclin-1 and LC3-II expression in A375 cells. However, Tan IIA reduced the phosphorylation of PI3K, P-AKT, P-mTOR, and P-p7036k1. We also confirmed that Tan II A reduced melanoma A375 induced tumor volume and weight in mouse model. We concluded that Tan II A reduced A375 cells proliferation by activation of autophagy production, blocked PI3K- Akt - mTOR - p70S6K1

Endoscopic transnasal management of sinonasal malignancies – our initial experience

PubMed Central

Osuch-Wójcikiewicz, Ewa; Held-Ziółkowska, Marta; Kużmińska, Magdalena; Niemczyk, Kazimierz

2014-01-01

Introduction Malignant tumors of the paranasal sinuses are traditionally managed through external approaches. Advances in endoscopic transnasal surgery have allowed for the endoscopic treatment of some of these tumors. Aim To present the results of treatment of a series of patients with paranasal sinus malignancies treated with an endoscopic approach at a single institution. Material and methods The data on tumor type, operative technique, perioperative complications and postoperative course were analyzed. Results Eleven patients meeting the inclusion criteria were identified. The histopathology was as follows: malignant melanoma in 3 patients, squamous cell carcinoma in 2, adenocarcinoma in 2, poorly differentiated carcinoma in 1, hemangiopericytoma in 1, adenoid cystic carcinoma in 1 and fibrosarcoma in 1. There were no severe perioperative complications with the exception of 1 case of cerebrospinal fluid leak, which was successfully closed. The mean observation period was 13.5 months. One of the patients died of disease, another was lost to follow-up, and one was reoperated on due to recurrence. The remaining 8 patients are alive with no signs of recurrence. Conclusions Our initial experience seems to confirm results obtained by other authors indicating that in selected cases endoscopic surgery of sinonasal malignancies is similarly effective as external approach surgery. PMID:25097677

Intra-arterial 4-hydroxyanisole chemotherapy for locally recurrent malignant melanoma: a re-appraisal.

PubMed

Belcher, H J; Nizam, M; O'Neill, T J

1992-04-01

Ten female patients with recurrent cutaneous malignant melanoma (MM) confined to the lower limb were treated with 4-hydroxyanisole (4HA) infused intra-arterially. 10 g of 4HA was infused twice per day up to a maximum dose of 80 g. 4HA infusion caused significant alterations in liver function which precluded completion of the treatment regimen in all but two patients. No tumour regression was observed in any patient. We cannot recommend this technique for managing patients with recurrent cutaneous MM.

Exosome-mediated transfer of miR-222 is sufficient to increase tumor malignancy in melanoma.

PubMed

Felicetti, Federica; De Feo, Alessandra; Coscia, Carolina; Puglisi, Rossella; Pedini, Francesca; Pasquini, Luca; Bellenghi, Maria; Errico, Maria Cristina; Pagani, Elena; Carè, Alessandra

2016-02-24

Growing evidence is showing that metastatic cell populations are able to transfer their characteristics to less malignant cells. Exosomes (EXOs) are membrane vesicles of endocytic origin able to convey their cargo of mRNAs, microRNAs (miRs), proteins and lipids from donors to proximal as well as distant acceptor cells. Our previous results indicated that miR-221&222 are key factors for melanoma development and dissemination. The aim of this study was to verify whether the tumorigenic properties associated with miR-222 overexpression can be also propagated by miR-222-containing EXOs. EXOs were isolated by UltraCentrifugation or Exoquick-TC(®) methods. Preparations of melanoma-derived vesicles were characterized by using the Nanosight™ technology and the expression of exosome markers analyzed by western blot. The expression levels of endogenous and exosomal miRNAs were examined by real time PCR. Confocal microscopy was used to evaluate transfer and uptake of microvesicles from donor to recipient cells. The functional significance of exosomal miR-222 was estimated by analyzing the vessel-like process formation, as well as cell cycle rates, invasive and chemotactic capabilities. Besides microvesicle marker characterization, we evidenced that miR-222 exosomal expression mostly reflected its abundance in the cells of origin, correctly paralleled by repression of its target genes, such as p27Kip1, and induction of the PI3K/AKT pathway, thus confirming its functional implication in cancer. The possible differential significance of PI3K/AKT blockade was assessed by using the BKM120 inhibitor in miR-222-transduced cell lines. In addition, in vitro cultures showed that vesicles released by miR-222-overexpressing cells were able to transfer miR-222-dependent malignancy when taken-up by recipient primary melanomas. Results were confirmed by antagomiR-221&222 treatments and by functional observations after internalization of EXOs devoid of these miRs. All together these data

Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma.

PubMed

Blüher, Susann; Schulz, Manuela; Bierbach, Uta; Meixensberger, Jürgen; Tröbs, Ralf-Bodo; Hirsch, Wolfgang; Schober, Ralf; Kiess, Wieland; Siekmeyer, Werner

2008-04-01

Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected.

Comparative Aspects of Canine Melanoma

PubMed Central

Nishiya, Adriana Tomoko; Massoco, Cristina Oliveira; Felizzola, Claudia Ronca; Perlmann, Eduardo; Batschinski, Karen; Tedardi, Marcello Vannucci; Garcia, Jéssica Soares; Mendonça, Priscila Pedra; Teixeira, Tarso Felipe; Zaidan Dagli, Maria Lucia

2016-01-01

Melanomas are malignant neoplasms originating from melanocytes. They occur in most animal species, but the dog is considered the best animal model for the disease. Melanomas in dogs are most frequently found in the buccal cavity, but the skin, eyes, and digits are other common locations for these neoplasms. The aim of this review is to report etiological, epidemiological, pathological, and molecular aspects of melanomas in dogs. Furthermore, the particular biological behaviors of these tumors in the different body locations are shown. Insights into the therapeutic approaches are described. Surgery, chemotherapy, radiotherapy, immunotherapy, and the outcomes after these treatments are presented. New therapeutic perspectives are also depicted. All efforts are geared toward better characterization and control of malignant melanomas in dogs, for the benefit of these companion animals, and also in an attempt to benefit the treatment of human melanomas. PMID:29056717

Sunburn, suntan and the risk of cutaneous malignant melanoma--The Western Canada Melanoma Study.

PubMed Central

Elwood, J. M.; Gallagher, R. P.; Davison, J.; Hill, G. B.

1985-01-01

A comparison of interview data on 595 patients with newly incident cutaneous melanoma, excluding lentigo maligna melanoma and acral lentiginous melanoma, with data from comparison subjects drawn from the general population, showed that melanoma risk increased in association with the frequency and severity of past episodes of sunburn, and also that melanoma risk was higher in subjects who usually had a relatively mild degree of suntan compared to those with moderate or deep suntan in both winter and summer. The associations with sunburn and with suntan were independent. Melanoma risk is also increased in association with a tendency to burn easily and tan poorly and with pigmentation characteristics of light hair and skin colour, and history freckles; the associations with sunburn and suntan are no longer significant when these other factors are taken into account. This shows that pigmentation characteristics, and the usual skin reaction to sun, are more closely associated with melanoma risk than are sunburn and suntan histories. PMID:3978032

Sunnier European countries have lower melanoma mortality.

PubMed

Shipman, A R; Clark, A B; Levell, N J

2011-07-01

Doubt has been cast on sunlight as the major causative factor for malignant melanoma. We performed statistical analysis of the average annual sunlight hours in 36 European capital cities compared with the country's melanoma mortality rate. A significant inverse proportionality was identified in both men and women, indicating that sun exposure is unlikely to be the strongest factor affecting mortality from malignant melanoma. © The Author(s). CED © 2011 British Association of Dermatologists.

Morphogenesis of early stage melanoma

NASA Astrophysics Data System (ADS)

Chatelain, Clément; Amar, Martine Ben

2015-08-01

Melanoma early detection is possible by simple skin examination and can insure a high survival probability when successful. However it requires efficient methods for identifying malignant lesions from common moles. This paper provides an overview first of the biological and physical mechanisms controlling melanoma early evolution, and then of the clinical tools available today for detecting melanoma in vivo at an early stage. It highlights the lack of diagnosis methods rationally linking macroscopic observables to the microscopic properties of the tissue, which define the malignancy of the tumor. The possible inputs of multiscale models for improving these methods are shortly discussed.

Improved malignant melanoma prognosis at a consultant-delivered multidisciplinary pigmented lesion clinic in Cork.

PubMed

Field, S; Deady, S; Fitzgibbon, J; Murphy, M; Comber, H

2010-02-01

Early detection and excision is the only effective treatment for malignant melanoma. To assess the effect of a consultant-delivered, rapid-access pigmented lesion clinic (PLC) established at the South Infirmary-Victoria University Hospital (SIVUH), we analyzed melanoma tumour-stage prior to (1998-2002) and after (2003-2007) the advent of the PLC. Patients attending SIVUH had a greater proportion of early-stage tumours (65.3%) compared to the rest of Cork (51.2%), County Cork as a whole (56.7%) and all of Ireland (57.4%). The proportion of SIVUH males with early-stage tumours was statistically significantly higher than the rest of County Cork (chi2 = 11.23, P < 0.05). The proportion of patients > 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P < 0.05), the whole of County Cork (chi2 = 7.84, P < 0.05) and all of Ireland (chi2 = 9.67, P < 0.05). We believe that the early detection and improved prognosis of Cork melanoma patients is at least partly due to the PLC.

Mucosal malignant melanoma - a clinical, oncological, pathological and genetic survey.

PubMed

Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian; Drzewiecki, Krzysztof T; Prause, Jan U; Heegaard, Steffen

2016-06-01

Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). © 2016 APMIS. Published by John Wiley & Sons Ltd.

Nonpigmented Metastatic Melanoma in a Two-Year-Old Girl: A Serious Diagnostic Dilemma

PubMed Central

Diniz, Gulden; Tosun Yildirim, Hulya; Yamaci, Selcen

2015-01-01

Although rare, malignant melanoma may occur in children. Childhood melanomas account for only 0.3–3% of all melanomas. In particular the presence of congenital melanocytic nevi is associated with an increased risk of development of melanoma. We herein report a case of malignant melanoma that developed on a giant congenital melanocytic nevus and made a metastasis to the subcutaneous tissue of neck in a two-year-old girl. The patient was hospitalized for differential diagnosis and treatment of cervical mass with a suspicion of hematological malignancy, because the malignant transformation of congenital nevus was not noticed before. In this case, we found out a nonpigmented malignant tumor of pleomorphic cells after the microscopic examination of subcutaneous lesion. Nonpigmented metastatic melanoma was diagnosed by several immunohistochemical and flow cytometric studies. She was offered palliative chemotherapy; however, her parents did not accept treatment. The patient died within 9 months of diagnosis. We emphasized here that the possibility of malignant melanoma in the differential diagnosis of childhood tumors should be kept in mind. PMID:25763285

Hereditary Melanoma: Update on Syndromes and Management - Genetics of familial atypical multiple mole melanoma syndrome

PubMed Central

Soura, E.; Eliades, P.; Shannon, K.; Stratigos, A.; Tsao, H.

2015-01-01

Malignant melanoma is considered the most lethal skin cancer if not detected and treated at its early stages. About 10% of melanoma patients report a family history of melanoma; however, individuals with features of true hereditary melanoma (i.e. unilateral lineage, multi-generational, multiple primary lesions, and early onset of disease) are in fact quite rare. Although many new loci have been implicated in hereditary melanoma, CDKN2A mutations remain the most common. Familial melanoma in the presence of multiple atypical nevi should raise suspicion for a germline CDKN2A mutation. Such patients have a high risk of developing multiple primary melanomas and internal organ malignancies especially pancreatic cancer; thus, a multidisciplinary approach is necessary in many cases. The value of dermoscopy examination and total body photography performed at regular intervals has been suggested by a number of studies, and should therefore be considered for these patients and their first degree relatives. In addition, genetic counseling with the possibility of testing can be a valuable adjunct for familial melanoma patients. But, this must be performed with care and only by qualified individuals trained in cancer risk analysis. PMID:26892650

Validating malignant melanoma ICD-9-CM codes in Umbria, ASL Napoli 3 Sud and Friuli Venezia Giulia administrative healthcare databases: a diagnostic accuracy study

PubMed Central

Orso, Massimiliano; Serraino, Diego; Fusco, Mario; Giovannini, Gianni; Casucci, Paola; Cozzolino, Francesco; Granata, Annalisa; Gobbato, Michele; Stracci, Fabrizio; Ciullo, Valerio; Vitale, Maria Francesca; Orlandi, Walter; Montedori, Alessandro; Bidoli, Ettore

2018-01-01

Objectives To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying subjects with melanoma. Design A diagnostic accuracy study comparing melanoma ICD-9-CM codes (index test) with medical chart (reference standard). Case ascertainment was based on neoplastic lesion of the skin and a histological diagnosis from a primary or metastatic site positive for melanoma. Setting Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli Venezia Giulia (FVG) Region. Participants 112, 130 and 130 cases (subjects with melanoma) were randomly selected from Umbria, NA and FVG, respectively; 94 non-cases (subjects without melanoma) were randomly selected from each unit. Outcome measures Sensitivity and specificity for ICD-9-CM code 172.x located in primary position. Results The most common melanoma subtype was malignant melanoma of skin of trunk, except scrotum (ICD-9-CM code: 172.5), followed by malignant melanoma of skin of lower limb, including hip (ICD-9-CM code: 172.7). The mean age of the patients ranged from 60 to 61 years. Most of the diagnoses were performed in surgical departments. The sensitivities were 100% (95% CI 96% to 100%) for Umbria, 99% (95% CI 94% to 100%) for NA and 98% (95% CI 93% to 100%) for FVG. The specificities were 88% (95% CI 80% to 93%) for Umbria, 77% (95% CI 69% to 85%) for NA and 79% (95% CI 71% to 86%) for FVG. Conclusions The case definition for melanoma based on clinical or instrumental diagnosis, confirmed by histological examination, showed excellent sensitivities and good specificities in the three operative units. Administrative databases from the three operative units can be used for epidemiological and outcome research of melanoma. PMID:29678984

Validating malignant melanoma ICD-9-CM codes in Umbria, ASL Napoli 3 Sud and Friuli Venezia Giulia administrative healthcare databases: a diagnostic accuracy study.

PubMed

Orso, Massimiliano; Serraino, Diego; Abraha, Iosief; Fusco, Mario; Giovannini, Gianni; Casucci, Paola; Cozzolino, Francesco; Granata, Annalisa; Gobbato, Michele; Stracci, Fabrizio; Ciullo, Valerio; Vitale, Maria Francesca; Eusebi, Paolo; Orlandi, Walter; Montedori, Alessandro; Bidoli, Ettore

2018-04-20

To assess the accuracy of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes in identifying subjects with melanoma. A diagnostic accuracy study comparing melanoma ICD-9-CM codes (index test) with medical chart (reference standard). Case ascertainment was based on neoplastic lesion of the skin and a histological diagnosis from a primary or metastatic site positive for melanoma. Administrative databases from Umbria Region, Azienda Sanitaria Locale (ASL) Napoli 3 Sud (NA) and Friuli Venezia Giulia (FVG) Region. 112, 130 and 130 cases (subjects with melanoma) were randomly selected from Umbria, NA and FVG, respectively; 94 non-cases (subjects without melanoma) were randomly selected from each unit. Sensitivity and specificity for ICD-9-CM code 172.x located in primary position. The most common melanoma subtype was malignant melanoma of skin of trunk, except scrotum (ICD-9-CM code: 172.5), followed by malignant melanoma of skin of lower limb, including hip (ICD-9-CM code: 172.7). The mean age of the patients ranged from 60 to 61 years. Most of the diagnoses were performed in surgical departments.The sensitivities were 100% (95% CI 96% to 100%) for Umbria, 99% (95% CI 94% to 100%) for NA and 98% (95% CI 93% to 100%) for FVG. The specificities were 88% (95% CI 80% to 93%) for Umbria, 77% (95% CI 69% to 85%) for NA and 79% (95% CI 71% to 86%) for FVG. The case definition for melanoma based on clinical or instrumental diagnosis, confirmed by histological examination, showed excellent sensitivities and good specificities in the three operative units. Administrative databases from the three operative units can be used for epidemiological and outcome research of melanoma. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Hypersensitivity to dacarbazine in patients with metastatic malignant melanoma].

PubMed

Levy, A; Guitera, P; Kerob, D; Ollivaud, L; Archimbaud, A; Dubertret, L; Basset-Seguin, N

2006-02-01

Dacarbazine (DTIC) is the first-line chemotherapy for metastatic malignant melanoma without cerebral metastasis. Its clinical and hematological safety is usually good. Hypersensitivity in hepatic failure patients is the most serious side effect described. This was a retrospective study of the prevalence of hypersensitivity in patients treated with DTIC for metastatic melanoma between 11/01/2002 and 10/31/2003. Hypersensitivity was diagnosed in the event of fever, hypereosinophilia (> 500/mm3) with or without liver dysfunction (> twice pre-therapeutic values). Clinical data, DTIC administration modalities, number of courses and clinical and laboratory safety data were recorded. Twenty patients were included, 11 women and 9 men of median age 58.6 years (22-82 years) with multiple metastases in all cases. DTIC was the first-line treatment for 19 patients, being administered for 4 days to 10 patients and for 1 day to the other 10 patients, depending on their overall health status. Five hypersensitivity-like manifestations were observed, all in the 4-day treatment group. In 3 patients, fever and hypereosinophilia were seen without liver dysfunction at D3 of the second course of treatment. In 2 patients, treatment was stopped after the second course because of disease progression. In the third patient, 4 courses were given with recurrence of symptoms, although the latter were controlled during the fifth course with corticosteroids and antihistamines given 15 minutes before the start of treatment. Two patients experienced severe forms of hypersensitivity with fever, hypereosinophilia, liver dysfunction (cytolysis and cholestasis) and delayed medullar aplasia, after the first and second course respectively. In one patient, bone marrow examination showed a block at the promyelocytic stage consistent with a toxic etiology. Treatment with DTIC was stopped, and all signs regressed with symptomatic treatment. Hypersensitivity with DTIC seems to be frequent, being observed in 20

Updates in the management of sinonasal mucosal melanoma.

