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Sample records for anorectal malignant melanoma

  1. Approach to Malign Melanoma in Anorectal Area

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    Huseyin Pulat

    2014-12-01

    Full Text Available Aim: Anorectal malign melanoma comprise 0.2-1 % of all malign melanoma. They are extremely aggressive. Most patients are lost beacuse of incurable systemic illness. In our study, we aim to evaluate the results of surgical and oncological follow-up of our patients that we operated because of anorectal malign melanoma. Material and Method: Our 4 patients operated because of anorectal malign melanoma between October 2008 and April 2013 were analysed. The patients were analysed in terms of demographic datas, complaint and its time, physical examination and imaging findings, treatment procedure, local recurrence or presence of metastasis and follow-up results.Results: Our study group comprised 4 people (2 men and 2 women with the mean age of 64,2 years. The main complaint was rectal bleeding. The avarage complaint duration was 7.5 months. In all patients, anorectal mass was detected after physical examination and imaging studies. Biopsies of the mass were reported to be consistent with malign melanoma. With the further studies, one patient was detected to have metastasis in liver. Abdominoperineal resection was applied to one patient after wide local excision and to three patients during the first aplication. The avarage follow-up time was 19,25 months. The avarage diameter of tumor was 3,9 cm. One patient was applied lymph node dissection because of recurrence in iliac region. The avarage stay time at hospital of the patients who had no postoperative problems was 9,7 days. During follow-up time, three of the patients died because of common metastasis. A patient followed regularly is still continuing his life without illness in his postoperative 22nd month. Discussion: Anorectal malign melanoma is a rare, with a bad prognosis and a late diagnosed entity as it has a similarity with benign illnesses which are mostly seen in anorectal area in terms of clinical symptoma. To correct the prognosis of the illness, the suitable surgery and adjuvant treatment

  2. Combined laparoscopic abdomino-endoscopic perineal total mesorectal excision for anorectal malignant melanoma: A case report

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    Ryo Ohta

    Full Text Available Introduction: This report presents a case of anorectal malignant melanoma treated with combined laparoscopic abdomino-endoscopic perineal total mesorectal excision. Presentation of case: An 82-year-old female presented with hematochezia. Colonoscopy revealed a 5-cm tumor in the anorectal junction, and biopsy specimen showed malignant melanoma. Modified ransanal total mesorectal excision was performed to get the sufficient surgical resection margins. After lymph node dissection in usual manner, mobilizing the rectum to the level of levator ani muscle. Then a skin incision was made around the anus and the transperineal access platform was placed. The fat tissue of the ischioanal fossa was divided until the levator ani muscle was exposed. The oral side of the colon was transected and specimen was extracted through the perineal incision site. Then stoma was placed laparoscopically. Discussion: This procedure provides not only better exposure of the extralevator surgical field, but also efficient resection margins compared with the conventional andominoperineal resection. Conclusion: To the best of our knowledge, this is the first report of combined laparoscopic abdomino-endoscopic perineal total mesorectal excision for anorectal malignant melanoma. Our experience showed safety and feasible option for anorectal malignant diseases. Keywords: Anorectal malignant melanoma, Transanal total mesorectal excision, Laparoscopic abdominoperineal resection, Case report

  3. Primary Anorectal Melanoma

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    Maliha Khan

    2014-03-01

    Full Text Available Primary malignant melanoma of the anus and rectum is a rare and aggressive neoplasm that tends to invade locally and metastasize early in the course of the disease. It is often misdiagnosed as hemorrhoids or as one of the other benign anorectal conditions and is thus linked to an overall poor prognosis and a 5-year survival rate of less than 20%. Optimal treatment is still controversial, and current evidence does not show any preferential survival benefit from abdominoperineal resection over wide local excision. Chemotherapy or radiotherapy may be used for advanced disease. We report a 71-year-old female presenting with painful bowel movements and blood in stools. She was eventually found to have a mass arising from the anorectal junction with regional lymph node involvement. The patient underwent an abdominoperineal resection and is currently scheduled for chemotherapy.

  4. DMBT1 expression distinguishes anorectal from cutaneous melanoma

    DEFF Research Database (Denmark)

    Helmke, Burkhard Maria; Renner, Marcus; Poustka, Annemarie

    2009-01-01

    tumours 1 (DMBT1) in cases of primary anorectal malignant melanoma and CM. METHODS AND RESULTS: Expression analyses of classical immunohistochemical markers (S100, HMB45, Melan A and MiTF) and of the protein DMBT1 were carried out in 27 cases of primary anorectal malignant melanoma and 26 cases of CM. All...

  5. Primary Anorectal Melanoma: An Update

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    P Carcoforo, M.T Raiji, G.M Palini, M Pedriali, U Maestroni, G Soliani, A Detroia, M.V Zanzi, A.L Manna, J.G Crompton, R.C Langan, A Stojadinovic, I Avital

    2012-01-01

    Full Text Available The anorectum is a rare anatomic location for primary melanoma. Mucosal melanoma is a distinct biological and clinical entity from the more common cutaneous melanoma. It portrays worse prognosis than cutaneous melanoma, with distant metastases being the overwhelming cause of morbidity and mortality. Surgery is the treatment of choice, but significant controversy exists over the extent of surgical resection. We present an update on the state of the art of anorectal mucosal melanoma. To illustrate the multimodality approach to anorectal melanoma, we present a typical patient.

  6. Treatment and outcomes of anorectal melanoma.

    LENUS (Irish Health Repository)

    Heeney, Anna

    2012-02-01

    INTRODUCTION: anorectal melanoma is an uncommon disease constituting less than 3% of all melanomas. Due to its rarity, there are a lack of randomized control trials regarding appropriate management and current evidence is based mainly on retrospective studies. METHODS: in view of the controversial surgical treatment of anorectal melanoma, we review the most published literature in an attempt to elucidate its typical clinical features along with current thinking with respect to management approaches to this aggressive disease. Using the keywords "anorectal" and "malignant melanoma", a medline search of all articles in English was performed and the relevant articles procured. Additional references were retrieved by cross reference from key articles. RESULTS: anorectal melanoma affects the elderly with a slight preponderance for females. It commonly presents disguised as benign disease with local bleeding or suspicion for haemorrhoidal disease. There is no convincing evidence to indicate that radical resection of primary anorectal melanoma is associated with improvement in local control or survival, and local excision is an acceptable treatment option. CONCLUSION: optimum management depends on several factors and the therapeutic goals should be to lengthen survival and preserve quality-of-life. Given that wide local excision is a more limited intervention with comparable survival it should be considered as the initial treatment choice. Unfortunately prognosis for patients with this disease remains poor despite choice of treatment strategy with overall five year disease-free survival less than twenty percent in most studies.

  7. Primary ovarian malignant melanoma

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    Kostov Miloš

    2010-01-01

    Full Text Available Background. Primary ovarian malignant melanoma is extremely rare. It usually appears in the wall of a dermoid cyst or is associated with another teratomatous component. Metastatic primary malignant melanoma to ovary from a primary melanoma elsewhere is well known and has been often reported especially in autopsy studies. Case report. We presented a case of primary ovarian malignant melanoma in a 45- year old woman, with no evidence of extraovarian primary melanoma nor teratomatous component. The tumor was unilateral, macroscopically on section presented as solid mass, dark brown to black color. Microscopically, tumor cells showed positive immunohistochemical reaction for HMB-45, melan-A and S-100 protein, and negative immunoreactivity for estrogen and progesteron receptors. Conclusion. Differentiate metastatic melanoma from rare primary ovarian malignant melanoma, in some of cases may be a histopathological diagnostic problem. Histopathological diagnosis of primary ovarian malignant melanoma should be confirmed by immunohistochemical analyses and detailed clinical search for an occult primary tumor.

  8. Anorectal complications in patients with haematological malignancies.

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    Loureiro, Rafaela V; Borges, Verónica P; Tomé, Ana L; Bernardes, Carlos F; Silva, Mário J; Bettencourt, Maria J

    2018-04-13

    Anorectal complications are common in patients with haematological malignancies. The objectives are to characterize anorectal complications in these patients, identify risk factors and shed light on treatment, morbidity and mortality rates. A retrospective, observational study that included 83 inpatients with haematological malignancies and proctological symptoms from January 2010 to September 2015 was conducted. Clinical outcomes were obtained through a detailed review of medical records. The median age was 56 years, and 52 (62.7%) patients were men. Fifty-six (67.5%) patients had nonseptic anorectal complications and 27 (32.5%) patients had septic anorectal complications. Patients with septic anorectal complications were more commonly male, older, and had lower absolute neutrophil counts, but the differences were not statistically significant (P=0.79, 0.67 and 0.89, respectively). In positive blood cultures [23/70 (32.9%)], Enterococcus faecium, Klebsiella pneumonia, and Escherichia coli were the most common isolated agents. In nonseptic anorectal complications, conservative treatments/minor proctological procedures were adopted, and patients with septic anorectal complications were treated with antibiotics±major proctological procedures and/or surgical drainage/debridement. Forty-eight (85.7%) patients in the nonseptic complications group improved compared with 23 (85.2%) patients in the septic complications group. The overall mortality rate was 2.4% (n=2), with one (1.2%) death related to perianal sepsis. Enterococcus spp. were more commonly identified in this study and can be increasing in this specific population. In contrast to other reports, we did not identify an association between septic anorectal complications and possible risk factors such as male sex, younger age or a low absolute neutrophil count. Most patients had nonseptic anorectal complications. A major proctological procedure/surgical debridement should always be applied in septic complications

  9. Primary malignant melanoma

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    A. Ferhat Mısır

    2016-04-01

    Full Text Available Malignant melanomas (MM of the oral cavity are extremely rare, accounting for 0.2% to 8.0% of all malignant melanomas. Malignant melanomas is more frequently seen at the level of the hard palate and gingiva. Early diagnosis and treatment are important for reducing morbidity. Malignant melanoma cells stain positively with antibodies to human melanoma black 45, S-100 protein, and vimentin; therefore, immunohistochemistry can play an important role in evaluating the depth of invasion and the location of metastases. A 76-year-old man developed an oral malignant melanoma, which was originally diagnosed as a bluish reactive denture hyperplasia caused by an ill-fitting lower denture. The tumor was removed surgically, and histopathological examination revealed a nodular-type MM. There was no evidence of recurrence over a 4-year follow-up period.

  10. Malignant melanoma - a warning

    International Nuclear Information System (INIS)

    Volden, G.; Rajka, G.; Thune, P.; Falk, E.S.; Krogh, H.K.

    1990-01-01

    Incidence of malignant melonoma of the skin has risen rapidly during the last decades. Mortality rates are also rising, although not so much as incidence rates. There is strong evidence that exposure to sunlight is a major factor in the etiology of melanomas. There appears to be no direct cumulative dose-response relationship, except in the case of lentigo maligna melanoma. Episodes of sunburn among children and young individuals seem to be more important as an etiologic factor for melanoma than chronic exposure to the sun. Very high risk of melanoma exists in persons with dysplastic nevus syndrome. Persons with giant congenital nevi are also at increased risk. However, many melanomas arise de novo. The intension of the authors is to reduce mortality by screening families at risk, by early detection and treatment of melanomas, and by education. 15 refs., 2 tabs

  11. Simulants of malignant melanoma

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    Gérald E. Piérard

    2015-08-01

    Full Text Available During the recent period, dermoscopy has yielded improvement in the early disclosure of various atypical melanocytic neoplasms (AMN of the skin. Beyond this clinical procedure, AMN histopathology remains mandatory for establishing their precise diagnosis. Of note, panels of experts in AMN merely report moderate agreement in various puzzling cases. Divergences in opinion and misdiagnosis are likely increased when histopathological criteria are not fine-tuned and when facing a diversity of AMN types. Furthermore, some AMN have been differently named in the literature including atypical Spitz tumor, metastasizing Spitz tumor, borderline and intermediate melanocytic tumor, malignant Spitz nevus, pigmented epithelioid melanocytoma or animal-type melanoma. Some acronyms have been further suggested such as MELTUMP (after melanocytic tumor of uncertain malignant potential and STUMP (after Spitzoid melanocytic tumor of uncertain malignant potential. In this review, such AMN at the exclusion of cutaneous malignant melanoma (MM variants, are grouped under the tentative broad heading skin melanocytoma. Such set of AMN frequently follows an indolent course, although they exhibit atypical and sometimes worrisome patterns or cytological atypia. Rare cases of skin melanocytomas progress to loco regional clusters of lesions (agminate melanocytomas, and even to regional lymph nodes. At times, the distinction between a skin melanocytoma and MM remains puzzling. However, multipronged immunohistochemistry and emerging molecular biology help profiling any malignancy risk if present.

  12. RARE METASTASES OF MALIGNANT MELANOMA

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    Marija Trenkić-Božinović

    2014-09-01

    Full Text Available Melanomas are malignant neoplasms that originate from melanocytes. The most common are on the skin and mucous membranes. Choroidal melanomas are quite different from cutaneous melanomas with regard to presentation, metastases, and treatment. We report two cases of metastatic gastric malignant melanoma of the eye and skin, with reference to the literature. The first patient was a woman aged 23 years, who underwent gastrectomy 22 months after enucleation of the eye due to malignant choroid melanoma. The second patient was a man, 72 years old, who underwent surgery 28 months before because of malignant melanoma of the skin of the forehead. Paraffin sections, 4 μm thick were stained using a classic method, as well as immunohistochemical DAKO APAAP method, using a specific S - 100 antibody and Melan A antibodies. The stomach is considered a rare place for the development of metastases. Metastases in the stomach are often limited to the submucosal as well as the serousmuscular layer, as noted in one of our patients. Metastatic melanoma of the gastrointestinal tract should be suspected in any patient with a history of malignant melanoma and new gastrointestinal symptoms. Because of the similarity between certain common histopathological types of malignant melanoma, primarily achromatic, and types of primary cancers of the stomach, the following immunohistochemical studies are needed: Melan A and S - 100 protein ( markers of malignant melanoma , as well as mucins: MUC5AC, MUC2 and CDX2 ( markers of different types of primary gastric carcinoma.

  13. Immunoscintigraphy of malignant melanomas

    International Nuclear Information System (INIS)

    Nicol, L.; Sandron, A.; Herry, J.Y.; Chevrant-Breton, J.

    1990-01-01

    This work is part of a multicentric European evaluation of the monoclonal antibody 225.28s targeted against malignant melanoma and its metastases. Twenty-eight patients (12 males, 16 females, mean age: 53 yrs), who had initially been treated by resection of the primary tumour, were included in the study. Twenty-three of the 26 metastases more than 1 cm in diameter were visualized by immunoscintigraphy. The sensitivity of the procedure (88%) is limited however by the small size of the lesions and their depth, as well as by background noise caused by circulating antibodies. Immunoscintigraphy enables non-invasive investigation of the whole body and can detect lesions that other conventional complementary explorations fail to identify [fr

  14. Radiation biology of malignant melanoma

    International Nuclear Information System (INIS)

    Rofstad, E.K.; Norwegian Cancer Society, Oslo)

    1986-01-01

    The survival curves for melanoma cells exposed to single radiation doses in vitro and the specific growth delays for melanoma xenografts irradiated with single doses in vivo were found to differ considerably among individual cell lines and tumours. In fact, the differences could be almost as large as the largest differences observed among cell lines and xenografts from tumours of different histology with very different clinical radiocurability. Moreover, radiobiologic parameters that may have significant influence on tumour response to fractionated irradiation, e.g. growth rate, hypoxic fraction, reoxygenation ability, PLD-repair capacity and contact repair capacity, were found to differ greatly in magnitude among individual melanomas. This review therefore concludes that malignant melanoma is a tumour type that is very heterogeneous in radioresponsiveness, i.e. malignant melanomas should no longer be considered to be radiation resistant in general. The values of the α/β ratio derived from cell survival curves for melanoma cells irradiated in vitro and melanoma xenografts irradiated in vivo were found to cover a wide range relative to those for acutely and late responding normal tissues. Although these α/β ratios are no more than estimates of the effective α/β ratios in a clinical situation, they still indicated that hyperfractionation may be beneficial in the treatment of some melanomas, whereas others may be more efficiently treated by use of conventional fractionation regimes, either based on 2 Gy or higher doses per fraction. Consequently, optimum radiation therapy of malignant melanoma will probably require an individualized treatment strategy. In vitro assays for prediction of radiocurability and choice of treatment strategy for individual melanoma patients seem therefore highly warranted. (orig.)

  15. Cutavirus in Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Mollerup, Sarah; Fridholm, Helena; Vinner, Lasse

    2017-01-01

    A novel human protoparvovirus related to human bufavirus and preliminarily named cutavirus has been discovered. We detected cutavirus in a sample of cutaneous malignant melanoma by using viral enrichment and high-throughput sequencing. The role of cutaviruses in cutaneous cancers remains to be in...

  16. Isolated malignant melanoma metastasis to the pancreas

    DEFF Research Database (Denmark)

    Larsen, Anne K; Krag, Christen; Geertsen, Poul

    2013-01-01

    SUMMARY: Malignant melanomas rarely develop isolated pancreatic metastases. We describe a unique patient who is still alive 22 years following an isolated pancreatic melanoma metastasis, and we review the sparse literature in the field....

  17. Rectal malignant melanoma mistaken for thrombotic hemorrhoids - rare tumor with poor prognosis

    International Nuclear Information System (INIS)

    Kovacova, E.; Hvizdakova, A.; Vyskocil, M.; Kinova, S.; Sesovsky, V.; Kobzova, D.; Palkovic, M.

    2011-01-01

    Rectal malignant melanoma originates in the melanocytes of the anorectal area. Represent less than 1 % of all melanomas, and 4 % of all malignant tumors of the rectum and anus. The most common clinical manifestation is bleeding, the clinical examination may be mistaken for benign lesions or hemorrhoids. Given the rarity of the diagnosis are not well-defined therapeutic procedures. Prognosis for patient is poor. The authors present a case of 70-year old patient with rectal melanoma diagnosed at an advanced stage of disease, initially with diagnosis a thrombotic hemorrhoid. (author)

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

    DEFF Research Database (Denmark)

    Mikkelsen, Lauge H; Larsen, Ann-Cathrine; von Buchwald, Christian

    2016-01-01

    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...

  19. Mistletoe in the treatment of malignant melanoma

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    Esin Sakallı Çetin

    2014-03-01

    Full Text Available Malignant melanoma is a malignant neoplasia drives from melanocytes. Malignant melanoma, the most causing death, is seen in the third place at skin cancer. Malignant melanoma shows intrinsic resistance to chemotherapeutic agents and variability in the course of the disease which are distinct features separating from other solid tumors. These features prevent the development and standardization of non-surgical treatment models of malignant melanoma. Although there is a large number of chemotherapeutic agents used in the treatment of metastatic malignant melanoma, it hasn’t been demonstrated the survival advantage of adjuvant treatment with chemotherapeutic agents. Because of the different clinical course of malignant melanoma, the disease is thought to be closely associated with immune system. Therefore, immunomodulatory therapy models were developed. Mistletoe stimulates the immune system by increasing the number and activity of dendritic cells, thus it has been shown to effect on tumor growth and metastasis of malignant melanoma patient. Outlined in this review are the recent developments in the understanding the role of mistletoe as a complementary therapy for malignant melanoma. J Clin Exp Invest 2014; 5 (1: 145-152

  20. PRIMARY MALIGNANT MELANOMA OF ARYEPIGLOTTIC FOLD

    African Journals Online (AJOL)

    2015-12-01

    Dec 1, 2015 ... commonly in larynx, tongue, and tonsil.2 Primary mel- anoma of the larynx and trachea are very rare among the group of non-cutaneous melanomas. In primary melanoma of the larynx, the least common site is the subglottic mucosa.3 Here we present a case of primary malignant melanoma of aryepiglottic ...

  1. Histopathological study of malignant melanoma in highlanders ...

    African Journals Online (AJOL)

    Histopathological study of malignant melanoma in highlanders. AZ Mohammed, AN Manasseh, BM Mandong, ST Edino. Abstract. Background:Malignant melanoma is a fatal skin cancer that is curable when detected and treated early. Recent reports indicate a rising incidence globally. This study aims at identifying the ...

  2. [Multiple conjunctival malignant melanomas (author's transl)].

    Science.gov (United States)

    Haddad, R

    1979-04-01

    5 1/2 years after excision of pigmented malignant melanoma which apparently arose in a nevus of the paralimbal bulbar conjunctiva, this 42-year-old male presented himself with a nonpigmented mass of the lid margin which also proved to be a malignant melanoma. "Acquired melanosis sine pigmento" was considered as a site of origin, but histopathologically there is more evidence that this melanoma arose in a non-pigmented compound nevus.

  3. Clinical radiobiology of malignant melanoma

    International Nuclear Information System (INIS)

    Bentzen, S.M.; Overgaard, J.; Overgaard, M.; Thames, H.D.; Vejby Hansen, P.; Von der Maase, H.; Meder, J.

    1989-01-01

    Tumor-control probability (TCP) was analyzed in a series of 121 patients having 239 histologically proven recurrent or metastatic malignant melanomas. These were treated with fractionated radiotherapy with various doses per fraction, total doses, and overall times. Cutaneous lesions (127,53%) were treated with electron beams, and more deeply seated tumors (112,47%) with 60 Co or 4-8 MV X-rays. The fraction size was highly variable, and this permitted determination of the α/β ration in the multifraction linearquadratic model, which was estimated at 0.57 Gy with 95% confidence limits [-1.07,2.5]Gy Threatment time had no demonstrable influenc on TCP. Thus this tumor exhibits the fractionation sensitivity characteristic of a late-responding normal tissue, suggesting that an adequate fractionation schedule for malignant melanomas would be characterized by larger-than-conventional doses per fraction, possibly about 6 Gy per fraction. This is consistent with the conclusions of other authors. Tumor size, evaluated as mean tumor diameter, S, had a major impact on TCP: the number of target cells increased as a power function of S with exponent 0.72 (95% confidence limits) [1.49, 0.94]. In fact, a considerable amount of the heterogeneity in the dose-responce data could be removed by accounting for size. Thus, the weak, or absent dose response became highly significant. When a patient had multiple lesions, the responses of these to radiotherapy tended to be similar, thus implying that results were significantly influenced by a 'hidden parameter' (such as inherent radiosensitivity or immunological status). A test of the predictive value of the TCP-model was performed in a different series of 183 cutaneous and lymph node malignant melanomas. The observed dose-response relationship in this data set was in good agreement with the model prediction. A chi-square test for goodness-of-fit showed that the variation between predicted and observed results could be explained by the

  4. CT findings of diffuse malignant leptomeningeal melanoma

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    Fujii, Katsuro; Sahashi, Ko; Takahashi, Akira; Nakagawa, Hiroshi [Aichi Medical Univ., Aichi (Japan); Sumi, Yasuhiko

    1982-04-01

    This was a case of malignant melanoma which spreaded diffusely in the meninges. The diagnosis was established by cytology of the cerebrospinal fluid. The CT images, cerebral angiographic findings and pathological findings by autopsy were presented.

  5. Metastatic breast disease from cutaneous malignant melanoma.

    Science.gov (United States)

    Moschetta, Marco; Telegrafo, Michele; Lucarelli, Nicola Maria; Martino, Gianluigi; Rella, Leonarda; Stabile Ianora, Amato Antonio; Angelelli, Giuseppe

    2014-01-01

    Malignant melanoma is one of the most rapidly increasing cancer in the world. Breast metastases from melanoma are uncommon but could reflect a widespread disease. We report a case of malignant widespread melanoma presenting with bilateral breast nodules in a 39 year-old pre-menopausal Caucasian woman with an history of cutaneous melanoma of the trunk. Breast clinical examination revealed the presence of a hard and mobile lump located on the left breast. Ultrasound detected two bilateral nodules corresponding to oval opacities with well-defined edges and without calcifications or architectural distortion on mammography. Fine needle aspiration cytology performed on both breast nodules confirmed that the breast lesions were metastases from primary cutaneous malignant melanoma. A total-body CT examination detected brain, lung and abdominal lymph nodes metastases. The breast represents an uncommon site of metastatic disease from extra-mammary tumors. Imaging features of breast metastases from melanoma usually do not allow a differential diagnosis with breast primary tumors. Breast metastases may be asymptomatic or palpable as dense and well-circumscribed nodules. Breast metastases indicate a widespread disease and should lead to avoid aggressive surgical procedures because of the poor prognosis of patients affected by metastatic melanoma. The detection of bilateral breast metastases from melanoma is highly suggestive of metastatic multi-organ disease and could be useful to address the therapeutic approach. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Management of anorectal melanoma: report of 17 cases and literature review.

    Science.gov (United States)

    Belbaraka, Rhizlane; Elharroudi, Tijani; Ismaili, Nabil; Fetohi, Mohammed; Tijami, Fouad; Jalil, Abdelouahed; Errihani, Hassan

    2012-03-01

    Primary anorectal melanoma is a rare and aggressive disease. It accounts for 0.5% of all rectal tumors. They are very agressive tumors with poor prognosis. The aim of this study is to report the clinical and evolutionary profile and therapeutical approach of these tumors. A retrospective study of 17 patients with anorectal melanoma diagnosed between January 1998 and December 2007 was performed. The signs and symptoms, diagnostic study, and surgical and medical treatments were analyzed. The average age was 58 years. Sex ratio was 12 men per five women. Patients had symptoms present for an average of 6 months. The most common symptom was rectal bleeding. According to Slingluff classification, five patients had stage I (localized tumor), four cases had stage II (regional nodes metastasis), and eight cases had stage III (distant metastasis). Seven patients have radical surgery. Only two patients received adjuvant immunotherapy. Eight patients received palliative chemotherapy based on dacarbazine or cisplatinum. The median survival was 8 months. Prognosis of anorectal melanoma is still very poor. However, some patients when treated by radical resection may experience long-term survival. The use of adjuvant immunotherapy needs large collaborative studies in view of the rarity of the tumor.

  7. primary malignant amelanotic melanoma arising from a vitiligo patch

    African Journals Online (AJOL)

    2014-05-05

    May 5, 2014 ... Malignant melanoma is a rare tumour in people of. African descent including those affected by albinism. (1). The incidence of malignant melanoma in Africans is estimated to ranging from 0.5 to 1.5 per 100,000 people (2). Acrolentiginous melanoma is the most common type of melanoma in this population.

  8. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

    Shy, C.M.; Checkoway, H.; Marshall, E.G.

    1985-01-01

    The general consensus of the seven reviewers is that occupational exposures at Lawrence Livermore National Laboratory have not been established as a causal factor for the observed excess of malignant melanoma. Several observations support the impression that some or all of the observed melanoma excess may be attributable to intense surveillance and enhanced detection of early stage melanoma lesions. Since the incidence of melanomas among Laboratory employees has not diminished, an early harvesting effect is unlikely. This suggests the distinct possibility that localized, in situ melanomas that would normally not be detected are being reported, and that in the absence of this enhanced detection, many of these early stage lesions would show little or no clinical progression. This phenomenon would explain the continued high incidence of melanomas in the absence of a physical or chemical inciting cause. A key point in this reasoning is the issue of the rate of growth of early stage melanomas, and this point remains a key question for study. Even if the observed excess cannot be explained by detection bias, the reviewers agree that the Austin and Reynolds' study does not make a convincing case for occupational factors being a cause of the high melanoma incidence. 6 refs

  9. Primary Malignant Melanoma of the Esophagus

    OpenAIRE

    Oya Yonal; Duygu Ibrisim; Yıldıran Songur; Yılmaz Cakaloglu; Koray Tuncer; Hale Kırımlıoglu; Sadakat Ozdil

    2013-01-01

    Primary malignant melanoma of the esophagus (PMME) comprises only 0.1?0.2% of all malignant esophageal tumors. PMME tumors are highly aggressive and metastasize early via hematogenic and lymphatic pathways. Treatment outcome is poor because the cancer has often advanced at the time of diagnosis. Inoperability, unsuccessful treatment with radiotherapy and chemotherapy in advanced tumors and metastases have contributed to its poor prognosis. Here, we present the endoscopic features, endoscopic ...

  10. Human malignant melanomas in nude mice

    International Nuclear Information System (INIS)

    Atlas, S.W.; Braffman, B.H.; Lo Brutto, R.; Elder, D.E.; Herlyn, D.

    1988-01-01

    The purpose of this study was to correlate signal intensities and relaxation times on MR images in malignant melanomas with histopathologic features and electron paramagnetic resonance (EPR) spectra. Cell lines from human malignant melanomas in tissue culture were implanted subcutaneously into nude mice. MR imaging was performed in vivo at 1.9 T to assess 12 separate lesions in ten mice using spin-echo and inversion-recovery techniques. T1,T2, and N(H) were calculated in all cases. Histopathologic examination was performed on specimens resected immediately after imaging, using hematoxylin and eosin, Prussian blue, and Fontan stains to assess for tumor necrosis, iron, and melanin content. EPR spectra were also obtained on four resected specimens. The authors' results indicate that the relaxation behavior of nonhemorrhagic malignant melanomas cannot be explained solely by the presence of necrosis, water content, or iron content. The degree of melanin within these tumors did correlate with T1 relaxation enhancement. T2 relaxation times did not correlate with the sole presence of either iron, melanin, or necrosis. Although the unique relaxation behavior of nonhemorrhagic malignant melanoma seems to have many causes, their data suggest that, contrary to previous investigations, it is influenced by the presence of melanin rather than iron

  11. [Acute dyspnea in malignant melanoma].

    Science.gov (United States)

    Franzen, A M; Günzel, T

    2011-09-01

    Metastases to the larynx are rare. The current article presents the case of a 75-year-old patient with a history of shortness of breath due to a supraglottic exophytic lesion that was identified as a metastasis of a cutaneous melanoma treated 2.5 years previously. As a result of our medline analysis we found approximately 30 cases of metastatic melanoma to the larynx published to date. Primary tumors are always cutaneous in origin and spread over the whole integument of trunk and extremities. The time interval between diagnosis of the primary and the laryngeal metastasis is often several years. In most reports a supraglottic exophytic, red coloured lesion is described. Diagnosis can only be proven by histological examination. Laryngeal metastasis is usually an indication of tumor dissemination and always has a fatal prognosis.

  12. Oral Malignant Melanoma in a Ferret ( Mustela putorius furo).

    Science.gov (United States)

    d'Ovidio, Dario; Rossi, Giacomo; Meomartino, Leonardo

    2016-06-01

    Oral malignant melanomas are one of the most common oral malignant neoplasms in dogs but are rare in other domesticated species. This case report describes the clinical manifestations and histological appearance of oral melanoma in a ferret ( Mustela putorius furo). To the authors' knowledge, this is the first published description of a clinical case and histopathological findings of oral melanoma in this species.

  13. Malignant melanoma in children: imaging spectrum

    International Nuclear Information System (INIS)

    Kaste, S.C.; Pappo, Alberto S.; Jenkins, J.J. III; Pratt, C.B.

    1996-01-01

    Objective. The objective of this study was to investigate the role of diagnostic imaging in detecting unsuspected metastatic disease in children with malignant melanoma. This has not been well studied previously. Materials and methods. We correlated imaging findings of 33 children diagnosed with melanoma with the level of invasion and clinical stage of disease. Results. Clinically undetectable metastases were identified in eight patients (25 %), four of whom had multiple metastases. All eight patients had deep lesions (Clark's level IV or V) or unknown primary sites of disease. Conclusion. Children with thick melanomas and those with unknown site of primary tumors are at increased risk of having clinically unsuspected metastases and should undergo CT of the chest, abdomen, and local-regional nodal basins at diagnosis to determine disease extent. (orig.). With 8 figs

  14. Psychosocial care to patients with Malignant Melanoma

    DEFF Research Database (Denmark)

    Thorup, Charlotte Brun

    Psychosocial care to patients with Malignant Melanoma Intensions: The intension of this project is to link new knowledge with the nurses experience based knowledge within the psychosocial care to patients, who have been diagnosed with Malignant Melanoma (MM), thereby improving the care...... to elaborate the care to these patients. Method: In 2007 the nurses from our ward gained experience from the psychosocial care to these patients. These experiences are a starting point to the study of literature the group has made. A group of five nurses have from this literature study, substantiated...... the psychosocial perspective. Results: After the literature review, the psychosocial aspects have been divided into five main areas: 1. Diagnosis, hospitalisation, and treatment 2. The body with cancer 3. Psychological 4. Social 5. Existential/spiritual Primary results show that patients with MM in general respond...

  15. Intramuscular metastasis from malignant melanoma: MR findings

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Hirohi; Itai, Yuji; Niitsu, Mamoru [Dept. of Radiology, Institute of Clinical Medicine, University of Tsukuba, Ibaraki (Japan); Fujiwara, Masachika; Watanabe, Teruo [Department of Pathology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan); Satomi, Hisae; Otsuka, Fujio [Department of Dermatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba (Japan)

    1999-12-01

    We present a rare case of intramuscular metastasis from malignant melanoma. The lesion showed intermediate to high signal intensity on T1-weighted magnetic resonance (MR) images and mixed signal intensities containing high and low signals on T2-weighted images. The signal intensity on T1-weighted images, which is due to the paramagnetic effect of melanin, is a characteristic MR finding of this entity. (orig.)

  16. Ultrasonic characterisation of malignant melanoma of choroid

    Directory of Open Access Journals (Sweden)

    John Sheila

    1998-01-01

    Full Text Available An in-vitro study of wave spectral analysis in 8 enucleated eyes was conducted in order to differentiate histological subtypes of malignant melanoma. To obtain the backscattering coefficient for the tissues, we used a broadband focussed transducer with a frequency range of 7-12 MHz and a centre frequency of 10 MHz. Experimental measurement of backscattering coefficient and attenuation coefficient at various frequencies was done by substitution techniques. The backscattering coefficient, scatterer size, and root mean square velocity fluctuation were derived by the numerical method, while the attenuation coefficient at 1 MHz was derived from attenuation coefficient at different frequencies. This study revealed that backscattering coefficient and attenuation coefficient, over a frequency range of 7-12 MHz, show an increase in the spindle cell type compared to the mixed cell type of malignant melanoma. Particularly, the scatterer size was significantly higher in the spindle cell group (p = 0.013 in contrast to the mixed cell type. Spindle cells have uniform and compact histological pattern which contributes to an increase in scatterer size and root mean square velocity fluctuation. The ultrasonically obtained parameters have been shown to have a good correlation with the histology of malignant melanoma.

  17. Current management and novel agents for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lee Byung

    2012-02-01

    Full Text Available Abstract Advanced malignant melanoma remains a challenging cancer. Over the past year, there have been 3 agents approved for treatment of melanoma by Food and Drug Administration. These include pegylated interferon alpha-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for treatment of unresectable or metastatic melanoma. This review will also update on the development of novel agents, including tyrosine kinase inhibitors and adoptive cellular therapy.

  18. Efficient adenovector CD40 ligand immunotherapy of canine malignant melanoma.

    Science.gov (United States)

    von Euler, Henrik; Sadeghi, Arian; Carlsson, Björn; Rivera, Patricio; Loskog, Angelica; Segall, Thomas; Korsgren, Olle; Tötterman, Thomas H

    2008-05-01

    Cutaneous canine melanomas are usually benign in contrast to human malignant melanoma. However, the canine oropharyngeal, uveal, and mucocutaneous neoplasms are aggressive and have metastatic potential. Surgery and to a lesser extent radiotherapy and chemotherapy are widely adopted treatments but are seldom curative in advanced stages. The similarities between human and canine melanoma make spontaneous canine melanoma an excellent disease model for exploring novel therapies. Herein, we report the first 2 adenovector CD40L immunogene (AdCD40L) treatments of aggressive canine malignant melanoma. Case no. 1 was an advanced stage III oral melanoma that was cured from malignant melanoma with 2 intratumor AdCD40L injections before cytoreductive surgery. After treatment, the tumor tissue was infiltrated with T lymphocytes and B lymphocytes suggesting immune activation. This dog survived 401 days after the first round of gene therapy and was free of melanoma at autopsy. Case no. 2 had a conjunctival malignant melanoma with a rapid progression. This case was treated with 6 AdCD40L injections over 60 days. One hundred and twenty days after start of gene therapy and 60 days after the last injection, the tumor had regressed dramatically, and the dog had a minimal tumor mass and no signs of progression or metastasis. Our results indicate that AdCD40L immunogene therapy is beneficial in canine malignant melanoma and could be considered for human malignant melanoma as well.

  19. Sun behaviour after cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Datta, P; Heydenreich, J

    2013-01-01

    Background  It has been reported that patients with cutaneous malignant melanoma (CMM) can lower their risk of a second primary melanoma by limiting recreational sun exposure. Previous studies based on questionnaires and objective surrogate measurements indicate that before their diagnosis......, patients with CMM are exposed to higher ultraviolet radiation (UVR) doses than controls, followed by a reduction after diagnosis. Objectives  In a prospective, observational case-control study, we aimed to assess sun exposure after diagnosis of CMM by objective measurements to substantiate advice about sun...... months and 6 years before the start of the study. During a summer season participants filled in sun exposure diaries daily and wore personal electronic UVR dosimeters in a wristwatch that continuously measured time-stamped UVR doses in standard erythema dose. Results  The UVR dose of recently diagnosed...

  20. Oral malignant melanoma: a rare case with unusual clinical ...

    African Journals Online (AJOL)

    Primary Oral malignant melanoma is a rare tumor with an indigent prognosis. This is a case report of 47-year-old Sudanese female diagnosed as Oral malignant melanoma of the mandible with an unusual pattern of growth and clinical presentation. Furthermore, a possibility of intraosseous origin is suggested. Pan African ...

  1. The presence of dysplastic nevus remnants in malignant melanomas. A population-based study of 551 malignant melanomas.

    Science.gov (United States)

    Hastrup, N; Osterlind, A; Drzewiecki, K T; Hou-Jensen, K

    1991-08-01

    We examined 512 malignant melanomas, representing all newly diagnosed cutaneous malignant melanomas, excluding lentigo maligna melanomas, from the period October 1, 1982 to March 31, 1985 occurring in the region of eastern Denmark in patients aged 20-79 years for the presence of dysplastic nevus remnants. Criteria for the diagnosis of a dysplastic nevus remnant include all the following changes (a) lentiginous or epithelioid melanocyte hyperplasia, (b) cytologic melanocyte atypia, (c) eosinophilic fibroplasia, (d) lamellar fibroplasia, and (e) lymphocytic infiltration in the dermis. Dysplastic nevus remnants were found in association with 34 (7%) of the evaluable 512 malignant melanomas. Fourteen (41%) of the remnants were of compound nevus type. In nine (27%) of the remnants, atypia was pronounced. Most (62%) dysplastic nevus remnants were contiguous to thin superficial spreading melanomas. We conclude from this population-based study that about 7% of malignant melanomas arise in prior dysplastic nevi.

  2. Radioimmunoscintigraphy of human malignant melanoma. I

    International Nuclear Information System (INIS)

    Svec, J.; Makaiova, I.; Veselovska, Z.; Keszeghova, V.; Reinerova, M.

    1989-01-01

    The novel RG-12 monoclonal antibody (MoAb) recognizing a high-molecular-weight antigen of human melanoma cells was radioiodinated and its biodistribution and tumor imaging was determined in immunosuppressed mice bearing xenografted human malignant melanoma HMB-2. Control and tumor-bearing mice were injected with 6 μg of 125 I-labeled RG-12 IgG (8.9 MBq 125 I-IgG/animal). Clearance of the MoAb from plasma had a mean half life of 20.6 hours. At day 2 after injection, radiolabeled RG-12 IgG localized in the tumor was 1.43% of the injected dose bound per gram tissue (ID/g), whereas the localization in the healthy kidney was below 0.5%. Tumor to tissue ratio of MoAb accumulation was low for hepatic tissue (1.25) but high for spleen (3.30) and kidney (3.25). Scanning with a gamma camera localized tumor mass in the right kidney and implanted peritoneal metastases. (author). 3 figs., 1 tab., 9 refs

  3. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    International Nuclear Information System (INIS)

    Godar, D. E.

    2011-01-01

    The incidence of cutaneous malignant melanoma (CMM) has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290-320 nm) exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321-400 nm) passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to∼ 50 degree N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  4. Malignant melanoma of the oral cavity: Report of two cases

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2014-01-01

    Full Text Available Primary malignant melanoma is a rare and aggressive neoplasm that originates from the proliferation of melanocytes. Although, it comprises 1.3% of all cancers, malignant melanoma of the oral cavity accounts for only 0.2-8% of all reported melanomas and occurs approximately 4 times more frequently in the oral mucosa of the upper jaw, usually on the palate or alveolar gingivae. Most of the mucosal melanomas are usually asymptomatic in early stages, and presents as pigmented patch or a mass delaying the diagnosis until symptoms of swelling, ulceration, bleeding, or loosening of teeth are noted. The prognosis is extremely poor, especially in advanced stages. Therefore, any pigmented lesion of undetermined origin should always be biopsied. We herewith report of two cases of oral malignant melanoma in a 60 and 75-year-old female.

  5. Primary cilium depletion typifies cutaneous melanoma in situ and malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Jinah Kim

    Full Text Available Cutaneous melanoma is a lethal malignancy that arises spontaneously or via in situ precursor neoplasms. While melanoma in situ and locally invasive malignant melanoma can be cured surgically, these lesions can sometimes be difficult to distinguish from melanocytic nevi. Thus, the identification of histolopathologic or molecular features that distinguish these biologically distinct lesions would represent an important advance. To this end, we determined the abundance of melanocytic primary cilia in a series of 62 cases composed of typical cutaneous melanocytic nevi, melanoma in situ, invasive melanoma, and metastatic melanoma. Primary cilia are sensory organelles that modulate developmental and adaptive signaling and notably, are substantially depleted from the neoplastic epithelium of pancreatic carcinoma at a stage equivalent to melanoma in situ. In this series, we find that while nearly all melanocytes in 22 melanocytic nevi possessed a primary cilium, a near-complete loss of this organelle was observed in 16 cases of melanoma in situ, in 16 unequivocal primary invasive melanomas, and in 8 metastatic tumors, each associated with a cutaneous primary lesion. These findings suggest that the primary cilium may be used to segregate cutaneous invasive melanoma and melanoma in situ from melanocytic nevi. Moreover, they place the loss of an organelle known to regulate oncogenic signaling at an early stage of melanoma development.

  6. Malignant melanoma of the tongue following low-dose radiation

    Energy Technology Data Exchange (ETDEWEB)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    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.

  7. Malignant melanoma of the tongue following low-dose radiation

    International Nuclear Information System (INIS)

    Kalemeris, G.C.; Rosenfeld, L.; Gray, G.F. Jr.; Glick, A.D.

    1985-01-01

    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

  8. Malignant melanoma. Current status; Malignes Melanom. Aktueller Stand

    Energy Technology Data Exchange (ETDEWEB)

    Winkler, J.K.; Buder-Bakhaya, K.; Enk, A.; Hassel, J.C. [Universitaetshautklinik, Nationales Centrum fuer Tumorerkrankungen, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [Deutsches Krebsforschungszentrum, Klinische Kooperationseinheit Nuklearmedizin, Heidelberg (Germany)

    2017-10-15

    The incidence of malignant melanoma is continuously increasing. The prognosis of metastatic disease is still limited. Until a few years ago palliative chemotherapy with a limited response rate was the standard treatment for metastatic melanoma. Immunotherapy and targeted therapy provide new treatment options. Immune checkpoint inhibitors have significantly improved the prognosis. Regional lymph node sonography, computed tomography (CT) of the neck, chest and abdomen and brain magnetic resonance imaging (MRI) are routinely used. As an alternative to CT scans 18 F fluorodeoxyglucose positron emission tomography (FDG-PET) may be used. Immunotherapy provides the chance of long-term disease control in metastatic melanoma. Ipilimumab may provide long-term tumor control in approximately 20% of patients. Median overall survival of approximately 2 years is achieved during therapy with anti-programmed cell death (PD) 1 antibodies. For combined therapy of ipilimumab and nivolumab a response rate of almost 60% is achieved and 2-year survival is also approximately 60%. The range of immune-mediated side effects demands particular consideration. For response evaluation immune-related response criteria were defined. Furthermore, immunotherapeutic approaches, such as talimogene laherparepvec (T-VEC), which is a modified herpes virus can be used for intralesional injection. An individual definition of the appropriate therapy for each patient is of particular importance. In the context of modern therapy regimens close patient monitoring is crucial. (orig.) [German] Die Inzidenz des Melanoms steigt stetig an. Die Prognose bei metastasierter Erkrankung ist weiterhin limitiert. Bis vor wenigen Jahren war eine palliative Chemotherapie mit begrenzten Ansprechraten Standardtherapie des metastasierten Melanoms. Immuntherapie und zielgerichtete Therapien stellen neue Behandlungsoptionen dar. Insbesondere Immuncheckpointinhibitoren haben die Prognose verbessert. Routinemaessig werden die

  9. Worldwide Increasing Incidences of Cutaneous Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Dianne E. Godar

    2011-01-01

    Full Text Available The incidence of cutaneous malignant melanoma (CMM has been increasing at a steady rate in fair-skinned populations around the world for decades. Scientists are not certain why CMM has been steadily increasing, but strong, intermittent UVB (290–320 nm exposures, especially sunburn episodes, probably initiate, CMM, while UVA (321–400 nm passing through glass windows in offices and cars probably promotes it. The CMM incidence may be increasing at an exponential rate around the world, but it definitely decreases with increasing latitude up to ~50°N where it reverses and increases with the increasing latitude. The inversion in the incidence of CMM may occur because there is more UVA relative to UVB for most of the year at higher latitudes. If windows, allowing UVA to enter our indoor-working environment and cars, are at least partly responsible for the increasing incidence of CMM, then UV filters can be applied to reduce the rate of increase worldwide.

  10. Malignant melanomas of the meninges (MR and CT)

    International Nuclear Information System (INIS)

    Schuknecht, B.; Nadjmi, M.; Mueller, J.

    1990-01-01

    Malignant melanoma of the meninges is a rare neoplasm derived from melanocytes of the cranial or spinal meninges. Histologically classified as grade IV tumours, malignant melanoma may present either as a diffuse meningeal neoplasm, first described by Virchow in 1859, or as a circumscribed tumour attached to the meninges. Although diagnosis is rarely established prior to surgery or autopsy, MR and CT may provide indispensable information probably leading to earlier diagnosis. In 4 patients, diagnosis of a primary meningeal melanoma was based on MR and CT findings and histology. Histology was obtained in 3 cases by surgery, in one patient by autopsy and showed a melanotic and an amelanotic malignant melanoma in 2 patients each. Autopsy was carried out in 3 cases after survival of 4, 5, and 18 months; in a single case, the follow-up period is almost 3 years. (orig.) [de

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

    Science.gov (United States)

    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.

  12. Diagnosis of Malignant Melanoma of Skin Cancer Types

    Directory of Open Access Journals (Sweden)

    Abbas Hassin Alasadi

    2017-08-01

    Full Text Available Malignant melanoma is a kind of skin cancer that begins in melanocytes. It can influence on the skin only, or it may expand to the bones and organs. It is less common, but more serious and aggressive than other types of skin cancer. Malignant Melanoma can happen anywhere on the skin, but it is widespread in certain locations such as the legs in women, the back and chest in men, the face, the neck, mouth, eyes, and genitals. In this paper, a proposed algorithm is designed for diagnosing malignant melanoma types by using digital image processing techniques. The algorithm consists of four steps: preprocessing, separation, features extraction, and diagnosis. A neural network (NN used to diagnosis malignant melanoma types. The total accuracy of the neural network was 100% for training and 93% for testing. The evaluation of the algorithm is done by using sensitivity, specificity, and accuracy. The sensitivity of NN in diagnosing malignant melanoma types was 95.6%, while the specificity was 92.2% and the accuracy was 93.9%. The experimental results are acceptable.

  13. Towards new therapeutic approaches for malignant melanoma.

    Science.gov (United States)

    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.

  14. Is UV-A radiation a cause of malignant melanoma?

    International Nuclear Information System (INIS)

    Moan, J.

    1994-01-01

    The first action spectrum for cutaneous malignant melanoma was published recently. This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B solaria rather than UV-A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagenic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filter (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. 34 refs., 2 figs

  15. Immunological correlates of treatment and response in stage IV malignant melanoma patients treated with Ipilimumab

    DEFF Research Database (Denmark)

    Bjoern, Jon; Juul Nitschke, Nikolaj; Zeeberg Iversen, Trine

    2016-01-01

    Introduction: Ipilimumab is effective in the treatment of metastatic malignant melanoma, but few biomarkers reliably predict treatment response. Methods: Patients were treated with Ipilimumab for metastatic malignant melanoma. Blood and serum samples were collected before and during treatment. Mo...

  16. Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds

    International Nuclear Information System (INIS)

    Mishima, Yutaka; Ichihashi, Masamitsu; Nakanishi, Takafumi

    1985-01-01

    Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, much attention has been paid to the establishment of selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells. This paper presents 10 B chlorpromazine compounds and 10 B 1 -para-boronophenylalanine ( 10 B 1 -BPA) as tumor-seeking 10 B compounds which themselves possess selective affinity for the specific metabolic activity of the target cancer cells. An overview of the following studies on the effects of 10 B 1 -BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10 B 1 -BPA; 2) in vivo studies on therapeutic effects of 10 B 1 -BPA using melanoma-bearing hamsters; and 3) preclinical therapeutic experiments using spontaneously occurring malignant melanoma in Duroc pig skin, including experiments in which melanoma was successfully cured. (Namekawa, K.)

  17. Isolated Pancreatic Metastasis from Malignant Melanoma: Is ...

    African Journals Online (AJOL)

    [1] Renal-cell cancer, colorectal cancer, melanoma and ... types of cancer, such as colorectal and renal cancers,[5] is the gold standard ... Department of Surgical Oncology, Institute Paoli Calmettes .... [20] Whether or not these innovative.

  18. Metastatic malignant subungal melanoma: Importance of FNAC

    Directory of Open Access Journals (Sweden)

    Radhika Punshi Nandwani

    2014-01-01

    Full Text Available Subungual melanoma is a rare type of skin cancer. It is an uncommon form of acral lentiginous melanoma. Approximately 85% of cases are misdiagnosed initially, and it is generally associated with a poor prognosis. Herein, we describe a case of metastatic subungal melanoma to the axillary lymph node in a 45-year-old male. Diagnosis of metastasis was made based on cytology, where the clinicians were guided to search for primary. This case report highlights the role of fine-needle aspiration cytology (FNAC in the diagnosis of this entity to draw the attention of the reader to the possible underreporting of melanoma because of a variant that evades diagnosis and our reluctance to think about its existence.

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

    Science.gov (United States)

    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.

  20. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases......; this report is the first to document complete spontaneous regression of cerebral metastases from malignant melanoma by means of computed tomography scans. Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour in the absence of all treatment or in the presence...

  1. A case of malignant melanoma of the penis

    OpenAIRE

    渡辺, 徹; 蔵, 尚樹; 山田, 拓巳; 根岸, 壮治

    1991-01-01

    We experienced a 53-year-old male with malignant melanoma of the penis. A lentigo was noted in the dorsal penis in 1980. On February 4, 1982, he was referred to our Hospital with the complaint of enlargement of the lentigo of the penis and swelling of the bilateral inguinal lymph nodes. Lymph node biopsy disclosed metastasis of the malignant melanoma. He was hospitalized for treatment of the lesion. On physical examination at admission, a black tumor, 3 cm in diameter, with necrosis at the ce...

  2. Classical and molecular genetics of malignant melanoma and dysplastic naevi

    International Nuclear Information System (INIS)

    Traupe, H.; Macher, E.

    1988-01-01

    The authors conclude that the prevailing concept of monogenic autosomaldominant inheritance of dysplastic naevi and familial melanoma is not compatible with the principles of formal (Mendelian) genetics. The concept of polygenic inheritance offers instead a sound basis to explain familial aggregation of dysplastic naevi and melanoma. The various genes involved have not yet been identified at the molecular level. The recent advances made possible by modern DNA technology have given us a new view of carcinogenesis. In human malignant melanoma, chromosomes 1, 6, 7 are of particular interest and oncogenes located on these chromosomes may be involved with the initiation, promotion and progression of melanoma. Carcinogenesis is viewed as a multistep process and even tumour initiation requires the input of at least two independent oncogenes. Molecular genetics thus adds an important argument for the existence of a polygenic predisposition to melanoma. The concept of polygenic inheritance is not restricted to familial melanoma, but implies that all melanomas basically share the same predisposition and are due to similar genetic mechanisms. In some patients an inherited genetic predisposition is of great importance, whereas in others (the majority) environmental factors (e.g. UV-light-induced mutations) will be the cause of initial steps in the malignant transformation. The concept of polygenic inheritance has consequences for the management of our patients. In contrast to simple Mendelian inheritance, the risk for dysplastic naevi and melanoma is not constantly 50%, but increases with the number of family members already affected. Persons belonging to families with more that 2 affected close relatives should be considered at high risk regardless of the dysplastic naevus status. Strict surveillance of this patient group is warranted for melanoma prevention

  3. Electron Paramagnetic Resonance Spectrometry and Imaging in Melanomas: Comparison between Pigmented and Nonpigmented Human Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Quentin Godechal

    2013-06-01

    Full Text Available It has been known for a long time that the melanin pigments present in normal skin, hair, and most of malignant melanomas can be detected by electron paramagnetic resonance (EPR spectrometry. In this study, we used EPR imaging as a tool to map the concentration of melanin inside ex vivo human pigmented and nonpigmented melanomas and correlated this cartography with anatomopathology. We obtained accurate mappings of the melanin inside pigmented human melanoma samples. The signal intensity observed on the EPR images correlated with the concentration of melanin within the tumors, visible on the histologic sections. In contrast, no EPR signal coming from melanin was observed from nonpigmented melanomas, therefore demonstrating the absence of EPR-detectable pigments inside these particular cases of skin cancer and the importance of pigmentation for further EPR imaging studies on melanoma.

  4. Intercellular crosstalk in human malignant melanoma

    Czech Academy of Sciences Publication Activity Database

    Dvořánková, Barbora; Szabo, Pavol; Kodet, O.; Strnad, Hynek; Kolář, Michal; Lacina, L.; Krejčí, E.; Nanka, O.; Sedo, A.; Smetana, K.

    2017-01-01

    Roč. 254, č. 3 (2017), s. 1143-1150 ISSN 0033-183X R&D Projects: GA ČR GA16-05534S; GA MŠk(CZ) LQ1604; GA MŠk(CZ) ED1.1.00/02.0109 Grant - others:GA MŠk(CZ) LM2015042 Institutional support: RVO:68378050 Keywords : Melanocyte * Melanoma cells * Melanoma ecosystem * cancer -associated fibroblast * Keratinocyte * Cytokine Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Cell biology Impact factor: 2.870, year: 2016

  5. CT of malignant choroidal melanoma - morphology and perfusion characteristics

    International Nuclear Information System (INIS)

    Heller, M.; Hagemann, J.; Jend, H.H.; Guthoff, R.

    1982-01-01

    The computed tomographic morphology of malignant choroidal melanoma and its perfusion characteristics are described. Thirty-three static and serial CT examinations made on 29 patients with choroidal melanoma, three with pseudotumors of the macula and one with choroidal metastasis revealed the choroidal melanoma to be usually a hyperdense, markedly perfused tumor, while the non-contrast, diagnostically undifferentiable pseudotumors and the choroidal metastasis, revealed no significant change in density after the administration of contrast material. Density values or perfusion characteristics of choroidal melanoma that are outside of the normal range are a result of secondary changes within the immediate surroundings of the tumor, such as detachment of the retina, tumor-induced glaucoma, or tumor necrosis. (orig.)

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Gong Li

    2012-09-01

    Full Text Available Abstract 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. Virtual slide The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1480477335765055.

  9. Malignant Melanoma in an Albino | Efem | Sudan Journal of Medical ...

    African Journals Online (AJOL)

    Oculocutaneous albinism is a rare autosomal recessive disorder characterised by generalised depigmentation, photophobia, decreased visual acuity, and nystagmus. Malignant melanoma is rare in patients with albinism. We report a case of a large advanced fumigating tumour on the right forearm of a male Nigerian albino ...

  10. Malignant melanoma of the choroid in a naevus of Ota.

    Science.gov (United States)

    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.

  11. Malignant melanoma of the choroid in a naevus of Ota.

    OpenAIRE

    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.

  12. Socioeconomic status and cutaneous malignant melanoma in Northern Europe

    DEFF Research Database (Denmark)

    Idorn, L W; Wulf, H C

    2014-01-01

    Socioeconomic status (SES) is associated with cutaneous malignant melanoma (CMM), also in Northern Europe despite equal access to health care. SES per se is not responsible for this association which must be ascribed to important risk factors for CMM such as intermittent UVR exposure, and screening...

  13. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Figueroa, Alejandro Yuri Joan; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2009-01-01

    The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM)

  14. The Relationship between Werner Syndrome and Sinonasal Malignant Melanoma: Two Sibling Cases of Werner Syndrome with Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Yoshinori Kadowaki

    2017-01-01

    Full Text Available Werner syndrome (WS is an autosomal recessive disease characterized by premature aging. Malignant tumors such as thyroid carcinoma and malignant melanoma occur frequently in WS patients. We describe 2 siblings with WS who suffered from sinonasal malignant melanoma (MM. Both patients initially experienced nasal obstruction and recurrent nasal bleeding and died within 2 years of the diagnosis of MM. Otolaryngologists should recognize that WS patients have a high risk for head and neck malignant disease, particularly sinonasal MM, even if they are aged below the expected age range and undergo periodic examinations. Furthermore, it is important that WS patients are aware that a prompt nasal examination is indicated if they experience continuous nasal obstruction or recurrent nasal bleeding.

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

    Science.gov (United States)

    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.

  16. Tyrosinase expression in malignant melanoma, desmoplastic melanoma, and peripheral nerve tumors

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B

    2002-01-01

    of tyrosinase expression in the differential diagnosis of melanoma, desmoplastic melanoma, and peripheral nerve sheath tumors. DESIGN: Immunoreactivity for tyrosinase, HMB-45 (anti-gp100 protein), S100 protein, CD34, and vimentin was studied in 70 tumors, including 15 melanomas (5 desmoplastic, 4 amelanotic, 6...... at 121 degrees C. RESULTS: All melanomas demonstrated positive immunostaining for tyrosinase, HMB-45, and S100 protein. Immunoreactivity for HMB-45 was generally stronger than that for tyrosinase in amelanotic lesions and significantly stronger in 1 of the desmoplastic lesions. The 4 pigmented...... neurofibromas were focally positive for tyrosinase, but did not stain for HMB-45. The pigmented schwannoma was focally positive for both tyrosinase and HMB-45. The malignant peripheral nerve sheath tumors, dermatofibrosarcoma protuberans, and dermatofibromas were nonreactive for tyrosinase and HMB-45...