PubMed

Crippen, Meghan M; Kılıç, Suat; Eloy, Jean A

2018-02-01

Sinonasal mucosal melanoma (SNMM) is an aggressive cancer with a poor prognosis. Although there is significant study surrounding the treatment of sinonasal malignancies and cutaneous melanomas, the rarity of this tumor has largely precluded robust outcomes analyses. The authors of this review seek to provide an overview of the recent literature related to the treatment of SNMM with added context from our institutional experience with this disease. In the surgical management of sinonasal malignancies and SNMM specifically, resection via endoscopic endonasal technique appears to offer comparable oncologic outcomes versus an open approach. The role of adjuvant therapy continues to be debated, but there is strong evidence for improved rates of local control with radiotherapy after complete resection. In the last few years, significant developments have been made in the study of systemic therapies for cutaneous melanoma. The identification of genetic mutations common to mucosal melanoma has allowed for early trials of targeted therapies, but study is ongoing. Although the study of SNMM is largely limited to small retrospective case series, treatment continues to evolve. Until effective systemic therapies can be identified, endoscopic resection with adjuvant radiotherapy may offer the best disease-free survival with acceptably low morbidity.

Ascorbic acid, but not dehydroascorbic acid increases intracellular vitamin C content to decrease Hypoxia Inducible Factor -1 alpha activity and reduce malignant potential in human melanoma.

PubMed

Fischer, Adam P; Miles, Sarah L

2017-02-01

Accumulation of hypoxia inducible factor-1 alpha (HIF-1α) in malignant tissue is known to contribute to oncogenic progression and is inversely associated with patient survival. Ascorbic acid (AA) depletion in malignant tissue may contribute to aberrant normoxic activity of HIF-1α. While AA supplementation has been shown to attenuate HIF-1α function in malignant melanoma, the use of dehydroascorbic acid (DHA) as a therapeutic means to increase intracellular AA and modulate HIF-1α function is yet to be evaluated. Here we compared the ability of AA and DHA to increase intracellular vitamin C content and decrease the malignant potential of human melanoma by reducing the activity of HIF-1α. HIF-1α protein accumulation was evaluated by western blot and transcriptional activity was evaluated by reporter gene assay using a HIF-1 HRE-luciferase plasmid. Protein expressions and subcellular localizations of vitamin C transporters were evaluated by western blot and confocal imaging. Intracellular vitamin C content following AA, ascorbate 2-phosphate (A2P), or DHA supplementation was determined using a vitamin C assay. Malignant potential was accessed using a 3D spheroid Matrigel invasion assay. Data was analyzed by One or Two-way ANOVA with Tukey's multiple comparisons test as appropriate with p<0.05 considered significant. Melanoma cells expressed both sodium dependent vitamin C (SVCT) and glucose (GLUT) transporters for AA and DHA transport respectively, however advanced melanomas responded favorably to AA, but not DHA. Physiological glucose conditions significantly impaired intracellular vitamin C accumulation following DHA treatment. Consequently, A2P and AA, but not DHA treated cells demonstrated lower HIF-1α protein expression and activity, and reduced malignant potential. The ability of AA to regulate HIF-1α was dependent on SVCT2 function and SVCT2 was not significantly inhibited at pH representative of the tumor microenvironment. The use of ascorbic acid as an

Whole Body Melanoma Transcriptome Response in Medaka

PubMed Central

Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K.; Postlethwait, John; Warren, Wesley C.

2015-01-01

The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model. PMID

Whole Body Melanoma Transcriptome Response in Medaka.

PubMed

Schartl, Manfred; Shen, Yingjia; Maurus, Katja; Walter, Ron; Tomlinson, Chad; Wilson, Richard K; Postlethwait, John; Warren, Wesley C

2015-01-01

The incidence of malignant melanoma continues to increase each year with poor prognosis for survival in many relapse cases. To reverse this trend, whole body response measures are needed to discover collaborative paths to primary and secondary malignancy. Several species of fish provide excellent melanoma models because fish and human melanocytes both appear in the epidermis, and fish and human pigment cell tumors share conserved gene expression signatures. For the first time, we have examined the whole body transcriptome response to invasive melanoma as a prelude to using transcriptome profiling to screen for drugs in a medaka (Oryzias latipes) model. We generated RNA-seq data from whole body RNA isolates for controls and melanoma fish. After testing for differential expression, 396 genes had significantly different expression (adjusted p-value <0.02) in the whole body transcriptome between melanoma and control fish; 379 of these genes were matched to human orthologs with 233 having annotated human gene symbols and 14 matched genes that contain putative deleterious variants in human melanoma at varying levels of recurrence. A detailed canonical pathway evaluation for significant enrichment showed the top scoring pathway to be antigen presentation but also included the expected melanocyte development and pigmentation signaling pathway. Results revealed a profound down-regulation of genes involved in the immune response, especially the innate immune system. We hypothesize that the developing melanoma actively suppresses the immune system responses of the body in reacting to the invasive malignancy, and that this mal-adaptive response contributes to disease progression, a result that suggests our whole-body transcriptomic approach merits further use. In these findings, we also observed novel genes not yet identified in human melanoma expression studies and uncovered known and new candidate drug targets for further testing in this malignant melanoma medaka model.

Management of primary and metastasized melanoma in Germany in the time period 1976-2005: an analysis of the Central Malignant Melanoma Registry of the German Dermatological Society.

PubMed

Schwager, Silke S; Leiter, Ulrike; Buettner, Petra G; Voit, Christiane; Marsch, Wolfgang; Gutzmer, Ralf; Näher, Helmut; Gollnick, Harald; Bröcker, Eva Bettina; Garbe, Claus

2008-04-01

This study analysed the changes of excision margins in correlation with tumour thickness as recorded over the last three decades in Germany. The study also evaluated surgical management in different geographical regions and treatment options for metastasized melanoma. A total of 42 625 patients with invasive primary cutaneous melanoma, recorded by the German Central Malignant Melanoma Registry between 1976 and 2005 were included. Multiple linear regression analysis was used to investigate time trends of excision margins adjusted for tumour thickness. Excision margins of 5.0 cm were widely used in the late 1970s but since then have been replaced by smaller margins that are dependent on tumour thickness. In the case of primary melanoma, one-step surgery dominated until 1985 and was mostly replaced by two-step excisions since the early 1990s. In eastern Germany, one-step management remained common until the late 1990s. During the last three decades loco-regional metastases were predominantly treated by surgery (up to 80%), whereas systemic therapy decreased. The primary treatment of distant metastases has consistently been systemic chemotherapy. This descriptive retrospective study revealed a significant decrease in excision margins to a maximum of 2.00 cm. A significant trend towards two-step excisions in primary cutaneous melanoma was observed throughout Germany. Management of metastasized melanoma showed a tendency towards surgical procedures in limited disease and an ongoing trend to systemic treatment in advanced disease.

[Soft tissue melanoma: a clinical case].

PubMed

Frikh, Rachid; Oumakhir, Siham; Chahdi, Hafsa; Oukabli, Mohammed; Albouzidi, Abderrahmane; Baba, Noureddine; Hjira, Naoufal; Boui, Mohammed

2017-01-01

Soft tissue melanoma was first described by Enzinger in 1965 under the name of clear cell sarcoma. In 1983, Chung and Enzinger renamed it soft tissue melanoma due to its immunohistochemical similarities with melanoma. We here report the case of a 22-year old young man with this rare type of melanoma, presenting with molluscoid lesion on his ankle without any clinical sign of malignancy. Histology examination confirmed the diagnosis of soft tissue melanoma.

CONCENTRIC DECILE SEGMENTATION OF WHITE AND HYPOPIGMENTED AREAS IN DERMOSCOPY IMAGES OF SKIN LESIONS ALLOWS DISCRIMINATION OF MALIGNANT MELANOMA

PubMed Central

Dalal, Ankur; Moss, Randy H.; Stanley, R. Joe; Stoecker, William V.; Gupta, Kapil; Calcara, David A.; Xu, Jin; Shrestha, Bijaya; Drugge, Rhett; Malters, Joseph M.; Perry, Lindall A.

2011-01-01

Dermoscopy, also known as dermatoscopy or epiluminescence microscopy (ELM), permits visualization of features of pigmented melanocytic neoplasms that are not discernable by examination with the naked eye. White areas, prominent in early malignant melanoma and melanoma in situ, contribute to early detection of these lesions. An adaptive detection method has been investigated to identify white and hypopigmented areas based on lesion histogram statistics. Using the Euclidean distance transform, the lesion is segmented in concentric deciles. Overlays of the white areas on the lesion deciles are determined. Calculated features of automatically detected white areas include lesion decile ratios, normalized number of white areas, absolute and relative size of largest white area, relative size of all white areas, and white area eccentricity, dispersion, and irregularity. Using a back-propagation neural network, the white area statistics yield over 95% diagnostic accuracy of melanomas from benign nevi. White and hypopigmented areas in melanomas tend to be central or paracentral. The four most powerful features on multivariate analysis are lesion decile ratios. Automatic detection of white and hypopigmented areas in melanoma can be accomplished using lesion statistics. A neural network can achieve good discrimination of melanomas from benign nevi using these areas. Lesion decile ratios are useful white area features. PMID:21074971

Incidence of cutaneous malignant melanoma in Denmark, 1978-2007.

PubMed

Fuglede, N B; Brinck-Claussen, U Ø; Deltour, I; Boesen, E H; Dalton, S O; Johansen, C

2011-08-01

Incidence rates of cutaneous malignant melanoma (CMM) have been increasing markedly worldwide. The ongoing debate about possible overdiagnosis remains unresolved. To determine the population-based incidence of CMM in Denmark between 1978 and 2007 and to analyse sex-, site- and extent of disease-specific changes in incidence rates of CMM over time. We used the virtually complete nationwide Danish Cancer Register in this population-based study, which contains data on 25,851 cases reported in Denmark between 1978 and 2007. We calculated age-standardized (world standard population) incidence rates per 100,000 person-years and age-specific rates. The age-standardized incidence rates increased from 6·5 to 14·4 among men and from 8·6 to 18·9 among women. During the last 5 years of the study period, a sudden marked increase was seen in women of all ages and in men aged 65 years or older. The most marked site-specific change was in the incidence of melanoma on the trunk in both men and women. An increase in the rates of disease with regional spread was seen during the last 10 years of observation. The incidence rate of CMM more than doubled in Denmark between 1978 and 2007. The increases in both site-specific incidence rates and CMM with regional spread suggest an association with risk behaviour, such as intermittent sun exposure, although possible overdiagnosis must be taken into account in evaluating the implications of the increase. © 2011 The Authors. BJD © 2011 British Association of Dermatologists 2011.

Reliability and cost-effectiveness of sentinel lymph node excision under local anaesthesia versus general anaesthesia for malignant melanoma: a retrospective analysis in 300 patients with malignant melanoma AJCC Stages I and II.

PubMed

Stoffels, I; Dissemond, J; Körber, A; Hillen, U; Poeppel, T; Schadendorf, D; Klode, J

2011-03-01

Sentinel lymph node excision (SLNE) for the detection of regional nodal metastases and staging of malignant melanoma has resulted in some controversies in international discussions, as it is a cost-intensive surgical intervention with potentially significant morbidity. The present retrospective study seeks to clarify the effectiveness and reliability of SLNE performed under tumescent local anaesthesia (TLA) and whether SLNE performed under TLA can reduce costs and morbidity. Therefore, our study is a comparison of SLNE performed under TLA and general anaesthesia (GA). We retrospectively analysed data from 300 patients with primary malignant melanoma with a Breslow index of ≥1.0 mm. Altogether, 211 (70.3%) patients underwent SLNE under TLA and 89 (29.7%) patients underwent SLNE under GA. A total of 637 sentinel lymph nodes (SLN) were removed. In the TLA group 1.98 SLN/patient and in the GA group 2.46 SLN/patient were removed (median value). Seventy patients (23.3%) had a positive SLN. No major complications occurred. The costs for SLNE were significantly less for the SLNE in a procedures room performed under TLA (mean € 30.64) compared with SLNE in an operating room under GA (mean € 326.14, P<0.0001). In conclusion, SLNE performed under TLA is safe, reliable, and cost-efficient and could become the new gold standard in sentinel lymph node diagnostic procedures. © 2010 The Authors. Journal of the European Academy of Dermatology and Venereology © 2010 European Academy of Dermatology and Venereology.

Immunohistochemical Analysis of PD-L1 Expression in Canine Malignant Cancers and PD-1 Expression on Lymphocytes in Canine Oral Melanoma

PubMed Central

Maekawa, Naoya; Konnai, Satoru; Okagawa, Tomohiro; Nishimori, Asami; Ikebuchi, Ryoyo; Izumi, Yusuke; Takagi, Satoshi; Kagawa, Yumiko; Nakajima, Chie; Suzuki, Yasuhiko; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

2016-01-01

Spontaneous cancers are common diseases in dogs. Among these, some malignant cancers such as oral melanoma, osteosarcoma, hemangiosarcoma, and mast cell tumor are often recognized as clinical problems because, despite their high frequencies, current treatments for these cancers may not always achieve satisfying outcomes. The absence of effective systemic therapies against these cancers leads researchers to investigate novel therapeutic modalities, including immunotherapy. Programmed death 1 (PD-1) is a costimulatory receptor with immunosuppressive function. When it binds its ligands, PD-ligand 1 (PD-L1) or PD-L2, PD-1 on T cells negatively regulates activating signals from the T cell receptor, resulting in the inhibition of the effector function of cytotoxic T lymphocytes. Aberrant PD-L1 expression has been reported in many human cancers and is considered an immune escape mechanism for cancers. In clinical trials, anti-PD-1 or anti-PD-L1 antibodies induced tumor regression for several malignancies, including advanced melanoma, non-small cell lung carcinoma, and renal cell carcinoma. In this study, to assess the potential of the PD-1/PD-L1 axis as a novel therapeutic target for canine cancer immunotherapy, immunohistochemical analysis of PD-L1 expression in various malignant cancers of dogs was performed. Here, we show that dog oral melanoma, osteosarcoma, hemangiosarcoma, mast cell tumor, mammary adenocarcinoma, and prostate adenocarcinoma expressed PD-L1, whereas some other types of cancer did not. In addition, PD-1 was highly expressed on tumor-infiltrating lymphocytes obtained from oral melanoma, showing that lymphocytes in this cancer type might have been functionally exhausted. These results strongly encourage the clinical application of PD-1/PD-L1 inhibitors as novel therapeutic agents against these cancers in dogs. PMID:27276060

First application of dynamic infrared imaging in boron neutron capture therapy for cutaneous malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santa Cruz, G. A.; Gonzalez, S. J.; Bertotti, J.

2009-10-15

Purpose: The purpose of this study is to assess the potential of dynamic infrared imaging (DIRI) as a functional, noninvasive technique for evaluating the skin acute toxicity and tumor control within the framework of the Argentine boron neutron capture therapy (BNCT) program for cutaneous malignant melanoma. Methods: Two patients enrolled in the Argentine phase I/II BNCT clinical trial for cutaneous malignant melanoma were studied with DIRI. An uncooled infrared camera, providing a video output signal, was employed to register the temperature evolution of the normal skin and tumor regions in patients subjected to a mild local cooling (cold stimulus). Inmore » order to study the spatial correlation between dose and acute skin reactions, three-dimensional representations of the superficial dose delivered to skin were constructed and cameralike projections of the dose distribution were coregistered with visible and infrared images. Results: The main erythematous reaction was observed clinically between the second and fifth week post-BNCT. Concurrently, with its clinical onset, a reactive increase above the basal skin temperature was observed with DIRI in the third week post-BNCT within regions that received therapeutic doses. Melanoma nodules appeared as highly localized hyperthermic regions. 2 min after stimulus, these regions reached a temperature plateau and increased in size. Temperature differences with respect to normal skin up to 10 deg. C were observed in the larger nodules. Conclusions: Preliminary results suggest that DIRI, enhanced by the application of cold stimuli, may provide useful functional information associated with the metabolism and vasculature of tumors and inflammatory processes related to radiation-induced changes in the skin as well. These capabilities are aimed at complementing the clinical observations and standard imaging techniques, such as CT and Doppler ultrasound.« less

Melanoma thickness measurement in two-layer tissue phantoms using pulsed photothermal radiometry (PPTR)

NASA Astrophysics Data System (ADS)

Wang, Tianyi; Qiu, Jinze; Paranjape, Amit; Milner, Thomas E.

2009-02-01

Melanoma is a malignant tumor of melanocytes which are found predominantly in skin. Melanoma is one of the rarer types of skin cancer but causes the majority of skin cancer related deaths. The staging of malignant melanoma using Breslow thickness is important because of the relationship to survival rate after five years. Pulsed photothermal radiometry (PPTR) is based on the time-resolved acquisition of infrared (IR) emission from a sample after pulsed laser exposure. PPTR can be used to investigate the relationship between melanoma thickness and detected radiometric temperature using two-layer tissue phantoms. We used a Monte Carlo simulation to mimic light transport in melanoma and employed a three-dimensional heat transfer model to obtain simulated radiometric temperature increase and, in comparison, we also conducted PPTR experiments to confirm our simulation results. Simulation and experimental results show similar trends: thicker absorbing layers corresponding to deeper lesions produce slower radiometric temperature decays. A quantitative relationship exists between PPTR radiometric temperature decay time and thickness of the absorbing layer in tissue phantoms.

Immunohistochemical detection of XIAP in melanoma.

PubMed

Emanuel, Patrick O M; Phelps, Robert G; Mudgil, Adarsh; Shafir, Michail; Burstein, David E

2008-03-01

The X-linked inhibitor of apoptosis protein (XIAP) is the most potent of the inhibitor of apoptosis family of eight proteins. High levels of XIAP have been found in melanoma cell lines and are believed to play a role in therapeutic resistance in a number of malignancies. XIAP expression has not been investigated in clinically obtained melanoma tissue samples, nor have studies attempted to correlate XIAP expression with prognostic variables or clinical aggressiveness of melanomas. Sixty-seven patients with primary cutaneous malignant melanoma for whom clinical follow up was available were identified from the records of the Mount Sinai Hospital, comprising 37 thin melanomas (Breslow thickness < 1.0 mm) and 30 thick melanomas (Breslow thickness > 1.0 mm). Archival paraffin sections from primary lesions and corresponding metastases were stained with monoclonal anti-XIAP antibody using routine immunohistochemical methods. Six benign intradermal nevi and four in situ melanomas were XIAP negative. 9 of 37 thin melanomas (24%) were XIAP positive. In contrast, 21 of 30 (73%) thick melanomas were XIAP positive, including 3 of 4 ulcerated melanomas that were strongly positive. Over a follow-up period ranging from 6 months to 6 years, 23 melanomas metastasized (22 thick, 1 thin). In total, XIAP was immunohistochemically detected in 17 of 23 metastases (74%). Metastasis occurred in 1 of 9 XIAP-positive thin melanomas; 0 of 28 XIAP-negative thin melanomas; 17 of 22 XIAP-positive thick melanomas, and 5 of 8 XIAP-negative thick melanomas (63%). XIAP is immunohistochemically detectable nearly three times more frequently in thick compared with thin melanomas. These results suggest that XIAP elevation may be correlated with increasing melanoma thickness and tumor progression.

A proposed computer diagnostic system for malignant melanoma (CDSMM).

PubMed

Shao, S; Grams, R R

1994-04-01

This paper describes a computer diagnostic system for malignant melanoma. The diagnostic system is a rule base system based on image analyses and works under the PC windows environment. It consists of seven modules: I/O module, Patient/Clinic database, image processing module, classification module, rule base module and system control module. In the system, the image analyses are automatically carried out, and database management is efficient and fast. Both final clinic results and immediate results from various modules such as measured features, feature pictures and history records of the disease lesion can be presented on screen or printed out from each corresponding module or from the I/O module. The system can also work as a doctor's office-based tool to aid dermatologists with details not perceivable by the human eye. Since the system operates on a general purpose PC, it can be made portable if the I/O module is disconnected.

Diagnosis and treatment of a dermal malignant melanoma in an African lion (Panthera leo).

PubMed

Steeil, James C; Schumacher, Juergen; Baine, Katherine; Ramsay, Edward C; Sura, Patricia; Hodshon, Rebecca; Donnell, Robert L; Lee, Nathan D

2013-09-01

A 13-yr-old intact male African lion (Panthera leo) presented with a 4-mo history of left maxillary lip swelling. On physical examination, a 10-cm-diameter, ulcerated, round, firm, and pigmented mass at the level of the left maxillary canine tooth was noticed. All other organ systems examined were within normal limits. Multiple biopsies of the mass were collected and fixed in 10% neutral buffered formalin. Histopathologic evaluation of the biopsies revealed a malignant dermal melanoma. Hematologic and plasma biochemical parameters were within normal reference ranges. Thoracic radiographs taken 3 days following initial presentation showed no evidence of metastasis of the tumor. Computed tomography of the skull and neck was performed to evaluate local tumor invasion and to plan for hypofractionated radiation therapy. Therapy included four weekly treatments of 8 gray external-beam hypofractionated radiation and four bimonthly immunotherapy treatments. Following this treatment regime, the tumor size was reduced by 50%, and surgical excision was performed. No major side effects associated with radiation or immunotherapy were seen. Six months after diagnosis, hematologic and plasma biochemical parameters were within normal limits, thoracic radiographs showed no evidence of metastasis, and the lion showed no clinical signs of disease. The lion will continue to receive immunotherapy every 6 mo for the rest of its life. To the authors' knowledge, this is the first report of a successful treatment of a malignant dermal melanoma with external-beam hypofractionated radiation, immunotherapy, and surgical excision in an African lion.

CD147/basigin promotes progression of malignant melanoma and other cancers.

PubMed

Kanekura, Takuro; Chen, Xiang

2010-03-01

CD147/basigin, a transmembrane protein belonging to the immunoglobulin super family, was originally cloned as a carrier of Lewis X carbohydrate antigen. CD147 is strongly related to cancer progression; it is highly expressed by various cancer cells including malignant melanoma (MM) cells and it plays important roles in tumor invasiveness, metastasis, cellular proliferation, and in vascular endothelial growth factor (VEGF) production, tumor cell glycolysis, and multi-drug resistance (MDR). CD147 on cancer cells induces matrix metalloproteinase expression by neighboring fibroblasts, leading to tumor cell invasion. In a nude mouse model of pulmonary metastasis from MM, the metastatic potential of CD147-expressing MM cells injected into the tail vein is abolished by CD147 silencing. CD147 enhances cellular proliferation and VEGF production by MM cells; it promotes tumor cell glycolysis by facilitating lactate transport in combination with monocarboxylate transporters, resulting in tumor progression. CD147 is responsible for the MDR phenotype via P-glycoprotein expression. These findings strongly suggest CD147 as a possible therapeutic target for overcoming metastasis and MDR, major obstacles to the effective treatment of malignant cancers. 2009 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Addison's disease as a presentation of metastatic malignant melanoma.

PubMed

Srinivasan, B; Patel, M; Ethunandan, M; Ilankovan, V

2016-01-01

Melanoma accounts for 5% of all skin cancers. The risk of metastasis is related to the thickness of the tumour, and can affect local, regional and distant sites. Adrenal metastasis from melanoma of the head and neck is uncommon and often asymptomatic. Addison's disease as a presentation of metastatic melanoma is extremely rare and we are unaware of previous reports in the world literature. We report a case of a patient with metastatic melanoma presenting with signs and symptoms of Addison's disease.

Results of a Phase II Study to Evaluate the Efficacy of Docetaxel and Carboplatin in Metastatic Malignant Melanoma Patients Who Failed First-Line Therapy Containing Dacarbazine.

PubMed

Lee, Choong-kun; Jung, Minkyu; Choi, Hye Jin; Kim, Hye Ryun; Kim, Hyo Song; Roh, Mi Ryung; Ahn, Joong Bae; Chung, Hyun Cheol; Heo, Su Jin; Rha, Sun Young; Shin, Sang Joon

2015-10-01

There is no standard second-line regimen for malignant melanoma patients with disease progression after first-line chemotherapy, and platinum-alkylating agents combined with paclitaxel have shown modest efficacy. We conducted a phase II, open-label, single-arm study to test the efficacy of docetaxel combined with carboplatin for malignant melanoma patients who failed previous treatment with dacarbazine. Intravenous docetaxel (35 mg/m(2) on days 1 and 8 of each cycle) and carboplatin (area under the curve 3 on days 1 and 8 of each cycle) was administered every 21 days. Primary end point was objective response rate (ORR). Thirty patients were enrolled in the study, and the median follow-up duration was 19.8 months. Among 25 per-protocol patients, there were three responders (1 with complete response and 2 with partial response) and 17 stable disease patients (ORR, 12.0%). Among the per-protocol population, the median progression-free survival (PFS) was 4.3 months and the median overall survival (OS) was 9.6 months. Uveal melanoma patients (n=9) showed the best prognosis compared to other subtypes (median PFS, 7.6 months; OS, 9.9 months). The most common grade 3 or 4 adverse event was neutropenia (n=15, 50.0%). Docetaxel combined with carboplatin showed association with an acceptable safety profile and overall efficacy for patients with malignant melanoma who had progressed on chemotherapy containing dacarbazine.

Cutaneous Malignant Melanoma With Rhabdoid Morphology and Smooth Muscle Differentiation: A Challenging Histopathologic Diagnosis.

PubMed

Prieto-Torres, Lucía; Alegría-Landa, Victoria; Llanos, Concepción; Córdoba, Alicia; Kutzner, Heinz; Requena, Luis

2017-05-01

Divergent differentiation or metaplastic change is a rare feature exhibited occasionally in malignant melanoma (MM), which is characterized by the development of morphologically, immunochemically, and/or ultrastructurally nonmelanocytic cells within the tumor. Smooth muscle differentiation in MM is an exceedingly rare phenomenon reported only in a few cases in the literature. We report the case of a 69-year-old woman who presented with a pure dermal amelanotic MM with smooth muscle cell differentiation and an area of rhabdoid morphology, which made the accurate histopathologic diagnostic of MM challenging.

Noninvasive and label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Wei, Xunbin

2015-03-01

Melanoma is a malignant tumor of melanocytes. Circulating melanoma cell has high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC). PAFC is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. In our research, we developed in vitro experiments to prove the ability of PAFC system of detecting PA signals from melanoma cells. For in vivo experiments, we constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells B16F10 with subcutaneous injection. PA signals were detected in the blood vessels of mouse ears in vivo. By counting circulating melanoma cells termly, we obtained the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation. Our PAFC system is an efficient tool to monitor melanoma metastases, cancer recurrence and therapeutic efficacy.

[A Case of Delayed Dia-gnosis of Acral Lentiginous Melanoma].

PubMed

Gottvaldová, M; Jedličková, H; Poprach, A; Vašků, V

2015-01-01

Melanoma is a malignant skin disease. The tumor development is caused by an uncontrollable proliferation of melanocytes. The most common occurrence is on the skin, but melanoma may also develop on the mucous membrane, meninges, and eyes. Some melanomas develop from melanocytic nevus. Acral lentiginous melanoma occurs on palms, feet, fingers and under nails, and is the most common type of melanoma for phototype VI. The most important factor for successful treatment of malignant melanoma is an early detection, excision of the primary tumor and histological staging. Surgical treatment of an early-stage melanoma is a key to successful therapy; however, many patients (mostly men) do not seek medical attention before it istoo late. This case study presents a 59-year-old patient, who suffers from white coat syndrome and whose finger was amputated for alleged gangrene. Subsequently, brownish black nodules appeared across his arm. Histological examination proved metastases of malignant melanoma. It was only at this phase, when the patient admitted a nevus at the tip of his amputated finger, from which ulceration and gangrene gradually emerged. This case demonstrates a combination of multiple unfavorable factors, which led to delayed diagnosis and therapy.

Metastatic malignant blue nevus: a case report.

PubMed

Ozgür, F; Akyürek, M; Kayikçioğlu, A; Barişta, I; Gököz, A

1997-10-01

This report presents a 63-year-old Caucasian woman with a malignant blue nevus, which is an extremely rare form of melanoma originating from or associated with a preexisting blue nevus. The background blue nevus on the left upper arm, which had been present for 5 to 6 years, increased in size and darkened in color for 3 months prior to histological diagnosis of malignant blue nevus. Although the tumor looked much like a nodular melanoma clinically, the diagnosis of malignant blue nevus was established histologically. The patient had a poor outcome due to metastatic spread of the tumor to the visceral organs 1 year following the initial excision of the tumor. To distinguish this rare tumor from other melanocytic lesions, strict histological criteria are needed to make the diagnosis of malignant blue nevus. Differential diagnosis includes cellular blue nevus, atypical cellular blue nevus, primary malignant melanoma, and metastatic melanoma to the dermis. Malignant blue nevus is most commonly seen on the scalp. The tumor has an aggressive behavior and metastasizes in the majority of patients. This paper describes the second reported case of malignant blue nevus involving the upper arm. Clinical and histological features of this uncommon tumor are presented, along with a review of the literature.

Ensemble approach for differentiation of malignant melanoma

NASA Astrophysics Data System (ADS)

Rastgoo, Mojdeh; Morel, Olivier; Marzani, Franck; Garcia, Rafael

2015-04-01

Melanoma is the deadliest type of skin cancer, yet it is the most treatable kind depending on its early diagnosis. The early prognosis of melanoma is a challenging task for both clinicians and dermatologists. Due to the importance of early diagnosis and in order to assist the dermatologists, we propose an automated framework based on ensemble learning methods and dermoscopy images to differentiate melanoma from dysplastic and benign lesions. The evaluation of our framework on the recent and public dermoscopy benchmark (PH2 dataset) indicates the potential of proposed method. Our evaluation, using only global features, revealed that ensembles such as random forest perform better than single learner. Using random forest ensemble and combination of color and texture features, our framework achieved the highest sensitivity of 94% and specificity of 92%.

Anti-tumor effects of differentiation-inducing factor-1 in malignant melanoma: GSK-3-mediated inhibition of cell proliferation and GSK-3-independent suppression of cell migration and invasion.

PubMed

Arioka, Masaki; Takahashi-Yanaga, Fumi; Kubo, Momoko; Igawa, Kazunobu; Tomooka, Katsuhiko; Sasaguri, Toshiyuki

2017-08-15

Differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium discoideum strongly inhibits the proliferation of various mammalian cells through the activation of glycogen synthase kinase-3 (GSK-3). To evaluate DIF-1 as a novel anti-cancer agent for malignant melanoma, we examined whether DIF-1 has anti-proliferative, anti-migratory, and anti-invasive effects on melanoma cells using in vitro and in vivo systems. DIF-1 reduced the expression levels of cyclin D1 and c-Myc by facilitating their degradation via GSK-3 in mouse (B16BL6) and human (A2058) malignant melanoma cells, and thereby strongly inhibited their proliferation. DIF-1 suppressed the canonical Wnt signaling pathway by lowering the expression levels of transcription factor 7-like 2 and β-catenin, key transcription factors in this pathway. DIF-1 also inhibited cell migration and invasion, reducing the expression of matrix metalloproteinase-2; however, this effect was not dependent on GSK-3 activity. In a mouse lung tumor formation model, repeated oral administrations of DIF-1 markedly reduced melanoma colony formation in the lung. These results suggest that DIF-1 inhibits cell proliferation by a GSK-3-dependent mechanism and suppresses cell migration and invasion by a GSK-3-independent mechanism. Therefore, DIF-1 may have a potential as a novel anti-cancer agent for the treatment of malignant melanoma. Copyright © 2017 Elsevier Inc. All rights reserved.

LncRNA MEG3 repressed malignant melanoma progression via inactivating Wnt signaling pathway.

PubMed

Li, Peng; Gao, Ying; Li, Jun; Zhou, Yu; Yuan, Jing; Guan, Huiwen; Yao, Peng

2018-05-21

Accumulating evidence has indicated that MEG3 can serve as a tumor suppressive lncRNA in various tumors. It is aberrantly expressed in multiple cancers. However, the biological roles of MEG3 in melanoma are poorly understood. Therefore, in our study, we concentrated on the biological mechanism of MEG3 in melanoma progression. First, we observed that MEG3 was obviously decreased in melanoma cells including A375, SK-MEL-1, B16, and A2058 cells compared to human epidermal melanocytes HEMa-LP. MEG3 was restored by transfecting LV-MEG3 in to A375 and A2058 cells. Subsequently, we found that overexpression of MEG3 was able to inhibit cell proliferation and colony formation capacity. Meanwhile, melanoma cell apoptosis was induced by up-regulation of MEG3. Overexpression of MEG3 greatly repressed melanoma cell migration and invasion ability. In addition, Wnt signaling pathway has been identified in the progression of various cancers. Here, in our study, it was indicated that Wnt signaling was highly activated in melanoma cells with β-catenin expression significantly increased and GSK-3β decreased. Interestingly, MEG restoration strongly inactivated Wnt signaling pathway by reducing β-catenin and CyclinD1, elevating GSK-3β levels in vitro. Finally, in vivo experiments were carried out to confirm the inhibitory roles of MEG3 in vivo. Taken these together, we suggested that MEG3 can inhibit melanoma development through blocking Wnt signaling pathway. © 2018 Wiley Periodicals, Inc.

Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Howell, J.N.; Greene, M.H.; Corner, R.C.

Because of a possible etiologic link between mutations and carcinogenesis, the authors compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistant to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killingmore » by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer. 46 references, 3 figures.« less

Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells.

PubMed

Lin, Shuw-Yuan; Lai, Wan-Wen; Chou, Chi-Chung; Kuo, Hsiu-Maan; Li, Te-Mao; Chung, Jing-Gung; Yang, Jen-Hung

2006-12-01

Vitamin C has been reported to be useful in the treatment and prevention of cancer. Inconsistent effects from growth stimulation to induction of apoptosis of malignant tumor cells, however, have been reported. Melanoma is an increasingly common and potentially lethal malignancy. It was reported that melanoma cells were more susceptible to ascorbate toxicity than any other tumor cells. The mechanisms accounting for ascorbate-induced apoptosis in human melanoma cells, however, have remained unclear. This study was undertaken to investigate the effect of sodium ascorbate on cytotoxicity and apoptosis in human malignant melanoma A375.S2 cells. A375.S2 cells were incubated with a certain range of concentrations of sodium ascorbate for various time periods. In order to examine the effects of sodium ascorbate on cell proliferation, cell cycle, apoptosis and necrosis, we performed 4,6-diamidino-2-phenylindole dihydrochloride assays and flow cytometry analysis. Polymerase chain reaction was used to examine the mRNA levels of p53, p21, p27, cyclin A, cyclin E, CDK2 and CDK4, which are associated with cell cycle S-phase arrest and apoptosis. Flow cytometric analysis showed that sodium ascorbate significantly induced cell cycle arrest and apoptosis in the A375.S2 cell line in a dose-dependent manner. The increased expressions of p53 and p21, and the decreased expressions of cyclin A, cyclin E, CDK2 and CDK4, indicated the cell cycle arrest at G1/S phase after the cells had been treated with sodium ascorbate. Induction of apoptosis involved an increase in the levels of p53, p21 and cellular Ca, and a decrease in mitochondrial membrane potential and activation of caspase 3 before culminating in apoptosis in sodium ascorbate-treated A375.S2 cells.

Childhood Body Size and the Risk of Malignant Melanoma in Adulthood

PubMed Central

Meyle, Kathrine D.; Gamborg, Michael; Sørensen, Thorkild I. A.; Baker, Jennifer L.

2017-01-01

Abstract Malignant melanoma (MM) is the most aggressive form of skin cancer. Adult anthropometry influences MM development; however, associations between childhood body size and future melanomagenesis are largely unknown. We investigated whether height, body mass index (BMI; weight (kg)/height (m)2), and body surface area (BSA) at ages 7–13 years and birth weight are associated with adult MM. Data from the Copenhagen School Health Records Register, containing annual height and weight measurements of 372,636 Danish children born in 1930–1989, were linked with the Danish Cancer Registry. Cox regression analyses were performed. During follow-up, 2,329 MM cases occurred. Height at ages 7–13 years was significantly associated with MM, even after BMI and BSA adjustments. No significant BMI-MM or BSA-MM associations were detected when adjusting for height. Children who were persistently tall at both age 7 years and age 13 years had a significantly increased MM risk compared with children who grew taller between those ages. Birth weight was positively associated with MM. We conclude that associations between body size and MM originate early in life and are driven largely by height and birth weight, without any comparable influence of BMI or BSA. Melanoma transformation is unlikely to be due to height per se; however, height-regulating processes in childhood present new areas for mechanistic explorations of this disease. PMID:28369155

Phase I study of pegylated interferon-alpha-2b as an adjuvant therapy in Japanese patients with malignant melanoma.