  17. Linear Malignant Melanoma In Situ: Reports and Review of Cutaneous Malignancies Presenting as Linear Skin Cancer.

    Science.gov (United States)

    Cohen, Philip R

    2017-09-18

    Melanomas usually present as oval lesions in which the borders may be irregular. Other morphological features of melanoma include clinical asymmetry, variable color, diameter greater than 6 mm and evolving lesions. Two males whose melanoma in situ presented as linear skin lesions are described and cutaneous malignancies that may appear linear in morphology are summarized in this report. A medical literature search engine, PubMed, was used to search the following terms: cancer, cutaneous, in situ, linear, malignant, malignant melanoma, melanoma in situ, neoplasm, and skin. The 25 papers that were generated by the search and their references, were reviewed; 10 papers were selected for inclusion. The cancer of the skin typically presents as round lesions. However, basal cell carcinoma and squamous cell carcinoma may arise from primary skin conditions or benign skin neoplasms such as linear epidermal nevus and linear porokeratosis. In addition, linear tumors such as basal cell carcinoma can occur. The development of linear cutaneous neoplasms may occur secondary to skin tension line or embryonal growth patterns (as reflected by the lines of Langer and lines of Blaschko) or exogenous factors such as prior radiation therapy. Cutaneous neoplasms and specifically melanoma in situ can be added to the list of linear skin lesions.

  18. Meningeal Melanomas Associated With Transforming Ota Nevus to Malignant Melanoma: A Case Report

    Directory of Open Access Journals (Sweden)

    Seyed-Mohammad Fereshtehnejad

    2010-11-01

    Full Text Available Intracranial invasion of cellular blue nevus (CBN from the skin is extremely rare and such a condition with malignant transformation is even rarer.A case of meningeal melanoma with malignant transformation which was derived from an Ota   nevus is presented in this report.   A21-year-old man with a neurocutaneous syndrome since childhood was referred with headache and mild left hemiparesia. CT scan and MRI demonstrated intracranial lesions and conjunctival biopsy leads to the pathologic diagnosis of blue nevus.Thereafter his parietal lesion was operated by craniotomy with total gross excision.On histopathological examination, diagnosis of malignant melanoma was confirmed.Approximately 2 months after radiotherapy and chemotherapy, he afflicted to diplopia and blurred vision on the leftside due to enlargement of orbital and cavernous sinus lesion. Following one year follow-up,he was survived and thrived with diffuse leptomeningeal nodular enhancement in favor of melanoma dissemination.Primary intracranial melanomas are though rare, but it should be suspected especially in the presence of periorbital blue nevus or nevus of Ota. Moreover, although CBN is considered benign, scalp or periorbital CBN has the potential for intracranial invasion and malignant ransformation.

  19. Malignant Melanoma of Nose and Paranasal Sinuses: 2 Case Reports

    Directory of Open Access Journals (Sweden)

    Sanjeev Bhagat

    2010-04-01

    Full Text Available Malignant melanoma is one of the rare and highly aggressive diseases of the sinonasal cavity. High index of suspicion is required for diagnosis as the patient usually presents with non specific signs and symptoms. In the natural course of the disease, higher rate of loco regional recurrences and distant metastasis are seen making the overall prognosis of disease very poor. In reviewing the various treatment modalities used in the past, surgical resection of the tumour with postoperative radiotherapy is preferred one. Advances in surgery, radiotherapy and chemotherapy don’t have any impact on improved survival, which remains poor in this disease. We report two cases of malignant melanoma, which were treated at our institute.

  20. Primary Malignant Melanoma of the Lung: A Case Report

    Directory of Open Access Journals (Sweden)

    Karagianni Evangelia

    2003-11-01

    Full Text Available Abstract Background Primary melanoma of the lung is an extremely rare pathological entity and sparsely reported in the literature. Case presentation A case of primary malignant melanoma of the lung in a 41-year-old female is reported. The clinical, radiological and histopathological features are discussed. The initial symptom was cough, whereas the chest radiography showed a round opacity of the right lung. The computed tomography of the chest revealed a well-demarcated mass lesion in the right upper lobe. Endobronchial mass causing obstruction of the upper lobar bronchus was the bronchoscopic finding. Patient underwent pneumonectomy. A diagnosis of melanoma was confirmed postoperatively after the immunohistochemistry. Primary nature of the tumour in the lung results from the demonstration of characteristic junctional pattern of melanoma cells beneath the bronchial epithelium on histopathology, and from exclusion of other potential primary sites in the clinical, paraclinical and laboratory examination. Conclusions Primary melanoma of the lung represents a rare pathological entity. Careful interpretation of histopathological information in correlation with all other findings from clinical and paraclinical studies can establish a diagnosis. Follow-up is necessary in order to diagnose potential dissemination or secondary sites of the disease. Due to the small number of cases reported in the literature, there is no experience on the management and the prognosis of the disease, but surgical resection remains the cornerstone of the treatment.

  1. Sentinel lymphoscintigraphy in malignant melanoma and Merkel cell carcinoma

    International Nuclear Information System (INIS)

    Dekova, M.; Kirov, V.; Donchev, M.; Slavova, M.; Tsarovska, T.

    2013-01-01

    Full text:Introduction: The concept of a biopsy of the sentinel lymph node (SLN) was developed by Mortan in 1992, using blue dye. In 1993. Alex and Krag identified SLN with radiocolloid and gamma probe in case of malignant melanoma. Today, both methods are applied separately or together with a success rate above 90% and false negative rate of 5 %. Materials and Methods: The study includes 10 patients, 9 of whom have been diagnosed with malignant melanoma and 1 – with Merkel cancer. All patients were of a higher risk of lymphatic metastases without distinct clinical symptoms. Lymphoscintigraphy was performed with double-headed SPECT gamma camera Toshiba CGA 7200 UI. The visualized lymph nodes were projected and marked on the skin by a point radioactive source under monitoring. The marked lymph nodes were verified during the operation by staining and patent Blau then removed and studies histopathologically. Results: In all patients the Lymphoscintigraphy visualized SLN, which were surgically found just below the skin markers and removed. In the SLN of one patient a diffuse metastasis was found. In the SLN of nine patients no evidence for metastatic process was found. Conclusion: The technique of marking the SLN with subsequent biopsy is a minimally invasive method for the detection of lymph node metastases in patients with malignant melanoma and Merkel carcinoma with a high degree of reliability of the results

  2. Aggressive solitary intracranial metastatic malignant melanoma from a primary mediastinal tumour.

    Science.gov (United States)

    Sivaraju, Laxminadh; Aryan, Saritha; Hegde, Vinay S; Ghosal, Nandita; Hegde, Alangar S

    2016-08-01

    Malignant melanoma is the third most common tumour to cause cerebral metastases, following breast and lung cancer. Central nervous system metastases occur in 10-40% of patients with melanoma. Intracranial metastasis from a primary malignant melanoma of the anterior mediastinum is uncommon. We report a case of solitary intracranial metastatic melanoma arising from a primary mediastinal tumour. We then discuss the clinico-radiological features and treatment options. © The Author(s) 2016.

  3. Hypercalcemia and high parathyroid hormone-related protein concentration associated with malignant melanoma in a dog.

    Science.gov (United States)

    Pressler, Barrak M; Rotstein, David S; Law, Jerry M; Rosol, Thomas J; LeRoy, Bruce; Keene, Bruce W; Jackson, Mark W

    2002-07-15

    A 12-year-old Cocker Spaniel with an oral malignant melanoma was evaluated for progressive lethargy and anorexia. No metastases were identified during antemortem evaluation, but severe hypercalcemia was evident. Antemortem diagnostic testing failed to identify a cause for the hypercalcemia. No neoplasms other than the melanoma were identified on postmortem examination. Serum parathyroid hormone-related protein concentration was markedly high, and the melanoma had moderate to marked immunostaining for this protein. Paraneoplastic syndromes are rare in dogs with malignant melanoma.

  4. Impact of hypothyroidism on primary anal malignant melanoma: a rare entity.

    Science.gov (United States)

    Singh, Siddharth; Verma, Satyajeet; Kala, Sanjay

    2014-01-01

    Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

  5. Impact of hypothyroidism on primary anal malignant melanoma: A rare entity

    Directory of Open Access Journals (Sweden)

    Siddharth Singh

    2014-01-01

    Full Text Available Primary melanoma of the anal canal is rare and highly malignant condition, which is 1% of all invasive tumors in this site. This condition is often mistaken for benign conditions as either hemorrhoids or rectal polyp. Thyroid-stimulating hormone stimulation causes high proliferation of malignant melanoma. The association of hypothyroidism with primary malignant melanoma of anal canal is very rare. We are reporting such a very rare case.

  6. Sun exposure before and after a diagnosis of cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Idorn, L W; Philipsen, P A; Wulf, H C

    2011-01-01

    Previous studies on ultraviolet radiation (UVR) exposure before and after a diagnosis of cutaneous malignant melanoma (CMM) have been based primarily on questionnaires. Objective measures are needed....

  7. Primary gastric melanoma: case report of a rare malignancy

    Directory of Open Access Journals (Sweden)

    Alexander Augustyn

    2015-03-01

    Full Text Available We report the case of a 64-year-old white male who presented to his primary care physician with complaints of fatigue. Physical exam was unremarkable and laboratory studies revealed profound anemia, for which the patient received a transfusion. Esophagogastroduodenoscopy revealed a bleeding mass in the proximal stomach that was histologically determined to be malignant melanoma, with immunohistochemical staining demonstrating positivity for SOX10, S100, MART-1, and HMG-45. After an extensive dermatological exam no other primary lesion was identified. Whole body positron emission tomography (18-FDG-PET/CT demonstrated pathologic uptake only in the area of the proximal stomach. For this reason, primary gastric melanoma was suspected in this patient. The patient underwent subtotal gastrectomy with mass excision followed by Roux-en-Y reconstruction. Very few cases of primary gastric melanoma have been reported. We report this case and present diagnostic criteria for primary non-cutaneous melanoma and discuss potential non-surgical therapies.

  8. Breast metastasis from cutaneous malignant melanoma mimicking a breast cancer.

    Science.gov (United States)

    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.

  9. Cancer immunology and canine malignant melanoma: A comparative review.

    Science.gov (United States)

    Atherton, Matthew J; Morris, Joanna S; McDermott, Mark R; Lichty, Brian D

    2016-01-01

    Oral canine malignant melanoma (CMM) is a spontaneously occurring aggressive tumour with relatively few medical treatment options, which provides a suitable model for the disease in humans. Historically, multiple immunotherapeutic strategies aimed at provoking both innate and adaptive anti-tumour immune responses have been published with varying levels of activity against CMM. Recently, a plasmid DNA vaccine expressing human tyrosinase has been licensed for the adjunct treatment of oral CMM. This article reviews the immunological similarities between CMM and the human counterpart; mechanisms by which tumours evade the immune system; reasons why melanoma is an attractive target for immunotherapy; the premise of whole cell, dendritic cell (DC), viral and DNA vaccination strategies alongside preliminary clinical results in dogs. Current "gold standard" treatments for advanced human malignant melanoma are evolving quickly with remarkable results being achieved following the introduction of immune checkpoint blockade and adoptively transferred cell therapies. The rapidly expanding field of cancer immunology and immunotherapeutics means that rational targeting of this disease in both species should enhance treatment outcomes in veterinary and human clinics. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. WITHDRAWN: Chemoimmunotherapy versus chemotherapy for metastatic malignant melanoma.

    Science.gov (United States)

    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

  11. Desmoplastic malignant melanoma presenting as large lung mass.

    LENUS (Irish Health Repository)

    Al-Alao, Bassel Suffian

    2010-08-01

    We describe a case of successful minimally invasive thoracoscopic surgical resection of metastatic desmoplastic malignant melanoma replacing the entire right lower lobe of the lung, presenting 4 years after the initial complete resection of the primary scalp lesion. An 89-year-old man presented with a 6-month history of right-sided chest pain. A computed tomographic scan showed a large paravertebral mass with possibility of chest wall invasion. Core biopsy initially raised the suspicion of a schwannoma. We also discussed the atypical delayed presentation and misleading radiologic and histologic findings.

  12. A Case of Primary Subglottic Malignant Melanoma with a Successful Surgical Treatment

    Directory of Open Access Journals (Sweden)

    Shahzad Ahmad

    2014-01-01

    Full Text Available Primary subglottic malignant melanoma is a very rare and underdiagnosed neoplasm. We are reporting a case of primary malignant melanoma of subglottic mucosa in a 78-year-old woman who presented to our hospital with shortness of breath and hoarseness of voice. Laryngoscopy and excisional biopsy along with immunoreactivity to S-100 and human melanoma black-45 (HMB-45 confirmed the diagnosis. The patient was treated with laryngectomy followed by radiotherapy. Five years following surgical treatment, she continues to be asymptomatic. To our knowledge, there is only one reported case of primary malignant melanoma of subglottic mucosa in the medical literatures.

  13. Up-regulation of hepatoma-derived growth factor facilitates tumor progression in malignant melanoma [corrected].

    Directory of Open Access Journals (Sweden)

    Han-En Tsai

    Full Text Available Cutaneous malignant melanoma is the fastest increasing malignancy in humans. Hepatoma-derived growth factor (HDGF is a novel growth factor identified from human hepatoma cell line. HDGF overexpression is correlated with poor prognosis in various types of cancer including melanoma. However, the underlying mechanism of HDGF overexpression in developing melanoma remains unclear. In this study, human melanoma cell lines (A375, A2058, MEL-RM and MM200 showed higher levels of HDGF gene expression, whereas human epidermal melanocytes (HEMn expressed less. Exogenous application of HDGF stimulated colony formation and invasion of human melanoma cells. Moreover, HDGF overexpression stimulated the degree of invasion and colony formation of B16-F10 melanoma cells whereas HDGF knockdown exerted opposite effects in vitro. To evaluate the effects of HDGF on tumour growth and metastasis in vivo, syngeneic mouse melanoma and metastatic melanoma models were performed by manipulating the gene expression of HDGF in melanoma cells. It was found that mice injected with HDGF-overexpressing melanoma cells had greater tumour growth and higher metastatic capability. In contrast, mice implanted with HDGF-depleted melanoma cells exhibited reduced tumor burden and lung metastasis. Histological analysis of excised tumors revealed higher degree of cell proliferation and neovascularization in HDGF-overexpressing melanoma. The present study provides evidence that HDGF promotes tumor progression of melanoma and targeting HDGF may constitute a novel strategy for the treatment of melanoma.

  14. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2012-02-01

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  15. Malignant melanoma and breast carcinoma: a bidirectional correlation.

    LENUS (Irish Health Repository)

    Ho, W L

    2009-03-05

    BACKGROUND: Epidemiologic and genetic studies have suggested a bidirectional association between breast carcinoma (BC) and malignant melanoma (MM). OBSERVATION: We present a series of patients with MM and BC detected in our department within a span of 6 months, raising concerns for the high associations between the two malignancies. This led us to match the concordance of the two tumours in the National Irish Cancer Registry. CONCLUSION: The national figures provide evidence of a link between BC and MM. We recommend increased awareness among clinicians leading to more detailed surveillance of both second primary tumours. All MM patients with a family history of BC should be referred to a breast clinic. Women above the age of 40 with MM should undergo annual mammography and those less than 40 may be better evaluated with a breast MRI. All breast cancer patients should be made aware of the significance of changing moles and those with suspicious lesions referred to a dermatologist for evaluation.

  16. Immunotherapy in Melanoma, Gastrointestinal (GI, and Pulmonary Malignancies

    Directory of Open Access Journals (Sweden)

    Alexander B. Dillon

    2015-03-01

    Full Text Available Oncologic immunotherapy involves stimulating the immune system to more effectively identify and eradicate tumor cells that have successfully adapted to survive the body's natural immune defenses. Immunotherapy has shown great promise thus far by prolonging the lives of patients with a variety of malignancies, and has added a crucial new set of tools to the oncologists' armamentarium. The aim of this paper is to provide an overview of immunotherapy treatment options that are currently available and under active research for melanoma, gastrointestinal (esophageal, gastric, pancreatic, and colorectal, and pulmonary malignancies. Potential biomarkers that may predict favorable responses to immunotherapies are discussed where applicable, as are future avenues of research in this rapidly evolving field.

  17. Gene expression profile associated with radioresistance and malignancy in melanoma

    International Nuclear Information System (INIS)

    Ibañez, I.L.; Molinari, B.; Notcovich, C.; García, F.M.; Bracalente, C.; Zuccato, C.F.; Durán, H.

    2015-01-01

    The incidence of melanoma has substantially increased over the last decades. Melanomas respond poorly to treatments and no effective therapy exists to inhibit its metastatic spread. The aim of this study was to evaluate the association between radioresistance of melanoma cells and malignancy. A melanoma model developed in our laboratory from A375 human amelanotic melanoma cells was used. It consists in two catalase-overexpressing cell lines with the same genetic background, but with different phenotypes: A375-A7, melanotic and non-invasive and A375-G10, amelanotic and metastatic; and A375-PCDNA3 (transfected with empty plasmid) as control. Radiosensitivity was determined by clonogenic assay after irradiating these cells with a “1”3”7 Cs gamma source. Survival curves were fitted to the linear-quadratic model and surviving fraction at 2 Gy (SF2) was calculated. Results showed that A375-G10 cells were significantly more radioresistant than both A375-A7 and control cells, demonstrated by SF2 and α parameter of survival curves: SF2=0.32±0.03, 0.43±0.16 and 0.89±0.05 and α=0.45±0.05, 0.20±0.05 and 0 for A375-PCDNA3, A375-A7 and A375-G10 respectively. Bioinformatic analysis of whole genome expression microarrays data (Affymetrix) from these cells was performed. A priori defined gene sets associated with cell cycle, apoptosis and MAPK signaling pathway were collected from KEGG (Kyoto Encyclopedia of Genes and Genomes) to evaluate significant differences in gene set expression between cells by GSEA (Gene Set Enrichment Analysis). A375-G10 showed significant decrease in the expression of genes related to DNA damage response (ATM, TP53BP1 and MRE11A) compared to A375-A7 and controls. Moreover, A375-G10 exhibited down-regulated gene sets that are involved in DNA repair, checkpoint and negative regulation of cell cycle and apoptosis. In conclusion, A375-G10 gene expression profile could be involved in radioresistance mechanisms of these cells. Thus, this expression

  18. Expression of Estrogen Receptor Alpha in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2017-01-01

    Full Text Available Background: Features of malignant melanoma (MM vary in the different geographic regions of the world. This may be attributable to environmental, ethnic, and genetic factors. The aim of this study was to determine the expression of estrogen receptor alpha (ER-α in MM in Isfahan, Iran. Materials and Methods: This study was planned as a descriptive, analytical, cross-sectional investigation. During this study, paraffin-embedded tissue blocks of patients with a histopathologic diagnosis of MM was studied for ER-α using immunohistochemistry (IHC. Results: In this study, 38 patients (female/male; 20/18 with a definite diagnosis of malignant cutaneous melanoma and mean age of 52.4 ± 11.2 years were investigated. Using envision IHC staining, there were not any cases with ER-α expression. Conclusion: In confirmation to the most previous studies, expression of ER-α was negative in MM. It is recommended to investigate the expression of estrogen receptor beta and other markers in MM.

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

    Science.gov (United States)

    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.

  20. Survival after a psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Boesen, Sidsel H; Frederiksen, Kirsten

    2007-01-01

    The results of a randomized, intervention study done in 1993 of psychoeducation for patients with early-stage malignant melanoma showed a beneficial effect on recurrence and survival 6 years after the intervention. In the present study, we replicated the study with 258 Danish patients with malign...... with malignant melanoma. We also compared recurrence and survival among the participants in the randomized study with 137 patients who refused to participate....

  1. Biatrial Cardiac Metastases in a Patient with Uterine Cervix Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Caglayan Geredeli

    2015-01-01

    Full Text Available Primary malignant melanomas of uterine cervix are quite rarely seen neoplasms, and long-life prognosis of patients with this disease is poor. Immunohistochemical methods and exclusion of other primary melanoma sites are used to confirm the diagnosis. As with other melanomas, cervix malignant melanomas may also cause cardiac metastases. Cardiac metastases are among rarely seen but more commonly encountered cases, compared to primary cardiac tumors. Here, we present a case of biatrial cardiac metastases in a 73-year-old patient with uterine cervix malignant melanomas. The patient underwent echocardiography, cardiac magnetic resonance imaging, and computed tomography. Our report shows the importance of advanced diagnostic techniques, such as cardiac magnetic resonance, not only for the detection of cardiac masses, but for a better anatomic definition and tissue characterization. Although the cases of malignant melanomas leading to multiple cardiac metastasis were reported in literature, the metastatic concurrence of malignant melanomas in both right and left atriums is quite rarely encountered as metastatic malignant melanomas. Also, another intriguing point in our case is that the primary lesion of our case was stemmed from uterine cervix, but not skin.

  2. Lymphoscintigraphic Identification of Sentinel Nodes in Malignant Melanoma

    International Nuclear Information System (INIS)

    Andries, G.; Dindelegan, G.; Ciule, Larisa; Cosgarea, Rodica; Cobzac, Gh.

    2006-01-01

    Full text: The most important prognostic factor in malignant melanoma is the presence or absence of metastasis in lymph nodes. It has been demonstrated the orderly progression of different types of tumours. Sentinel lymph node identification is done lymphoscintigraphically, followed by surgical excision and morpho pathological exam. Material and methods: We studied 33 patients with malignant melanoma (age 26-84 years) divided in 2 subgroups: group A without gamma probe (18 patients) and group B with gamma probe (15 patients). The lymphoscintigraphy (LS) was performed with a totally dose of 20-30 MBq of 99mTc-nanocoloid (Amersham) injected peritumoral or pericicatriceal in 4-6 points in volume of 0,1-0,2 ml per point. Acquisition was performed dynamic for 10-15 min and static at 30-60 min p.i. on perpendicular projections. Patent blue dye was injected prior surgery. In group A has performed sentinel node excision (13 patients) or ELND (4), one patient has died before surgery. In group B sentinel nodes were surgically excised with gamma probe and ELND was performed in patients with positive lymph nodes. Histopathologically, sentinel nodes were stained with HE and in 6 cases with HMB45. Results: In group A we identified the sentinel nodes scintigraphically in all patients (median 1,83±-1,50 nodes, range 1-7). Surgically with PBD were identified 1,69±1,18 sentinel nodes, in 2 patients the SN lymphadenectomy was negative. All nodes excised were histopathologically negative, but in 4 patients loco-regional recurrence or distant metastasis developed. In group B we identified scintigraphically 33 SNs (median 2,20±1,37 nodes, range 1-5) and 4 in transit nodes in 14 patients, 24 of them being blue dye positive (80%), in 1 patient LS was negative. With gamma probe surgeon excised 39 radioactive nodes and 1 SN blue dye positive only, 10 of them being histopathologically positive (25% node metastasis). No metastasis were identified after ELND in patients with positive SNs

  3. Characterization of ex vivo expanded tumor infiltrating lymphocytes from patients with malignant melanoma for clinical application

    DEFF Research Database (Denmark)

    Junker, Niels; Thor Straten, Per; Andersen, Mads Hald

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have establis......Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have...

  4. Malignant melanoma among employees of Lawrence Livermore National Laboratory

    International Nuclear Information System (INIS)

    Austin, D.F.; Reynolds, P.J.; Snyder, M.A.; Biggs, M.W.; Stubbs, H.A.

    1981-01-01

    19 cases of malignant melanoma (MM) were observed during 1972-77 among approximately 5100 employees of the Lawrence Livermore National Laboratory, where high energy physics research is conducted. This number was significantly higher (p -6 ) than that expected in a comparable age/race/sex/geographical segment of the population of the San Francisco Bay area. That excess seemed to occur only among laboratory employees and not among the surrounding community, which suggests that an occupational factor is responsible. Preliminary case-comparison findings suggest that MM risk is not associated with length of employment at the laboratory nor with type of monitored radiation exposure. Although the data did not support an association between MM incidence and all scientific job classifications combined, an excess relative risk was observed among chemists. The reasons for the MM excess have not been identified. (author)

  5. Primary malignant melanoma of the vagina with repeated local recurrences and brain metastasis

    Directory of Open Access Journals (Sweden)

    Li-Te Lin

    2011-08-01

    Full Text Available Malignant melanoma of the vagina, a very rare malignancy, has a notoriously aggressive behavior associated with a high risk of local recurrence and distant metastasis. At present, there are various treatment options for this disease but no standard guideline. We describe a case of a 54-year-old woman with a locally advanced melanoma of the vagina, who underwent radical surgery, biochemotherapy with interferon-α-2b, chemotherapy, radiotherapy, and repeat excision of local recurrent lesions and brain metastasis. In conclusion, malignant melanoma of the vagina has a high risk for local recurrence. Repeated local excision followed by biochemotherapy is a tolerable treatment.

  6. Genetic Background of Iris Melanomas and Iris Melanocytic Tumors of Uncertain Malignant Potential.

    Science.gov (United States)

    van Poppelen, Natasha M; Vaarwater, Jolanda; Mudhar, Hardeep S; Sisley, Karen; Rennie, Ian G; Rundle, Paul; Brands, Tom; van den Bosch, Quincy C C; Mensink, Hanneke W; de Klein, Annelies; Kiliç, Emine; Verdijk, Robert M

    2018-01-19

    Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Iris melanoma comprises 4% to 10% of all UMs and has a lower mortality rate. The genetic changes in iris melanoma are not as well characterized as ciliary body or choroidal melanoma. The aim of this study was to gain more insight into the genetic background of iris melanoma and iris nevi. Multicenter, retrospective case series. Patients diagnosed with iris melanoma or iris nevi who underwent surgical intervention as primary or secondary treatment. Next-generation sequencing of GNAQ, GNA11, EIF1AX, SF3B1, BAP1, NRAS, BRAF, PTEN, c-Kit, TP53, and TERT was performed on 30 iris melanomas and 7 iris nevi. Copy number status was detected using single nucleotide polymorphisms (SNPs) included in the next-generation sequencing (NGS) panel, SNP array, or fluorescent in situ hybridization. BAP1 immunohistochemistry was performed on all samples. Mutation and copy number status were analyzed. Results of BAP1 immunohistochemistry were used for survival analysis. In 26 of the 30 iris melanoma and all iris nevi, at least 1 mutation was identified. Multiple mutations were detected in 23 iris melanoma and 5 nevi, as well as mutations in GNAQ and GNA11. Furthermore, 13 of 30 BAP1, 5 of 30 EIF1AX, and 2 of 30 SF3B1 mutations were identified in iris melanoma. No correlation between BAP1 status and disease-free survival was found. The iris nevi showed 1 EIF1AX and 3 BAP1 mutations. Two of the nevi, with a BAP1 mutation, were histologically borderline malignant. Mutations in NRAS, BRAF, PTEN, c-KIT, and TP53 were detected in 6 iris melanomas and 4 iris nevi. Mutations that are often found in uveal and cutaneous melanoma were identified in this cohort of iris melanomas and iris nevi. Therefore, iris melanomas harbor a molecular profile comparable to both choroidal melanoma and cutaneous melanoma. These findings may offer adjuvant targeted therapies for iris melanoma. There was no prognostic significance of

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

    Directory of Open Access Journals (Sweden)

    Namita Bhutani

    Full Text Available Introduction: 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. Presentation of case: 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. Discussion: 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. Conclusion: 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. Keywords: Case report, Female urethral cancer, Immunohistochemistry, Malignant melanoma, Urethral neoplasm

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

    Science.gov (United States)

    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.

  9. Does the sun play a role in the aetiology of malignant melanoma ...

    African Journals Online (AJOL)

    The role of the sun in the aetiology of malignant melanoma is controversial. In 1992 Schuster1 wrote provocatively, 'Despite the lack of evidence of a causal link between sun exposure and melanoma, fear has been used shamelessly to frighten people out of the sun and into pigmented lesion clinics.' He claimed that the ...

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

    DEFF Research Database (Denmark)

    Hannibal, C.G.; Jensen, A.; Sharif, H.

    2008-01-01

    . 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. RESULTS: 112 malignant melanomas were identified......OBJECTIVE: 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. METHODS: A cohort of 54,362 women with infertility problems referred to Danish fertility clinics in the period 1963-1998 was established...... 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). CONCLUSIONS: Our findings showed no strong association between malignant melanoma risk and use of fertility drugs, although the results indicated that use...

  11. Analysis of KIT expression and KIT exon 11 mutations in canine oral malignant melanomas.

    Science.gov (United States)

    Murakami, A; Mori, T; Sakai, H; Murakami, M; Yanai, T; Hoshino, Y; Maruo, K

    2011-09-01

    KIT, a transmembrane receptor tyrosine kinase, is one of the specific targets for anti-cancer therapy. In humans, its expression and mutations have been identified in malignant melanomas and therapies using molecular-targeted agents have been promising in these tumours. As human malignant melanoma, canine malignant melanoma is a fatal disease with metastases and the poor response has been observed with all standard protocols. In our study, KIT expression and exon 11 mutations in dogs with histologically confirmed malignant oral melanomas were evaluated. Although 20 of 39 cases were positive for KIT protein, there was no significant difference between KIT expression and overall survival. Moreover, polymerase chain reaction amplification and sequencing of KIT exon 11 in 17 samples did not detect any mutations and proved disappointing. For several reasons, however, KIT expression and mutations of various exons including exon 11 should be investigated in more cases. © 2011 Blackwell Publishing Ltd.

  12. A case of collision tumor or transdifferentiation between malignant melanoma and leiomyosarcoma

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Rasmussen, Helle; Breiting, Line

    2012-01-01

    with a seborrheic keratosis. There have also been occasional reports of rhabdomyosarcomatous differentiation. However, mesenchymal differentiation, and in this case leiomysarcoma, with formation of heterologous elements in melanocytic tumor is very rare. Another plausible explanation may be that malignant melanoma...

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  14. CHEK2*1100delC and risk of malignant melanoma

    DEFF Research Database (Denmark)

    Weischer, Maren; Heerfordt, Ida M; Bojesen, Stig E

    2012-01-01

    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...

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

    Science.gov (United States)

    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.

  16. Primary Malignant Melanoma of the Gingiva: A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Niti Singhal

    2011-01-01

    In contrast to cutaneous melanoma, the mucosal melanomas have an aggressive vertical growth phase. Different cell types, like spindled, plasmacytoid, and epithelioid may be observed. The treatment of choice is complete excision with adequate negative margins. The role of radiotherapy is not clearly defined since malignant melanoma is relatively insensitive to radiation. The prognosis for mucosal melanoma is generally quite poor because of its tendency to invade and cause early hematogenous metastasis. Nodal involvement reduces survival time and multiple local recurrences are the most common cause of treatment failure.

  17. Common anorectal disorders.

    Science.gov (United States)

    Foxx-Orenstein, Amy E; Umar, Sarah B; Crowell, Michael D

    2014-05-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management.

  18. Nivolumab in the treatment of malignant melanoma: review of the literature

    Directory of Open Access Journals (Sweden)

    Mashima E

    2015-08-01

    Full Text Available Emi Mashima, Akiha Inoue, Yumiko Sakuragi, Takashi Yamaguchi, Natsuko Sasaki, Yoko Hara, Daisuke Omoto, Shun Ohmori, Sanehito Haruyama, Yu Sawada, Manabu Yoshioka, Daisuke Nishio, Motonobu Nakamura Department of Dermatology, University of Occupational and Environmental Health, Kitakyushu, Japan Abstract: Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. Intravenous administration of nivolumab was approved for the treatment of unresectable malignant melanoma in 2014 in Japan. When advanced melanoma patients were treated with nivolumab, median overall survival became longer. Overall survival rate was significantly better in nivolumab-treated melanoma patients than dacarbazine-treated melanoma patients. Nivolumab had an acceptable long-term tolerability profile, with 22% of patients experiencing grade 3 or 4 adverse events related to the drug. Therefore, nivolumab can become an alternative therapy for advanced malignant melanoma. Keywords: monoclonal antibody, PD-1, PD-L1

  19. Conjunctival malignant melanoma in Denmark: epidemiology, treatment and prognosis with special emphasis on tumorigenesis and genetic profile

    DEFF Research Database (Denmark)

    Larsen, Ann-Cathrine

    2016-01-01

    Conjunctival malignant melanoma is a rare disease associated with considerable mortality. Most published data have been based on case reports or series of referred patients. In addition, very little is known about the genetic and epigenetic profile of conjunctival melanoma and the resemblance to ...... melanoma patients may benefit from therapies that are effective for cutaneous and mucosal melanoma. Additionally, the identification of several up-regulated microRNAs may prove to be useful as prognostic or therapeutic targets in conjunctival melanoma...

  20. Ovarian metastasis of malignant melanoma: The first pediatric case

    Directory of Open Access Journals (Sweden)

    Yuko Araki

    2014-10-01

    Full Text Available We report a case of an 8-year-old girl with metastasis of malignant melanoma (MM to the ovary. She was initially diagnosed with cutaneous MM on the left buttock for which she underwent wide local excision, left inguinal/pelvic lymph node dissection, and subcutaneous injection of interferon beta. In spite of the treatment, she developed dissemination of MM to the liver, the bone, and the right ovary. All the lesions responded well to systemic chemotherapy (intravenous dacarbazine, except for the right ovarian tumor. She underwent an elective right salpingo-oophorectomy to avoid torsion or rupture of the tumor. However, she developed metastases to the contralateral ovary with peritoneal dissemination in 4 months. She received home palliative care and died at home 14 months after the last surgery. Ovarian metastasis of MM is a rare form of dissemination, and only 15 adult cases have ever been reported. Our patient is the first pediatric case. Since there is no standard of surgical indication for metastatic MM to the ovary, palliative resection can be an option for improving quality of life of a patient with this rare condition.

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

    Science.gov (United States)

    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.

  2. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Adachi, Nanao; Nimura, Yoshinori

    2004-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  3. Quantitative analysis of genes regulating sensitivity to heavy ion irradiation in cultured cell lines of malignant choroid melanoma

    International Nuclear Information System (INIS)

    Kumagai, Ken; Nimura, Yoshinori; Kato, Masaki; Seki, Naohiko; Miyahara, Nobuyuki; Aoki, Mizuho; Shino, Yayoi; Furusawa, Yoshiya; Mizota, Atsushi

    2005-01-01

    As a treatment strategy for malignant melanoma, heavy ion irradiation has been planned in National Institute of Radiological Sciences (NIRS). However, the molecular biology of the malignant melanoma cell after irradiation of heavy ion is still unknown. In this study, we used resistant and sensitive cell lines of malignant melanoma to study the effects of heavy ion irradiation. Furthermore, gene expression profiling of early response genes for heavy ion irradiation was carried out on these cell lines using microarray technology. (author)

  4. Oral malignant melanoma: A case report of an unusual clinical and histologic presentation

    Directory of Open Access Journals (Sweden)

    Uzma Iqbal Belgaumi

    2013-01-01

    Full Text Available Malignant melanoma is a potentially aggressive tumor of melanocytic origin. Primary oral malignant melanoma is a rare neoplasm, accounting for 0.5% of all oral malignancies. The present case occurred in a 60-year-old female patient, as a pedunculated growth involving the palate and alveolar ridge and histologically showing a desmoplastic differentiation. The article discusses the distinct clinico-pathologic presentation of this case and emphasizes on the need to identify and report such cases for further understanding of their biologic behavior.

  5. Development of radioiodine-labeled 4-hydroxyphenylcysteamine for specific diagnosis of malignant melanoma

    International Nuclear Information System (INIS)

    Kobayashi, Masato; Nishii, Ryuichi; Shikano, Naoto; Flores, Leo G.; Mizutani, Asuka; Ogai, Kazuhiro; Sugama, Jyunko; Nagamachi, Shigeki; Kawai, Keiichi

    2015-01-01

    Introduction: A specific diagnosis for melanoma is strongly desired because malignant melanoma has poor prognosis. In a previous study, although radioiodine-125-labeled 4-hydroxyphenyl-L-cysteine ( 125 I-L-PC) was found to have good substrate affinity for tyrosinase enzyme in the melanin metabolic pathway, 123/131 I-L-PC had insufficient substrate affinity for tyrosinase to diagnose melanoma. In this study, we synthesized 4-hydroxyphenylcysteamine (4-PCA) and developed a novel radioiodine-125-labeled 4-hydroxyphenylcysteamine ( 125 I-PCA) to increase affinity for the melanin biosynthesis pathway. Methods: 4-PCA was separated with 2-hydroxyphenylcysteamine (2-PCA), which is an isomer of 4-PCA, and was examined using melting point, proton nuclear magnetic resonance, mass spectrometry and elemental analysis. 125 I-PCA was prepared using the chloramine-T method under no-carrier added conditions. We performed biodistribution experiments using B16 melanoma-bearing mice using 125 I-PCA, 125 I-L-PC, 125 I-α-methyl-L-tyrosine, 123 I-m-iodobenzylguanidine and 67 Ga-citrate. In vitro assay was performed with B16 melanoma cells, and affinity for tyrosinase, DNA polymerase and amino acid transport was evaluated using phenylthiourea, thymidine, ouabine and L-tyrosine inhibitor. In addition, partition coefficients of 125 I-PCA were evaluated. Results: In the synthesis of 4-PCA, analysis values did not differ between calculated and reported values, and 4-PCA was separated from 2-PCA at high purity. In biodistribution experiments, 125 I-PCA was accumulated and retained in B16 melanoma cells when compared with 125 I-L-PC. 125 I-PCA showed the highest values at 60 min after radiotracer injection in melanoma-to-muscle ratios, melanoma-to-blood ratios and melanoma-to-skin ratios. Accumulation of 125 I-PCA was significantly inhibited by phenylthiourea and thymidine. Partition coefficients of 125 I-PCA were lower than those of N-isopropyl-p-[ 123 I]iodoamphetamine and were not

  6. Relationship between regulatory and type 1 T cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Horiuchi, Yutaka; Tominaga, Makiko; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Nakajima, Yuko; Kuwabara, Masato; Yukawa, Masayoshi

    2010-03-01

    Recent data suggest a decreased prevalence of IFN-gamma-producing T lymphocytes (Type 1 T cells) in tumor-bearing hosts. Moreover, it has been reported that Treg have a strong impact on the activation and proliferation of CD4 (+) and CD8 (+) lymphocytes; however, no previous reports have described the relationship between Treg and the progression of tumor, or Type 1 T cell populations in dogs with malignant tumor. In this study, the percentage of Treg, Th1, and Tc1 in the peripheral blood of dogs with oral malignant melanoma and healthy dogs was measured and compared. Although the percentages of Th1 and Tc1 in dogs with oral malignant melanoma were less than those in healthy dogs (Th1: P dogs with oral malignant melanoma. In dogs, Treg appears to suppress Type 1 immunity, which may be responsible for anti-tumor responses.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Xiao; Zhang, Haiping [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Lian, Shi [Department of Dermatology and Venereal Disease, Capital Medical University, Beijing 100069 (China); Zhu, Wei, E-mail: zhuwei_2020@163.com [Department of Dermatology and Venereal Disease, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    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. -- 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.

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

    Science.gov (United States)

    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.

  9. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Joan Figueroa, AlejandroYuri; Diaz Anaya, Amnia; Montero Leon, Jorge Felipe; Jimenez Mendes, Lourdes

    2010-01-01

    INTRODUCTION: The aim of present research was to determine the independent prognostic value and the 3 and 5 years survival of more significant clinicopathological prognostic factors and in each stage, according to pathological staging system of tumor-nodule-metastasis (TNM) in patients with cutaneous malignant melanoma (CMM). METHODS: A longitudinal, descriptive and retrospective study was conducted applying the Cox proportional risk form and the Kaplan-Meier method, aimed to search of different risk variables in patients with CMM. We studied 157 patients with CMM, seen during 8 years (1993 to 2001), diagnosed and treated in National Institute of Oncology and Radiobiology of La Habana. RESULTS: The more powerful prognostic variables related to localized disease (stage I and II) were the Breslow density (P: 0,000), the mitosis rate (P: 0,004), and the Clark level (P: 0,04); among the variables related to the regional disease (stage III) the number of lymphatic ganglia involved was the more weighthy (P:0,000) and the more important in Stage IV was the distant visceral metastasis (P:0,003). Survival was decreasing according to the advance of the pathological stage of disease. CONCLUSIONS: The more involved independent prognostic factors were the Breslow rate, the number of involved regional lymphatic nodules and the distant visceral metastasis, which is endorsed by a world consensus. However, variables as age, sex, lesion site, ulceration, host-tumor inflammatory response, histological subtype, satellitosis and transient metastasis, considered as independent prognostic indicators in big casuistries, had not statistical significance in present paper. (author)

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

    Science.gov (United States)

    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.

  11. Correlations between cutaneous malignant melanoma and other cancers: An ecological study in forty European countries

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    Pablo Fernandez-Crehuet Serrano

    2016-01-01

    Full Text Available Background: The presence of noncutaneous neoplasms does not seem to increase the risk of cutaneous malignant melanoma; however, it seems to be associated with the development of other hematological, brain, breast, uterine, and prostatic neoplasms. An ecological transversal study was conducted to study the geographic association between cutaneous malignant melanoma and 24 localizations of cancer in forty European countries. Methods: Cancer incidence rates were extracted from GLOBOCAN database of the International Agency for Research on Cancer. We analyzed the age-adjusted and gender-stratified incidence rates for different localizations of cancer in forty European countries and calculated their correlation using Pearson′s correlation test. Results: In males, significant correlations were found between cutaneous malignant melanoma with testicular cancer (r = 0.83 [95% confidence interval (CI: 0.68-0.89], myeloma (r = 0.68 [95% CI: 0.46-0.81], prostatic carcinoma (r = 0.66 [95% CI: 0.43-0.80], and non-Hodgkin lymphoma (NHL (r = 0.63 [95% CI: 0.39-0.78]. In females, significant correlations were found between cutaneous malignant melanoma with breast cancer (r = 0.80 [95% CI: 0.64-0.88], colorectal cancer (r = 0.72 [95% CI: 0.52-0.83], and NHL (r = 0.71 [95% CI: 0.50-0.83]. Conclusions: These correlations call to conduct new studies about the epidemiology of cancer in general and cutaneous malignant melanoma risk factors in particular.

  12. Stereological estimates of nuclear volume in thin malignant melanomas

    DEFF Research Database (Denmark)

    Björnhagen, V; Månsson-Brahme, E; Lindholm, J

    1998-01-01

    melanomas were individually compared with 33 thin non-metastasizing melanomas after individual matching of cases with one or two randomly chosen controls for site of primary tumour, tumour thickness, level of invasion, tumour regression and follow-up. Conditional logistic regression analysis showed...

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

    Science.gov (United States)

    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

  14. Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

    International Nuclear Information System (INIS)

    Martinez-Cadenas, Conrado; Lozoya, Rafael; Boldó, Enrique; Bosch, Nuria; Peñas, Lucas; Flores-Couce, Esther; Ochoa, Enrique; Munárriz, Javier; Aracil, Juan P; Tajahuerce, Marcos; Royo, Ramón

    2011-01-01

    Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A) mutation was detected in exon 15 of the BRAF gene. Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations

  15. A case of desmoplastic melanoma that was difficult to distinguish from malignant peripheral nerve sheath tumor

    Directory of Open Access Journals (Sweden)

    Kenji Yorita

    2018-03-01

    Full Text Available The clinical and pathological diagnosis of desmoplastic melanoma is difficult, because almost 50% of desmoplastic melanoma cases involve non-pigmented lesions and the tumor cells can resemble fibroblasts or Schwannian cells based on their frequent amelanotic features. Moreover, desmoplastic melanoma typically has low positive rates for melanoma markers, with the exception of the S-100 protein. We report the case of an 81-year-old Japanese man with an 8-mm desmoplastic melanoma. He initially noticed a painless and non-pigmented skin lesion that did not grow noticeably for 6 months. It was unlikely that he had von Recklinghausen disease, and the mass was initially considered a dermatofibroma. Excisional biopsy revealed an intradermal mass, with the superficial portion mimicking neurofibroma and the deeper portion exhibiting nodular growth of sarcomatoid spindle cells. The tumor region lacked intradermal proliferation of atypical melanocytic cells, intracytoplasmic melanin, and expression of melanoma markers (except S-100 protein and Sox10. Although a malignant peripheral nerve sheath tumor derived from neurofibroma was possible, the slow growth with diffuse and strong immunoreactivity to the S-100 protein and Sox10 favored a diagnosis of desmoplastic melanoma. Pathologists should recognize that desmoplastic melanoma may not involve in situ lesions or the immunohistochemical expression of standard melanoma markers.

  16. Intralesional and metastatic heterogeneity in malignant melanomas demonstrated by stereologic estimates of nuclear volume

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Erlandsen, M

    1990-01-01

    Regional variability of nuclear 3-dimensional size can be estimated objectively using point-sampled intercepts obtained from different, defined zones within individual neoplasms. In the present study, stereologic estimates of the volume-weighted mean nuclear volume, nuclear vv, within peripheral...... melanomas showed large interindividual variation. This finding emphasizes that unbiased estimates of nuclear vv are robust to regional heterogeneity of nuclear volume and thus suitable for purposes of objective, quantitative malignancy grading of melanomas....

  17. Speculations on the role of ultraviolet radiation in the development of malignant melanoma

    International Nuclear Information System (INIS)

    Kripke, M.L.

    1979-01-01

    Interest in the etiology of human malignant melanoma has increased considerably in recent years. The basis for this heightened concern can be attributed to two seemingly unrelated issues. The first is that the incidence of malignant melanoma is increasing at an alarming rate. At the present time, both the incidence of melanoma and the mortality rate are doubling every 10 to 17 years. Thus identification of causal factors in the development of melanoma is an urgent necessity if this upward trend is to be curbed. The second issue that has directed attention to the identification of etiologic factors in malignant melanoma is ozone depletion. The layer of ozone surrounding the earth shields it from solar uv radiation. Anticipated decreases in stratospheric ozone, resulting from high-altitude aircraft, nuclear explosions, and the release into the atmosphere of chlorofluoromethanes from refrigerants and aerosol sprays, raised concerns about the effects of an increased exposure of all life forms to uv light. One anticipated effect of increased exposure of humans to uv light is a corresponding increase in some types of skin cancer in humans. If malignant melanoma is included among the types of skin cancer at risk of increasing, then the impact of ozone depletion on humans is serious indeed. In the prognosis for melanoma is less favorable, particularly in cases in which the tumor is already invasive at the time of diagnosis. Thus the threat of an increased level of exposure to light has stimulated a careful reevaluation of the role of radiation in the induction of melanoma

  18. Analysis of alpha-synuclein in malignant melanoma - development of a SRM quantification assay.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available Globally, malignant melanoma shows a steady increase in the incidence among cancer diseases. Malignant melanoma represents a cancer type where currently no biomarker or diagnostics is available to identify disease stage, progression of disease or personalized medicine treatment. The aim of this study was to assess the tissue expression of alpha-synuclein, a protein implicated in several disease processes, in metastatic tissues from malignant melanoma patients. A targeted Selected Reaction Monitoring (SRM assay was developed and utilized together with stable isotope labeling for the relative quantification of two target peptides of alpha-synuclein. Analysis of alpha-synuclein protein was then performed in ten metastatic tissue samples from the Lund Melanoma Biobank. The calibration curve using peak area ratio (heavy/light versus concentration ratios showed linear regression over three orders of magnitude, for both of the selected target peptide sequences. In support of the measurements of specific protein expression levels, we also observed significant correlation between the protein and mRNA levels of alpha-synuclein in these tissues. Investigating levels of tissue alpha-synuclein may add novel aspect to biomarker development in melanoma, help to understand disease mechanisms and ultimately contribute to discriminate melanoma patients with different prognosis.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  1. Establishment and characterization of human uveal malignant melanoma xenografts in nude mice

    DEFF Research Database (Denmark)

    Heegaard, S; Spang-Thomsen, M; Prause, J U

    2003-01-01

    the characteristic properties of malignant melanoma. However, the transplanted cells demonstrated vimentin reactivity, whereas the primary tumour cells were negative for vimentin. It can be concluded that a new experimental model of malignant uveal melanoma with tumours that were easy to observe and access...... model. Tumour tissue blocks (2 x 2 x 2 mm) from enucleated eyes with choroidal malignant melanoma were transplanted subcutaneously into the flanks of nude mice. The growing tumours were measured and serially transplanted. The tumour samples were investigated by histology, immunohistochemistry....... The transplanted tumour cells were epithelioid and slightly larger than the primary tumour cells and had prominent nucleoli. However, the transplanted tumour retained a morphological appearance similar to that of the primary tumour. Immunohistochemical examinations demonstrated that the cells preserved...

  2. Immunohistochemical diagnosis of malignant melanoma of the conjunctiva and uvea: comparison of the novel antibody against melan-A with S100 protein and HMB-45

    DEFF Research Database (Denmark)

    Heegaard, Steffen; Jensen, O.A.; Prause, J.U.

    2000-01-01

    ophthalmology, A103, conjunctiva, gp100, HMB-45, malignant melanoma, MART-1, melan-A, S100, uvea......ophthalmology, A103, conjunctiva, gp100, HMB-45, malignant melanoma, MART-1, melan-A, S100, uvea...

  3. Anorectal emergencies

    Science.gov (United States)

    Lohsiriwat, Varut

    2016-01-01

    Anorectal emergencies refer to anorectal disorders presenting with some alarming symptoms such as acute anal pain and bleeding which might require an immediate management. This article deals with the diagnosis and management of common anorectal emergencies such as acutely thrombosed external hemorrhoid, thrombosed or strangulated internal hemorrhoid, bleeding hemorrhoid, bleeding anorectal varices, anal fissure, irreducible or strangulated rectal prolapse, anorectal abscess, perineal necrotizing fasciitis (Fournier gangrene), retained anorectal foreign bodies and obstructing rectal cancer. Sexually transmitted diseases as anorectal non-surgical emergencies and some anorectal emergencies in neonates are also discussed. The last part of this review dedicates to the management of early complications following common anorectal procedures that may present as an emergency including acute urinary retention, bleeding, fecal impaction and anorectal sepsis. Although many of anorectal disorders presenting in an emergency setting are not life-threatening and may be successfully treated in an outpatient clinic, an accurate diagnosis and proper management remains a challenging problem for clinicians. A detailed history taking and a careful physical examination, including digital rectal examination and anoscopy, is essential for correct diagnosis and plan of treatment. In some cases, some imaging examinations, such as endoanal ultrasonography and computerized tomography scan of whole abdomen, are required. If in doubt, the attending physicians should not hesitate to consult an expert e.g., colorectal surgeon about the diagnosis, proper management and appropriate follow-up. PMID:27468181

  4. Primary Malignant Melanoma of the Genitourinary Tract with Upper and Lower Tracts Involvement

    Directory of Open Access Journals (Sweden)

    Broderick Sutton

    2013-01-01

    Full Text Available A 91-year-old female presented with lower extremity swelling and shortness of breath. Laboratory analysis revealed elevations in blood urea nitrogen and creatinine along with microscopic hematuria on urinalysis. Computed tomography imaging showed moderate right hydronephrosis with dilatation of the proximal ureter with a soft tissue density at a transition point. Endoscopic evaluation revealed multiple raised, fleshy, and hemorrhagic masses throughout the bladder which are present in both ureters. Biopsy of these lesions revealed malignant melanoma invading the lamina propria. No dermatologic lesions were identified suggesting a primary malignant melanoma of the genitourinary system.

  5. THE STUDY OF MECHANISMS OF PHOTOINDUCED APOPTOSIS IN THE SKIN MALIGNANT MELANOMA CELL MODEL

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    M. L. Gelfond

    2016-01-01

    Full Text Available The results of the experimental study of immune response of human skin malignant melanoma cells Mel 226 on photodynamic exposure are represented in the article. Photoinduced apoptosis of skin malignant melanoma was studied in vitro. The study showed that irradiation with the agent fotoditazin at dose of 0.5–2.5 µg/ml (6 and 10 min exposure 30 min before irradiation; irradiation parameters: wavelength of 662 nm, total light dose from 40 to 60 J/cm2 induced early apoptosis. The increase of the time of laser irradiation significantly accelerates the conversion of photosensitized tumor cells from early to late apoptosis.

  6. Matrix Metalloproteinase-9 (MMP-9 polymorphisms in patients with cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Busam Klaus

    2007-03-01

    Full Text Available Abstract Background Cutaneous Malignant Melanoma causes over 75% of skin cancer-related deaths, and it is clear that many factors may contribute to the outcome. Matrix Metalloproteinases (MMPs play an important role in the degradation and remodeling of the extracellular matrix and basement membrane that, in turn, modulate cell division, migration and angiogenesis. Some polymorphisms are known to influence gene expression, protein activity, stability, and interactions, and they were shown to be associated with certain tumor phenotypes and cancer risk. Methods We tested seven polymorphisms within the MMP-9 gene in 1002 patients with melanoma in order to evaluate germline genetic variants and their association with progression and known risk factors of melanoma. The polymorphisms were selected based on previously published reports and their known or potential functional relevance using in-silico methods. Germline DNA was then genotyped using pyrosequencing, melting temperature profiles, heteroduplex analysis, and fragment size analysis. Results We found that reference alleles were present in higher frequency in patients who tend to sunburn, have family history of melanoma, higher melanoma stage, intransit metastasis and desmoplastic melanomas among others. However, after adjustment for age, sex, phenotypic index, moles, and freckles only Q279R, P574R and R668Q had significant associations with intransit metastasis, propensity to tan/sunburn and primary melanoma site. Conclusion This study does not provide strong evidence for further investigation into the role of the MMP-9 SNPs in melanoma progression.

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

    Science.gov (United States)

    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.

  8. Solitary Secondary Malignant Melanoma of Clavicle Two Years after Enuclation for Ocular Melanoma

    Directory of Open Access Journals (Sweden)

    Halil Tozum

    2013-01-01

    Full Text Available Solitary metastasis of uveal melanoma to bone is extremely rare and usually associated with other organ involvement. We present a rare case of an ocular melanoma patient presenting with solitary metastasis to the clavicle two years after enucleation, without any other organ involvement. In this report, we tried to present our treatment strategy for the solitary metastasis of bone.

  9. Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18

    Directory of Open Access Journals (Sweden)

    Barry Richard D

    2011-01-01

    Full Text Available Abstract Many RNA viruses are displaying great promise in the field of oncolytic virotherapy. Previously, we reported that the picornavirus Coxsackievirus A21 (CVA21 possessed potent oncolytic activity against cultured malignant melanoma cells and melanoma xenografts in mice. In the present study, we demonstrate that three additional Group A Coxsackieviruses; Coxsackievirus A13 (CVA13, Coxsackievirus A15 (CVA15 and Coxsackievirus A18 (CVA18, also have similar oncolytic activity against malignant melanoma. Each of the viruses grew quickly to high titers in cancer cells expressing ICAM-1 and intratumoral injection of preformed subcutaneous SK-Mel-28 xenografts in mice with CVA13, CVA15 and CVA18 resulted in significant tumor volume reduction. As preexisting immunity could potentially hinder oncolytic virotherapy, sera from stage IV melanoma patients and normal controls were tested for levels of protective antibody against the panel of oncolytic Coxsackieviruses. Serum neutralization assays revealed that 3 of 21 subjects possessed low levels of anti-CVA21 antibodies, while protective antibodies for CVA13, CVA15 and CVA18 were not detected in any sample. Serum from individuals who were seropositive for CVA21 failed to exhibit cross-neutralization of CVA13, CVA15 and CVA18. From these studies it can be concluded that the administration of CVA13, CVA15 or CVA18 could be employed as a potential multivalent oncolytic therapy against malignant melanoma.

  10. Differing lectin-binding patterns of malignant melanoma and nevocellular and Spitz nevi.

    Science.gov (United States)

    Kohchiyama, A; Oka, D; Ueki, H

    1987-01-01

    The lectin-binding patterns of primary malignant melanoma, nevocellular nevus, and Spitz nevus were studied on formalin-fixed, paraffin-embedded sections using a series of biotinylated lectins--concanavalin A (ConA), Ricinus communis agglutinin-1 (RCA1), dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), maclura pomifera agglutinin (MPA), peanut agglutinin (PNA), wheat germ agglutinin (WGA), and Ulex europeus agglutinin-1(UEA1)--and employing the avidin-biotin-peroxidase complex method. In nevocellular and Spitz nevi, all of the nevus cells were positively stained with ConA and RCA1. No positive staining was observed, however, with the other lectins and no change in binding patterns occurred following neuraminidase pretreatment. In malignant melanoma, all of the melanoma cells were positively stained with ConA and RCA1, and some were also stained with MPA, PNA, and WGA. In addition, DBA, SBA, MPA, PNA, and WGA labeled all of the melanoma cells after neuraminidase pretreatment. No positive staining was observed with UEA1 despite neuraminidase pretreatment. The present results showed that malignant melanoma and nevocellular and Spitz nevi have different lectin-binding patterns and different responses to neuraminidase pretreatment. We, therefore, believe that the lectin staining on paraffin-embedded sections can be a useful probe for the differentiation of these diseases.

  11. Using computer graphics to preserve function in resection of malignant melanoma of the foot.

    Science.gov (United States)

    Kaufman, M; Vantuyl, A; Japour, C; Ghosh, B C

    2001-08-01

    The increasing incidence of malignant melanoma challenges physicians to find innovative ways to preserve function and appearance in affected areas that require partial resection. We carefully planned the resection of a malignant lesion between the third and fourth toes of a 77-year-old man with the aid of computer technology. The subsequent excision of the third, fourth, and fifth digits was executed such that the new metatarsal arc formed would approximate the dimensions of the optimal hyperbola, thereby minimizing gait disturbance.

  12. Primary Oral Malignant Melanoma - A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    R Sathawane

    2005-01-01

    Malignant melanoma (MM is a neoplasm of melanocytic origin that arises from a benign melanocytic lesion or de novo from melanocytes within otherwise normal mucosa or skin. It is one of most biologically unpredictable and deadly of all human neoplasms. It is third most common skin cancer, and accounts for 5% of all tumours. Although it comprises 1.3% of all cancers, MM of oral cavity accounts for only 0.2 to 8% of all reported melanomas. The mucosal melanoma tends to appear at a higher stage and is much aggressive than its cutaneous counterpart. The prognosis of oral melanoma is extremely poor, until recently less than 29% of affected patients survived for 5 years or more.

  13. In vitro and in vivo studies in boron neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    Allen, B.J.

    1982-01-01

    A multidisciplinary research project in boron neutron capture therapy of malignant melanoma is under consideration by the Australian Atomic Energy Commission. This paper reviews the biochemistry of melanoma and the properties of some melanoma-affined radiopharmaceuticals and their boron analogues. Human cell lines are being used for in vitro tests of uptake and incorporation of some of these compounds, and selected lines will then be implanted in nude mice for in vivo distribution studies. The fidelity of human melanoma xenografts in nude mice has been well studied, and results are reviewed in this paper. Boron concentration will be measured directly by plasma arc emission spectroscopy or liquid scintillation counting with 14 C-labelled boron analogues. Track-etch techniques will be used for the microscopic determination of boron in tumor sections. Neutron irradiation and radiobiology experiments are outlined

  14. Intralesional and metastatic heterogeneity in malignant melanomas demonstrated by stereologic estimates of nuclear volume

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Erlandsen, M

    1990-01-01

    Regional variability of nuclear 3-dimensional size can be estimated objectively using point-sampled intercepts obtained from different, defined zones within individual neoplasms. In the present study, stereologic estimates of the volume-weighted mean nuclear volume, nuclear vv, within peripheral...... on average larger in the peripheral zones of primary melanomas, than nuclear vv in central zones (2p = 6.7 x 10(-4), whereas no zonal differences were demonstrated in metastatic lesions (2p = 0.21). A marked intraindividual variation was demonstrated between primary and corresponding secondary melanomas (2p...... melanomas showed large interindividual variation. This finding emphasizes that unbiased estimates of nuclear vv are robust to regional heterogeneity of nuclear volume and thus suitable for purposes of objective, quantitative malignancy grading of melanomas....