PubMed

Yamazaki, Naoya; Uhara, Hisashi; Wada, Hidefumi; Matsuda, Kenji; Yamamoto, Keiko; Shimamoto, Takashi; Kiyohara, Yoshio

2016-10-01

In the adjuvant setting for malignant melanoma, interferon (IFN)-α-2b and pegylated (PEG) IFN-α-2b were approved in several countries including the USA before these were approved in Japan. To resolve the "drug-lag" issue, this phase I study was designed to evaluate the safety and tolerability in Japanese patients with stage II or III malignant melanoma who had undergone surgery, by treating with PEG IFN-α-2b. As with a previously reported phase III study, patients were to receive PEG IFN-α-2b 6 μg/kg per week s.c. during an 8-week induction phase, followed by a maintenance phase at a dose of 3 μg/kg per week up to 5 years. Dose-limiting toxicity and pharmacokinetics were assessed during the initial 8 weeks. Of the nine patients enrolled, two patients had dose-limiting toxicities that resolved after discontinuation of treatment. The most frequently reported drug-related adverse events (DRAE) included pyrexia, decreased neutrophil and white blood cell counts, and arthralgia. Grade 3 DRAE included decreased neutrophil count. No deaths, serious adverse events and grade 4 adverse events were reported. Distant metastasis occurred in one patient. No apparent differences in area under the concentration-time curve and maximum observed serum concentration were observed between Japanese and historical non-Japanese pharmacokinetic data, suggesting no marked racial differences. No neutralizing antibody was detected in these patient samples. PEG IFN-α-2b was tolerated in Japanese patients, and eventually approved in Japan in May 2015 for adjuvant therapy in patients with stage III malignant melanoma. Because the number of patients was limited, further investigation would be crucial. © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.

Kinase Gene Fusions in Defined Subsets of Melanoma

PubMed Central

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Summary Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in-situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by IHC or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought-and should be further explored particularly in melanomas lacking known driver mutations. PMID:27864876

Expression of monoacylglycerol lipase as a marker of tumour invasion and progression in malignant melanoma.

PubMed

Baba, Yuko; Funakoshi, T; Mori, M; Emoto, K; Masugi, Y; Ekmekcioglu, S; Amagai, M; Tanese, K

2017-12-01

Accumulating evidence suggests that the lipid lytic enzyme monoacylglycerol lipase (MAGL) promotes tumour invasion and metastasis through up-regulation of pro-tumorigenic signalling lipids in several tumour cell lines. However, the expression status of MAGL in clinical melanoma tissues and its clinicopathological significance remain unclear. To correlate the tumour expression status of MAGL with the clinicopathological information of patients with malignant melanoma. Polymerase chain reaction (PCR) array screening was performed, and the results were validated using immunocytochemical analysis of tumour and non-tumour melanocytic cell lines. Immunohistochemical staining for MAGL was performed for 74 melanoma samples, including 48 primary and 26 metastatic tumours, in which the expression of MAGL was determined by evaluating the percentage of MAGL-positive tumour cells and the MAGL staining intensity. Finally, we analysed the association of MAGL expression status with tumour progression, tumour thickness and vascular invasion of the primary lesion. Immunocytochemical analysis revealed that MAGL was expressed in all 12 melanoma cell lines, but not in normal human epidermal melanocytes. In the immunohistochemical analysis, positive staining for MAGL was noted in 32 of 48 (64.5%) primary lesions, 14 of 17 (82.4%) lymph node metastatic lesions and 7 of 9 (77.8%) skin metastatic lesions. Metastatic tumours had a significantly higher staining intensity (P = 0.033 for lymph node, P = 0.010 for skin). In the analysis of primary lesions, higher MAGL expression correlated with greater tumour thickness (P = 0.015) and the presence of vascular invasion (P = 0.017). On further evaluation of MAGL-positive primary lesions, staining intensity of MAGL tended to be higher in deeper areas of the tumour mass. The expression of MAGL in tumour cells reflects the aggressiveness of melanoma cells and may serve as a marker of tumour progression. © 2017 European Academy of Dermatology and

Anorectal melanoma: not a haemorrhoid.

PubMed

Turner, Greg; Abbott, Sarah; Eglinton, Tim; Wakeman, Chris; Frizelle, Frank

2014-06-06

Melanoma of the anorectum is a rare malignancy which is particularly aggressive compared to cutaneous melanoma. Due to its presenting symptoms, location and rarity there is often a delay in diagnosis. The purpose of this paper is to raise awareness of anorectal melanoma in New Zealand by presenting our institution's experience of four cases. The presentation, management and outcomes of four cases are described. A review of the literature surrounding anorectal melanoma was also carried out. The four cases (3 male, 1 female, aged 30-87 years) all presented with haemorrhoidal symptoms of anal discomfort and/or outlet rectal bleeding. Three patients had metastatic disease at presentation, and the remaining patient was found to have a concurrent lymphoma which was treated with chemotherapy before he underwent excision of the melanoma. Surgical excision is the mainstay of treatment and recent literature suggests transanal excision of the primary tumour to have equivalent overall survival to abdominoperineal resection. Anorectal melanoma is rare tumour with a poor prognosis. Patients are commonly misdiagnosed as having haemorrhoids; therefore a high index of suspicion is needed to enable early diagnosis. Metastatic disease is common at presentation, and the key prognostic indicator. Local control can be obtained with transanal excision, avoiding the morbidity of abdominoperineal resection. Adjuvant therapies available at present provide little survival advantage.

Identification and clinical relevance of PD-L1 expression in primary mucosal malignant melanoma of the head and neck.

PubMed

Thierauf, Julia; Veit, Johannes A; Affolter, Annette; Bergmann, Christoph; Grünow, Jennifer; Laban, Simon; Lennerz, Jochen K; Grünmüller, Lisa; Mauch, Cornelia; Plinkert, Peter K; Hess, Jochen; Hoffmann, Thomas K

2015-12-01

Mucosal melanoma of the head and neck is a rare and aggressive tumor entity with a poor prognosis. The standard treatment is radical tumor resection, with or without adjuvant radiation, where conventional chemotherapies in advanced stage or recurrent diseases have shown little benefit. Overexpression of the programmed cell death ligand 1 (PD-L1) is a common feature in human cancer. Although PD-L1 is an acknowledged prognostic biomarker for dismal prognosis in other tumors of the head and neck, expression and clinical relevance of PD-L1 in mucosal melanoma have not been addressed so far. We assessed PD-L1 expression using immunohistochemical staining in 23 tumor samples from patients with primary mucosal melanoma and correlated expression status with clinicopathological and outcome data. Tumors were derived from the nasal cavity (43.5%), nasal sinuses (43.5%), and the conjunctiva (13%). All patients had undergone surgery; 39% of all patients received adjuvant radiation and 13% were administered systemic interferon therapy. The probability of 1- and 5-year overall survival was 87 and 34.8%, respectively. The mean overall survival was 51 months and the mean recurrence-free survival was 23 months. Immunohistochemical staining showed PD-L1 expression in 13% (3/23) of mucosal melanoma. In contrast, prominent PD-L1 staining was detected in 100% of tissue sections from a control group of cutaneous melanoma (n=9). PD-L1 expression in mucosal melanoma was not correlated with age, sex, nor anatomical localization of the tumor. Interestingly, patients with PD-L1-positive mucosal melanoma had a significantly longer recurrence-free survival (P=0.026). In contrast to cutaneous melanoma and some other malignancies, a relevant PD-L1 overexpression in mucosal melanoma could not be confirmed.

Radioactive phosphorus uptake test for the diagnosis of malignant melanoma of the choroid

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shields, J.A.; Packer, S.

The most frequently used radioisotope in ophthalmology is radioactive phosphorus (/sup 32/P). Since its introduction into ophthalmology in 1951, it has been used primarily as an aid in the diagnosis of malignant melanoma of the choroid. During the thirty years of clinical use, the indications for this test have been clearly defined. The maximum tissue penetration of /sup 32/P is 7 mm. Surgical dissection is therefore frequently necessary to enable the ophthalmologist to place the Geiger-Muller probe on the sclera in proximity to the tumor. False positive and false negative results are unusual and the test is between 96% andmore » 100% accurate.« less

A case-control study of malignant melanoma among Lawrence Livermore National Laboratory employees: A critical evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kupper, L.L.; Setzer, R.W.; Schwartzbaum, J.

1987-07-01

This document reports on a reevaluation of data obtained in a previous report on occupational factors associated with the development of malignant melanomas at Lawrence Livermore National Laboratory. The current report reduces the number of these factors from five to three based on a rigorous statistical analysis of the original data. Recommendations include restructuring the original questionnaire and trying to contact more individuals that worked with volatile photographic chemicals. 17 refs., 7 figs., 22 tabs. (TEM)

Molecular pathogenesis of malignant melanoma: a different perspective from the studies of melanocytic nevus and acral melanoma.

PubMed

Takata, Minoru; Murata, Hiroshi; Saida, Toshiaki

2010-02-01

The Clark model for melanoma progression emphasizes a series of histopathological changes beginning from benign melanocytic nevus to melanoma via dysplastic nevus. Several models of the genetic basis of melanoma development and progression are based on this Clark's multi-step model, and predict that the acquisition of a BRAF mutation can be a founder event in melanocytic neoplasia. However, our recent investigations have challenged this view, showing the polyclonality of BRAF mutations in melanocytic nevi. Furthermore, it is suggested that many melanomas, including acral and mucosal melanomas, arise de novo, not from melanocytic nevus. While mutations of the BRAF gene are frequent in melanomas on non-chronic sun damaged skin which are prevalent in Caucasians, acral and mucosal melanomas harbor mutations of the KIT gene as well as the amplifications of cyclin D1 or cyclin-dependent kinase 4 gene. Amplifications of the cyclin D1 gene are detected in normal-looking 'field melanocytes', which represent a latent progression phase of acral melanoma that precedes the stage of atypical melanocyte proliferation in the epidermis. Based on these observations, we propose an alternative genetic progression model for melanoma.

Increased incidence of malignant melanoma of the skin in workers in a telecommunications industry.

PubMed Central

De Guire, L; Theriault, G; Iturra, H; Provencher, S; Cyr, D; Case, B W

1988-01-01

In 1982 physicians at a hospital melanoma clinic in Montreal noticed that among their patients there had been seven men working in a single telecommunications company. This raised suspicions that working in that industry might be associated with development of malignant melanoma of the skin (MMS). A preliminary gross comparison with general population rates indicated that there was an increased risk in this working group. To estimate the risk of MMS more accurately, a standardised incidence ratio (SIR) was calculated based on the rates of MMS in the local population of the Greater Metropolitan Montreal Area for the years 1976-83. During that period, among workers in all plants for the company, 10 male cases of MMS were observed for an expected number of 3.7 (SIR = 2.7; 95% CI = 1.31-5.02). No cases were observed among female workers (expected = 1.3). The excess was significant among cases with a short latency (less than 20 years since beginning of employment). There was no apparent pattern of exposure based on job titles or departments. PMID:3265335

Multiple cutaneous melanomas associated with gastric and brain metastases*

PubMed Central

Grander, Lara Caroline; Cabral, Fernanda; Lisboa, Alice Paixão; Vale, Gabrielle; Barcaui, Carlos Baptista; Maceira, Juan Manuel Pineiro

2016-01-01

The occurrence of multiple primary melanomas in a single individual is rare. Most commonly, malignant melanocytic lesions subsequent to the initial diagnosis of melanoma are secondary cutaneous metastases. We report a patient with gastrointestinal bleeding from gastric metastasis of cutaneous melanoma. During clinical evaluation and staging, we discovered a brain metastasis associated with 3 synchronous primary cutaneous melanomas. We suggest the research on the mutation in the cyclin-dependent kinase inhibitor 2A (CDKN2A) (INK4a) in such cases. We also emphasize the importance of clinical examination and dermoscopy of the entire tegument, even after a malignant melanocytic lesion is identified. PMID:28300909

Growth-inhibitory and antiangiogenic activity of the MEK inhibitor PD0325901 in malignant melanoma with or without BRAF mutations.

PubMed

Ciuffreda, Ludovica; Del Bufalo, Donatella; Desideri, Marianna; Di Sanza, Cristina; Stoppacciaro, Antonella; Ricciardi, Maria Rosaria; Chiaretti, Sabina; Tavolaro, Simona; Benassi, Barbara; Bellacosa, Alfonso; Foà, Robin; Tafuri, Agostino; Cognetti, Francesco; Anichini, Andrea; Zupi, Gabriella; Milella, Michele

2009-08-01

The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC(50) in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G(1)-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27(KIP1)) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma.

Visual screening for malignant melanoma: a cost-effectiveness analysis.

PubMed

Losina, Elena; Walensky, Rochelle P; Geller, Alan; Beddingfield, Frederick C; Wolf, Lindsey L; Gilchrest, Barbara A; Freedberg, Kenneth A

2007-01-01

To evaluate the cost-effectiveness of various melanoma screening strategies proposed in the United States. We developed a computer simulation Markov model to evaluate alternative melanoma screening strategies. Hypothetical cohort of the general population and siblings of patients with melanoma. Intervention We considered the following 4 strategies: background screening only, and screening 1 time, every 2 years, and annually, all beginning at age 50 years. Prevalence, incidence, and mortality data were taken from the Surveillance, Epidemiology, and End Results Program. Sibling risk, recurrence rates, and treatment costs were taken from the literature. Outcomes included life expectancy, quality-adjusted life expectancy, and lifetime costs. Cost-effectiveness ratios were in dollars per quality-adjusted life year (US dollars/QALY) gained. In the general population, screening 1 time, every 2 years, and annually saved 1.6, 4.4, and 5.2 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of US dollars 10,100/QALY, US dollars 80,700/QALY, and US dollars 586,800/QALY, respectively. In siblings of patients with melanoma (relative risk, 2.24 compared with the general population), 1-time, every-2-years, and annual screenings saved 3.6, 9.8, and 11.4 QALYs per 1000 persons screened, with incremental cost-effectiveness ratios of US dollars 4000/QALY, US dollars 35,500/QALY, and US dollars 257,800/QALY, respectively. In higher risk siblings of patients with melanoma (relative risk, 5.56), screening was more cost-effective. Results were most sensitive to screening cost, melanoma progression rate, and specificity of visual screening. One-time melanoma screening of the general population older than 50 years is very cost-effective compared with other cancer screening programs in the United States. Screening every 2 years in siblings of patients with melanoma is also cost-effective.

Kinase gene fusions in defined subsets of melanoma.

PubMed

Turner, Jacqueline; Couts, Kasey; Sheren, Jamie; Saichaemchan, Siriwimon; Ariyawutyakorn, Witthawat; Avolio, Izabela; Cabral, Ethan; Glogowska, Magdelena; Amato, Carol; Robinson, Steven; Hintzsche, Jennifer; Applegate, Allison; Seelenfreund, Eric; Gonzalez, Rita; Wells, Keith; Bagby, Stacey; Tentler, John; Tan, Aik-Choon; Wisell, Joshua; Varella-Garcia, Marileila; Robinson, William

2017-01-01

Genomic rearrangements resulting in activating kinase fusions have been increasingly described in a number of cancers including malignant melanoma, but their frequency in specific melanoma subtypes has not been reported. We used break-apart fluorescence in situ hybridization (FISH) to identify genomic rearrangements in tissues from 59 patients with various types of malignant melanoma including acral lentiginous, mucosal, superficial spreading, and nodular. We identified four genomic rearrangements involving the genes BRAF, RET, and ROS1. Of these, three were confirmed by Immunohistochemistry (IHC) or sequencing and one was found to be an ARMC10-BRAF fusion that has not been previously reported in melanoma. These fusions occurred in different subtypes of melanoma but all in tumors lacking known driver mutations. Our data suggest gene fusions are more common than previously thought and should be further explored particularly in melanomas lacking known driver mutations. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Synthesis and characterization of a novel radioiodinated phenylacetamide and its homolog as theranostic agents for malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Shen, Chih-Chieh; Chen, Chuan-Lin; Liu, Ren-Shyan; Lin, Ming-Hsien; Wang, Hsin-Ell

2016-01-01

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. This study reports the preparation and biological characterizations of N-(2-(diethylamino)ethyl)-2-(3-(123/131)I-iodo-4- hydroxyphenyl)acetamide and N-(2-(diethylamino)ethyl)-3-(3-(123/131)I-iodo-4-hydroxyphenyl)propanamide (123/131)I-IHPA and 123/131I-IHPP) as novel melanin-specific theranostic agents. These two tracers were hydrophilic, exhibited good serum stability and high binding affinity to melanin. In vitro and in vivo studies revealed rapid, high and tenacious uptakes of both 131I-IHPA and 131I-IHPP in melanotic B16F0 cell line and in C57BL/6 mice bearing B16F0 melanoma, but not in amelanonic A375 cell line and tumors. Small-animal SPECT imaging also clearly delineate B16F0 melanoma since 1 h postinjection of 123I-IHPA and 123I-IHPP in tumor-bearing mice. Owing to the favorable biodistribution of 131I-IHPA and 131I-IHPP after intravenous administration, the estimated absorption dose was low in most normal organs and relatively high in melanotic tumor. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and acceptable projected human dosimetry supported that these two tracers are promising theranostic agents for melanin-positive melanoma.

Melanoma-specific mortality and competing mortality in patients with non-metastatic malignant melanoma: a population-based analysis.

PubMed

Shen, Weidong; Sakamoto, Naoko; Yang, Limin

2016-07-07

The objectives of this study were to evaluate and model the probability of melanoma-specific death and competing causes of death for patients with melanoma by competing risk analysis, and to build competing risk nomograms to provide individualized and accurate predictive tools. Melanoma data were obtained from the Surveillance Epidemiology and End Results program. All patients diagnosed with primary non-metastatic melanoma during the years 2004-2007 were potentially eligible for inclusion. The cumulative incidence function (CIF) was used to describe the probability of melanoma mortality and competing risk mortality. We used Gray's test to compare differences in CIF between groups. The proportional subdistribution hazard approach by Fine and Gray was used to model CIF. We built competing risk nomograms based on the models that we developed. The 5-year cumulative incidence of melanoma death was 7.1 %, and the cumulative incidence of other causes of death was 7.4 %. We identified that variables associated with an elevated probability of melanoma-specific mortality included older age, male sex, thick melanoma, ulcerated cancer, and positive lymph nodes. The nomograms were well calibrated. C-indexes were 0.85 and 0.83 for nomograms predicting the probability of melanoma mortality and competing risk mortality, which suggests good discriminative ability. This large study cohort enabled us to build a reliable competing risk model and nomogram for predicting melanoma prognosis. Model performance proved to be good. This individualized predictive tool can be used in clinical practice to help treatment-related decision making.