  15. Establishment of optimal thermal neutron capture therapy for 5 types of human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1993-03-01

    A series of boron neutron capture therapy (BNCT) studies has already germinated in 1972, with a view to establishing the BNCT particularly suited for the treatment of various types of malignant melanoma, and has been succeeded by research teams comprised of multi-disciplinary members. Twelve patients (7 men and 5 women, aged from 50 to 85 years) with malignant melanoma have been treated with BNCT; among them, six patients were completely cured, four had extremely reduced tumors, and two were still in the clinical process. The present Progress Report is a compilation of 39 research presentations for the recent two years. In this report, three patients are described. Of these, one patient had deep-seated lesions in right and left lymph nodes. These lesions were cured by the use of D 2 O that allowed neutron beams to reach them. Application of positron emission tomography to the diagnosis of melanoma is a highlight in this Report. (N.K.)

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

    Science.gov (United States)

    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) Pxxx)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.

  17. T-Cell Mediated Immune Responses Induced in ret Transgenic Mouse Model of Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Abschuetz, Oliver [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Osen, Wolfram [Division of Translational Immunology, German Cancer Center, Heidelberg 69120 (Germany); Frank, Kathrin [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany); Kato, Masashi [Unit of Environmental Health Sciences, Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, Aichi 487-8501 (Japan); Schadendorf, Dirk [Department of Dermatology, University Hospital Essen, Essen 45122 (Germany); Umansky, Viktor, E-mail: v.umansky@dkfz.de [Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg and Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, Mannheim , Heidelberg 69120 (Germany)

    2012-04-26

    Poor response of human malignant melanoma to currently available treatments requires a development of innovative therapeutic strategies. Their evaluation should be based on animal models that resemble human melanoma with respect to genetics, histopathology and clinical features. Here we used a transgenic mouse model of spontaneous skin melanoma, in which the ret transgene is expressed in melanocytes under the control of metallothionein-I promoter. After a short latency, around 25% mice develop macroscopic skin melanoma metastasizing to lymph nodes, bone marrow, lungs and brain, whereas other transgenic mice showed only metastatic lesions without visible skin tumors. We found that tumor lesions expressed melanoma associated antigens (MAA) tyrosinase, tyrosinase related protein (TRP)-1, TRP-2 and gp100, which could be applied as targets for the immunotherapy. Upon peptide vaccination, ret transgenic mice without macroscopic melanomas were able to generate T cell responses not only against a strong model antigen ovalbumin but also against typical MAA TRP-2. Although mice bearing macroscopic primary tumors could also display an antigen-specific T cell reactivity, it was significantly down-regulated as compared to tumor-free transgenic mice or non-transgenic littermates. We suggest that ret transgenic mice could be used as a pre-clinical model for the evaluation of novel strategies of melanoma immunotherapy.

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

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    Ke-Jia Wu

    Full Text Available 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.

  19. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1995-03-01

    This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

  20. DNA-index and stereological estimation of nuclear volume in primary and metastatic malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt; Kristensen, I B; Grymer, F

    1990-01-01

    The aim of this study was to investigate the relationship between physical nuclear volume and ploidy level in malignant melanomas, and to analyse the heterogeneity of these two parameters among primary and corresponding secondary tumours. Unbiased stereological estimates of nuclear volume can...

  1. Is the identification of in-transit sentinel lymph nodes in malignant melanoma patients really necessary?

    International Nuclear Information System (INIS)

    Vidal-Sicart, Sergi; Pons, Francesca; Fuertes, Silvia; Ortega, Marisa; Vilalta, Antonio; Puig, Susana; Palou, Josep M.; Castel, Teresa; Rull, Ramon

    2004-01-01

    The sentinel lymph node (SLN) is the first node in a nodal basin to receive the direct lymphatic flow from a malignant melanoma. However, in some patients, lymphoscintigraphic study reveals the presence of lymphatic nodes in the area between the primary melanoma and the regional basin. These nodes are called ''in-transit nodes'' or ''interval nodes'' and, by definition, are also SLNs. The purpose of this study was to determine the incidence and location of in-transit SLNs in patients with malignant melanoma and to assess whether it is really necessary to harvest them. The evaluation involved 600 consecutive malignant melanoma patients. Lymphoscintigraphy was performed on the day before surgery following intradermal injection of 74-111 MBq of 99m Tc-nanocolloid in four doses around the primary melanoma or the biopsy scar. Dynamic and static images were obtained and revealed SLNs in 599 out of 600 patients. The SLN was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. Lymphoscintigraphy showed in-transit SLNs in 59/599 patients (9.8%). During surgery, all these in-transit SLNs were harvested, with those in the popliteal and epitrochlear regions being the most difficult to identify and excise. Metastatic cell deposits were subsequently identified in ten (16.9%) of these in-transit SLNs. In conclusion, lymphoscintigraphy has a key role in the identification of in-transit SLNs. Although the incidence of these nodes is relatively low in malignant melanoma patients, such SLNs present metastatic deposits in a significant percentage of cases and therefore the identification of in-transit SLNs in these patients is really necessary. (orig.)

  2. Xenogeneic murine tyrosinase DNA vaccine for malignant melanoma of the digit of dogs.

    Science.gov (United States)

    Manley, C A; Leibman, N F; Wolchok, J D; Rivière, I C; Bartido, S; Craft, D M; Bergman, P J

    2011-01-01

    Malignant melanoma of dogs is a highly aggressive neoplasm and is the 2nd most common digit tumor. Metastatic disease is a common sequela for which few effective treatment options exist. Studies show that xenogeneic tyrosinase DNA vaccination yields immune responses and prolongation of survival in dogs with oral malignant melanoma. Describe clinical findings and tumor characteristics of a cohort of dogs with digit malignant melanoma, and evaluate the prognostic utility of a proposed staging system. Determine if a novel xenogeneic DNA vaccine is safe and potentially effective for treatment of dogs with digit melanoma. Fifty-eight dogs with digit malignant melanoma treated at the Animal Medical Center between 2004 and 2007. Retrospective, medical records review of dogs with digit melanoma treated with xenogeneic DNA vaccine. Overall median survival time (MST) for dogs treated with loco-regional control and xenogeneic DNA vaccine was 476 days with a 1-year survival rate of 63%. MST for dogs presenting with metastasis was 105 days versus 533 days for dogs presenting without metastasis (P dogs in the latter group were alive at 2 and 3 years. A proposed staging system proved prognostic with stages I-IV dogs surviving >952, >1,093, 321, and 76 days, respectively. The xenogeneic murine tyrosinase DNA vaccine was safe and appears effective when used in conjunction with local and regional disease control. The proposed staging system was prognostic in this study and future studies might benefit from utilizing this staging system. Copyright © 2010 by the American College of Veterinary Internal Medicine.

  3. Outcomes of dogs undergoing radiotherapy for treatment of oral malignant melanoma: 111 cases (2006-2012).

    Science.gov (United States)

    Kawabe, Mifumi; Mori, Takashi; Ito, Yusuke; Murakami, Mami; Sakai, Hiroki; Yanai, Tokuma; Maruo, Kohji

    2015-11-15

    To evaluate the characteristics and outcomes of dogs with stage I, II, III, or IV oral malignant melanoma treated by various types of radiotherapy. Retrospective case series. 111 dogs. Medical records of dogs with oral malignant melanoma treated by radiotherapy (with or without adjunctive treatments) at a veterinary medical center between July 2006 and December 2012 were reviewed. Information regarding signalment, tumor location, disease stage, treatment protocols, adverse effects, and survival time were obtained from medical records and by telephone follow-up. Associations between variables of interest and outcome were analyzed. Dogs received orthovoltage x-ray (n = 68), megavoltage x-ray (39), or electron beam (4) radiotherapy. Adjunctive treatments included debulking surgery (n = 18), chemotherapy (39), or both (27). Median survival times for dogs with stage I, II, III, and IV melanoma were 758 days (n = 19), 278 days (24), 163 days (37), and 80 days (31), respectively, and differed significantly between dogs with stage I disease and those with all other disease stages. Among dogs with stage III melanoma, risk of death was significantly higher in those that received orthovoltage x-ray treatment than in those that received megavoltage x-ray treatment. Severe (primary or secondary) adverse effects were identified in 9 dogs. Median survival time was significantly longer for dogs with stage I oral malignant melanoma than for dogs with more advanced disease at the time of staging. The staging system used may be a useful tool for prognosis prediction in dogs undergoing similar treatment protocols for oral malignant melanomas.

  4. Relationship Between LAPTM4B Gene Polymorphism and Susceptibility of Malignant Melanoma in Chinese Patients

    Directory of Open Access Journals (Sweden)

    Meng Zhang

    2014-10-01

    Full Text Available Lysosomal-associated protein transmembrane 4 beta (LAPTM4B is known as an oncogene associated with many human malignant tumors. There are two alleles of the gene, LAPTM4B*1 and LAPTM4B*2. Previous studies have shown that LAPTM4B polymorphism contributes to the risk of many cancers. This case-control study was to investigate the relationship between LAPTM4B gene polymorphism and susceptibility of malignant melanoma. The genotypes of LAPTM4B were determined in 617 control subjects and 220 patients with malignant melanoma by utilizing polymerase chain reaction based on specific primers. The genotypic distribution of LAPTM4B and Hardy–Weinberg equilibrium were analyzed by χ2 test. Odds ratio and 95% confidence interval was calculated by unconditional logistic regression. The distributions of LAPTM4B genotypes were significantly different between melanoma patients (45.9% for *1/1, 46.4% for *1/2 and 7.7 for *2/2 and controls (54.5% for *1/1, 39.9% for *1/2 and 5.7 for *2/2. LAPTM4B *1/2 and LAPTM4B *2/2 had a 1.396-fold and 1.619-fold higher risk for melanoma occurrence than *1/1, and subjects with LAPTM4B*2 have a 1.308-fold higher risk than LAPTM4B*1 carriers. No association between LAPTM4B genotypes and gender, age, subtype, Clark level of invasion, Breslow thickness, ulceration, clinical stage, and C-KIT, BRAF gene mutation status was observed. LAPTM4B*2 is associated with the high risk of malignant melanoma and carrying LAPTM4B *2 may be a susceptible factor to Chinese melanoma patients.

  5. Radiation-induced malignant melanoma following radiation treatment for squamous cell carcinoma of the oral cavity - a case report and review of literature -

    International Nuclear Information System (INIS)

    Shin, Young Ju; Yang, Koang Mo; Suh, Hyun Suk

    1998-01-01

    Malignant melanoma of the oral cavity is rare, accounting for 1 to 8% of all malignant melanomas. The overall prognosis remains poor despite the available treatments such as radical surgery, adjuvant radiotherapy, chemotherapy and immunotherapy due to failure in early detection and tendency in early metastasis. The etiology of mucosal malignant melanoma remains unkown. However, there are few cases of malignant melanoma of the oral cavity reported in the literature, which might be related to preexisting melanosis and radiation treatment. A case with malignant melanoma developed on the same site after 6 years following irradiation for squamous cell carcinoma of the oral cavity is reported in this article

  6. Electrochemotherapy in the treatment of metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Kunte, C; Letulé, V; Gehl, J

    2017-01-01

    BACKGROUND: (ECT) is an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. OBJECTIVES: To investigate the effectiveness of ECT in cutaneous metastases of melanoma and to ident...

  7. Spontaneous regression of metastases from malignant melanoma: a case report

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin

    2008-01-01

    A case of a 61-year-old male with widespread metastatic melanoma is presented 5 years after complete spontaneous cure. Spontaneous regression occurred in cutaneous, pulmonary, hepatic and cerebral metastases. A review of the literature reveals seven cases of regression of cerebral metastases; thi...

  8. ORIGINAL ARTICLE Malignant melanoma in a Nigerian tertiary ...

    African Journals Online (AJOL)

    Test

    incidence of melanoma is in Australia.3 The combined effects of predominantly light skinned population in a .... traditional healers and patent medicine dealers may contribute to this late presentation. Two of our ... endemic countries like Australia, and its high incidence in the rural African population where walking bare foot, ...

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

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    Sercan Göde

    2017-06-01

    Full Text Available Background: 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. Aims: 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. Study Design: Retrospective cross-sectional study. Methods: 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. Results: 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. Conclusion: 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

  10. Cryotherapy for conjunctival primary acquired melanosis and malignant melanoma. Experience with 62 cases.

    Science.gov (United States)

    Jakobiec, F A; Rini, F J; Fraunfelder, F T; Brownstein, S

    1988-08-01

    Sixty-two patients were treated by some combination of cryotherapy and surgery with an average follow-up of 3.3 years for one of the following diseases: focal or diffuse flat conjunctival primary acquired melanosis (PAM) with atypia but without a nodule of melanoma (10 cases); unifocal malignant melanoma with or without focal or diffuse PAM (30 cases); and multinodular/multicentric melanoma with and without PAM (22 cases). Of the ten patients who had PAM with atypia, invasive nodules of malignant melanoma did not develop. A second treatment was required to control the disease in four of the ten patients with extensive or diffuse lesions, and one has mild persistent disease. Of the 30 patients with unifocal nodules of malignant melanoma, 27 remained free of recurrence after one treatment, and 2 are asymptomatic after two treatments. One patient with a thick nodule at presentation required a parotidectomy and radical neck dissection for cervical metastases after recurrence in the conjunctival sac. In the group of 22 patients with multinodular malignant melanoma, only two did not have recurrent disease after one treatment. Of those who received multiple therapies, seven remained free of recurrence for at least 2 years after the last treatment; regional or distant metastases developed in nine; four required exenteration; and eight died. Conjunctival adjunctive cryotherapy avoids exenteration in extensive lesions of pure PAM and in unifocal melanoma, but even after multiple therapies, multinodular malignant melanoma had a 45% rate of metastasis. Metastasis was related to the presence of PAM sine pigmento in four patients (microscopically but not clinically detectable PAM); to the location of the nodules (9 of 10 patients who experienced metastases had forniceal, palpebral, and/or caruncular nodules); to the thickness or depth of invasion of the nodules (greater than 2 mm); and to the development of intralymphatic spread ("in-transit" local metastasis) within the

  11. Malignant melanoma arising from a perianal fistula and harbouring a BRAF gene mutation: a case report

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    Tajahuerce Marcos

    2011-08-01

    Full Text Available Abstract Background Melanoma of the anal region is a very uncommon disease, accounting for only 0.2-0.3% of all melanoma cases. Mutations of the BRAF gene are usually absent in melanomas occurring in this region as well as in other sun-protected regions. The development of a tumour in a longstanding perianal fistula is also extremely rare. More frequent is the case of a tumour presenting as a fistula, that is, the fistula being a consequence of the cancerous process, although we have found only two cases of fistula-generating melanomas reported in the literature. Case Presentation Here we report the case of a 38-year-old male who presented with a perianal fistula of four years of evolution. Histopathological examination of the fistulous tract confirmed the presence of malignant melanoma. Due to the small size and the central location of the melanoma inside the fistulous tract, we believe the melanoma reported here developed in the epithelium of the fistula once the latter was already formed. Resected sentinel lymph nodes were negative and the patient, after going through a wide local excision, remains disease-free nine years after diagnosis. DNA obtained from melanoma tissue was analysed by automated direct sequencing and the V600E (T1799A mutation was detected in exon 15 of the BRAF gene. Conclusion Since fistulae experience persistent inflammation, the fact that this melanoma harbours a BRAF mutation strengthens the view that oxidative stress caused by inflammatory processes plays an important role in the genesis of BRAF gene mutations.

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

    Directory of Open Access Journals (Sweden)

    Joanna Jaworek-Korjakowska

    2016-01-01

    Full Text Available 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.

  13. Dark sputum: An atypical presentation of primary pulmonary malignant melanoma

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    Alida Filippini

    2015-01-01

    Primary lung melanoma is an uncommon neoplasm that may be confused with more conventional types of lung cancer. Careful interpretation of histopathological information in correlation with all other clinical, laboratory and imaging studies may be needed to establish a diagnosis. Evaluation for metastases should include looking at the eyes, brain, skin. Due to the small number of cases reported in literature, there is no experience on the management and the prognosis of the disease.

  14. Boron neutron capture therapy for malignant melanoma: An experimental approach

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, B.S.; Larsson, B.; Roberto, A. (Uppsala Univ. (Sweden))

    1989-07-01

    Previous studies have shown that some thioamides, e.g., thiouracil, are incorporated as false precursors into melanin during its synthesis. If boronated analogs of the thioamides share this property, the melanin of melanotic melanomas offers a possibility for specific tumoural uptake and retention of boron as a basis for neutron capture therapy. We report on the synthesis of boronated 1H-1,2,4-triazole-3-thiol (B-TZT), boronated 5-carboxy-2-thiouracil (B-CTU), and boronated 5-diethylaminomethyl-2-thiouracil (B-DEAMTU) and the localization of these substances in melanotic melanomas transplanted to mice. The distribution in the mice was studied by boron neutron capture radiography. B-TZT and B-CTU showed the highest tumour:normal tissue concentration ratios, with tumour:liver ratios of about 4 and tumour:muscle ratios of about 14; B-DEAMTU showed corresponding ratios of 1.4 and 5, respectively. The absolute concentration of boron in the tumours, however, was more than three times higher in the mice injected with B-TZT, compared with B-CTU. The results suggest that B-TZT may be the most promising compound of the three tested with regard to possible therapy of melanotic melanomas.

  15. Aldehyde dehydrogenase (ALDH activity does not select for cells with enhanced aggressive properties in malignant melanoma.

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    Lina Prasmickaite

    Full Text Available BACKGROUND: Malignant melanoma is an exceptionally aggressive, drug-resistant and heterogeneous cancer. Recently it has been shown that melanoma cells with high clonogenic and tumourigenic abilities are common, but markers distinguishing such cells from cells lacking these abilities have not been identified. There is therefore no definite evidence that an exclusive cell subpopulation, i.e. cancer stem cells (CSC, exists in malignant melanoma. Rather, it is suggested that multiple cell populations are implicated in initiation and progression of the disease, making it of importance to identify subpopulations with elevated aggressive properties. METHODS AND FINDINGS: In several other cancer forms, Aldehyde Dehydrogenase (ALDH, which plays a role in stem cell biology and resistance, is a valuable functional marker for identification of cells that show enhanced aggressiveness and drug-resistance. Furthermore, the presence of ALDH(+ cells is linked to poor clinical prognosis in these cancers. By analyzing cell cultures, xenografts and patient biopsies, we showed that aggressive melanoma harboured a large, distinguishable ALDH(+ subpopulation. In vivo, ALDH(+ cells gave rise to ALDH(- cells, while the opposite conversion was rare, indicating a higher abilities of ALDH(+ cells to reestablish tumour heterogeneity with respect to the ALDH phenotype. However, both ALDH(+ and ALDH(- cells demonstrated similarly high abilities for clone formation in vitro and tumour initiation in vivo. Furthermore, both subpopulations showed similar sensitivity to the anti-melanoma drugs, dacarbazine and lexatumumab. CONCLUSIONS: These findings suggest that ALDH does not distinguish tumour-initiating and/or therapy-resistant cells, implying that the ALDH phenotype is not associated with more-aggressive subpopulations in malignant melanoma, and arguing against ALDH as a "universal" marker. Besides, it was shown that the ability to reestablish tumour heterogeneity is not

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

    Science.gov (United States)

    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 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.

  17. Two unusual cases of brain metastases from lung primary malignant melanoma

    International Nuclear Information System (INIS)

    Rodríguez, A.; Mañana, G.; Panuncio, A.; Rodríguez, R.; Roldán, G.; Sosa, A.

    2004-01-01

    Start with two cases of brain metastases from lung melanoma are presented who were diagnosed in the Neuropathology Laboratory of the Department of Anatomy Pathology, Institute of Neurology, Hospital de Clinicas, Montevideo, emphasizing the pathological diagnostic criteria and their evolution clinic. Both patients presented at the time of the initial consultation injuries amelánica respectively pigmented single brain. In both cases ruled by the morphology and the use of complementary techniques metastasis carcinoma. The main differential diagnosis of these lesions is whether is a primitive brain tumor, pigmented or not, or of a secondary tumor melanin: metastatic malignant melanoma. In both cases the patients had been studied one being in an unresectable lung injury, and in the other showed a single pulmonary nodule was resected in its entirety. the pulmonary lesions were for malignant melanoma, one with ample pigment and the other for the most part amelánico, with few areas retained pigment. He studied dermatologist, discarded the presence of a cutaneous malignant melanoma primitive. Other locations were also excluded

  18. Epidemiology of Malignant Melanoma over a Thirty-two Year Period (1981-2013 in Southern Iran

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    Farhad Handjani

    2016-10-01

    Full Text Available Background:Malignant melanoma, one of the most deadly skin cancers, is a skin tumor that arises from the epidermal melanocytes. The aim of this study is to evaluate the demographic and clinical data of malignant melanoma patients in a referral dermatology center in the south of Iran. Methods: In this retrospective study, we have reviewed files of 116 patients diagnosed with malignant melanoma at hospitals affiliated with Shiraz University of Medical Sciences, Shiraz, Iran from March 1981 to March 2013. Results: There was a total 116 malignant melanoma patients (79 male and 37 female with the mean age of 54.7 (SD=13.9 years old for men and 51.7 (SD=12.4 years old for women. The male to female ratio of malignant melanoma was approximately two, as was the male to female mortality ratio. The most common clinical form was acral lentiginous melanoma. We have identified the most common site to be the sole of the foot. Malignant melanoma mostly presented as a mass and it was most common in farmers. Conclusion: The national health system should improve the quality and quantity of cancer registry offices so that better and more complete data can be collected for further research and possible implementation of preventive measures with respect to this cancer.

  19. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600-800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800-400-400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  20. The relationship between mitotic rate and depth of invasion in biopsies of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Ghasemi Basir HR

    2018-03-01

    Full Text Available Hamid Reza Ghasemi Basir,1,2 Pedram Alirezaei,2 Sara Ahovan,3 Abbas Moradi3 1Department of Pathology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran; 2Psoriasis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran; 3School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran Background: Malignant melanoma of the skin is a potentially lethal neoplasm that generally originates from atypical melanocytes in the dermal–epidermal junction. When the neoplasm penetrates into the dermis, several variables can affect the extent of its spread, among which depth of invasion has the most important prognostic value. Mitotic rate is another prognostic factor that reflects the biological behavior of the neoplasm.Objective: This study was designed to evaluate the probable relationship between the depth of invasion of malignant melanoma and its mitotic rate.Materials and methods: This study was performed on 50 excisional biopsy specimens that had received the diagnosis of malignant melanoma histopathologically. Tumor characteristics including Breslow thickness, Clark level, T-stage, and tumor mitotic rate were recorded.Results: We observed that at higher Clark levels and higher T-stages, and the mean mitotic rate was significantly increased. Moreover, there was a positive and significant correlation between Breslow thickness and mitotic rate. We demonstrated that one unit increase in mitotic rate was correlated with 0.8 mm increase in Breslow thickness of the tumor.Conclusion: In malignant melanoma, mitotic activity may probably indicate the depth of tumor invasion. Therefore, in incisional biopsies where depth of invasion cannot be accurately determined, the mitotic activity may be used to estimate Breslow thickness, which is necessary for planning surgical management. Keywords: melanoma, mitosis, Breslow, invasion, thickness, proliferation

  1. Trends in the incidence of malignant melanoma in Denmark 1978-2007. Incidence on the island of Bornholm compared with the whole country incidence in Denmark

    DEFF Research Database (Denmark)

    Drejøe, Jennifer Berg; Drzewiecki, Krzysztof Tadeusz; Klit, Anders

    2011-01-01

    In Denmark, malignant melanoma is among the most rapidly increasing cancer types. Malignant melanoma accounts for the majority of skin cancer-related deaths. Sunshine is the main cause of the increase seen in melanoma incidence. Within Denmark, Bornholm is the area that receives most sunshine....... It is therefore relevant to compare incidence data between Denmark and Bornholm....

  2. Synthesis and evaluation of novel radioiodinated nicotinamides for malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Liu Xiang; Pham, Tien Q.; Berghofer, Paula; Chapman, Janette; Greguric, Ivan; Mitchell, Peter; Mattner, Filomena; Loc' h, Christian [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia); Katsifis, Andrew [Radiopharmaceuticals Research Institute, Australian Nuclear Science and Technology Organisation, Sydney, NSW 2234 (Australia)], E-mail: akx@ansto.gov.au

    2008-10-15

    Introduction: A series of iodonicotinamides based on the melanin-binding iodobenzamide compound N-2-diethylaminoethyl-4-iodobenzamide was prepared and evaluated for the potential imaging and staging of disseminated metastatic melanoma. Methods: [{sup 123}I]Iodonicotinamides were prepared by iododestannylation reactions using no-carrier-added iodine-123 and evaluated in vivo by biodistribution and competition studies and by single photon emission computed tomography (SPECT) imaging in black and albino nude mice bearing B16F0 murine melanotic and A375 human amelanotic melanoma tumours, respectively. Results: The iodonicotinamides displayed low-affinity binding for {sigma}{sub 1}-{sigma}{sub 2} receptors (K{sub i}>300 nM). In biodistribution studies in mice, N-(2-(diethylamino)ethyl)-5-[{sup 123}I]iodonicotinamide ([{sup 123}I]1) exhibited the fastest and highest uptake of the nicotinamide series in the B16F0 tumour at 1 h ({approx}8% ID/g), decreasing slowly over time. No uptake was observed in the A375 tumour. Clearance from the animals by urinary excretion was more rapid for N-alkyl-nicotinamides than for piperazinyl derivatives. At 1 h postinjection, the urinary excretion was 66% ID for [{sup 123}I]1, while the gastrointestinal tract amounted to 17% ID. Haloperidol was unable to reduce the uptake of [{sup 123}I]1 in pigmented mice, indicating that this uptake was likely due to an interaction with melanin. SPECT imaging of [{sup 123}I]1 in black mice bearing the B16F0 melanoma indicated that the radioactivity was predominately located in the tumour and eyes. No specific localisation was observed in nude mice bearing A375 amelanotic tumours. Conclusion: These findings suggest that [{sup 123}I]1, which displays high tumour uptake with rapid clearance from the body, could be a promising imaging agent for the detection of melanotic tumours.

  3. Imaging malignant melanoma with {sup 18}F-5-FPN

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Hongyan; Xia, Xiaotian; Li, Chongjiao; Song, Yiling; Qin, Chunxia; Liu, Qingyao; Zhang, Yongxue; Lan, Xiaoli [Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (China); Hubei Key Laboratory of Molecular Imaging (China)

    2016-01-15

    Radiolabelled benzamides are attractive candidates for targeting melanoma because they bind to melanin and exhibit high tumour uptake and retention. {sup 18}F-5-Fluoro-N-(2-[diethylamino]ethyl)picolinamide ({sup 18}F-5-FPN), a benzamide analogue, was prepared and its pharmacokinetics and binding affinity evaluated both in vitro and in vivo to assess its clinical potential in the diagnosis and staging of melanoma. {sup 18}F-5-FPN was prepared and purified. Its binding specificity was measured in vitro in two different melanoma cell lines, one pigmented (B16F10 cells) and one nonpigmented (A375m cells), and in vivo in mice xenografted with the same cell lines. Dynamic and static PET images using {sup 18}F-5-FPN were obtained in the tumour-bearing mice, and the static images were also compared with those acquired with {sup 18}F-FDG. PET imaging with {sup 18}F-5-FPN was also performed in B16F10 tumour-bearing mice with lung metastases. {sup 18}F-5-FPN was successfully prepared with radiochemical yields of 5 - 10 %. Binding of {sup 18}F-5-FPN to B16F10 cells was much higher than to A375m cells. On dynamic PET imaging B16F10 tumours were visible about 1 min after injection of the tracer, and the uptake gradually increased over time. {sup 18}F-5-FPN was rapidly excreted via the kidneys. B16F10 tumours were clearly visible on static images acquired 1 and 2 h after injection, with high uptake values of 24.34 ± 6.32 %ID/g and 16.63 ± 5.41 %ID/g, respectively, in the biodistribution study (five mice). However, there was no visible uptake by A375m tumours. {sup 18}F-5-FPN and {sup 18}F-FDG PET imaging were compared in B16F10 tumour xenografts, and the tumour-to-background ratio of {sup 18}F-5-FPN was ten times higher than that of {sup 18}F-FDG (35.22 ± 7.02 vs. 3.29 ± 0.53, five mice). {sup 18}F-5-FPN PET imaging also detected simulated lung metastases measuring 1 - 2 mm. {sup 18}F-5-FPN specifically targeted melanin in vitro and in vivo with high retention and affinity

  4. Activation of the Canonical Wnt/β-Catenin Signalling Pathway is Rare in Canine Malignant Melanoma Tissue and Cell Lines

    Science.gov (United States)

    Chon, E.; Thompson, V.; Schmid, S.; Stein, T. J.

    2012-01-01

    Summary Canine malignant melanoma is a highly aggressive tumour associated with a poor overall survival rate due to both local disease recurrence and its highly metastatic nature. Similar to advanced melanoma in man, canine oral melanoma is poorly responsive to conventional anti-cancer therapies. The lack of sustainable disease control warrants investigation of novel therapies, preferably targeting features specific to the tumour and different from normal cells. The Wnt signalling pathway is known to contribute to melanocytic lineage development in vertebrates and perturbation of the Wnt/β-catenin pathway has been implicated in numerous cancer types. Alterations of the Wnt/β-catenin pathway are suggested to occur in a subset of human melanomas, although the precise role of the Wnt/β-catenin pathway in melanoma is yet to be defined. This study investigates the activation status of the canonical Wnt/β-catenin pathway in canine malignant melanoma and its potential as a therapeutic target for treating this disease. The data indicate canonical Wnt/β-catenin pathway activation is a rare event in canine oral malignant melanoma tissue and canine malignant melanoma cell lines. PMID:22901430

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

    Science.gov (United States)

    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.

  6. Cutaneous malignant melanoma show geographic and socioeconomic disparities in stage at diagnosis and excess mortality

    DEFF Research Database (Denmark)

    Strömberg, Ulf; Peterson, Stefan; Holmberg, Erik

    2016-01-01

    Background Preventive measures are needed to counteract the increasing burden of cutaneous malignant melanoma (CMM). As a basis for rational melanoma prevention, we investigated geographic differences and impact from socioeconomic factors related to incidence, clinical stage at diagnosis...... and the national Melanoma Quality Register. Geographic and socioeconomic differences in incidence per stage at diagnosis were mapped and correlated to excess mortality. Results Disease mapping based on 9743 cases in 99 municipalities and 20 metropolitan districts showed marked, regional disparities in stage.......37-2.40). Conclusion Residential region and educational level influenced CMM stage and, thereby, excess mortality. These observations suggest that geographic as well as socioeconomic data should be considered in prevention of CMM....

  7. Preliminary studies of monoclonal antibody lymphoscintigraphy in malignant melanoma

    International Nuclear Information System (INIS)

    Nelp, W.B.; Eary, J.F.; Jones, R.F.; Hellstrom, K.E.; Hellstrom, I.; Beaumier, P.L.; Krohn, K.A.

    1987-01-01

    Lymphoscintigraphy was performed at 3 and 20 hr following subcutaneous injection of 131 I anti-melanoma antibody (Fab) in 11 patients who had surgical resection of lymph nodes (neck, axilla, groin) at 24 hr for suspected metastatic melanoma. Comparable amounts of 125 I nonspecific control antibody (Fab) were co-administered. Six patients had nodal metastases and three showed positive images at both time periods. Five patients had no metastases though one was image positive. Four other nondiseased inguinal node groups were image negative. A total of 28 tumored nodes and 110 normal nodes were removed, counted and histologically examined. All metastatic tumors expressed antigen against which the specific Fab was directed. The concentrations of both specific and nonspecific Fab were similar in tumored nodes and both were significantly greater than in normal nodes showed essentially identical intranodal spatial distribution of the specific and control Fab in areas containing tumor. These preliminary results suggest the increased concentration of murine immunoglobulin (Fab) retained in diseased nodes was a nonspecific phenomenon

  8. Characteristic findings of computed tomography in cerebral metastatic malignant melanomas

    International Nuclear Information System (INIS)

    Kukita, Chikashige; Nose, Tadao; Nakagawa, Kunio; Tomono, Yuji; Enomoto, Takao; Hashikawa, Masanori; Egashira, Taihei; Maki, Yutaka

    1986-01-01

    Four cases with metastatic cerebral melanoma were studied by means of computed tomography (CT). Two cases were male, and the other two were female, with an average age of 55 years. Their primary lesions were on the chest wall in two cases, around the calcaneus in one, and around the genitalia in one. All cases died within 6 months after the metastatic brain lesions were found. Necropsies were carried out in two cases. CT revealed high-density areas in all cases, and contrast studies showed an enhancement of the lesions, as has previously been reported. On the other hand, autopsied cases revealed neither fresh nor old intratumoral bleedings such as a scattered focus of hemosiderin. These findings suggest that the high-density tumoral shadows in CT are probably not intratumoral bleedings due to a bleeding tendency of the tumors, as some authors have previously supposed. We mentioned some other factors contributing to the high density of the melanoma on computed tomograms. (author)

  9. Majority of the most-cited articles on cutaneous malignant melanoma are published in non-dermatology/melanoma specialized journals.

    Science.gov (United States)

    Tas, Faruk

    2016-01-01

    The most-cited articles. (MCAs) are likely those that impressed other researchers and had profound influence on clinical practice or future developments in the related scientific field. This study was conducted to explore a bibliometric approach to assess in where the cutaneous malignant melanoma. (CMM) related MCAs have been published. We identified journals for publications with the word "melanoma" in the title by using the ISI Web of Knowledge Database between 2000 and 2010. The term MCAs arbitrarily defined as equal or more than 100 citations. A total of 425 MCAs were published in 93 journals, led by the Cancer Research. (n = 58) and Journal of Clinical Oncology. (n = 53). Journal categories with the MCAs were the Oncology with 232 articles, followed by the Medicine with 138. articles. The median number of citations was 147. The total numbers of citations were most prominent for the journal Nature and the New England Journal of Medicine. (NEJM) (median 385 and 354, respectively). Total number of citations was the highest for the Science.categorized journals. (median 211). Articles categorized as Dermatology and Melanoma was the least (median 132.5). The median number of citations per year was 14.91. The most valuable cited articles of per year were also published in the journal Nature. (median 59.67) and the NEJM. (median 48.67). The number of citation was the highest for the Science-categorized journals. (median 25.92). Majority of the MCAs on CMM were published in non-dermatology/melanoma specialized journals.

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

    Science.gov (United States)

    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

  11. Immunosuppressive cytokines in the regional lymph node of a dog suffering from oral malignant melanoma.

    Science.gov (United States)

    Catchpole, B; Gould, S M; Kellett-Gregory, L M; Dobson, J M

    2002-10-01

    A 10-year-old male cross-breed dog was referred for investigation of oral malignant melanoma. Fine-needle aspirates were taken from the draining submandibular lymph node. The presence of metastatic melanoma cells was confirmed by cytological examination and reverse transcription polymerase chain reaction (RT-PCR) using primers for the melanoma-associated antigens: tyrosinase and mart-1/melan A. Cytokine expression in the lymph node was evaluated by multiplex RT-PCR, which demonstrated the presence of mRNA for IL-10 and TGF-beta1. However, IL-2, IL-4 and IFNgamma mRNA could not be detected, suggesting a lack of immune activation. Thoracic radiographs showed a lesion within the caudal lung fields suggestive of pulmonary metastasis. The dog developed signs of dyspnoea and collapse and was euthanased four days later. This case illustrates that molecular techniques can be used to aid clinical staging of canine oral malignant melanoma, and suggests that immunosuppressive cytokines could be involved in the pathogenesis of disease.

  12. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2012-02-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

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

    Science.gov (United States)

    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.

  14. Neuropsychiatric complications associated with interferon - alpha -2b treatment of malignant melanoma.

    LENUS (Irish Health Repository)

    Enudi, W

    2009-08-01

    Several adverse effects have been associated with interferon alpha 2b treatment and neuropsychiatric effects have also been commonly reported. Psychosis and mood disorders have been described in the literature. This case report is of a 30 year old man with malignant melanoma stage 3a who was receiving adjuvant alpha 2b interferon and developed a manic episode two weeks post switching after one month of treatment on a high dose to a low dose. There was no previous psychiatric illness and no known family history of mental illness. This is in keeping with previous reports that mania has been observed in patients undergoing interferon treatment especially after significant dose-reduction or treatment breaks. Mania induced by interferon responds well to antimanic drugs .Since interferon alpha 2b is now commonly used in the treatment of malignant melanoma and other conditions, the need to be aware of its neuropsychiatric complications is essential.

  15. Asymptomatic brain metastases in patients with cutaneous metastatic malignant melanoma

    DEFF Research Database (Denmark)

    Zukauskaite, Ruta; Schmidt, Henrik; Asmussen, Jon T

    2013-01-01

    -enhanced CT scan of the brain before the start of interleukin-2 (IL-2)-based immunotherapy. Among the 697 patients, 80 had asymptomatic brain metastases (12%). Patients' characteristics did not differ significantly between groups with and without brain metastases. Patients received systemic treatment (IL-2......The aim of the study was to identify the frequency of asymptomatic brain metastases detected by computed tomography (CT) scans in patients with metastatic cutaneous melanoma referred to first-line systemic treatment. Between 1995 and 2009, 697 Danish patients were screened with a contrast......-based or cytotoxic chemotherapy), local treatment (stereotactic radiotherapy, whole-brain radiotherapy or surgery), or best supportive care only. The survival was significantly shorter for patients with asymptomatic brain metastases compared with patients without brain metastases (P...

  16. Some Molecular and Clinical Aspects of Genetic Predisposition to Malignant Melanoma and Tumours of Various Site of Origin

    Directory of Open Access Journals (Sweden)

    Dębniak Tadeusz

    2007-06-01

    Full Text Available Abstract Based on epidemiological data we can assume that at least some malignant melanoma (MM and breast cancer cases can be caused by the same genetic factors. CDKN2A, which encodes the p16 protein, a cyclin-dependent kinase inhibitor suppressing cell proliferation, is regarded as a major melanoma susceptibility gene and the literature has also implicated this gene in predisposition to breast cancer. Genes also known to predispose to MM include XPD and MC1R. We studied CDKN2A/ARF, XPD and MC1R for their associations with melanoma and breast cancer risk in Polish patients and controls. We found that CDKN2A and ARF do not contribute significantly to either familial melanoma or malignant melanoma within the context of a cancer familial aggregation of disease with breast cancer. However, the common variant of the CDKN2A gene A148T, previously regarded as non-pathogenic, may predispose to malignant melanoma, early-onset breast cancer and lung cancer. Compound carriers of common XPD variants may be at slightly increased risk of breast cancer or late–onset malignant melanoma. Common recurrent variants of the MC1R gene (V60L, R151C, R163Q and R160W may predispose to malignant melanoma. In general, the establishment of surveillance protocols proposed as an option for carriers of common alterations in CDKN2A, XPD or MC1R variants requires additional studies. It is possible that missense variants of genes for which truncating mutations are clearly pathogenic may also be deleterious, but with reduced penetrance. This may be overlooked unless large numbers of patients and controls are studied. A registry that includes 2000 consecutive breast cancer cases, 3500 early onset breast cancer patients, 500 unselected malignant melanoma and over 700 colorectal cancer patients has been established in the International Hereditary Cancer Centre and can contribute to these types of large association studies.

  17. Sentinel node biopsy (SNB) in malignant melanoma as same day procedure vs delayed procedure

    DEFF Research Database (Denmark)

    Rødgaard, Jes Christian; Kramer, Stine; Stolle, Lars B

    2013-01-01

    The aim of this study was to compare a delayed sentinel node biopsy (dSNB) procedure with a same-day procedure (sSNB) in malignant melanoma. In March 2012, Aarhus University Hospital went from the dSNB to the sSNB procedure defined by lymphoscintigraphy (LS) and sentinel node biopsy (SNB) perform......, essential to keep the morbidity and economic costs low, while keeping the quality of the procedure high....

  18. The role of lysosomal proteolytic enzymes in invasion and dissemination of malignant melanoma

    International Nuclear Information System (INIS)

    Bassalyk, L.S.; Tsanev, P.E.; Parshikova, S.M.; Demidov, L.V.

    1992-01-01

    Preoperative chemo- and radiation therapy was followed by a decrease in lysosomal cathepsins activity in metastatic lymph nodes which, however, did not reach the level established for intact lymph nodes. The pathogenetic role of proteolytic endopeptidases in invasion and sissemination of malignant melanoma is discussed as well as the value of their level measurement for assessing metastatic potential of tumor and prognosis of disease of disease on the basis of tumor site, degree of invasion regional lymph node status

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

    Science.gov (United States)

    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.

  20. Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision.

    Science.gov (United States)

    Dank, G; Rassnick, K M; Sokolovsky, Y; Garrett, L D; Post, G S; Kitchell, B E; Sellon, R K; Kleiter, M; Northrup, N; Segev, G

    2014-03-01

    Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively. The overall median progression-free survival for all dogs was 259 days [95% confidence interval (CI95), 119-399 days]. The first progression-free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI95, 247-633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia. © 2012 John Wiley & Sons Ltd.

  1. Termoterapia transpupilar em melanoma maligno da coróide Transpupillary thermotherapy for malignant choroidal melanoma

    Directory of Open Access Journals (Sweden)

    Martha M. Motomo Chojniak

    2001-04-01

    Full Text Available Objetivo: Vários métodos vem sendo utilizados para o tratamento dos melanomas da coróide. A proposta deste trabalho preliminar é avaliar a eficácia da termoterapia transpupilar (TTT como tratamento primário de melanomas da coróide pequenos. Métodos: Foi realizado um trabalho prospectivo e não-randomizado para avaliar os aspectos clínicos, resposta do tumor, complicações e resultados visuais de pacientes portadores de melanomas da coróide pequenos (até 4,0 mm de espessura e 12 mm de diâmetro basal tratados por termoterapia transpupilar utilizando-se sucessivas aplicações de laser diodo contínuo de 810 nm. Resultados: Foram tratados 11 pacientes portadores de melanomas da coróide pequenos. O tumor era único e pigmentado em 100% dos casos. Crescimento documentado esteve presente em 5 pacientes (45,45% previamente ao tratamento e fatores de risco para crescimento ou metástase estavam presentes em todos os pacientes. O tempo de seguimento destes pacientes a partir do tratamento foi em média de 5,72 meses (3 - 8 meses. Foram utilizadas 3 sessões de laser em 5 pacientes (45,45% e 4 sessões em 6 pacientes (64,64%. As lesões apresentavam, por ocasião do diagnóstico, uma espessura média de 2,65 mm (1,85-3,86 mm, com maior diâmetro basal médio de 7,98 mm (4,2-11,33 mm. Após o tratamento, a espessura média foi de 1,83 mm (0,98-2,93 mm e o maior diâmetro basal médio foi de 6,59 mm (3,81 mm -10,67 mm. Das lesões tratadas, 100% apresentaram diminuição da altura e do máximo diâmetro basal, tendo sido a diminuição média da espessura de 0,89 mm e do máximo diâmetro basal de 1,39 mm. A acuidade visual manteve-se inalterada em 5 casos (45,45% e piorou após o tratamento em 6 casos (54,54%. Ocorreram complicações em 9 casos, tendo sido considerada complicação grave 1 caso de descolamento parcial da retina (9,09%; as outras complicações foram consideradas leves: pequenas hemorragias intra-retinianas em 7 pacientes (63

  2. Primary amelanotic malignant melanoma of the male urethra with inguinal lymph node metastasis successfully controlled by nivolumab: A case report

    Directory of Open Access Journals (Sweden)

    Takashi Tokita

    2018-05-01

    Full Text Available We report a rare case of primary amelanotic malignant melanoma of the male urethra. A 65-year-old man with a urethral mass was referred to our hospital. A pathological diagnosis of a biopsy specimen revealed malignant melanoma. Thereafter, the patient underwent partial penectomy. The histopathological diagnosis was amelanotic malignant melanoma of the urethra. The patient had received DAV-Feron in an adjuvant setting; however, PET-CT revealed multiple metastasis. After receiving more than 10 cycles of nivolumab, the accumulation of FDG was no longer observed on PET-CT. The patient is currently free from recurrence at 20 months after nivolumab treatment. Keywords: Melanoma, Urethral neoplasm, Inguinal lymphadenectomy, Nivolumab

  3. Anorectal Disorders

    Science.gov (United States)

    Rao, Satish S. C.; Bharucha, Adil E.; Chiarioni, Giuseppe; Felt-Bersma, Richelle; Knowles, Charles; Malcolm, Allison; Wald, Arnold

    2016-01-01

    This report defines criteria and reviews the epidemiology, pathophysiology, and management of the following common anorectal disorders: fecal incontinence (FI), functional anorectal pain, and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals, and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into 3 subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome and unspecified anorectal pain, the pain lasts more than 30 minutes, but in levator ani syndrome there is puborectalis tenderness. Functional defecation disorders are defined by ≥2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with ≥2 features of impaired evacuation, that is, abnormal evacuation pattern on manometry, abnormal balloon expulsion test, or impaired rectal evacuation by imaging. It includes 2 subtypes: dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating levator ani syndrome and defecatory disorders. PMID:27144630

  4. Melanoma maligno anaplásico em um eqüino Anaplastic malignant melanoma in a horse

    Directory of Open Access Journals (Sweden)

    Daniel Ricardo Rissi

    2008-10-01

    Full Text Available Descreve-se um caso de melanoma maligno anaplásico em uma égua Crioula, tordilha, com 10 anos de idade, com histórico clínico de apatia, perda de peso progressiva, febre, anorexia e dispnéia. Múltiplas massas pigmentadas e não-pigmentadas, bem delimitadas ou infiltrativas, foram observadas no tecido subcutâneo e em vários órgãos. Histologicamente o neoplasma era composto de populações de células fusiformes, redondas ou poliédricas e, menos freqüentemente, de células multinucleadas e "células em anel de sinete". O diagnóstico foi realizado com base nos achados clinicopatológicos e confirmado pela microscopia eletrônica de transmissão.A case of anaplastic malignant melanoma in a 10-year-old gray mare is described. Clinical signs included depression, progressive weight loss, fever, anorexia, and dyspnea. Multiple circumscribed or infiltrative, pigmented, and non-pigmented tumors were observed in subcutaneous tissue and in several organs. Histological examination revealed a marked variation in neoplastic cell population, which was composed by spindle, round, polyhedrical, and less frequently, multinucleated or signet ring cells. The diagnostic was based up on clinical and pathological findings, and confirmed by transmission electronic microscopy.

  5. Lymph-scintigraphic identification of sentinel lymph nodes in breast carcinoma and malignant melanoma patients

    International Nuclear Information System (INIS)

    Sergieva, S; Bajchev, G.; Aleksandrova, E.

    1999-01-01

    It is the purpose of the study to assay the possibilities of lymphoscintigraphy (LS) in evaluating local lymphatic drainage and sentinel lymph nodes (SLNs) location in patients presenting breast carcinoma and malignant melanoma. Twenty-nine women with breast carcinoma (TI-IIa clinical stage, age range 31 to 74 y) and 7 patients with malignant melanoma (Clark III-V) are scanned in the period 1997 through 1998. 99m Tc-sulphur colloid (Solco Lymphoscint, SORIN) with mean size of particles 50 nm is used. Planar images are obtained at 20 and 120-180 min after sc injection in the region of primary tumor, at mean radioactivity 20 MBq per injection site in a volume 0.2-0.3 ml. In the breast cancer patients Patent Blue V or Mitoxantrone is injected around the tumor twice - 20 and 3 to 1/2 hours prior to surgery. In malignant melanoma patients immunoscintigraphy using 740 MBq 99m Tc-anti-melanoma monoclonal antibodies (Technemab-K-1) is carried out before lymph node dissection. SLNs are visualized in 25 patients (86.2%) with breast cancer. In 21 (72%) patients to 4 SLNs are scanned in level I of the local axillary region, in 4 cases (14%) - in the region of axillary level II, in one female patient (3%) - at axillary level III, and in 3 patients (10%) i psilateral internal mammary lymph nodes are scanned. Two patients are suspected for the so-called s kip t ype of tumor lymphatic dissemination. In 4 patients no SLN images are visible. In breast carcinoma patients SLN are additionally stained blue and following intraoperative revision, evidence of metastatic involvement is established in 12 instances (41.3%). In 3 patients with melanoma in the abdomen and back SLNs are located in the region of inguinal and axillary lymph node groups, while in 3 patients presenting lesions to the surface of extremities only local lymph nodes draining the melanoma are visualized. Immunoscintigraphy shows enhanced uptake in the region of SLNs in 3 cases with the metastatic changes in them

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

    Science.gov (United States)

    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

  7. Radioimmunoimaging in malignant melanoma with 111In-labeled monoclonal antibody 96.5

    International Nuclear Information System (INIS)

    Murray, J.L.; Rosenblum, M.G.; Sobol, R.E.

    1985-01-01

    A radiolabeled monoclonal antibody (96.5) reactive with an Mr 97,000 antigen found on over 80% of melanoma cell lines and tissue extracts was examined for its ability to detect malignant melanoma metastases in vivo. For imaging purposes, it was conjugated with diethyltriaminepentaacetic acid and subsequently labeled with 111 In by chelation. Thirty-one patients with metastatic melanoma received single injections of monoclonal antibody 96.5 at concentrations ranging from 0.5 to 20 mg and at specific activities of 111 In ranging from 0.125 to 4 mCi/mg. Total-body scans were performed at various time intervals following administration. No serious side effects were observed. Of a total of 100 previously documented metastatic sites, 50 imaged for a specificity of 50%. The number of sites imaged increased significantly as the amount of antibody administered increased relative to the average radiation dose. Considerable background uptake of isotope was observed in blood pool and other organs with gradual acquisition of label in tumor sites by 48 to 72 h. Hence, tumor imaging of melanoma using 111 In-labeled monoclonal antibody 96.5 appeared feasible, especially at antibody doses above 2 mg

  8. Workplace investigation of increased diagnosis of malignant melanoma among employees of Lawrence Livermore National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Moore, D.H. II; Patterson, H.W.; Hatch, F.; Discher, D.; Schneider, J.S.; Bennett, D.

    1994-08-01

    Based on rates for the surrounding communities, the diagnosis rate of malignant melanoma for employees of Lawrence Livermore National Laboratory (LLNL) during 1972 to 1977 was three to four times higher than expected. In 1984 Austin and Reynolds concluded, as a result of a case-control study, that five occupational factors were {open_quotes}causally associated{close_quotes} with melanoma risk at LLNL. These factors were: (1) exposure to radioactive materials, (2) work at Site 300, (3) exposure to volatile photographic chemicals, (4) presence at the Pacific Test Site, and (5) chemist duties. Subsequent reviews of the Austin and Reynolds report concluded that the methods used were appropriate and correctly carried out. These reports did determine, however, that Austin and Reynolds` conclusion concerning a causal relationship between occupational factors and melanoma among employees was overstated. There is essentially no supporting evidence linking the occupational factors with melanoma from animal studies or human epidemiology. Our report summarizes the results of further investigation of potential occupational factors.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. A Case of Malignant Melanoma of the Uterine Cervix with Disseminated Metastases throughout the Vaginal Wall

    Directory of Open Access Journals (Sweden)

    Tomoko Noguchi

    2017-01-01

    Full Text Available Malignant melanoma (MM in the female genital tract accounts for less than 2% of all melanomas, and the vast majority associated occur in the vulva and vagina. Primary MM of the uterine cervix is extremely rare and its prognosis is very poor. We report a case of primary MM of the cervix with dissemination throughout the vaginal wall. A 66-year-old woman presented with postmenopausal bleeding. Gynecologic examination demonstrated a 2 cm polypoid blackish-pigmented tumor on the cervix with multiple small blackish-pigmented lesions throughout the vaginal wall. Cervical Pap smear cytology showed malignant melanoma. MRI and PET/CT did not detect any distant or lymph node metastases. She underwent radical hysterectomy, pelvic lymphadenectomy, and total vaginectomy. The pathological diagnosis was FIGO stage IIIA primary cervical MM. She received adjuvant chemotherapy with 6 courses of dacarbazine, but 6 months later, multiple lung metastases were detected. Despite 4 courses of anti-PD-1 antibody (nivolumab treatment, she died of the disease 13 months after surgery.

  13. Amelanotic Esophageal Malignant Melanoma: Case Report and Short Review of the Literature

    Directory of Open Access Journals (Sweden)

    Michael Kranzfelder

    2008-07-01

    Full Text Available Malignant melanoma in the esophagus is a rare condition which has been described only occasionally in case reports or in larger series of patients with esophageal disease. We describe here the very rare case of a patient who presented initially with a 2-month history of dysphagia and weight loss which led to the endoscopic diagnosis of an unclear lesion in the distal esophagus. Biopsies were taken revealing positive immunohistochemical staining against HMB-45. As there were no signs of skin melanoma and there was an absence of pigmentation, a diagnosis of primary amelanotic malignant melanoma was made. Primary staging of the lesion was completed with computed tomography (CT, which revealed a locally advanced tumor with lymph node metastases at the lesser curvature of the stomach and celiac trunk. As there is still a lack of potential protocols for multimodal neoadjuvant treatment for this rare tumor entity, a palliative abdominothoracic esophagectomy with systemic lymphadenectomy and intrathoracic anastomosis was carried out. Due to an intraoperative R2 situation, clip marking was performed to allow postoperative radiotherapy. Two months postoperatively, the planning CT scan for radiotherapy revealed progression of the retroperitoneal tumor mass, which was enclosing the celiac trunk, renal vein, and superior mesenteric artery. Multiple new liver and lung metastases were also found. During the following weeks, the patient developed acute renal failure and was admitted for dialysis, and the planned radiotherapy was deferred. At the end of May 2007, 4 months after the primary diagnosis, the patient died due to acute renal failure.

  14. A case of malignant melanoma of the maxilla treated by adoptive immunotherapy after fast neutron therapy

    International Nuclear Information System (INIS)

    Morifuji, Masayo; Ohishi, Masamichi; Higuchi, Yoshinori; Ozeki, Satoru; Tashiro, Hideo

    1992-01-01

    A 77-year-old male patient with malignant melanoma was treated by fast neutron therapy and immunotherapy. Total dose of fast neutron applied to the primary lesion was 1905 cGy per 21 fractionation for 46 days. For adoptive immunotherapy, lymphocytes were collected from the peripheral blood drawn from the patient 2 days after the injection of cyclophosphamide. T cells were further purified by passing the lymphocytes through nylon wool. Cytotoxic T cells were induced by incubating the T cells mixed with allogeneic malignant melanoma cells and a small number of patient's adherent cells, and activated with recombinant interleukin-2 (γ IL-2). Our patient and the patient from whom stimulating melanoma cells were derived shared A locous 24 and B locous 51 of MHC class I antigens in common. Thus prepared cytotoxic T cells were inoculated to the patient via the maxillary artery, 3 to 4 times a week for one month. Total amount of cells transferred was 5.6 x 10 8 (97% lymphocytes). Primary lesion reduced markedly by the therapies. During adoptive immunotherapy, increase in natural killer cells and decrease in both suppressor/inducer T-cells and macrophages were observed. However, lung metastases appeared 3 months after adoptive immunotherapy. While the nonspecific immunotherapy (OK-432 injection) was being conducted thereafter, growth of the metastatic lesions of the lung was kept gentle but became obvious after the suspension of the treatment. (author)

  15. [Psychological aspects of immunotherapies in the treatment of malignant melanoma].

    Science.gov (United States)

    Kovács, Péter; Pánczél, Gitta; Melegh, Krisztina; Balatoni, Tímea; Pörneczy, Edit; Lõrincz, Lenke; Czirbesz, Kata; Gorka, Eszter; Liszkay, Gabriella

    2016-03-02

    Psychological problems may arise in connection with oncomedical treatments in three ways: 1. acute and/or 2. chronic ways, as well as 3. co-morbid psychiatric diseases that already exist must also be taken into account. Immunotherapies have the most common and also clinically relevant psychological side effects. Fatigue, anhedonia, social isolation, psychomotor slowness is reported during treatment. Anti-CTLA-4 antibody (ipilimumab) immunotherapy can present one of the most modern opportunities for adequate treatment for patients having distant metastasis or unresectable tumour. In relation to immunotherapies, acute psychological side effects (acute stress) emerging during treatments develop in a way that can mostly be linked to environmental factors, e.g. notification of diagnosis, hospitalisation, progression, deterioration in quality of life, imminent dates of control. Crisis is a temporary and threatening condition that endangers psychological balance. In such conditions, enhanced psychological vulnerability must be taken into account and doctors play a key role in the rapid recognition of the condition. Chronic psychological problems, which may arise from the depressogenic effect of the applied treatment or originated from a pre-melanoma psychiatric condition, may exceed the diagnostic and psychotherapeutic competences of a clinical psychologist. Even in case of a well-defined depressogenic biological mechanism such as the activation of the pro-inflammatory cytokine pathway, positive environmental effects can reduce symptoms and thus increase compliance. Side effects can be treated successfully using psychotherapeutic methods and/or psychiatric medicines. The application of routinely used complex psychosocial screening packages can provide the easiest method to identify worsening psychological condition during immunotherapy and give rapid feedback to the oncologist and the patient. Team work is of particular importance in a situation like this as it requires

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

    Science.gov (United States)

    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

  17. Radiation therapy of malignant melanomas: an evaluation of clinically used fractionation schemes

    International Nuclear Information System (INIS)

    Strauss, A.; Dritschilo, A.; Nathanson, L.; Piro, A.J.

    1981-01-01

    To assess the importance of radiation dose fraction size in the treatment of malignant melanomas, the records of 48 patients (83 sites) treated at Tufts-New England Medical Center from 1971 to 1979 have been retrospectively reviewed. During this period, the dose fractionation schemes evolved from standard fraction size to large-dose techniques. Radiation fraction size was observed to be the major factor in the clinical response of melanoma. Fractions of 600 to 800 rad resulted in the best overall response (80%). The rapid fractionation scheme of 800 to 400 to 400 rad on successive days resulted in intermediate response (58%) and may be useful for the palliative treatment of selected patients

  18. The relationship between MDM2 expression and tumor thickness and invasion in primary cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2012-01-01

    Full Text Available Background: Malignant melanoma is the most invasive cutaneous tumor which is associated with an incredibly high mortality rate. The most reliable histological factors associated with melanoma prognosis are tumor thickness- measured by the Breslow index- and invasion depth- measured by Clark level. Murine double minute 2 (MDM2 gene inhibits p53-dependent apoptosis. An increase in MDM2 expression has been found in many tumors. This study aimed to investigate MDM2 expression and its correlation with tumor thickness and invasion level in malignant melanoma. Materials and Methods: This study evaluated paraffin blocks from 43 randomly selected patients with primary cutaneous melanoma who referred to the main university pathology center in Isfahan, Iran. MDM2 expression rate was assessed via immunohistochemical techniques and hematoxylin and eosin staining to determine tumor thickness and invasion level. Correlations between MDM2 expression and tumor thickness and invasion were analyzed using Spearman′s correlation coefficient in SPSS 17 . Results: The mean age of patients was 61.2 ± 15 years. Men and women constituted 55.8% and 44.2% of the participants, respectively. The rate of MDM2 positivity was 28.9%. MDM2 expression was directly associated with tumor thickness (r = 0.425; p = 0.002 and weakly with invasion level (r = 0.343; p = 0.01. Conclusions: Despite the low MDM2 expression rate observed in this study, direct relationships between MDM2 positivity and tumor thickness and invasion level were identified. MDM2 expression can thus be suggested as a potential new predictive prognostic factor.