Noncutaneous malignant melanoma: a prognostic model from a retrospective multicenter study

PubMed Central

2010-01-01

Background We performed multicenter study to define clinical characteristics of noncutaneous melanomas and to establish prognostic factors patients who received curative resection. Methods Of the 141 patients who were diagnosed of non-cutaneous melanoma at 4 institutions in Korea between June 1992 and May 2005, 129 (91.5%) satisfied the selection criteria. Results Of the 129 noncutaneous melanoma patients, 14 patients had ocular melanoma and 115 patients had mucosal melanoma. For mucosal melanoma, anorectum was the most common anatomic site (n = 39, 30.2%) which was followed by nasal cavity (n = 30, 23.3%), genitourinary (n = 21, 16.3%), oral cavity (n = 14, 10.9%), upper gastrointestinal tract (n = 6, 4.7%) and maxillary sinus (n = 5, 3.9%) in the order of frequency. With the median 64.5 (range 4.3-213.0) months follow-up, the median overall survival were 24.4 months (95% CI 13.2-35.5) for all patients, and 34.6 (95% CI 24.5-44.7) months for curatively resected mucosal melanoma patients. Adverse prognostic factors of survival for 87 curatively resected mucosal melanoma patients were complete resection (R1 resection margin), and age > 50 years. For 14 ocular melanoma, Survival outcome was much better than mucosal melanoma with 73.3% of 2 year OS and 51.2 months of median OS (P = .04). Conclusion Prognosis differed according to primary sites of noncutaneous melanoma. Based on our study, noncutaneous melanoma patients should be treated differently to improve survival outcome. PMID:20426858

Malignant melanoma with preserved hairs: a snap shot could suggest the development from an acquired melanocytic nevus.

PubMed

Kiyohara, Takahiro; Kouraba, Sachio; Takahashi, Hidenori; Kawasaki, Takeo; Takeuchi, Akiteru; Kumakiri, Masanobu

2010-02-01

63-year-old man presented with a dome-shaped, black nodule on his right forehead, where hairs were preserved. The black surface tone measured 7 mm in diameter and spread irregularly from the periphery of the nodule. He had been conscious of the preceding, black macule for approximately 50 years. A snap shot of the patient in adolescence showed a tiny, black macule, which was a few millimeters in diameter. Histological examination demonstrated irregular proliferation of melanoma cells from the epidermis to the dermis. Partially, there were well-circumscribed, oval nests composed of nevus cells in the acanthotic epidermis and follicles. Nevus cells were also seen in the dermal component, presenting a burnt-out appearance. In this case, the small final size, the preserved hairs and the snap shot suggested a preceding, acquired melanocytic nevus. Malignant melanoma could arise from acquired melanocytic nevus.

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma.

PubMed

Law, Matthew H; Bishop, D Timothy; Lee, Jeffrey E; Brossard, Myriam; Martin, Nicholas G; Moses, Eric K; Song, Fengju; Barrett, Jennifer H; Kumar, Rajiv; Easton, Douglas F; Pharoah, Paul D P; Swerdlow, Anthony J; Kypreou, Katerina P; Taylor, John C; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A; Andresen, Per A; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M; Dębniak, Tadeusz; Duffy, David L; Elder, David E; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M; Goldstein, Alisa M; Gruis, Nelleke A; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A; Chen, Wei V; Landi, Maria Teresa; Lang, Julie; Lathrop, G Mark; Lubiński, Jan; Mackie, Rona M; Mann, Graham J; Molven, Anders; Montgomery, Grant W; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A; Radford-Smith, Graham L; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C; Craig, Jamie E; Schadendorf, Dirk; Simms, Lisa A; Burdon, Kathryn P; Nyholt, Dale R; Pooley, Karen A; Orr, Nick; Stratigos, Alexander J; Cust, Anne E; Ward, Sarah V; Hayward, Nicholas K; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M; Bishop, Julia A Newton; Demenais, Florence; Amos, Christopher I; MacGregor, Stuart; Iles, Mark M

2015-09-01

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5 × 10(-8)), as did 2 previously reported but unreplicated loci and all 13 established loci. Newly associated SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes in the associated regions, including one involved in telomere biology.

Genome-wide meta-analysis identifies five new susceptibility loci for cutaneous malignant melanoma

PubMed Central

Law, Matthew H.; Bishop, D. Timothy; Martin, Nicholas G.; Moses, Eric K.; Song, Fengju; Barrett, Jennifer H.; Kumar, Rajiv; Easton, Douglas F.; Pharoah, Paul D. P.; Swerdlow, Anthony J.; Kypreou, Katerina P.; Taylor, John C.; Harland, Mark; Randerson-Moor, Juliette; Akslen, Lars A.; Andresen, Per A.; Avril, Marie-Françoise; Azizi, Esther; Scarrà, Giovanna Bianchi; Brown, Kevin M.; Dębniak, Tadeusz; Duffy, David L.; Elder, David E.; Fang, Shenying; Friedman, Eitan; Galan, Pilar; Ghiorzo, Paola; Gillanders, Elizabeth M.; Goldstein, Alisa M.; Gruis, Nelleke A.; Hansson, Johan; Helsing, Per; Hočevar, Marko; Höiom, Veronica; Ingvar, Christian; Kanetsky, Peter A.; Chen, Wei V.; Landi, Maria Teresa; Lang, Julie; Lathrop, G. Mark; Lubiński, Jan; Mackie, Rona M.; Mann, Graham J.; Molven, Anders; Montgomery, Grant W.; Novaković, Srdjan; Olsson, Håkan; Puig, Susana; Puig-Butille, Joan Anton; Qureshi, Abrar A.; Radford-Smith, Graham L.; van der Stoep, Nienke; van Doorn, Remco; Whiteman, David C.; Craig, Jamie E.; Schadendorf, Dirk; Simms, Lisa A.; Burdon, Kathryn P.; Nyholt, Dale R.; Pooley, Karen A.; Orr, Nick; Stratigos, Alexander J.; Cust, Anne E.; Ward, Sarah V.; Hayward, Nicholas K.; Han, Jiali; Schulze, Hans-Joachim; Dunning, Alison M.; Bishop, Julia A. Newton; MacGregor, Stuart; Iles, Mark M.

2015-01-01

Thirteen common susceptibility loci have been reproducibly associated with cutaneous malignant melanoma (CMM). We report the results of an international 2-stage meta-analysis of CMM genome-wide association studies (GWAS). This meta-analysis combines 11 GWAS (5 previously unpublished) and a further three stage 2 data sets, totaling 15,990 CMM cases and 26,409 controls. Five loci not previously associated with CMM risk reached genome-wide significance (P < 5×10–8), as did two previously-reported but un-replicated loci and all thirteen established loci. Novel SNPs fall within putative melanocyte regulatory elements, and bioinformatic and expression quantitative trait locus (eQTL) data highlight candidate genes including one involved in telomere biology. PMID:26237428

Coexistence of amelanotic melanoma and liposarcoma.

PubMed

Jeong, Taek Jo; Lee, Eun Ju; Haw, Sik; Shin, Min Kyung; Haw, Choong Rim

2009-11-01

An amelanotic malignant melanoma is characterized by little or no pigment. It is frequently misdiagnosed because it is a rare entity in general, and because of its unusual clinical features. Liposarcoma is one of the most common adult soft tissue sarcomas. We encountered a case of amelanotic melanoma with a concurrent liposarcoma. A 68-year-old man presented with a single, 1.5x1.5 cm round erythematous, eroded nodule on the left heel. A biopsy specimen showed atypical, pleomorphic tumor cells with little melanin pigment. The tumor cells were positive for S-100, HMB-45 and negative for cytokeratins. These findings were consistent with amelanotic melanoma. On positron emission tomography/computed tomography (PET/CT), a hypermetabolic lesion was found in the left buttock. This lesion was excised and diagnosed as a well-differentiated liposarcoma. An association between sarcomas and other primary malignancies has been reported. However, an association between melanoma and liposarcoma is rare.

Can Melan-A replace S-100 and HMB-45 in the evaluation of sentinel lymph nodes from patients with malignant melanoma?

PubMed

Kucher, Cynthia; Zhang, Paul J; Acs, Geza; Roberts, Shelley; Xu, Xiaowei

2006-09-01

The sentinel lymph node (SLN) biopsy has become an increasingly important procedure used in the primary staging of malignant melanoma. However, micrometastases in a lymph node can be easily missed on routine H&E-stained sections. Therefore, S-100 and HMB-45 IHC stains are standardly performed on grossly negative SLNs for detection of metastatic melanoma. Each of these IHC markers, however, is not ideal. The authors investigated whether the newer IHC marker Melan-A would improve the detection of metastatic melanoma in SLN biopsies. Forty lymph nodes previously diagnosed with metastatic melanoma were retrospectively evaluated for S-100, HMB-45, and Melan-A expression. In addition, 42 SLN biopsies for metastatic melanoma detection were prospectively collected and evaluated for S-100, HMB-45, and Melan-A expression. All lymph nodes with metastatic melanoma from the retrospective study demonstrated S-100 reactivity. Five of the lymph nodes with metastatic melanoma from the retrospective study failed to express either HMB-45 or Melan-A, all of which displayed a desmoplastic morphology. One of the metastases positive for S-100 and HMB-45 failed to show reactivity with Melan-A (3%). The prospective study found 10 lymph nodes from 42 cases to be positive for metastatic melanoma, which were positive for S-100 (100%). Nine of the involved lymph nodes were positive for HMB-45(90%), and nine were positive for Melan-A (90%). Melan-A, although very specific, cannot replace the use of S-100 and HMB-45 for the detection of metastatic melanoma in SLNs. It can, however, substitute for HMB-45 with equally good results.

Unusual Severe Complication Following Transarterial Chemoembolization for Metastatic Malignant Melanoma: Giant Intrahepatic Cyst and Fatal Hepatic Failure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ataergin, Selmin, E-mail: sataergin@superonline.co; Tasar, Mustafa; Solchaga, Luis

2009-03-15

We describe a 45-year-old male patient with malignant melanoma who underwent hepatic arterial chemoembolization due to liver metastases. Four months after the procedure, the patient developed a giant cystic cavity in the liver. Cytologic examination of the cystic fluid retention revealed necrotic tumor material. The fluid was drained by percutaneous catheter, but the patient developed hepatic failure. This case represents another rare complication of transarterial chemoembolization and shows that transarterial chemoembolization may have rare fatal complications.

A challenging case of ocular melanoma.

PubMed

Costache, Mariana; Dumitru, Adrian Vasile; Pătraşcu, Oana Maria; Popa-Cherecheanu, Daniela Alina; Bădilă, Patricia; Miu, Jeni Cătălina; Procop, Alexandru; Popa, Manuela; Tampa, Mircea Ştefan; Sajin, Maria; Simionescu, Olga; Cîrstoiu, Monica Mihaela

2015-01-01

Ocular melanoma is a rare malignancy found in clinical practice. In this paper, we present a case of highly aggressive ocular melanoma, which was surgically removed at the Department of Ophthalmology and diagnosed at the Department of Pathology, Emergency University Hospital, Bucharest, Romania, using conventional histopathological techniques. Uveal melanoma, a subset of ocular melanoma, has a distinct behavior in comparison to cutaneous melanoma and has a widely divergent prognosis. Approximately half of patients with ocular melanoma will develop metastatic disease, predominantly with hepatic, pulmonary or cerebral location, over a 10 to 15 years period. No systemic therapy was associated with an evident clinical outcome for patients with advanced disease and overall survival rate remains poor.

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations12

PubMed Central

Ciuffreda, Ludovica; Del Bufalo, Donatella; Desideri, Marianna; Di Sanza, Cristina; Stoppacciaro, Antonella; Ricciardi, Maria Rosaria; Chiaretti, Sabina; Tavolaro, Simona; Benassi, Barbara; Bellacosa, Alfonso; Foà, Robin; Tafuri, Agostino; Cognetti, Francesco; Anichini, Andrea; Zupi, Gabriella; Milella, Michele

2009-01-01

The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma. PMID:19649202

Photothermal therapy combined with dinitrophenyl hapten for the treatment of late stage malignant melanoma

NASA Astrophysics Data System (ADS)

Li, Xiaosong; Du, Nan; Li, Haijun; Long, Shan; Chen, Dianjun; Zhou, Feifan; Xu, Yuanyuan; Wang, Fuli; Chen, Wei R.

2017-02-01

To evaluate the efficacy and safety of photothermal with dinitrophenyl hapten (DNP) for patients with malignant melanoma (MM), Patients with pathology confirmed stage III or IV MM were enrolled. Seventy-two patients were randomized into two groups, DNP alone group (n=36) and DNP plus photothermal therapy group (n=36). The results showed that the patients in the combination treatment group had longer median progression-free survival time (19.0m vs. 12.0m, p=0.007). No severe adverse events were observed in both groups. Thus, the combination of photothermal therapy and DNP maybe a new therapeutic strategy for patients with advanced MM.

Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells.

PubMed

Kim, Ji Sung; Kim, Yong Guk; Pyo, Minji; Lee, Hong Kyung; Hong, Jin Tae; Kim, Youngsoo; Han, Sang-Bae

2015-04-01

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.

Adoptive Cell Therapy of Melanoma with Cytokine-induced Killer Cells

PubMed Central

Kim, Ji Sung; Kim, Yong Guk; Pyo, Minji; Lee, Hong Kyung; Hong, Jin Tae; Kim, Youngsoo

2015-01-01

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity. PMID:25922594

DEK oncogene is overexpressed during melanoma progression.

PubMed

Riveiro-Falkenbach, Erica; Ruano, Yolanda; García-Martín, Rosa M; Lora, David; Cifdaloz, Metehan; Acquadro, Francesco; Ballestín, Claudio; Ortiz-Romero, Pablo L; Soengas, María S; Rodríguez-Peralto, José L

2017-03-01

DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Blue nevus-like and blue nevus-associated melanoma: a comprehensive review of the literature.

PubMed

Borgenvik, Thore L; Karlsvik, Tina M; Ray, Saikat; Fawzy, Monica; James, Nick

2017-05-01

Malignant blue nevus, blue nevus-associated melanoma and blue nevus-like melanoma are all terms used to describe malignant melanomas arising from, in association with, or resembling blue nevi. This review is aimed at summarizing the available literature to reduce the confusion surrounding this rare malignancy, and aid the surgeon in choosing further diagnostic or therapeutic measures. We conducted a search of Medline, Embase, Science Direct, Scopus and the Cochrane Library for all full text articles published in English that reported on a malignant melanoma arising from, in association with, or resembling a blue nevus. We identified 91 cases that fit the criteria above. The mean age at diagnosis was 45 years, with a slight male predominance (males: 48; females: 43). Metastatic cases were reported in 55% (n = 50), of which 16 were metastatic at the time of diagnosis, 16 developed metastases within the first year and 18 within 5 years of initial diagnosis. The mean Breslow thickness was 6.8 mm at the time of diagnosis (n = 39). The histological criteria for diagnosing this malignancy are very poorly defined, and may contribute to the substantial confusion surrounding the terminology. There is no consensus on which prognostic indicators predictive of outcome in 'conventional' malignant melanoma are applicable to blue nevus-like melanoma/blue nevus-associated melanoma. However, two larger case series have demonstrated a significant association between Breslow thickness (or largest tumour dimension when non-epidermal) and recurrence-free survival, as well as rate of local recurrence, but larger studies are needed to confirm this. © 2017 Royal Australasian College of Surgeons.

Identification of cells initiating human melanomas.

PubMed

Schatton, Tobias; Murphy, George F; Frank, Natasha Y; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M; Weishaupt, Carsten; Fuhlbrigge, Robert C; Kupper, Thomas S; Sayegh, Mohamed H; Frank, Markus H

2008-01-17

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.

Identification of cells initiating human melanomas

PubMed Central

Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M.; Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Sayegh, Mohamed H.; Frank, Markus H.

2012-01-01

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1,2 and solid cancers3–6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5− bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ sub-populations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5− progeny, whereas ABCB5− tumour populations give rise, at lower rates, exclusively to ABCB5− cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. PMID:18202660

Management of vulvar melanoma.

PubMed

Trimble, E L; Lewis, J L; Williams, L L; Curtin, J P; Chapman, D; Woodruff, J M; Rubin, S C; Hoskins, W J

1992-06-01

Considerable debate centers on the optimal treatment for vulvar melanoma, as well as those clinicopathological factors influencing prognosis. We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990. Primary tumors were assessed according to Chung (47 patients) and Breslow (65 patients) microstaging systems. Fifty-nine patients (76%) underwent radical vulvectomy, ten patients (13%) had a partial vulvectomy, and nine patients (12%) had a wide local excision. Fifty-six also underwent inguinal node dissection. Median follow-up was 193 months. Median survival was 63 months. Ten-year survival by Chung level was as follows: I 100%; II, 81%; III, 87%; IV, 11%; V, 33%. Ten-year survival by tumor thickness was as follows: 0.75 mm, 48%; 0.75-1.5 mm, 68%; 1.51-3.0 mm, 44%; greater than 3.0 mm, 22%. Increased depth of invasion was associated with increased incidence of inguinal node metastasis. Cox regression analysis demonstrated prognostic significance for tumor thickness (P less than 0.001), inguinal node metastasis (P less than 0.001), and older age at diagnosis (P less than 0.001). Radical vulvectomy did not seem to improve survival over less radical procedures. Based on this experience, we recommend radical local excision for patients with malignant melanoma of the vulva. Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection.

Assessment of the presence of mucosal human papillomaviruses in malignant melanomas using combined fluorescent in situ hybridization and chemiluminescent immunohistochemistry.

PubMed

Ambretti, S; Venturoli, S; Mirasoli, M; La Placa, M; Bonvicini, F; Cricca, M; Zerbini, M; Roda, A; Musiani, M

2007-01-01

The vast majority of studies aimed at detecting human papillomavirus (HPV) DNA in skin cancer have used sensitive polymerase chain reaction (PCR) methods but the PCR technique, despite its high sensitivity, is not suitable to ascertain whether (i) the presence of HPV can be related only to few cells harbouring the virus, (ii) the presence of HPV is due to a tumour surface contamination and (iii) the presence of HPV is localized in cancer cells, rather than in normal keratinocytes present in the tumour biopsy. In a recent work we have found mucosal high-risk (HR) HPV genotypes in primary melanoma by PCR. To localize mucosal HR-HPV nucleic acids and tumoural melanocytic marker in the same sections of primary melanoma samples in order to understand the relationship between HPVs and melanoma cells. We have developed a very sensitive method that combines an enzyme-amplified fluorescent in situ hybridization (ISH) for the detection of HPV nucleic acids (types 16 and 18) with a chemiluminescent immunohistochemistry (IHC) method for the detection of the tumoural melanocytic marker HMB-45 sequentially in the same section. Digital images of fluorescent ISH and chemiluminescent IHC were separately recorded, assigned different colours and merged using specific software for image analysis. The combined fluorescent ISH and chemiluminescent IHC demonstrated a sharp colocalization (in the range 60-80%) of HPV nucleic acids and melanoma marker inside the same sections of melanoma biopsies, with a strong specificity and sensitivity. The strong colocalization of mucosal HR-HPV nucleic acids and HMB-45 melanocytic marker emphasized that viral nucleic acids were specifically present in melanoma cells and supported a possible active role of HPV in malignant melanoma.