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

    Science.gov (United States)

    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).

  20. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark.

    Science.gov (United States)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P; Thygesen, Sandra K; Nelson, Jeanenne J

    2016-05-03

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997-2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40% of patients died within one year of metastatic diagnosis and ~70% died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6% with cuSCC or basal cell carcinoma (BCC), 3.9% with actinic keratosis (AK), and 0.7% with Bowen's disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8% (42.5 per 1000 person-years [PY]); AK, 0.8% (18.6 per 1000 PY); cuSCC, 0.1% (1.7 per 1000 PY); Bowen's disease, 0.04% (0.8 per 1000 PY); and keratoacanthoma (KA), 0%. Non-cuSCC was observed in 3 patients (0.1%; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and non-cuSCC were

  1. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients: an observational cohort study in Denmark

    International Nuclear Information System (INIS)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette; Ulrichsen, Sinna P.; Thygesen, Sandra K.; Nelson, Jeanenne J.

    2016-01-01

    Inhibitors of mutant BRAF are emerging as standard of care in patients with metastatic melanoma who carry relevant oncogenic mutations. However, BRAF inhibitors are found to induce cutaneous squamous cell carcinoma (cuSCC). Population-based background rates of cuSCC and non-cutaneous squamous cell carcinoma (non-cuSCC) in the metastatic melanoma population may contextualize safety signals from randomized clinical trials or the clinics. However, these background rates are lacking. We conducted a historical cohort study to evaluate the background rates of new-onset non-melanoma skin lesions and non-cuSCC among 2,814 metastatic malignant melanoma patients diagnosed in 1997–2010, identified through the Danish Cancer Registry and the National Pathology Registry. Patients were excluded if they had a history of cancer before the metastatic melanoma diagnosis, other than skin cancers. We determined the incidence of non-melanoma malignant skin lesions and non-cuSCC that occurred post metastatic melanoma diagnosis, censoring patients at death, emigration, or December 31, 2011 (end of study period), whichever came first. The median age at metastatic melanoma diagnosis was 64 years. Over 40 % of patients died within one year of metastatic diagnosis and ~70 % died within 5 years. The percentages of patients with prior history or prevalent disease at metastatic melanoma diagnosis included: 8.6 % with cuSCC or basal cell carcinoma (BCC), 3.9 % with actinic keratosis (AK), and 0.7 % with Bowen’s disease. No patients had past or current non-cuSCC per study exclusion criterion. The incidence of non-melanoma skin lesions during the 6 months post-metastatic melanoma diagnosis was as follows: BCC, 1.8 % (42.5 per 1000 person-years [PY]); AK, 0.8 % (18.6 per 1000 PY); cuSCC, 0.1 % (1.7 per 1000 PY); Bowen’s disease, 0.04 % (0.8 per 1000 PY); and keratoacanthoma (KA), 0 %. Non-cuSCC was observed in 3 patients (0.1 %; 2.5 per 1000 PY) at 3 sites: bronchi, heart and lung. CuSCC and

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

    Science.gov (United States)

    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.

  3. Differentiation of Human Malignant Melanoma Cells that Escape Apoptosis After Treatment with 9-Nitrocamptothecin In Vitro

    Directory of Open Access Journals (Sweden)

    Panayotis Pantazis

    1999-08-01

    Full Text Available After in-vitro exposure to 0.05 μmol/L 9-nitrocamptothecin (9NC for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1 B cells die by apoptosis, whereas the remaining cells are arrested at the G2-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G2-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G2 exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G1-arrested, but downregulated in density G1-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells.

  4. Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.

    Science.gov (United States)

    Zecena, Helma; Tveit, Daniel; Wang, Zi; Farhat, Ahmed; Panchal, Parvita; Liu, Jing; Singh, Simar J; Sanghera, Amandeep; Bainiwal, Ajay; Teo, Shuan Y; Meyskens, Frank L; Liu-Smith, Feng; Filipp, Fabian V

    2018-04-04

    Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma. The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential. Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors. The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance

  5. Radiation therapy of malignant melanoma: Experience with high individual treatment doses

    International Nuclear Information System (INIS)

    Habermalz, H.J.; Fischer, J.J.

    1984-01-01

    Melanoma is a complex tumor, metastasizes early both by lymphatic and blood vessels, and which may invoke a significant host ''immune,'' response. One can imagine a number of potentially useful roles for an effective radiation therapy regimen: 1. Treatment of the primary lesion. For small lesions located on the extremities, surgery may be simpler and obviate the risk of radiation failure. In other areas, e.g., head and neck, which may require more cosmetically or functionally debilitating surgery, a trial of radiation therapy may be worthwhile. 2. Preoperative radiation to the primary lesion before surgical resection in the hope of preventing tumor dissemination. 3. Prophylactic, local and regional lymph node radiation therapy. It has been popular in the past to remove malignant melanoma with wide local excision and dissection of adjacent node areas. It is still an open question whether some or any additional patients will be cured by the more vigorous local and extended treatment. Generally, those procedures have fallen into disfavor because of the associated morbidity. Presumably subclinical amounts of malignant melanoma could be sterilized with doses of radiation smaller than those necessary for bulk tumor. Wide field irradiation to the areas surrounding the primary lesion and the adjacent lymph nodes, to doses causing little morbidity, may well be worth clinical trial. 4. In combination with other forms of therapy, e.g., chemotherapy, immunotherapy, hyperthermia, to reduce the number of malignant cells in localized areas known to contain diseases. This may be particularly important prior to initiation of immunotherapy which may be much more effective in the absence of gross disease

  6. Comparison of results with CO2 laser and traditional surgical treatment of stage I malignant melanoma

    International Nuclear Information System (INIS)

    Reali, U.M.; Donati, E.; Quercetani, R.; Ciardi, C.; Chiarugi, C.

    1987-01-01

    The follow-up data on 39 cases of stage I malignant melanoma treated with CO 2 laser are compared to those of an analogous group of cases treated by traditional surgical methods and selected for their clinical and pathologic similarities with the laser-treated group. The findings ware expressed in terms of tumor-free time and were evaluated by variance analysis. The data showed that traditional methods gave better results. CO 2 laser surgery requires longer headling time, which may have a negative effect on the course of the disease

  7. Is UV-A radiation a cause of malignant melanoma. Er UV-A aarsak til malignt melanom

    Energy Technology Data Exchange (ETDEWEB)

    Moan, J. (Det Norske Radiumhospital, Oslo (Norway))

    1994-03-01

    The first action spectrum for cutaneous malignant melanoma was published recently. This spectrum was obtained using the fish Xiphophorus. If the same action spectrum applies to humans, the following statements are true: Sunbathing products (agents to protect against the sun) that absorb UV-B radiation provide almost no protection against cutaneous malignant melanoma. UV-A-solaria are more dangerous than expected so far. If people are determined to use artificial sources of radiation for tanning, they should choose UV-B solaria rather than UV-A-solaria. Fluorescent tubes and halogen lamps may have weak melanomagenic effects. Ozone depletion has almost no effect on the incidence rates of CMM, since ozone absorbs very little UV-A radiation. Sunbathing products which contain UV-A-absorbing compounds or neutral filter (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. 34 refs., 2 figs.

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

    Science.gov (United States)

    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/.

  9. Repressing CD147 is a novel therapeutic strategy for malignant melanoma.

    Science.gov (United States)

    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.

  10. Atypical fibroxanthoma-like amelanotic malignant melanoma: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Chao-Kai Hsu

    2013-09-01

    Full Text Available Atypical fibroxanthoma (AFX-like malignant melanoma is very rare. Here, we report a case of amelanotic AFX-like melanoma in a 72-year-old Taiwanese woman presenting with two separate, asymptomatic, enlarging erythematous nodules within a large hypopigmented patch on her left cheek. Histologically, both lesions showed cellular nodules in the reticular dermis separated from the overlying flattened epidermis by a zone of solar elastosis or fibrosis. The tumor consisted of sheets of atypical epithelioid cells arranged in a vague nesting pattern, as well as many atypical large or gigantic cells with one or more, large hyperchromatic, vesicular, or pleomorphic nuclei with prominent nucleoli, and moderate-to-abundant eosinophilic or foamy cytoplasm. Focal intraepidermal proliferation of atypical melanocytes with a pagetoid pattern was found only in the periphery of the main tumor. The tumor cells were moderately to strongly positive for S-100, Melan-A, and HMB-45. The pleomorphic giant cells were focally CD68-positive but CD163-negative. The patient underwent tumor excision followed by radiotherapy due to the narrow surgical margins. A sentinel lymph node biopsy revealed no metastasis of the melanoma. This case illustrates the importance of scrutinizing any subtle proliferation of atypical melanocytes in the epidermis in an AFX-like tumor in order to avoid misdiagnosis.

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

    LENUS (Irish Health Repository)

    Field, S

    2012-02-01

    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.

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

    Science.gov (United States)

    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 50y with early-stage tumours was also statistically significantly higher than the rest of County Cork (chi2 = 18.88, P Cork (chi2 = 7.84, P Cork melanoma patients is at least partly due to the PLC.

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

    LENUS (Irish Health Repository)

    Field, S

    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.

  14. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Jakobsen, Annika Loft; Andersson, A P; Dahlstrøm, K

    2000-01-01

    Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty......-eight patients with malignant melanoma of clinical stage II (local recurrence, in-transit and regional lymph node metastases) or III (metastases to other sites than in stage II) were included in the study. The results of the PET scans were compared with those obtained by clinical examination, computed tomography...

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

    Science.gov (United States)

    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.

  16. Collision Tumour of Squamous Cell Carcinoma and Malignant Melanoma in the Oral Cavity of a Dog.

    Science.gov (United States)

    Rodríguez, F; Castro, P; Ramírez, G A

    2016-05-01

    A 7-year-old, male cocker spaniel was presented with a gingival proliferative lesion in the rostral maxilla and enlargement of the regional lymph node. Morphological and immunohistochemical analysis revealed a collision tumour composed of two malignant populations, epithelial and melanocytic, with metastasis of the neoplastic melanocytes to the regional lymph node. The epithelial component consisted of trabeculae and islands of well-differentiated squamous epithelium immunoreactive to cytokeratins. The melanocytic component had a varying degree of pigmentation of polygonal and spindle-shaped cells, growing in nests or densely packed aggregates and immunolabelled with S100, melanoma-associated antigen (melan A), neuron-specific enolase and vimentin antibodies. Protein markers involved in tumorigenesis or cell proliferation (i.e. COX-2, p53, c-kit and Ki67), were overexpressed by the neoplastic cells. To the authors' knowledge, this is the first description of an oral collision tumour involving malignant melanoma and squamous cell carcinoma in the dog. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Balloon Cell Malignant Melanoma in a Young Female: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yui Hattori

    2016-04-01

    Full Text Available Balloon cell malignant melanoma (BCMM is a very rare malignant melanoma subtype. The clinical appearance of BCMM varies; it may be nodular, ulcerated, polypoid, papillomatous and often non-pigmented. The tumor cells histologically appear large, polygonal or round and contain abundant granular or vacuolated cytoplasm. We herein report the case of a 32-year-old female who presented with a focal eccentric pigmented mass in the left lumbar region of 15 mm in diameter that had been present for several years. She underwent tumor excision. The histopathological analysis showed epithelioid melanocytes with clear cytoplasm. An immunohistochemical analysis revealed that the cells were positive for HMB-45 and S-100 protein and negative for cytokeratin. The balloon cell component stained negative for Fontana-Masson. A month later, the patient underwent excision of the bilateral inguinal lymph nodes and metastatic BCMM was revealed. The lymph node metastases showed the complete replacement of lymph nodes by balloon cells. A diagnosis of BCMM (Breslow depth 10 mm, Clark level V without ulcer was rendered. Staining with Ki-67 was positive in almost 44% of the balloon cells.

  18. Malignant melanoma: A retrospective series from a regional cancer center in India

    Directory of Open Access Journals (Sweden)

    Sharma Kuldeep

    2009-01-01

    Full Text Available Purpose : To present our experience in treating malignant melanoma patients. Methods and Materials : All melanoma patients treated at the Department of Radiotherapy, All India Institute of Medical Sciences, New Delhi, India, from 1995 to 2007 were studied retrospectively. The endpoints were loco-regional recurrence, distant recurrence, recurrence-free survival (RFS, and duration of follow-up (DOFU. RFS and DOFU were analyzed with respect to the factors like age, sex, tissue of origin, site of disease, number of nodes, lymphadenopathy, ulceration, stage, and operability to find out any association. Results : Seventy-two patients were found evaluable with 40 males and 32 females (median age 46.5 years. Eye was the commonest primary site with visual disturbance as the commonest symptom. Overall, 87% of the lesions were single, with most of the nonocular lesions presenting in the advanced stage. During the disease course, regional lymphadenopathy and distant metastases were seen in 33% and 32% of cases, respectively. Highest incidence of lymphadenopathy was seen in skin lesions and in primaries from trunk and extremities. Of all treated patients, 47% achieved complete response, 18% partial response, and others had either stable or progressive disease. The median DOFU was 6.2 months. RFS was studied only in curatively treated cases with a median of 10 months. Operability at presentation was the only prognostic factor influencing DOFU. Conclusion : Malignant melanoma is an uncommon disease in India carrying a lot of morbidity due to late presentation. Its management is still not clear regarding the optimum use and schedule of treatment modalities. More prospective studies in the future are required to come to a definite conclusion.

  19. Epidemiology of malignant melanoma of the skin in Norway with special reference to the effect of solar radiation

    International Nuclear Information System (INIS)

    Magnus, K.

    1976-01-01

    This study deals with the epidemiology of malignant melanoma of the skin with special reference to the effect of solar radiation. It studies the time trends and geographical variations in incidence and mortality, and the marked differences in the topographic distribution of the tumors according to sex and age. The study indicates that the increasing exposure of the human skin to sunlight leads to a substantial rise in the incidence of a serious malignant disease

  20. Regression of uveal malignant melanomas following cobalt-60 plaque. Correlates between acoustic spectrum analysis and tumor regression

    International Nuclear Information System (INIS)

    Coleman, D.J.; Lizzi, F.L.; Silverman, R.H.; Ellsworth, R.M.; Haik, B.G.; Abramson, D.H.; Smith, M.E.; Rondeau, M.J.

    1985-01-01

    Parameters derived from computer analysis of digital radio-frequency (rf) ultrasound scan data of untreated uveal malignant melanomas were examined for correlations with tumor regression following cobalt-60 plaque. Parameters included tumor height, normalized power spectrum and acoustic tissue type (ATT). Acoustic tissue type was based upon discriminant analysis of tumor power spectra, with spectra of tumors of known pathology serving as a model. Results showed ATT to be correlated with tumor regression during the first 18 months following treatment. Tumors with ATT associated with spindle cell malignant melanoma showed over twice the percentage reduction in height as those with ATT associated with mixed/epithelioid melanomas. Pre-treatment height was only weakly correlated with regression. Additionally, significant spectral changes were observed following treatment. Ultrasonic spectrum analysis thus provides a noninvasive tool for classification, prediction and monitoring of tumor response to cobalt-60 plaque

  1. Diagnosis of sentinel lymph nodal metastases in malignant melanoma. Usefulness of genetic diagnosis by reverse transcriptase-polymerase chain reaction

    International Nuclear Information System (INIS)

    Isoda, Hideka; Mori, Tomoko; Nishio, Daisuke; Tokura, Yoshiki; Yasuda, Hiroshi

    2005-01-01

    Sentinel lymph node (SLN) biopsy has been performed in 25 patients with malignant melanoma for the last four years at the Department of Dermatology, University of Occupational and Environmental Health. SLNs were identified by using both patent blue dye and redionucleotide-labeled colloid methods. The removed SLNs were subjected to routine haematoxylin-eosin staining and immunohistochemical stainings for Melan-A, S-100 protein and HMB45, and 10 of 25 cases had positive SLN metastases. In 8 cases, mRNA for malignant melanoma related molecules, gp100, MART-1 and tyrosinase, was analyzed by RT-PCR, and 7 of 8 cases gave agreement with the histopathological results. One case had negative SLN metastasis on histopathological examination but exhibited amplification of mRNA for the melanoma-related molecules on RT-PCR analysis. (author)

  2. Association between lymph node size and metastasis in dogs with oral malignant melanoma: 100 cases (1987-2001).

    Science.gov (United States)

    Williams, Laurel E; Packer, Rebecca A

    2003-05-01

    To determine the association between lymph node size and metastasis and to assess measurement of lymph node size as an accurate and reliable means of tumor staging in dogs with oral malignant melanoma. Retrospective study. 100 dogs with histologically confirmed oral malignant melanoma. Clinical records for dogs with oral malignant melanoma were reviewed. Data regarding size and results of cytologic or histologic examination of lymph nodes were evaluated. The association between lymph node size and metastasis was determined. Forty-seven (47%) dogs, of which 23 (49%) had enlarged mandibular lymph nodes, had no cytologic or histologic evidence of metastasis. Of 53 (53%) dogs with cytologic or histologic evidence of mandibular lymph node metastasis, 37 (70%) had enlarged mandibular lymph nodes, and 16 (30%) had mandibular lymph nodes of normal size. Overall, 16 of the 40 (40%) dogs with normal-sized lymph nodes had microscopic evidence of metastatic disease. Sensitivity and specificity of lymph node size as a predictor of metastasis were 70 and 51%, respectively, and the positive and negative predictive values were 62 and 60%, respectively. Although a significant relationship was identified between lymph node size and metastasis to the lymph node, this association did not appear strong enough to be clinically relevant. Results suggest that lymph node size alone is insufficient for accurate clinical staging of oral malignant melanoma in dogs; cytologic or histologic examination of regional lymph nodes should routinely be performed, regardless of size of those nodes.

  3. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of silent metastases from malignant melanoma

    DEFF Research Database (Denmark)

    Eigtved, A; Andersson, A P; Dahlstrøm, K

    2000-01-01

    Correct staging is crucial for the management and prognosis of patients with malignant melanoma. The aim of this prospective study was to compare staging by whole-body positron emission tomography using fluorine-18 fluorodeoxyglucose (18F-FDG) with staging by conventional methods. Thirty...

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

    Energy Technology Data Exchange (ETDEWEB)

    Li Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); Guo Bo [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China); West China Eye Center of Huaxi Hospital, Sichuan University, Chengdu 610064 (China); Fan Hongsong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)], E-mail: leewave@126.com; Zhang Xingdong [National Engineering Research Center for Biomaterial, Sichuan University, Chengdu 610064 (China)

    2008-11-15

    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.

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

    Directory of Open Access Journals (Sweden)

    Louise J. Smith

    2012-04-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  7. Extract of Cordyceps militaris inhibits angiogenesis and suppresses tumor growth of human malignant melanoma cells.

    Science.gov (United States)

    Ruma, I Made Winarsa; Putranto, Endy Widya; Kondo, Eisaku; Watanabe, Risayo; Saito, Ken; Inoue, Yusuke; Yamamoto, Ken-Ichi; Nakata, Susumu; Kaihata, Masaji; Murata, Hitoshi; Sakaguchi, Masakiyo

    2014-07-01

    Angiogenesis is essential for tumor development and metastasis. Among several angiogenic factors, vascular endothelial growth factor receptor (VEGF) is important for tumor-derived angiogenesis and commonly overexpressed in solid tumors. Thus, many antitumor strategies targeting VEGF have been developed to inhibit cancer angiogenesis, offering insights into the successful treatment of solid cancers. However, there are a number of issues such as harmful effects on normal vascularity in clinical trials. Taking this into consideration, we employed Cordyceps militaris as an antitumor approach due to its biological safety in vivo. The herbal medicinal mushroom Cordyceps militaris has been reported to show potential anticancer properties including anti-angiogenic capacity; however, its concrete properties have yet to be fully demonstrated. In this study, we aimed to elucidate the biological role of Cordyceps militaris extract in tumor cells, especially in regulating angiogenesis and tumor growth of a human malignant melanoma cell line. We demonstrated that Cordyceps militaris extract remarkably suppressed tumor growth via induction of apoptotic cell death in culture that links to the abrogation of VEGF production in melanoma cells. This was followed by mitigation of Akt1 and GSK-3β activation, while p38α phosphorylation levels were increased. Extract treatment in mouse model xenografted with human melanoma cells resulted in a dramatic antitumor effect with down-regulation of VEGF expression. The results suggest that suppression of tumor growth by Cordyceps militaris extract is, at least, mediated by its anti-angiogenicity and apoptosis induction capacities. Cordyceps militaris extract may be a potent antitumor herbal drug for solid tumors.

  8. Use of cabalt 60 and ruthenium 106 in the treatment of uveal malignant melanomas

    International Nuclear Information System (INIS)

    Bacin, F.; Rozan, R.; Escudero, P.; Donnarieix, D.; Dalens, H.

    1988-01-01

    Forty-one patients with uveal malignant melanomas were treated using local radiotherapy. Mean follow-up was two years. Tumor size was small (23.5%), intermediate (36.5%) or large (34%). Tumors were located in the mid-periphery (63.4%), posterior pole (24.3%) or outermost posterior segment (12.1%). Approximately 85 Gys were delivered to the tumor apex. 60 Co was used in 40 patients, and 106 Ru 106 Rh in one patient with a ciliary melanoma. Metastases developed in four patients, and three of these died (8.3%). A good response was observed in 55% of tumors, and stabilization with no further growth in 36.1%. Three lesions (8.3%) continued to grow despite treatment; one was enucleated and the two others were retreated conservatively. Visual acuity decreased in 43.3% of cases, but remained greater than 0.1 in 77.4% of patients. 63.3% of treated eyeballs developed complications including radiation-induced retinopathy (30%), exudative retinal detachment (26.6%), and vitreous hemorrhage (23.3%). These rates increased over time and after two years complications had developed in 80% of eyeballs [fr

  9. Unique cytologic features of thyroiditis caused by immune checkpoint inhibitor therapy for malignant melanoma

    Directory of Open Access Journals (Sweden)

    Trevor E. Angell

    2018-03-01

    Full Text Available Blockade of immune checkpoint molecules to reverse cancer-induced immune suppression can improve anti-tumor immune responses in cancer patients. Monoclonal antibodies targeting two such molecules, Programmed cell death protein 1 (PD-1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4 have shown clinical benefit in the treatment of advanced malignancies, including metastatic melanoma. Adverse effects of these immune checkpoint inhibitors include immune-related adverse events (irAE, of which one of the most common is autoimmune thyroiditis. Though thyroiditis is increasingly recognized, there are no reports of the pathological findings that occur in immunotherapy-induced thyroiditis. We present a case of immunotherapy-induced thyroiditis demonstrating its unique cytopathologic features. A 51-year-old woman with metastatic melanoma was found to have a suppressed TSH and elevated free thyroxine concentration 14 days after starting treatment with nivolumab (PD-1 antagonist plus ipilimumab (CTLA-4 antagonist therapy. A thyroid biopsy was performed based on ultrasound findings and cytopathology revealed unique features including abundant clusters of necrotic cells, lymphocytes and CD163-positive histiocytes. This case reports cytopathologic features found in immune checkpoint inhibitor related thyroiditis. These appear to be unique findings and may help inform future research regarding the pathophysiology and mechanisms of this condition.

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

    Science.gov (United States)

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

    1988-12-01

    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.

  11. The burden of occupationally-related cutaneous malignant melanoma in Britain due to solar radiation.

    Science.gov (United States)

    Rushton, Lesley; J Hutchings, Sally

    2017-02-14

    Increasing evidence highlights the association of occupational exposure and cutaneous malignant melanoma (CMM). We estimated the burden of CMM and total skin cancer burden in Britain due to occupational solar radiation exposure. Attributable fractions (AF) and numbers were estimated for CMM mortality and incidence using risk estimates from the published literature and national data sources for proportions exposed. We extended existing methods to account for the exposed population age structure. The estimated total AF for CMM is 2.0% (95% CI: 1.4-2.7%), giving 48 (95% CI: 33-64) deaths in (2012) and 241 (95% CI: 168-325) registrations (in 2011) attributable to occupational exposure to solar radiation. Higher exposure and larger numbers exposed led to much higher numbers for men than women. Industries of concern are construction, agriculture, public administration and defence, and land transport. These results emphasise the urgent need to develop appropriate strategies to reduce this burden.

  12. Coexisting Malignant Melanoma and Blue Nevus of the Uterine Cervix: An Unusual Combination

    Directory of Open Access Journals (Sweden)

    David Parada

    2012-01-01

    Full Text Available Malignant melanoma (MM and blue nevi of the uterine cervix are an extremely rare neoplasm, probably derived from embryologic migration of melanocytes from the neural crest. MM displays aggressive behavior with a poor prognosis. We report the case of a 76-year-old postmenopausal woman abnormal vaginal bleeding. She underwent a hysterectomy and bilateral salpingo-oophorectomy with paraaortic-iliac lymphadenectomy. Histopathological and immunohistochemical studies were consistent with the diagnosis of MM and blue nevi in the uterine cervix. Although it is extremely rare, this case suggests that MM of the uterine cervix should be considered in the differential diagnosis of undifferentiated neoplasm. Early diagnosis is essential in order to warrant a better prognosis, although there are no cases of cure described.

  13. A 3-Year Follow-up of Sun Behavior in Patients With Cutaneous Malignant Melanoma

    DEFF Research Database (Denmark)

    Idorn, Luise Winkel; Datta, Pameli; Heydenreich, Jakob

    2014-01-01

    IMPORTANCE UV radiation (UVR) exposure is the primary environmental risk factor for developing cutaneous malignant melanoma (CMM). OBJECTIVE To measure changes in sun behavior from the first until the third summer after the diagnosis of CMM using matched controls as a reference. DESIGN, SETTING...... that measured time-related UVR in standard erythema dose (SED) and corresponding sun diaries (mean, 74 days per participant each participation year). RESULTS Patients' daily UVR dose and UVR dose in connection with various behaviors increased during follow-up (quantified as an increase in daily UVR dose each...... suggest that patients with CMM do not maintain a cautious sun behavior in connection with an increase in UVR exposure, especially on days with body exposure, when abroad, and on holidays....

  14. Claudin11 Promoter Hypermethylation Is Frequent in Malignant Melanoma of the Skin, but Uncommon in Nevus Cell Nevi

    Energy Technology Data Exchange (ETDEWEB)

    Walesch, Sara K.; Richter, Antje M. [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany); Helmbold, Peter [Department of Dermatology, University of Heidelberg, D-69120 Heidelberg (Germany); Dammann, Reinhard H., E-mail: reinhard.dammann@gen.bio.uni-giessen.de [Institute for Genetics, Justus-Liebig-University Giessen, D-35392 Giessen (Germany)

    2015-07-07

    Epigenetic inactivation of tumor-related genes is an important characteristic in the pathology of human cancers, including melanomagenesis. We analyzed the epigenetic inactivation of Claudin 11 (CLDN11) in malignant melanoma (MM) of the skin, including six melanoma cell lines, 39 primary melanoma, 41 metastases of MM and 52 nevus cell nevi (NCN). CLDN11 promoter hypermethylation was found in 19 out of 39 (49%) of the primary MM and in 21 out of 41 (51%) of the MM metastases, but only in eight out of 52 (15%) of NCN (p = 0.001 and p = 0.0003, respectively). Moreover, a significant increase in the methylation level of CLDN11 from primary melanomas to MM metastases was revealed (p = 0.003). Methylation of CLDN11 was significantly more frequent in skin metastases (79%) compared to brain metastases (31%; p = 0.007). CLDN11 methylation was also found in five out of six MM cell lines (83%) and its promoter hypermethylation correlated with a reduced expression. Treatment of MM cell lines with a DNA methylation inhibitor reactivated CLDN11 transcription by its promoter demethylation. In summary, CLDN11 proved to be an epigenetically inactivated tumor related gene in melanomagenesis, and analysis of CLDN11 methylation level represents a potential tool for assisting in the discrimination between malignant melanoma and nevus cell nevi.

  15. Efficacy of systemic adjuvant therapies administered to dogs after excision of oral malignant melanomas: 151 cases (2001-2012).

    Science.gov (United States)

    Boston, Sarah E; Lu, Xiaomin; Culp, William T N; Montinaro, Vincenzo; Romanelli, Giorgio; Dudley, Robert M; Liptak, Julius M; Mestrinho, Lisa A; Buracco, Paolo

    2014-08-15

    To determine prognostic factors for and compare outcome among dogs with oral malignant melanoma following excision with or without various systemic adjuvant therapies. Retrospective case series. 151 dogs with naturally occurring oral malignant melanomas treated by excision with or without adjuvant therapies from 2001 to 2012. Case accrual was solicited from Veterinary Society of Surgical Oncology members via an email list service. Information collected from case records included signalment, tumor staging, tumor characteristics, type of surgical excision, histologic diagnosis, adjuvant therapy, and survival time. The overall median survival time was 346 days. Results of multivariate analysis indicated that tumor size, patient age, and intralesional excision (vs marginal, wide, or radical excision) were considered poor prognostic indicators. All other demographic and clinical variables were not significantly associated with survival time after adjusting for the aforementioned 3 variables. A clear survival benefit was not evident with any systemic adjuvant therapy, including vaccination against melanoma or chemotherapy; however, the number of dogs in each treatment group was small. Ninety-eight dogs received no postoperative adjuvant therapy, and there was no difference in survival time between dogs that did (335 days) and did not (352 days) receive systemic adjuvant therapy. For dogs with oral malignant melanoma, increasing tumor size and age were negative prognostic factors. Complete excision of all macroscopic tumor burden improved survival time. Long-term survival was possible following surgery alone. Although systemic adjuvant therapy was not found to improve survival time, this could have been due to type II error.