Familial association of specific histologic types of ovarian malignancy with other malignancies.

PubMed

Lorenzo Bermejo, Justo; Rawal, Rajesh; Hemminki, Kari

2004-04-01

Population-based data on the familial association of specific histologic types of ovarian malignancy with other malignancies are limited. Such data may help to elucidate etiologic differences among histologic types of ovarian malignancy. The nationwide Swedish Family-Cancer Database, which includes 10.3 million individuals and 20,974 ovarian carcinomas, was used to calculate standardized incidence ratios and 95% confidence intervals for age- and histology-specific ovarian malignancies in women whose parents or siblings were affected with malignancies at the most common disease sites. Ovarian malignancy was found to be associated with ovarian, laryngeal, breast, endometrial, liver, and colon carcinoma, as well as myeloma; epithelial ovarian malignancy was found to be associated with ovarian, endometrial, and skin malignancies and with melanoma and myeloma; papillary serous cystadenocarcinoma was found to be associated with ovarian and skin malignancies and with myeloma; and endometrioid carcinoma was found to be associated with endometrial, ovarian, and prostate malignancies and with melanoma. For younger women (ages 40-45 years) whose mothers were affected with endometrial malignancies, the risk of developing endometrioid carcinoma was slightly greater than the risk of developing papillary serous cystadenocarcinoma. Specific types of ovarian malignancy may be associated with specific familial disease sites, with such associations depending on age at diagnosis; the strength of the observed associations varied according to histology. Associations were found between endometrioid carcinoma and endometrial malignancy and between serous carcinoma and Hodgkin disease. Copyright 2004 American Cancer Society.

CHOROIDAL MELANOMA IN A PATIENT WITH WAARDENBURG SYNDROME.

PubMed

Itty, Sujit; Richter, Elizabeth R; McCannel, Tara A

2015-01-01

To report a case of choroidal malignant melanoma in a patient with Waardenburg syndrome and bilateral choroidal pigmentary abnormalities. Clinical examination and multimodal imaging of the case. A 45-year-old woman presented with asymptomatic flat choroidal pigmentation abnormalities in both eyes. A choroidal lesion was identified in the inferotemporal periphery of the left eye arising from an area of hyperpigmentation; ultrasonography findings were consistent with a choroidal melanoma. The patient endorsed a personal and family history of premature graying of hair and was identified to have dystopia canthorum consistent with the diagnosis of Waardenburg syndrome. The authors present the first reported case of concurrent Waardenburg syndrome and choroidal malignant melanoma. This cooccurrence may suggest that the relative hyperpigmented regions in affected fundi may be abnormal and should be monitored closely for the development of choroidal melanoma.

[Cutaneous melanoma associated with previous nevus].

PubMed

Gutiérrez, María P; Barengo, Mónica; Mainardi, Claudio; Garay, Iliana; Kurpis, María; Ruiz Lascano, Alejandro

2009-01-01

The malignant melanoma is a neoplasia originated from the melanocytes located in the skin and other locations. Even though there is not information regarding its incidence and prevalence in our country, its most important risk factors are known. The melanoma can originate de novo or from previous melanocytic lesions. The concept that a melanocytic nevus can serve as a precursor lesion is supported by clinical and histological evidence. An observational, retrospective and analytical study was carried out in the Hospital Privado de Córdoba. The objective was to determine which is the frequency of association of malignant melanomas that develop on previous nevus. A total of 134 melanomas were analyzed. In 32 cases (24%), the melanomas were histologically associated with nevus, in individuals with Breslow's depth bigger than 1 mm the percentage of association was 16.3% while in those exhibiting Breslow smaller than 1 mm the percentage of association was 38.1%. Having evaluated the melanomas in relation to the Breslow and Clark classification, we observed that the nevus associated melanoma group showed less Breslow thickness and low Clark levels, which, by statistical analysis were shown to be significant predictors of the probabilty of finding this association (p < 0.027). This study demonstrates that the tumor thickness by itself is an independent predictive factor of the association melanoma-nevus. However, the rest of the variables studied did not throw significant results from the statistical point of view. In conclusion, patients must be educated for the control of new pigmented injuries as well as for the modification of preexisting nevi.

Correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with malignant melanoma susceptibility and prognosis: A case-control study.

PubMed

Wang, Xin-Hua; Long, Zi-Wen

2017-06-20

This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression signatures of early-stage and advanced medaka melanomas.

PubMed

Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred

2018-06-01

Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

HTB140 melanoma cells under proton irradiation and/or alkylating agents

NASA Astrophysics Data System (ADS)

Korićanac, L.; Petrović, I.; Privitera, G.; Cuttone, G.; Ristić-Fira, A.

2007-09-01

Chemoresistance is a major problem in the treatment of malignant melanoma. The mainstay of treatment for melanoma is the DNA-alkylating agent dacarbazine (DTIC). Fotemustine (FM), a member of the chloroethylnitrosourea group of alkylating agents, has also demonstrated significant antitumor effects in malignant melanoma. However, the intrinsic and acquired resistance of melanoma limits the clinical application of these drugs. Melanomas are also extremely radioresistant. With the objective of enhancing growth inhibition of melanoma cells, combined treatments of FM or DTIC with proton irradiation have been investigated. These effects were studied on HTB140 melanoma cell viability and proliferation. Cells exposed to treatment with FM and protons have shown inhibition of cell growth and significant reduction of proliferation capacity compared to single irradiation or drug treatment. Treatment with DTIC and protons has shown improved growth inhibition compared to appropriate single drug treatment, while the effects of single proton irradiation have been the most pronounced.

[A case of ring melanoma found while treating traumatic glaucoma].

PubMed

Manabe, Kazuyo; Jo, Nobuo; Tateno, Hiroko; Shishidon, Nami; Takahashi, Kanji; Iwashita, Kenshiro; Isei, Taiki; Ohe, Chisato; Sakaida, Noriko; Uemura, Yoshiko

2013-04-01

Ring melanoma, a malignant melanoma which infiltrates over 180 degrees degrees of the ciliary body is very rare in Japan. We report a case of ring melanoma found while treating treatment of traumatic glaucoma with an ultrasound biomicroscope (UBM). A 44-year old woman presented with high intraocular pressure after blunt trauma in her left eye. Best-corrected visual acuity OS was 1.2, and intraocular pressure was 30 mmHg. Gonioscopy showed about 180 degrees of the angle recession. Intraocular pressure was difficult to control in spite of anti-glaucoma drug treatment. Rapid progression of iris elevation and 360 degrees thickening of the ciliary body were detected by UBM. We detected atypical cells with melanine granules in the aqueous fluid and positive findings in PET-CT, leading to a diagnosis of ciliary body malignant melanoma. Consequently we enucleated the left eye. The histopathological diagnosis was ring melanoma. Ring melanoma is an important element in the differential diagnosis for untreatable secondary glaucoma.

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature

PubMed Central

KALAMPOKAS, EMMANOUIL; KALAMPOKAS, THEODOROS; DAMASKOS, CHRISTOS

2017-01-01

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. PMID:28064232

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells.

PubMed

Testa, Ugo; Castelli, Germana; Pelosi, Elvira

2017-11-20

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells.

Radiopharmaceutical therapy of patients with metastasized melanoma with the melanin-binding benzamide 131I-BA52.

PubMed

Mier, Walter; Kratochwil, Clemens; Hassel, Jessica C; Giesel, Frederik L; Beijer, Barbro; Babich, John W; Friebe, Matthias; Eisenhut, Michael; Enk, Alexander; Haberkorn, Uwe

2014-01-01

The performance of cytotoxic drugs is defined by their selectivity of uptake and action in tumor tissue. Recent clinical responses achieved by treating metastatic malignant melanoma with therapeutic modalities based on gene expression profiling showed that malignant melanoma is amenable to systemic treatment. However, these responses are not persistent, and complementary targeted treatment strategies are required for malignant melanoma. Here we provide our experience with different labeling procedures for the radioiodination of benzamides and report on initial dosimetry data and the first therapeutic application of (131)I-BA52, a novel melanin-binding benzamide in patients with metastatic malignant melanoma. Twenty-six adults with histologically documented metastasized malignant melanoma received a single dose of 235 ± 62 MBq of (123)I-BA52 for planar and SPECT/CT imaging. Nine patients were selected for radionuclide therapy and received a median of 4 GBq (minimum, 0.51 GBq; maximum, 6.60 GBq) of the β-emitting radiopharmaceutical (131)I-BA52. A trimethyltin precursor-based synthesis demonstrated high radiochemical yields in the large-scale production of radioiodinated benzamides required for clinical application. (123)I-BA52 showed specific uptake and long-term retention in tumor tissue with low transient uptake in the excretory organs. In tumor tissue, a maximum dose of 12.2 Gy per GBq of (131)I-BA52 was calculated. The highest estimated dose to a normal organ was found for the lung (mean, 3.1 Gy/GBq). No relevant acute or mid-term toxicity was observed with the doses administered until now. Even though dosimetric calculations reveal that the doses applied in this early phase of clinical application can be significantly increased, we observed antitumor effects with follow-up imaging, and single patients of the benzamide-positive cohort of patients (3/5 of the patients receiving a dose > 4.3 GBq) demonstrated a surprisingly long survival of more than 2 y. These

MCAM, as a novel receptor for S100A8/A9, mediates progression of malignant melanoma through prominent activation of NF-κB and ROS formation upon ligand binding.

PubMed

Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Murata, Hitoshi; Watanabe, Masami; Huang, Peng; Kinoshita, Rie; Futami, Junichiro; Inoue, Yusuke; Yamauchi, Akira; Sumardika, I Wayan; Youyi, Chen; Yamamoto, Ken-Ichi; Nasu, Yasutomo; Nishibori, Masahiro; Hibino, Toshihiko; Sakaguchi, Masakiyo

2016-08-01

The dynamic interaction between tumor cells and their microenvironment induces a proinflammatory milieu that drives cancer development and progression. The S100A8/A9 complex has been implicated in chronic inflammation, tumor development, and progression. The cancer microenvironment contributes to the up-regulation of this protein complex in many invasive tumors, which is associated with the formation of pre-metastatic niches and poor prognosis. Changing adhesive preference of cancer cells is at the core of the metastatic process that governs the reciprocal interactions of cancer cells with the extracellular matrices and neighboring stromal cells. Cell adhesion molecules (CAMs) have been confirmed to have high-level expression in various highly invasive tumors. The expression and function of CAMs are profoundly influenced by the extracellular milieu. S100A8/A9 mediates its effects by binding to cell surface receptors, such as heparan sulfate, TLR4 and RAGE on immune and tumor cells. RAGE has recently been identified as an adhesion molecule and has considerably high identity and similarity to ALCAM and MCAM, which are frequently over-expressed on metastatic malignant melanoma cells. In this study, we demonstrated that ALCAM and MCAM also function as S100A8/A9 receptors as does RAGE and induce malignant melanoma progression by NF-κB activation and ROS formation. Notably, MCAM not only activated NF-κB more prominently than ALCAM and RAGE did but also mediated intracellular signaling for the formation of lung metastasis. MCAM is known to be involved in malignant melanoma development and progression through several mechanisms. Therefore, MCAM is a potential effective target in malignant melanoma treatment.

Pembrolizumab in Treating Patients With HIV and Relapsed, Refractory, or Disseminated Malignant Neoplasms

ClinicalTrials.gov

2018-03-22

AIDS-Related Non-Hodgkin Lymphoma; Classical Hodgkin Lymphoma; HIV Infection; Locally Advanced Malignant Neoplasm; Metastatic Malignant Neoplasm; Recurrent Hepatocellular Carcinoma; Recurrent Hodgkin Lymphoma; Recurrent Kaposi Sarcoma; Recurrent Malignant Neoplasm; Recurrent Melanoma of the Skin; Recurrent Non-Hodgkin Lymphoma; Recurrent Non-Small Cell Lung Carcinoma; Refractory Hodgkin Lymphoma; Refractory Malignant Neoplasm; Solid Neoplasm; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIA Hepatocellular Carcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIB Hepatocellular Carcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IIIC Hepatocellular Carcinoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IVA Hepatocellular Carcinoma AJCC v7; Stage IVB Hepatocellular Carcinoma AJCC v7

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study.

PubMed

Moslehi, Roxana; Zeinomar, Nur; Boscoe, Francis P

2018-03-01

Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996-2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR. Population-based rates representing all incident cases of melanoma (1996-2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated. We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996-2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state. The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56-0.64) and 0.46 (95%CI: 0.42-0.49), respectively, for Iran and 22.78 (95%CI: 22.42-23.14) and 16.61 (95%CI: 16.30-16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78-40.29) for males and 36.11 (95%CI: 33.69-38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state. The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the influence of other extrinsic and intrinsic factors on

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study☆

PubMed Central

Moslehi, Roxana; Zeinomar, Nur; Boscoe, Francis P.

2018-01-01

Objectives Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996–2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR. Methods Population-based rates representing all incident cases of melanoma (1996–2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated. We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996–2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state. Results The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56–0.64) and 0.46 (95%CI: 0.42–0.49), respectively, for Iran and 22.78 (95%CI: 22.42–23.14) and 16.61 (95%CI: 16.30–16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78–40.29) for males and 36.11 (95%CI: 33.69–38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state. Conclusion The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the

Melanoma-specific marker expression in skin biopsy tissues as a tool to facilitate melanoma diagnosis.

PubMed

Alexandrescu, Doru T; Kauffman, C Lisa; Jatkoe, Timothy A; Hartmann, Dan P; Vener, Tatiana; Wang, Haiying; Derecho, Carlo; Rajpurohit, Yashoda; Wang, Yixin; Palma, John F

2010-07-01

Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.

Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.

PubMed

Chang, Chih-Chao; Chang, Chih-Hsien; Lo, Yi-Hsuan; Lin, Ming-Hsien; Shen, Chih-Chieh; Liu, Ren-Shyan; Wang, Hsin-Ell; Chen, Chuan-Lin

2016-08-15

Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel (18)F-labeled NOTA-benzamide conjugate, Al(18)F-NOTA-BZA, which can be synthesized in 30min with a radiochemical yield of 20-35% and a radiochemical purity of >95%. Al(18)F-NOTA-BZA is highly hydrophilic (logP=-1.96) and shows good in vitro stability. Intravenous administration of Al(18)F-NOTA-BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67±0.91 and 1.50±0.26%ID/g at 15 and 120min p.i., respectively), but not in A375 amelanotic melanoma (0.87±0.21 and 0.24±0.09%ID/g at 15 and 120min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al(18)F-NOTA-BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al(18)F-NOTA-BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and thelow projected human dosimetry supported that Al(18)F-NOTA-BZA is a very promising melanin-specific PET probe for melanin-positive melanoma. Copyright © 2016 Elsevier Ltd. All rights reserved.

Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.

PubMed

Huang, Sharon K; Hoon, Dave S B

2016-03-01

Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post-treatment drug resistance often developed in melanoma patients. Non-invasive blood biomarker assays allow for regular dynamic monitoring of disease. "Liquid Biopsy" of blood, which exploits circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and cell-free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. With advancements of improving molecular assays, liquid biopsy analysis as a powerful, routine clinical assay for melanoma patients, is highly promising prospective. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Head and neck mucosal malignant melanoma: clinicopathologic correlation with contemporary review of prognostic indicators.

PubMed

Kerr, Elizabeth H; Hameed, Omar; Lewis, James S; Bartolucci, Alfred A; Wang, Dezhi; Said-Al-Naief, Nasser

2012-02-01

Unlike their cutaneous counterparts, head and neck mucosal malignant melanomas (HNMM) behave much more aggressively and their prognostic markers have not been fully elucidated. Therefore, the aim of this study was to review the clinicopathologic features of a contemporary series of primary HNMM, retrieved from archival material of 2 large medical centers, and to explore the association, if any, between these variables, the clinical features, and outcomes. The clinicopathologic, radiographic, and follow-up information as well as the dominant histologic pattern, mitotic rate, presence/absence of pigmentation, necrosis, ulceration, vascular invasion, and host-associated lymphocytic response were retrieved and recorded. Twenty cases were identified including 1 melanoma in situ. Eight-five percent of tumors arose in the sinonasal tract and 3 (15%) in the oral cavity. After a median follow-up of 25 months, all patients with invasive melanoma developed recurrence and/or metastasis. Local recurrences occurred in 82% of the patients after a median of 12 months, and distant metastasis occurred in 71% of the patients after a median of 13 months. Of those with adequate follow-up, 82% died with disease, and the remaining 3 had recurrent or metastatic disease. Fourth-seven percent of tumors were pigmented, 89% showed at least focal necrosis, and 93% demonstrated ulceration. Sixth-eight percent showed vascular invasion and 63% had a brisk host lymphocytic response. Mitotic rates ranged from 2 to 60/10 high-power fields. The absence of an invasive component might be associated with a better prognosis but other clinical and pathological features that predict outcome, and/or could influence therapy, remain to be determined in HNMM.

Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

PubMed

Paridaens, A D; McCartney, A C; Hungerford, J L

1992-03-01

Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure.

Facial resurfacing with a monoblock full-thickness skin graft after multiple malignant melanomas excision in xeroderma pigmentosum.

PubMed

Ozmen, Selahattin; Uygur, Safak; Eryilmaz, Tolga; Ak, Betul

2012-09-01

Xeroderma pigmentosum is an autosomal recessive disease, characterized by vulnerability of the skin to solar radiation. Increase in sunlight-induced cancer is a direct consequence of an increase in mutated cells of the skin of patients with xeroderma pigmentosum. There is no specific technique for facial resurfacing in patients with xeroderma pigmentosum. In this article, a patient with xeroderma pigmentosum with multiple malignant melanomas on her face and radical excision of total facial skin followed by facial resurfacing with monoblock full-thickness skin graft from the abdomen is presented.

Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma.

PubMed

Hou, June Y; Baptiste, Caitlin; Hombalegowda, Radhika Bangalore; Tergas, Ana I; Feldman, Rebecca; Jones, Nathaniel L; Chatterjee-Paer, Sudeshna; Bus-Kwolfski, Ama; Wright, Jason D; Burke, William M

2017-04-15

Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers. In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel. In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B-Raf proto-oncogene serine/threonine kinase (BRAF) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (P = .008). In BRAF-mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The KIT mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (P < .001) and 8.8% in mucosal (P = .05) melanoma subtypes. NRAS mutations were rare in VVMs compared with cutaneous (25.9%; P = .009) and acral (40.6%; P = .002) melanoma subtypes. PD-L1 (56%) and PD-1 (75%) were frequently expressed in VVM, whereas PI3KCA pathway mutations and estrogen receptor/progesterone receptor expression were rare. Compared with VVMs that had KIT mutations, wild-type KIT VVMs were more likely to express molecular markers suggestive of platinum resistance (ERCC1), alkylating sensitivity (MGMT), and anthracycline sensitivity (TOP2A). The unique molecular features of VVM render this disease a distinct subtype of melanoma. Gene-based molecular therapy and immunotherapies may be promising and should be evaluated in clinical trials. Cancer 2017;123:1333-1344. © 2016 American Cancer Society. © 2016 American Cancer Society.

The burden of malignant melanoma--lessons to be learned from Austria.

PubMed

Monshi, Babak; Vujic, Marin; Kivaranovic, Danijel; Sesti, Alma; Oberaigner, Willi; Vujic, Igor; Ortiz-Urda, Susana; Posch, Christian; Feichtinger, Hans; Hackl, Monika; Rappersberger, Klemens

2016-03-01

Incidence rates of melanoma, generated by cancer registries (CRs), are susceptible to reporting inconsistencies due to increasing decentralisation of diagnosis. We therefore independently assessed the burden of melanoma in Austria. We collected histopathological reports on melanoma of all patients diagnosed in Austria in 2011. Demographic and clinical characteristics, histopathological tumour stages were assessed. Their regional distributions and incidence rates were analysed and compared with data of national and international CRs. A total of 5246 patients were diagnosed with 1951 in-situ and 3295 invasive melanomas in Austria in 2011 (population 8.4 million). Age, sex and anatomic distribution corresponded to findings in other European countries, however, the incidence of 25/100,000 (world age-standardised rate) for invasive melanomas was two-fold higher than published by the Austrian CR (12/100,000). Varying frequencies in diagnosing thin melanomas (≤1 mm; n = 4415) accounted exclusively for significant regional disparities, while advanced tumours (>1 mm; n = 761) were evenly distributed. Western Austria showed the highest rates (36/100,000). Patients from eastern Austria whose melanomas were diagnosed in laboratories in western Austria (n = 76) showed significantly higher proportions of in-situ lesions (n = 43; 57%) compared to those whose tumours were diagnosed in eastern Austria (n = 4014; in-situ = 1369; 34%) (p < 0.0001). In Austria, the melanoma burden and its potential socio-economic implications are significantly underestimated. Similarities of incidences indicate this could affect other European countries with well-established CRs and compromise international comparability of data. Austrian regional disparities suggest overdiagnosis of thin melanomas due to the variability of pathologists' thresholds for the diagnosis of early stage tumours. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature.

PubMed

Kalampokas, Emmanouil; Kalampokas, Theodoros; Damaskos, Christos

2017-01-02

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma.

PubMed

Su, Juan; Gao, Tianyuan; Jiang, Minghao; Wu, Lisha; Zeng, Weiqi; Zhao, Shuang; Peng, Cong; Chen, Xiang

2016-10-04

Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma.

CD147 silencing inhibits tumor growth by suppressing glucose transport in melanoma

PubMed Central

Su, Juan; Gao, Tianyuan; Jiang, Minghao; Wu, Lisha; Zeng, Weiqi; Zhao, Shuang; Peng, Cong; Chen, Xiang

2016-01-01

Melanoma is a very malignant disease and there are still no effective treatments. CD147 participates in the carcinogenesis of multiple human cancers and GLUT-1, as a glucose transporter, is associated with tumor growth. However, the function of CD147 and GLUT-1 in melanoma have not been completely understood. Thus, in this study we investigated the expression of CD147 and GLUT-1 in melanoma tissue, which were overexpressed compared with that in nevus tissue. In addition, CD147 and GLUT-1 were co-localized in the cytoplasm of human melanoma A375 cells. Immunoprecipitation proved that CD147 interacted with GLUT-1 at D105-199. Silencing CD147 by specific siRNA could downregulate GLUT-1 level via inhibiting PI3K/Akt signaling and decrease glucose uptake in A375 cells. In vivo experiments also supported that CD147 knockdown suppressed the tumor growth in melanoma subcutaneous mice model, observed by micro PET/CT. Our results could help validate CD147 as a new therapeutic target for treating melanoma. PMID:27556188

Locoregional spread of cutaneous melanoma: sonography findings.

PubMed

Catalano, Orlando; Caracò, Corrado; Mozzillo, Nicola; Siani, Alfredo

2010-03-01

This article reviews various aspects of locoregional spread of malignant cutaneous melanoma, as imaged with gray-scale sonography and Doppler techniques. The scenarios illustrated include disease staging (primary melanoma, satellite metastasis, in-transit metastasis, and lymphadenopathies), sentinel lymph node biopsy procedure, patient follow-up, recurrence detection, cutaneous metastasis, and sonographically guided intervention. High-resolution sonography allows recognition of small, clinically-occult melanomatous foci. It plays a major role in locoregional staging and follow-up of patients with cutaneous melanoma.

Dacarbazine combined targeted therapy versus dacarbazine alone in patients with malignant melanoma: a meta-analysis.

PubMed

Jiang, Guan; Li, Rong-Hua; Sun, Chao; Liu, Yan-Qun; Zheng, Jun-Nian

2014-01-01

Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27-2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14-1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10-1.36), vomiting (combined RR = 1.73, 95% CI: 1.41-2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42-2.16) compared to the group for DTIC alone. These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion.

Label-free detection of circulating melanoma cells by in vivo photoacoustic flow cytometry

NASA Astrophysics Data System (ADS)

Wang, Xiaoling; Yang, Ping; Liu, Rongrong; Niu, Zhenyu; Suo, Yuanzhen; He, Hao; Gao, Wenyuan; Tang, Shuo; Wei, Xunbin

2016-03-01

Melanoma is a malignant tumor of melanocytes. Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. Compared to in vivo flow cytometry based on fluorescence, PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. The raw signal detected from target cells often contains some noise caused by electronic devices, such as background noise and thermal noise. We choose the Wavelet denoising method to effectively distinguish the target signal from background noise. Processing in time domain and frequency domain would be combined to analyze the signal after denoising. This algorithm contains time domain filter and frequency transformation. The frequency spectrum image of the signal contains distinctive features that can be used to analyze the property of target cells or particles. The processing methods have a great potential for analyzing signals accurately and rapidly. By counting circulating melanoma cells termly, we obtain the number variation of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.

Melanoma: Genetic Abnormalities, Tumor Progression, Clonal Evolution and Tumor Initiating Cells

PubMed Central

Castelli, Germana; Pelosi, Elvira

2017-01-01

Melanoma is an aggressive neoplasia issued from the malignant transformation of melanocytes, the pigment-generating cells of the skin. It is responsible for about 75% of deaths due to skin cancers. Melanoma is a phenotypically and molecularly heterogeneous disease: cutaneous, uveal, acral, and mucosal melanomas have different clinical courses, are associated with different mutational profiles, and possess distinct risk factors. The discovery of the molecular abnormalities underlying melanomas has led to the promising improvement of therapy, and further progress is expected in the near future. The study of melanoma precursor lesions has led to the suggestion that the pathway of tumor evolution implies the progression from benign naevi, to dysplastic naevi, to melanoma in situ and then to invasive and metastatic melanoma. The gene alterations characterizing melanomas tend to accumulate in these precursor lesions in a sequential order. Studies carried out in recent years have, in part, elucidated the great tumorigenic potential of melanoma tumor cells. These findings have led to speculation that the cancer stem cell model cannot be applied to melanoma because, in this malignancy, tumor cells possess an intrinsic plasticity, conferring the capacity to initiate and maintain the neoplastic process to phenotypically different tumor cells. PMID:29156643

Melanoma with rhabdomyosarcomatous differentiation.

PubMed

Kuwadekar, Aditya; Allard, Justin; Dardik, Michael; Smith, Franz

2018-06-06

Melanoma with rhabdomyosarcomatous differentiation is an extremely rare observation with a review of the literature revealing fewer than 15 previously identified cases. The authors describe a case of a 72-year-old man with a cutaneous lesion of the left scalp that was diagnosed as malignant melanoma on biopsy and wide excision. One month later, a punch biopsy of the excisional area revealed rhabdomyosarcomatous proliferation. Re-examination of the wide-excision specimen with muscle markers revealed areas of neoplastic melanoma cells consistent with rhabdomyosarcomatous differentiation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The Evolving Role of Radiation Therapy in the Management of Malignant Melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Khan, Niloufer; Khan, Mohammad K., E-mail: drkhurram2000@gmail.com; Almasan, Alex

2011-07-01

The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotacticmore » radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.« less

Targeted delivery of CYP2E1 recombinant adenovirus to malignant melanoma by bone marrow-derived mesenchymal stem cells as vehicles.

PubMed

Wang, Jishi; Ma, Dan; Li, Yan; Yang, Yuan; Hu, Xiaoyan; Zhang, Wei; Fang, Qin

2014-03-01

The aim of this study was to explore the effects of bone marrow-derived mesenchymal stem cells (BMSCs) as intermediate carriers on targeting of P450 gene recombinant adenovirus to malignant melanoma in vitro and in vivo. BMSCs were transduced with pAd5-CMV-CYP2E1 recombinant adenovirus. BMSC migration was detected by Transwell plates in vitro and by superparamagnetic iron oxide particles in vivo. Growth-inhibitory effect and apoptosis were determined by MTT and immunity fluorescence staining. Anticancer effects were examined by a human melanoma nude mouse model in vivo. BMSCs moved toward A375 cells in Transwell plates. Numerous superparamagnetic MSCs labeled with iron oxide were identified in the peripheral areas of the tumor, but were detected in primary organs by Prussian blue staining. BMSC-CYP2E1 cells mediated a bystander killing effect on CYP2E1-negative A375 cells during coculture (IC50 values for A375 cells cocultured with BMSC-EGFP and BMSC-CYP2E1 were 4.08 and 2.68 mmol/l, respectively). Intravenously injecting CYP2E1 recombinant adenovirus-loaded BMSCs in mice with established human melanoma managed to target the tumor site, and BMSCs with forced expression of CYP2E1 inhibited the growth of malignant cells in vivo by activating 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide. BMSCs may serve as a platform of P450 gene-directed enzyme prodrug therapy for the delivery of chemotherapeutic prodrugs to tumors.

Multifocal amelanotic conjunctival melanoma and acquired melanosis sine pigmento.

PubMed Central

Paridaens, A D; McCartney, A C; Hungerford, J L

1992-01-01

Clinical and histopathological features of four cases of multifocal amelanotic malignant melanoma of the conjunctiva in association with 'acquired melanosis sine pigmento' are reported. The absence of conjunctival pigmentation in this extremely rare combination of lesions prevented early diagnosis and clinical monitoring. As a result orbital exenteration was required in three cases. This multicentric non-pigmented variety of conjunctival malignant melanoma tends to present later than pigmented forms and may require exenteration of the orbit as a primary procedure. Images PMID:1540561

CANT1 lncRNA Triggers Efficient Therapeutic Efficacy by Correcting Aberrant lncing Cascade in Malignant Uveal Melanoma.

PubMed

Xing, Yue; Wen, Xuyang; Ding, Xia; Fan, Jiayan; Chai, Peiwei; Jia, Renbing; Ge, Shengfang; Qian, Guanxiang; Zhang, He; Fan, Xianqun

2017-05-03

Uveal melanoma (UM) is an intraocular malignant tumor with a high mortality rate. Recent studies have shown the functions of long non-coding RNAs (lncRNAs) in tumorigenesis; thus, targeting tumor-specific lncRNA abnormalities has become an attractive approach for developing therapeutics to treat uveal melanoma. In this study, we identified a novel nuclear CANT1 lncRNA (CASC15-New-Transcript 1) that acts as a necessary UM suppressor. CANT1 significantly reduced tumor metastatic capacity and tumor formation, either in cell culture or in animals harboring tumor xenograft. Intriguingly, XIST lncRNA serves as a potential target of CANT1, and JPX or FTX lncRNA subsequently serves as a contextual hinge to activate a novel CANT1-JPX/FTX-XIST long non-coding (lncing) pathway in UM. Moreover, CANT1 triggers the expression of JPX and FTX by directly binding to their promoters and promoting H3K4 methylation. These observations delineate a novel lncing cascade in which lncRNAs directly build a lncing cascade without coding genes that aims to modulate UM tumorigenesis, thereby specifying a novel "lncing-cascade renewal" anti-tumor therapeutic strategy by correcting aberrant lncing cascade in uveal melanoma. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Anorectal mucosal melanoma

PubMed Central

Malaguarnera, Giulia; Madeddu, Roberto; Catania, Vito Emanuele; Bertino, Gaetano; Morelli, Luca; Perrotta, Rosario Emanuele; Drago, Filippo; Malaguarnera, Michele; Latteri, Saverio

2018-01-01

Anorectal melanoma is an uncommon and aggressive mucosal melanocytic malignancy. Due to its rarity, the pre-operative diagnosis remains difficult. The first symptoms are non-specific such as anal bleeding, anal mass or pain. Although anorectal melanoma carries a poor prognosis; optimal therapeutics strategies are unclear. Surgical resection remains the mainstay of treatment. The optimal surgical procedure for primary tumours is controversial and can vary from wide local excision or endoscopic mucosal resection (EMR) to an abdomino-perineal resection. A high degree of uncertainly exists regarding the benefit of radiation therapy or chemotherapy. The treatment of advanced melanoma is evolving rapidly with better understanding of the disease biology and immunology. Considerable effort has been devoted to the identification of molecular determinants of response to target therapies and immunotherapy. PMID:29492238

Genetically fluorescent melanoma bone and organ metastasis models.

PubMed

Yang, M; Jiang, P; An, Z; Baranov, E; Li, L; Hasegawa, S; Al-Tuwaijri, M; Chishima, T; Shimada, H; Moossa, A R; Hoffman, R M

1999-11-01

We report here the establishment and metastatic properties of bright, highly stable, green fluorescent protein (GFP) expression transductants of the B16 mouse malignant melanoma cell line and the LOX human melanoma line. The highly fluorescent malignant melanoma cell lines allowed the visualization of skeletal and multiorgan metastases after i.v. injection of B16 cells in C57BL/6 mice and intradermal injection of LOX cells in nude mice. The melanoma cell lines were transduced with the pLEIN expression retroviral vector containing the GFP and neomycin resistance genes. Stable B16F0 and LOX clones expressing high levels of GFP were selected stepwise in vitro in levels of G418 of up to 800 microg/ml. Extensive bone and bone marrow metastases of B16F0 were visualized by GFP expression when the animals were sacrificed 3 weeks after cell implantation. Metastases for both cell lines were visualized in many organs, including the brain, lung, pleural membrane, liver, kidney, adrenal gland, lymph nodes, skeleton, muscle, and skin by GFP fluorescence. This is the first observation of experimental skeletal metastases of melanoma, which was made possible by GFP expression. These models should facilitate future studies of the mechanism and therapy of bone and multiorgan metastasis of melanoma.

Malignant melanoma in Ferrara, Northern Italy: epidemiologic survey focusing on tumor thickness.

PubMed

Borghi, A; Corazza, M; Minghetti, S; Masarà, A; Virgili, A

2015-12-01

Estimates of malignant melanoma (MM) incidence and prognosis vary widely. The present study was performed to analyze epidemiologic and prognostic aspects of primary MM mainly in relation to tumor thickness. We conducted a retrospective study on a cohort of 435 patients with diagnosis of primary MM between 1997 and 2011. In the period 2009-2011, among the MM diagnosed 50.00% were thin, 32.43% in situ and 17.57% thicker while in 1997-1999 MM>1 mm accounted for 51.61% of diagnoses. Mean age of patients affected with thin MM was significantly lower than that of patients with MM>1 mm, and mean thickness resulted significantly lower in female patients than in males. Mean thickness of MM located on easily self-evaluable body areas was significantly lower than in those not accessible for skin self-examination. The commonest histogenetic type was superficially spreading melanoma. Mitotic rate, ulceration and vertical growth phase all resulted related to MM thickness. Out of 61 patients with thin MM who underwent SLNB, 3 resulted positive (4.92%): neither thickness >0.75 mm, nor ulceration, mitotic rate or Clark level were found to be associated with SLNB positivity. Five-year survival rate was 98.3% for thin MM patients and 76.4% for thick MM patients. Our trend analysis evidences a continuing increase of thinner primary MM throughout the study period, potentially enhancing patient prognosis. Regular skin self-examination could contribute to earlier recognition of MM. Identification of more powerful predictors of thin MM prognosis is necessary.

[Endocrine factors influencing melanoma progression].

PubMed

Dobos, Judit

2009-03-01

According to recent findings that beside cancers traditionally considered as hormone-dependent, several other tumor types show different behavior in the two sexes, indicating the possible role of endocrine factors in the course of these diseases. The possibility that endocrine factors may influence the clinical course of human malignant melanoma is suggested by the higher survival rate in premenopausal vs. postmenopausal women or men of any ages. However, investigations on the sex hormone receptor status of human cutaneous melanomas and experiments attempting to support the epidemiological results yielded conflicting results. In our human melanoma cell lines we failed to detect steroid receptors at protein level, while quantitative PCR demonstrated that their mRNA expression level was orders of magnitude lower compared to the positive control cell lines. Sex hormones did not influence the in vitro features of the human melanoma cells considerably. On the other hand, glucocorticoid receptor was present both at mRNA and protein level, although dexamethasone was effective in vitro only at high doses. Our previous experiments showed that intrasplenic injection of human melanoma cells resulted in a significantly higher number of liver colonies in male than in female SCID mice. We now show that this difference evolves during the first day. After injection into the tail vein we did not observe gender-dependent difference in the efficiency of pulmonary colonization. Examining the pattern of metastasis formation after intracardiac injection, we have found differences between the two sexes in the incidence or number of colonies only in the case of the liver but not in other organs. We concluded that the observed phenomenon is specific to the liver; therefore we investigated the effects of 2-methoxyestradiol, an endogenous metabolite of estradiol produced mainly in the liver, with an estrogen receptor-independent antitumor activity. 2ME2 effectively inhibited melanoma cell

Melanoma genetics and the development of rational therapeutics

PubMed Central

Chudnovsky, Yakov; Khavari, Paul A.; Adams, Amy E.

2005-01-01

Melanoma is a cancer of the neural crest–derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. No current treatments substantially enhance patient survival once metastasis has occurred. This review focuses on recent insights into melanoma genetics and new therapeutic approaches being developed based on these advances. PMID:15841168

Ultrasound-mediated interferon {beta} gene transfection inhibits growth of malignant melanoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yamaguchi, Kazuki; Department of Anatomy, Fukuoka University School of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka City 814-0180; Feril, Loreto B., E-mail: ferilism@yahoo.com

2011-07-22

Highlights: {yields} Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-{beta} genes both in vitro and in vivo. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited proliferation of melanoma cells in vitro. {yields} Ultrasound-mediated IFN-{beta} transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon {beta} (IFN-{beta}) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-{beta} in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-{beta} genes mixed with microbubbles. Successful sonotransfection with IFN-{beta} gene in vitro was confirmed by ELISA,more » which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-{beta} gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.« less

Canine melanoma diagnosis: RACK1 as a potential biological marker.

PubMed

Campagne, C; Julé, S; Alleaume, C; Bernex, F; Ezagal, J; Château-Joubert, S; Estrada, M; Aubin-Houzelstein, G; Panthier, J-J; Egidy, G

2013-11-01

Melanoma diagnosis in dogs can be challenging due to the variety of histological appearances of canine melanocytic neoplasms. Markers of malignancy are needed. Receptor for activated C-kinase 1 (RACK1) was found to characterize melanomas in other mammals. We investigated the value of RACK1 detection in the classification of 19 cutaneous and 5 mucosal melanocytic neoplasms in dogs. These tumors were categorized as melanocytomas or benign and melanomas or malignant after evaluation of their morphology, mitotic index, and Ki-67 growth fraction. Using immunofluorescence, we confirmed microphthalmia-associated transcription factor (MITF) as a marker of normal and transformed melanocytic cells in dog tissues. All control (n = 10) and tumoral (n = 24) samples stained positively for MITF (34/34, 100%). Whereas RACK1 was not detected in healthy skin melanocytes, melanocytic lesions were all positive for RACK1 signal (24/24, 100%). RACK1 cytoplasmic staining appeared with 2 distinct distribution patterns: strong, diffuse, and homogeneous or granular and heterogeneous. All melanoma samples (13/13, 100%) stained homogeneously for RACK1. All melanocytomas (11/11, 100%) stained heterogeneously for RACK1. Immunohistochemistry was less consistent than immunofluorescence for all labelings in melanocytic lesions, which were often very pigmented. Thus, the fluorescent RACK1-MITF labeling pattern helped to distinguish melanomas from melanocytomas. Furthermore, RACK1 labeling correlated with 2 of 11 morphological features linked to malignancy: cell and nuclear size. These results suggest that RACK1 may be used as a marker in dog melanomas.

Can integrated 18F-FDG PET/MR replace sentinel lymph node resection in malignant melanoma?

PubMed

Schaarschmidt, Benedikt Michael; Grueneisen, Johannes; Stebner, Vanessa; Klode, Joachim; Stoffels, Ingo; Umutlu, Lale; Schadendorf, Dirk; Heusch, Philipp; Antoch, Gerald; Pöppel, Thorsten Dirk

2018-06-06

To compare the sensitivity and specificity of 18F-fluordesoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), 18F-FDG PET/magnetic resonance (18F-FDG PET/MR) and 18F-FDG PET/MR including diffusion weighted imaging (DWI) in the detection of sentinel lymph node metastases in patients suffering from malignant melanoma. Fifty-two patients with malignant melanoma (female: n = 30, male: n = 22, mean age 50.5 ± 16.0 years, mean tumor thickness 2.28 ± 1.97 mm) who underwent 18F-FDG PET/CT and subsequent PET/MR & DWI for distant metastasis staging were included in this retrospective study. After hybrid imaging, lymphoscintigraphy including single photon emission computed tomography/CT (SPECT/CT) was performed to identify the sentinel lymph node prior to sentinel lymph node biopsy (SLNB). In a total of 87 sentinel lymph nodes in 64 lymph node basins visible on SPECT/CT, 17 lymph node metastases were detected by histopathology. In separate sessions PET/CT, PET/MR, and PET/MR & DWI were assessed for sentinel lymph node metastases by two independent readers. Discrepant results were resolved in a consensus reading. Sensitivities, specificities, positive predictive values and negative predictive values were calculated with histopathology following SPECT/CT guided SLNB as a reference standard. Compared with histopathology, lymph nodes were true positive in three cases, true negative in 65 cases, false positive in three cases and false negative in 14 cases in PET/CT. PET/MR was true positive in four cases, true negative in 63 cases, false positive in two cases and false negative in 13 cases. Hence, we observed a sensitivity, specificity, positive predictive value and negative predictive value of 17.7, 95.6, 50.0 and 82.3% for PET/CT and 23.5, 96.9, 66.7 and 82.3% for PET/MR. In DWI, 56 sentinel lymph node basins could be analyzed. Here, the additional analysis of DWI led to two additional false positive findings, while the number of true

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma

PubMed Central

Palmieri, Giuseppe; Satriano, Sabrina MR; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-01-01

Background Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). Methods One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Results Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (≥2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Conclusion Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease. PMID:17107608

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma.

PubMed

Palmieri, Giuseppe; Satriano, Sabrina M R; Budroni, Mario; Cossu, Antonio; Tanda, Francesco; Canzanella, Sergio; Caracò, Corrado; Simeone, Ester; Daponte, Antonio; Mozzillo, Nicola; Comella, Giuseppe; Castello, Giuseppe; Ascierto, Paolo A

2006-11-15

Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (> or =2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

Drug targeting of oncogenic pathways in melanoma.

PubMed

Fecher, Leslie A; Amaravadi, Ravi K; Schuchter, Lynn M; Flaherty, Keith T

2009-06-01

Melanoma continues to be one of the most aggressive and morbid malignancies once metastatic. Overall survival for advanced unresectable melanoma has not changed over the past several decades. However, the presence of some long-term survivors of metastatic melanoma highlights the heterogeneity of this disease and the potential for improved outcomes. Current research is uncovering the molecular and genetic scaffolding of normal and aberrant cell function. The known oncogenic pathways in melanoma and the attempts to develop therapy for them are discussed. The targeting of certain cellular processes, downstream of the common genetic alterations, for which the issues of target and drug validation are somewhat distinct, are also highlighted.

Dacarbazine Combined Targeted Therapy versus Dacarbazine Alone in Patients with Malignant Melanoma: A Meta-Analysis

PubMed Central

Jiang, Guan; Li, Rong-Hua; Sun, Chao; Liu, Yan-Qun; Zheng, Jun-Nian

2014-01-01

Background Malignant melanoma is the most aggressive and deadly form of skin cancer. Dacarbazine (DTIC) has been the approved first-line treatment for metastatic melanoma in routine clinical practice. However, response rates with single-agent DTIC are low. The objective of this study was to compare the efficacy and safety of DTIC with or without placebo and DTIC-based combination therapies in patients with advanced metastatic melanoma. Methods We searched from electronic databases such as The Cochrane Library, MEDLINE, EBSCO, EMBASE, Ovid, CNKI, and CBMDisc from 2003 to 2013. The primary outcome measures were overall response and 1-year survival, and the secondary outcome measurements were adverse events. Results Nine randomized controlled trials (RCTs) involving 2,481 patients were included in the meta-analysis. DTIC-based combination therapies was superior to DTIC alone in overall response (combined risk ratio [RR]  = 1.60, 95% confidence interval [CI]: 1.27–2.01) and 1-year survival (combined RR = 1.26, 95% CI: 1.14–1.39). Patients with DTIC-based combination therapies had higher incidence of adverse events including nausea (combined RR = 1.23, 95% CI: 1.10–1.36), vomiting (combined RR = 1.73, 95% CI: 1.41–2.12) and neutropenia (combined RR = 1.75, 95% CI: 1.42–2.16) compared to the group for DTIC alone. Conclusion These data suggested that DTIC-based combination therapies could moderately improve the overall response and the 1-year survival but increased the incidence of adverse events. Further large-scale, high-quality, placebo-controlled, double-blind trials are needed to confirm this conclusion. PMID:25502446

Etiology of melanoma.

PubMed

Koh, H K; Sinks, T H; Geller, A C; Miller, D R; Lew, R A

1993-01-01

the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.

Vitamin E δ-tocotrienol triggers endoplasmic reticulum stress-mediated apoptosis in human melanoma cells

PubMed Central

Montagnani Marelli, Marina; Marzagalli, Monica; Moretti, Roberta M.; Beretta, Giangiacomo; Casati, Lavinia; Comitato, Raffaella; Gravina, Giovanni L.; Festuccia, Claudio; Limonta, Patrizia

2016-01-01

Malignant melanoma is the leading cause of death from skin cancer. Drug toxicity and resistance represent a serious challange for melanoma treatments. Evidence demonstrates that natural compounds may play a crucial role in cancer prevention, growth and progression. Vitamin E tocotrienols (TT) were shown to possess antitumor activity. Here, we analyzed the effects of δ-TT on melanoma cell growth and the involvement of the endoplasmic reticulum (ER) stress in this activity. The experiments were performed on human melanoma cell lines, BLM and A375. δ-TT exerted a significant proapoptotic effect on both cell lines, involving the intrinsic apoptosis pathway; importantly, this compound did not affect the viability of normal human melanocytes. In melanoma cells, δ-TT exerted its antitumor effect through activation of the PERK/p-eIF2α/ATF4/CHOP, IRE1α and caspase-4 ER stress-related branches. Salubrinal, an inhibitor of the ER stress, counteracted the cytotoxic activity of δ-TT. In vivo experiments performed in nude mice bearing A375 xenografts evidenced that δ-TT reduces tumor volume and tumor mass; importantly, tumor progression was significantly delayed by δ-TT treatment. In conclusion, δ-TT exerts a proapoptotic activity on melanoma cells, through activation of the ER stress-related pathways. δ-TT might represent an effective option for novel chemopreventive/therapeutic strategies for melanoma. PMID:27461002

Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy.

PubMed

Casula, Milena; Colombino, Maria; Satta, Maria P; Cossu, Antonio; Lissia, Amelia; Budroni, Mario; Simeone, Ester; Calemma, Rosa; Loddo, Cinzia; Caracò, Corrado; Mozzillo, Nicola; Daponte, Antonio; Comella, Giuseppe; Canzanella, Sergio; Guida, Michele; Castello, Giuseppe; Ascierto, Paolo A; Palmieri, Giuseppe

2007-01-01

Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR)=6.31; p=0.0009), multiple primary melanomas (RR=3.43; p=0.0014), and early onset age (RR=4.56; p=0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

Identifying and targeting determinants of melanoma cellular invasion.

PubMed

Jayachandran, Aparna; Prithviraj, Prashanth; Lo, Pu-Han; Walkiewicz, Marzena; Anaka, Matthew; Woods, Briannyn L; Tan, BeeShin; Behren, Andreas; Cebon, Jonathan; McKeown, Sonja J

2016-07-05

Epithelial-to-mesenchymal transition is a critical process that increases the malignant potential of melanoma by facilitating invasion and dissemination of tumor cells. This study identified genes involved in the regulation of cellular invasion and evaluated whether they can be targeted to inhibit melanoma invasion. We identified Peroxidasin (PXDN), Netrin 4 (NTN4) and GLIS Family Zinc Finger 3 (GLIS3) genes consistently elevated in invasive mesenchymal-like melanoma cells. These genes and proteins were highly expressed in metastatic melanoma tumors, and gene silencing led to reduced melanoma invasion in vitro. Furthermore, migration of PXDN, NTN4 or GLIS3 siRNA transfected melanoma cells was inhibited following transplantation into the embryonic chicken neural tube compared to control siRNA transfected melanoma cells. Our study suggests that PXDN, NTN4 and GLIS3 play a functional role in promoting melanoma cellular invasion, and therapeutic approaches directed toward inhibiting the action of these proteins may reduce the incidence or progression of metastasis in melanoma patients.

Identifying and targeting determinants of melanoma cellular invasion

PubMed Central

Jayachandran, Aparna; Prithviraj, Prashanth; Lo, Pu-Han; Walkiewicz, Marzena; Anaka, Matthew; Woods, Briannyn L.; Tan, BeeShin

2016-01-01

Epithelial-to-mesenchymal transition is a critical process that increases the malignant potential of melanoma by facilitating invasion and dissemination of tumor cells. This study identified genes involved in the regulation of cellular invasion and evaluated whether they can be targeted to inhibit melanoma invasion. We identified Peroxidasin (PXDN), Netrin 4 (NTN4) and GLIS Family Zinc Finger 3 (GLIS3) genes consistently elevated in invasive mesenchymal-like melanoma cells. These genes and proteins were highly expressed in metastatic melanoma tumors, and gene silencing led to reduced melanoma invasion in vitro. Furthermore, migration of PXDN, NTN4 or GLIS3 siRNA transfected melanoma cells was inhibited following transplantation into the embryonic chicken neural tube compared to control siRNA transfected melanoma cells. Our study suggests that PXDN, NTN4 and GLIS3 play a functional role in promoting melanoma cellular invasion, and therapeutic approaches directed toward inhibiting the action of these proteins may reduce the incidence or progression of metastasis in melanoma patients. PMID:27172792

Photodynamic therapy for melanoma: efficacy and immunologic effects

NASA Astrophysics Data System (ADS)

Avci, Pinar; Gupta, Gaurav K.; Kawakubo, Masayoshi; Hamblin, Michael R.

2014-02-01

Malignant melanoma is one of the fastest growing cancers and if it cannot be completely surgically removed the prognosis is bleak. Melanomas are known to be particularly resistant to both chemotherapy and radiotherapy. Various types of immunotherapy have however been investigated with mixed reports of success. Photodynamic therapy (PDT) has also been tested against melanoma, again with mixed effects as the melanin pigment is thought to act as both an optical shield and as an antioxidant. We have been investigating PDT against malignant melanoma in mouse models. We have compared B16F10 melanoma syngenic to C57BL/6 mice and S91 Cloudman melanoma syngenic to DBA2 mice. We have tested the hypothesis that S91 will respond better than B16 because of higher expression of immunocritical molecules such as MHC-1, tyrosinase, tyrosinase related protein-2 gp100, and intercellular adhesion molecule-1. Some of these molecules can act as tumor rejection antigens that can be recognized by antigen-specific cytotoxic CD8 T cells that have been stimulated by PDT. Moreover it is possible that DBA2 mice are intrinsically better able to mount an anti-tumor immune response than C57BL/6 mice. We are also studying intratumoral injection of photosensitzers such as benzoporphyrin monoacid ring A and comparing this route with the more usual route of intravenous administration.

In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography.

PubMed

Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R

2016-01-01

One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma

Efficacy and safety of bio-chemotherapy with dacarbazine plus interleukin-2 in patients with unresectable malignant melanoma.

PubMed

Wu, Chun-Feng; Wang, Hung-Ming; Huang, Wen-Kuan; Chang, John Wen-Cheng

2015-12-01

This study retrospectively evaluated the toxicity and efficacy of dacarbazine (DTIC) with low-dose subcutaneous interleukin-2 (IL-2) for patients with advanced melanoma. Patients with unresectable malignant melanoma received bio-chemotherapy DTIC (330 mg/m(2) , every 3 weeks ) and IL-2 18 MIU (million international units) in divided doses by subcutaneous injection three times a week for 4 weeks. Treatment was performed for six cycles or until disease progression or unbearable toxicity. From October 2006 to November 2013, up to 31 patients (17 men; 14 women) were enrolled. Their median age was 48 years (range, 22-81 years). Subtypes of melanoma included 11 (35.4%) acral lentiginous, nodular, 1 (3.2%) superficial spreading, 10 (32.2%) mucosal and 5 (16.1%) others. The response rate was 19.3%, including 3.2% with a complete response, 16.1% with a partial response and 6.3% with stable disease. The median progression-free survival time was 3.5 months (95% CI: 3.0-3.9 months). The median overall survival time was 8.6 months (95% CI: 4.1-10.9 months). The 1-year survival rate was 39% and the 5-year survival rate was 10%. Our data demonstrated that low-dose subcutaneous IL-2 plus DTIC has modest efficacy and may produce long-term survival in small proportion of patients. Furthermore, the treatment is well tolerated by patients. © 2015 Wiley Publishing Asia Pty Ltd.

Functional Erythropoietin Autocrine Loop in Melanoma

PubMed Central

Kumar, Suresh M.; Acs, Geza; Fang, Dong; Herlyn, Meenhard; Elder, David E.; Xu, Xiaowei

2005-01-01

Although erythropoietin (Epo) is a known stimulator of erythropoiesis, recent evidence suggests that its biological functions are not confined to hematopoietic cells. To elucidate the role of Epo and erythropoietin receptor (EpoR) in melanoma, we examined the expression and function of these proteins in melanocytes and melanoma cells. We found increased expression of Epo in melanoma cells compared to melanocyte in vitro. EpoR was also strongly expressed in all of the melanoma cell lines and two of the three melanocyte cell lines examined. Epo expression was significantly higher in melanoma than in benign nevi as determined by immunohistochemistry. Although melanoma cells secreted Epo in normoxic condition in vitro, hypoxia and CoCl2 treatment increased Epo secretion. EpoR in melanoma cells was functional, because exogenous Epo increased melanoma resistance to hypoxic stress, pretreatment of melanoma cells with Epo significantly increased resistance to dacarbazine treatment, and Epo increased the phosphorylation of EpoR, RAF, and MEK. In conclusion, we demonstrated constitutive expression of Epo and EpoR as well as autonomous secretion of Epo by melanoma cells, indicating a novel autocrine loop of Epo in melanoma. The results suggest that the autocrine and paracrine functions of Epo might play a role in malignant transformation of melanocytes and in the survival of melanoma cells in hypoxia and other adverse conditions. PMID:15743794