  16. PET/CT in malignant melanoma: contrast-enhanced CT versus plain low-dose CT

    International Nuclear Information System (INIS)

    Pfluger, Thomas; Schneider, Vera; Fougere, Christian la; Bartenstein, Peter; Weiss, Mayo; Melzer, Henriette Ingrid; Coppenrath, Eva; Berking, Carola

    2011-01-01

    The aim of this study was to evaluate the diagnostic value of contrast-enhanced CT (CECT) versus non-enhanced low-dose CT (NECT) in the staging of advanced malignant melanoma with 18 F-fluordeoxyglucose (FDG) positron emission tomography (PET)/CT. In total, 50 18 F-FDG PET/CT examinations were performed in 50 patients with metastasized melanoma. For attenuation correction, whole-body NECT was performed followed by diagnostic CECT with contrast agent. For the whole-body PET, 18 F-FDG was applied. Criteria for evaluation were signs of vital tumour tissue (extent of lesions, contrast enhancement, maximum standardized uptake value >2.5). Findings suspicious for melanoma were considered lesions. NECT, CECT and 18 F-FDG PET were evaluated separately, followed by combined analysis of PET/NECT and PET/CECT. Findings were verified histologically and/or by follow-up (>6 months). Overall, 232 lesions were analysed, and 151 proved to be metastases. The sensitivity of NECT, CECT, PET, PET/NECT and PET/CECT was 62, 85, 90, 97 and 100%, and specificity was 52, 63, 88, 93 and 93%, respectively. Compared to CECT, NECT obtained additional false-negative results: lymph node (n = 19) and liver/spleen metastases (n = 9). Misinterpreted physiological structures mainly caused additional false-positive findings (n = 17). In combined analysis of PET/NECT, six false-positive [other tumours (n = 2), inflammatory lymph nodes (n = 2), inflammatory lung lesion (n = 1), blood vessel (n = 1)] and five false-negative findings [liver (n = 3), spleen (n = 1), lymph node metastases (n = 1)] remained. On PET/CECT, six false-positive [inflammatory lymph nodes (n = 3), other tumours (n = 2), inflammatory lung lesion (n = 1)] and no false-negative findings occurred. However, additional false findings on PET/NECT (6 of 232) did not change staging compared to PET/CECT. Our results indicate that it is justified to perform PET/NECT instead of PET/CECT for melanoma staging. (orig.)

  17. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

    Directory of Open Access Journals (Sweden)

    Ludovica Ciuffreda

    2009-08-01

    Full Text Available The Raf/MEK/ERK pathway is an importantmediator of tumor cell proliferation and angiogenesis. Here, weinvestigated 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.

  18. Dermoscopic clues in the diagnosis of amelanotic and hypomelanotic malignant melanoma Pistas dermatoscópicas no diagnóstico de melanoma maligno amelanótico e hipomelanótico

    Directory of Open Access Journals (Sweden)

    Raquel Bissacotti Steglich

    2012-12-01

    Full Text Available The clinical identification of amelanotic malignant melanoma (AMM and hypomelanotic malignant melanoma (HMM becomes difficult due to the lack of pigmentation and to the diverse clinical presentations. Dermoscopy is very useful in these cases, increasing the level of suspicion of malignancy. We report 4 cases of amelanotic malignant melanoma and hypomelanotic malignant melanoma with characteristic dermoscopic findings. Dermoscopy under polarized light demonstrates vascular polymorphism, globules and milky-red areas, in addition to chrysalis and multiple blue-gray dots.A identificação clínica de melanoma maligno amelanótico e hipomelanótico torna-se difícil devido à falta de pigmentação e às diversas apresentações desse tipo de tumor. A dermatoscopia é muito útil nestes casos, aumentando o grau de suspeição de malignidade. Relatamos 4 casos de melanoma maligno amelanótico e melanoma maligno hipomelanótico com achados dermatoscópicos característicos. A dermatoscopia com luz polarizada demonstra polimorfismo vascular, glóbulos e áreas vermelholeitosas, assim como crisálides e múltiplos pontos azul-acinzentados.

  19. Melanoma

    Science.gov (United States)

    ... cancers in females aged 15 to 29 years old. Tanning-bed use contributes to this. Melanoma: Who ... Publications Connect With Us Contact Us Media contacts Advertising contacts AAD logo Advertising, marketing and sponsorships Legal ...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  2. Flow cytometric analysis of peripheral blood and tumor-infiltrating regulatory T cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Tominaga, Makiko; Horiuchi, Yutaka; Ichikawa, Mika; Yamashita, Masao; Okano, Kumiko; Jikumaru, Yuri; Nariai, Yoko; Kadosawa, Tsuyoshi

    2010-05-01

    It is well known that tumor-infiltrating lymphocytes (TILs) and peripheral blood lymphocytes (PBLs) from patients with advanced-stage cancer have a poor immune response. Regulatory T cells (Tregs), characterized by the expression of a cluster of differentiation 4 and intracellular FoxP3 markers, can inhibit antitumor immunoresponse. In the present study, the prevalence of Tregs in peripheral blood and tumor tissue from dogs with oral malignant melanoma was evaluated by triple-color flow cytometry. The percentage of Tregs in the peripheral blood of the dogs with malignancy was significantly increased compared with healthy control dogs, and the percentage of Tregs within tumors was significantly increased compared with Tregs in peripheral blood of dogs with oral malignant melanoma. This finding suggests that the presence of tumor cells induced either local proliferation or selective migration of Tregs to tumor-infiltrated sites. A better understanding of the underlying mechanisms of Treg regulation in patients with cancer may lead to an effective anticancer immunotherapy against canine malignant melanoma and possibly other tumors.

  3. Limitations of the nested reverse transcriptase polymerase chain reaction on tyrosinase for the detection of malignant melanoma micrometastases in lymph nodes

    NARCIS (Netherlands)

    Calogero, A; Timmer-Bosscha, H; Tiebosch, ATMG; Mulder, NH; Hospers, GAP; Schraffordt Koops, H.

    The specificity and sensitivity of the nested reverse transcriptase polymerase chain reaction (RT-PCR) on tyrosinase was studied, for the detection of micrometastases of malignant melanoma. The specificity was assessed in the blood of six healthy donors, four patients with non-melanoma cancers of

  4. New malignancies after squamous cell carcinoma and melanomas: a population-based study from Norway

    International Nuclear Information System (INIS)

    Robsahm, Trude E; Karagas, Margaret R; Rees, Judy R; Syse, Astri

    2014-01-01

    Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers. All invasive cutaneous malignant melanomas (CMM, N = 28 069) and squamous cell carcinomas (SCC, N = 24 620) diagnosed in Norway during 1955–2008 were included. Rates of new primary cancers in skin cancer survivors were compared to rates of primary malignancies in the general population using standardized incidence ratios (SIR). Discrete-time logistic regression models were applied to individual-level data to estimate cancer risk among those with and without a prior skin cancer, accounting for residential region, education, income, parenthood, marital status and parental cancer status, using a 20% random sample of the entire Norwegian population as reference. Further analyses of the skin cancer cohort were undertaken to determine risk factors related to subsequent cancers. During follow-up, 9608 new primary cancers occurred after an initial skin cancer. SIR analyses showed 50% and 90% increased risks for any cancer after CMM and SCC, respectively (p < 0.01). The logistic regression model suggested even stronger increase after SCC (130%). The highest risk was seen for subsequent skin cancers, but several non-skin cancers were also diagnosed in excess: oral, lung, colon, breast, prostate, thyroid, leukemia, lymphoma and central nervous system. Factors that were associated with increased risk of subsequent cancers include male sex, older age, lower residential latitude, being married and low education and income. Parental cancer did not increase the risk of a subsequent cancer after SCC, but was a significant predictor among younger CMM survivors. Our results provide information on shared environmental and genetic risk factors for first and later cancers and may help to identify

  5. Primary Dermal Melanoma in a Patient with a History of Multiple Malignancies: A Case Report with Molecular Characterization

    Directory of Open Access Journals (Sweden)

    Germana Sini

    2013-07-01

    Full Text Available Introduction: Primary dermal melanoma (PDM is a recently described clinical entity accounting for less than 1% of all melanomas. Histologically, it is located in the dermis or subcutaneous tissue, and it shows no connections with the overlying epidermis. The differential diagnosis is principally made along with that of metastatic cutaneous melanoma. Case Report: A 72-year-old Caucasian woman with a history of multiple cancers (metachronous bilateral breast cancer, meningioma, clear cell renal cell carcinoma, uterine fibromatosis and intestinal adenomatous polyposis, came to our attention with a nodular lesion on her back. After removal of the lesion, the histology report indicated malignant PDM or metastatic malignant melanoma. The clinical and instrumental evaluation of the patient did not reveal any other primary tumour, suggesting the primitive nature of the lesion. The absence of an epithelial component argued for a histological diagnosis of PDM. Subsequently, the patient underwent a wide surgical excision with sentinel node biopsy, which was positive for metastatic melanoma. Finally, the mutational status was studied in the main genes that regulate proliferation, apoptosis and cellular senescence. No pathogenetic mutations in CDKN2A, BRAF, NRAS, KRAS, cKIT, TP53 and PTEN genes were observed. This suggests that alternative pathways and low-frequency alterations may be involved. Conclusions: The differential diagnosis between PDM and isolated metastatic melanoma depends on the negativity of imaging studies and clinical findings for other primary lesions. This distinction is important because 5-year survival rates in such cases are higher than in metastatic cases (80-100 vs. 5-20%, respectively.

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

    Science.gov (United States)

    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.

  7. Malignant melanoma in Ferrara, Northern Italy: epidemiologic survey focusing on tumor thickness.

    Science.gov (United States)

    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.

  8. Malignant melanoma of the skin among workers in a telecommunications industry: mortality study 1976-83.

    Science.gov (United States)

    DeGuire, L; Cyr, D; Thériault, G; Provencher, S; Iturra, H; Case, B W

    1992-10-01

    An incidence study of malignant melanoma of the skin (MMS), conducted previously among the workers of four plants of a large telecommunications industry located in Montreal, Canada, showed a standardised incidence ratio of 2.7 (95% confidence interval (95% CI) 1.3-5.02) for the years 1976 to 1983. To describe more precisely the magnitude of the problem a mortality study was started among the same population (n = 9590) for the same period (1976-83). At the end of 1983, 9180 workers were alive, 261 were dead, and 149 (1.5%) were not traced. Standardised mortality ratios (SMRs) for all causes of death were surprisingly low for men (SMR = 0.57; 95% CI 0.50-0.64) and women (SMR = 0.56; 95% CI 0.37-0.82). The SMRs for major causes of death were also less than expected. These results may be explained by a pronounced selection bias (healthy worker effect) and by the short duration of follow up (eight years). For MMS, two deaths occurred among men (SMR = 2.00; 95% CI 0.24-7.22) and one among women (SMR = 4.81; 95% CI 0.12-26.78). A third man who died of MMS was miscoded as having a primary pulmonary melanoma. Including this case increased the SMR for MMS to 3.00 (95% CI 0.62-8.77; p = 0.08). Polyvinyl chloride and polychlorinated biphenyls were used in the plants and some of the workers did soldering. A planned case-control study will investigate other possible exposures at work.

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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

  11. Development of a practical guide for the early recognition for malignant melanoma of the foot and nail unit

    Directory of Open Access Journals (Sweden)

    de Berker David AR

    2010-09-01

    Full Text Available Abstract Background Malignant melanoma is a rare but potentially lethal form of cancer which may arise on the foot. Evidence suggests that due to misdiagnosis and later recognition, foot melanoma has a poorer prognosis than cutaneous melanoma elsewhere. Methods A panel of experts representing podiatry and dermatologists with a special interest in skin oncology was assembled to review the literature and clinical evidence to develop a clinical guide for the early recognition of plantar and nail unit melanoma. Results A systematic review of the literature revealed little high quality data to inform the guide. However a significant number of case reports and series were available for analysis. From these, the salient features were collated and summarised into the guide. Based on these features a new acronym "CUBED" for foot melanoma was drafted and incorporated in the guide. Conclusions The use of this guide may help clinicians in their assessment of suspicious lesions on the foot (including the nail unit. Earlier detection of suspicious pedal lesions may facilitate earlier referral for expert assessment and definitive diagnosis. The guide is currently being field tested amongst practitioners.

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

    Science.gov (United States)

    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 (P0.05) 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

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

    International Nuclear Information System (INIS)

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

    1987-01-01

    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

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

    Science.gov (United States)

    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

  16. Malignant melanoma as a model for cancer education and prevention. 1989 Harvey lecture American Association for Cancer Education.

    Science.gov (United States)

    Robinson, W A

    1990-01-01

    Cutaneous malignant melanoma is one of the most rapidly increasing and highly fatal cancers in the world today. Current estimates suggest that 1 in 90-100 Caucasians will develop MM by the year 2000, and 20%-30% will eventually die of the disease. The cause of the epidemic of malignant melanoma is clearly increasing exposure to the sun from lifestyle and clothing habits that have changed over the past 50 years. The disease occurs primarily in preexisting nevi in sun-exposed sites in specific high risk populations who can be, and have been, defined. These are primarily middle- and upper middle-class Caucasians with blue eyes, brown or blonde hair, and fair skin, with predominantly indoor occupations who spend, or have spent, considerable time outdoors in leisure and other activities. The presence of a clearly definable cause (exposure to the sun) in specific risk groups, the ease of early detection by simple means, and the devastating outcome of late diagnosis make malignant melanoma an ideal model for teaching the basic tenets of cancer causation, development, and prevention to the public and professionals alike.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Masaru Arima

    2014-03-01

    Full Text Available 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.

  19. Advantages of preoperative ultrasound in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph nodes: a retrospective analysis in 221 patients with malignant melanoma AJCC Stages I and II.

    Science.gov (United States)

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

    2012-01-01

    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 surgical intervention with potential morbidity. The present retrospective study seeks to clarify the reliability of preoperative ultrasonography (US) in direct comparison to the result of SLNE and seeks to identify potential advantages of preoperative ultrasound if performed in conjunction with lymphoscintigraphy in detecting malignant melanoma metastases in sentinel lymph node (SLN). We retrospectively analysed data from 221 patients with primary malignant melanoma with a Breslow index of ≥ 1.0 mm. Of the 221 patients, 77.4% (n = 171) had a negative SLN. In 50 patients (22.6%), the histopathological investigation of 71 excised lymph nodes resulted in a positive SLN. The US examination demonstrated a sensitivity of 13.6%, a specificity of 96.9%, a positive predictive value of 97.2% and a negative predictive value of 12.6%. SLNE alone shows a sensitivity of 94%, a specificity of 98.6%, a positive predictive value of 100% and a negative predictive value of 98.3%. Preoperative US in conjunction with dynamic lymphoscintigraphy, followed by SLNE, demonstrated a detecting ratio of 100% (n = 28) for micrometastases and 98.6% (n = 42/43) for macrometastases. In conclusion, this study confirms that preoperative US alone cannot replace the vital information obtained during dynamic lymphoscintigraphy. But preoperative US is an important component of the staging procedure in melanoma patients and has clear advantages when performed in conjunction with dynamic lymphoscintigraphy. Therefore, we recommend preoperative US before every SLNE. © 2011 The Authors. Journal of the European Academy of Dermatology and Venereology © 2011 European Academy of Dermatology and Venereology.

  20. Cerebral MR imaging of malignant melanoma; Zerebrale MR-Bildgebung beim malignen Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Breckwoldt, M.; Bendszus, M. [Universitaetsklinikum Heidelberg, Abteilung Neuroradiologie, Neurologische Klinik, Heidelberg (Germany)

    2015-01-16

    Melanoma is the third leading cancer entity to metastasize to the central nervous system (CNS) after lung and breast cancer. This is often an early event in the disease course and limits survival. Metastasis in the CNS is the cause of death in 10-40 % of melanoma patients and the incidence of brain metastasis is even higher (50-75 %). Cerebral metastases are commonly found in the subcortical white matter. The signal characteristics can vary substantially and may change over time due to hemorrhages or the accumulation of melanin and paramagnetic ions. It is not yet clear whether novel targeted therapies (e.g. immunotherapy and kinase inhibitors) alter imaging characteristics. Also immune-related side effects, such as hypophysitis (in approximately 5 % of patients receiving ipilimumab therapy) or granulomatous disease (neurosarcoid) can occur. Melanoma metastases are usually hyperdense in computed tomography (CT). In magnetic resonance imaging (MRI) T2-weighted (T2-w) fluid-attentuated inversion recovery (FLAIR) and T1-w sequences (with and without i.v. contrast) should be obtained. Coronal and axial imaging planes should be scanned to cross-correlate findings. Susceptibility-weighted imaging is a new sensitive method to detect melanoma metastases. Approximately 66 % of melanoma metastases show intratumoral susceptibility signals (ITSS). This sets them apart from other metastases (e.g. lung and breast cancer show less ITSSs, specificity approximately 81-96 %). Diffusion imaging plays no major role in melanoma brain imaging. Susceptibility-weighted imaging increases the sensitivity to detect metastases but lacks specificity. Differentiating metastases, microbleeding or calcification can be impossible. It is controversial how to interpret susceptibility signals without correlative signs on other sequences (differential diagnosis: metastasis, microbleeding and calcification). CNS metastases are common in melanoma. MRI screening starting in stage IIc should be considered

  1. IL-21 Modulates Activation of NKT Cells in Patients with Stage IV Malignant Melanoma.

    Science.gov (United States)

    Coquet, Jonathan M; Skak, Kresten; Davis, Ian D; Smyth, Mark J; Godfrey, Dale I

    2013-10-01

    Interleukin-21 (IL-21) is a common γ-chain cytokine produced by T helper and natural killer T (NKT) cells. It has been shown to regulate the response of various lymphocyte subsets including NK, NKT, T and B cells. Owing to its potent anti-tumor function in preclinical studies and its ability to induce cytotoxicity and interferon-γ (IFN-γ) production in NK and CD8 T cells, recombinant IL-21 (rIL-21) was fast-tracked into early-phase clinical trials of patients with various malignancies. In a phase 2a trial of patients with metastatic melanoma, we analyzed the frequency and function of NKT cells in patients receiving rIL-21. NKT cells were present at a low frequency, but their levels were relatively stable in patients administered rIL-21. Unlike our observations in NK and CD8 T cells, rIL-21 appeared to reduce IFN-γ and TNF production by NKT cells, whereas it enhanced IL-4 production. It also modulated the expression of cell surface markers, specifically on CD4(-) NKT cells. In addition, an increase in CD3(+)CD56(+) NKT-like cells was observed over the course of rIL-21 administration. These results highlight that IL-21 is a potent regulator of NKT cell function in vivo.

  2. Primary malignant melanoma of the urinary bladder: clinical, morphological, and molecular analysis of five cases.

    Science.gov (United States)

    Karabulut, Yasemin Y; Erdogan, Seyda; Sayar, Hamide; Ergen, Ali; Ertoy Baydar, Dilek

    2016-12-01

    The aim of our study was to evaluate the clinical and morphological features of primary malignant melanomas of the urinary bladder. We obtained information on five such cases from three different institutions. These were three men and two women between 52 and 76 years of age. Three tumors presented with hematuria, one with dysuria, and one was discovered incidentally on imaging studies. All were invasive to muscularis propria on transuretral resections performed for diagnosis. Neoplastic cells showed variable patterns (large cell epithelioid, small cell diffuse, storiform, or mixed) in different tumors. Pigmentation was prominent in all except one case. Each case was labeled diffusely for S-100, HMB-45, and Melan-A. Pan-cytokeratin showed a perinuclear dot-like reaction in two tumors. Three cases showed the BRAF mutation in molecular studies. Two patients were already metastatic at the time of diagnosis. Two patients died, one is alive with disease after 15 months, and two patients are disease free at 1 and 5 years of surveillance.

  3. PDGFRs expression in dogs affected by malignant oral melanomas: correlation with prognosis.

    Science.gov (United States)

    Iussich, S; Maniscalco, L; Di Sciuva, A; Iotti, B; Morello, E; Martano, M; Gattino, F; Buracco, P; De Maria, R

    2017-06-01

    Canine malignant melanoma (CMM) is the most common canine oral tumour, and up to 70-75% of dogs in stage II-III die within 1 year after surgery. The purpose of this study was to evaluate the expression of platelet-derived growth factors receptors (PDGFR)-α and -β in stage II and III CMMs and to correlate it with prognosis. PDGFRs expression was evaluated by immunohistochemistry on 48 cases of formalin-fixed CMM samples and correlated with clinical-pathological findings and outcome after surgery. PDGFRs co-expression was observed in 37.5% of cases. Positivity for PDGFR-α and -β receptor was present in 54.2 and 47.9% of cases, respectively. Ki67 values >19.5% were ascertained in 66.7% of cases. Statistical analysis showed that PDGFRs co-expression and Ki67 values > 19.5% were both associated with worse prognosis. PDGFRs expression suggests a role in the pathogenesis and progression of CMM, and α and β co-expression appears to be associated to worse prognosis. © 2016 John Wiley & Sons Ltd.

  4. Effect of therapy on five- and ten-year survival of malignant melanoma patients

    International Nuclear Information System (INIS)

    Siffnerova; Bustova; Zikmund

    1989-01-01

    The results are reported of five-year and ten-year survival of malignant melanoma patients treated postoperatively by actinotherapy. In patients where lymph flow was not apparent, 2.5 Gy of daily doses of electron irradiation from a 6-8 MeV betatron were used centred on the scar. The total dose was 60 Gy. Where the lymph flow could be identified, cobalt or cesium sources were used to deliver a total dose of 50 Gy in 2.5 Gy daily. Both five-year and ten-year survival was significantly better than in patients treated with surgery only, without irradiation. 55% of the patients on combined management survived for more than 5 years, 86% of them without relapses. 41% patients survived for 10 years, of which 92% without relapse. In contrast, the corresponding figures for the patients treated with surgery only were 42% and 71% respectively for the five-year survival, and 26% and 70% respectively for the ten-year survival. (L.O.). 3 figs., 2 tabs

  5. Rare variants analysis of cutaneous malignant melanoma genes in Parkinson's disease.

    Science.gov (United States)

    Lubbe, S J; Escott-Price, V; Brice, A; Gasser, T; Pittman, A M; Bras, J; Hardy, J; Heutink, P; Wood, N M; Singleton, A B; Grosset, D G; Carroll, C B; Law, M H; Demenais, F; Iles, M M; Bishop, D T; Newton-Bishop, J; Williams, N M; Morris, H R

    2016-12-01

    A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Surface modification of MPEG-b-PCL-based nanoparticles via oxidative self-polymerization of dopamine for malignant melanoma therapy

    Directory of Open Access Journals (Sweden)

    Xiong W

    2015-04-01

    Full Text Available Wei Xiong,1,2 Lixia Peng,1,2 Hongbo Chen,3 Qin Li1,2 1Southern Medical University, Guangzhou, 2Department of Plastic Surgery, General Hospital of Guangzhou Military Command of PLA, Guangzhou, People’s Republic of China; 3Division of Life Sciences and Health, Graduate School at Shenzhen, Tsinghua University, Shenzhen, People’s Republic of China Abstract: To enhance the therapeutic effects of chemotherapy on malignant melanoma, paclitaxel (PTX-loaded methoxy poly(ethylene glycol-b-poly(ε-caprolactone nanoparticles (MPEG-b-PCL NPs that had their surfaces modified with polydopamine (PTX-loaded MPEG-b-PCL NPs@PDA were prepared as drug vehicles. The block copolymer MPEG-b-PCL was synthesized by ring-opening polymerization and characterized by proton nuclear magnetic resonance spectroscopy and gel permeation chromatography. The PTX-loaded NPs were prepared by a modified nanoprecipitation technique. The PTX-loaded NPs and PTX-loaded NPs@PDA were characterized in terms of size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release. Confocal laser scanning microscopy showed that coumarin-6-loaded NPs@PDA could be internalized by human melanoma cell line A875 cells. The cellular uptake efficiency of NPs was greatly enhanced after PDA modification. The antitumor efficacy of the PTX-loaded NPs@PDA was investigated in vitro by the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay and in vivo by a xenograft tumor model. The PTX-loaded NPs@PDA could significantly inhibit tumor growth compared to Taxol® and precursor PTX-loaded NPs. All the results suggested that the PTX-loaded MPEG-b-PCL NPs that had their surfaces modified with PDA are promising nanocarriers for malignant melanoma therapy. Keywords: cancer nanotechnology, drug delivery, surface modification, polydopamine, malignant melanoma

  7. Are we seeing the effects of public awareness campaigns? A 10-year analysis of Breslow thickness at presentation of malignant melanoma in the South West of England.

    Science.gov (United States)

    Armstrong, A; Powell, C; Powell, R; Hallam, N; Taylor, J; Bird, J; Sarran, C; Oliver, D

    2014-03-01

    The last 20 years has seen a marked improvement in skin cancer awareness campaigns. We sought to establish whether this has affected the presenting Breslow thickness of malignant melanoma in the South West. This is a retrospective study looking at the first presentation of melanomas from 2003 to 2011. Data was accessed using the local online melanoma database. A total of 2001 new melanomas presented from 2003 to 2012 (Male:Female = 1:1.062). The average yearly number of melanomas was 200.1 (range = 138-312). The mean age was 62.5 years (range 12-99). Data was analysed using a Chi² test. For 0-1 mm melanomas, there is a significant difference in the observed versus expected values over the 10 years (p = 0.0018). There is an increasing proportion of 0-1 mm (thin) melanomas presenting year on year, with a positive linear trend. This is very statistically significant (p 4 mm melanomas (p = 0.1456). The proportion of thin 0-1 mm melanomas presenting in South West England has significantly increased from 2003 to 2012. There is no significant change in the thick >4 mm melanomas. This may be a result of increased public awareness due to effective public health campaigns which has significant prognostic and financial implications. Copyright © 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  8. High expression of Wee1 is associated with poor disease-free survival in malignant melanoma: potential for targeted therapy.

    Directory of Open Access Journals (Sweden)

    Gry Irene Magnussen

    Full Text Available Notoriously resistant malignant melanoma is one of the most increasing forms of cancer worldwide; there is thus a precarious need for new treatment options. The Wee1 kinase is a major regulator of the G(2/M checkpoint, and halts the cell cycle by adding a negative phosphorylation on CDK1 (Tyr15. Additionally, Wee1 has a function in safeguarding the genome integrity during DNA synthesis. To assess the role of Wee1 in development and progression of malignant melanoma we examined its expression in a panel of paraffin-embedded patient derived tissue of benign nevi and primary- and metastatic melanomas, as well as in agarose-embedded cultured melanocytes. We found that Wee1 expression increased in the direction of malignancy, and showed a strong, positive correlation with known biomarkers involved in cell cycle regulation: Cyclin A (p<0.0001, Ki67 (p<0.0001, Cyclin D3 (p = 0.001, p21(Cip1/WAF1 (p = 0.003, p53 (p = 0.025. Furthermore, high Wee1 expression was associated with thicker primary tumors (p = 0.001, ulceration (p = 0.005 and poor disease-free survival (p = 0.008. Transfections using siWee1 in metastatic melanoma cell lines; WM239(WTp53, WM45.1(MUTp53 and LOX(WTp53, further support our hypothesis of a tumor promoting role of Wee1 in melanomas. Whereas no effect was observed in LOX cells, transfection with siWee1 led to accumulation of cells in G(1/S and S phase of the cell cycle in WM239 and WM45.1 cells, respectively. Both latter cell lines displayed DNA damage and induction of apoptosis, in the absence of Wee1, indicating that the effect of silencing Wee1 may not be solely dependent of the p53 status of the cells. Together these results reveal the importance of Wee1 as a prognostic biomarker in melanomas, and indicate a potential role for targeted therapy, alone or in combination with other agents.

  9. Treatment side effects and follow-up of malignant melanoma; Therapienebenwirkungen und Nachsorge bei malignem Melanom

    Energy Technology Data Exchange (ETDEWEB)

    Stahl, T. [Klinikum der Stadt Ludwigshafen gGmbH, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany); Loquai, C. [Universitaetsmedizin der Johannes-Gutenberg Universitaet Mainz, Hautklinik und Poliklinik, Mainz (Germany)

    2015-01-30

    Side effects in the therapy of malignant melanoma are primarily of importance for radiologists in advanced tumor stages. The available treatment options and their respective side effect profiles have undergone a profound change in recent years after the introduction of modern oncological therapies (e.g. immunotherapy and targeted therapy) with an increasing focus on individual tumor biology and differ significantly from those of classical chemotherapy. The immunotherapeutic agents, in particular ipilimumab, take on a special position because of their specific immune-mediated mechanisms of action and the associated side effects, so-called immune-related adverse events (irAE). The majority of the treatment effects are manifested on the skin (> 50 %) and are generally not detectable by diagnostic radiology. Only a comparatively small proportion of treatment side effects is detectable with diagnostic imaging (15-20 %) but as in the example of therapy-induced colitis with ipilimumab, may be rapidly fatal. In addition to colitis (10-20 %) further therapy side effects apparent in diagnostic imaging are hypophysitis (1.8-17 %), thyroiditis (0.8 %), myositis (1.7 %), fasciitis and sarcoid-like lymph node alterations (6.8 %). To detect radiologically detectable side effects early on and to delineate them especially from tumor progression and (opportunistic) infections, detailed knowledge of the therapeutic methods for melanoma, the mechanisms of action and in particular the sometimes very specific side effects is imperative for radiologists. (orig.) [German] Nebenwirkungen der Therapie des malignen Melanoms sind fuer den Radiologen primaer in fortgeschrittenen Tumorstadien von Bedeutung. Die zur Verfuegung stehenden Therapieoptionen und ihre jeweiligen Nebenwirkungsprofile haben sich in den letzten Jahren nach Einfuehrung moderner onkologischer Therapieoptionen, die sich zunehmend an der individuellen Tumorbiologie orientieren (zielgerichtete Therapie, Immuntherapie), einem

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

    Science.gov (United States)

    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.

  11. Oral malignant melanomas and other head and neck neoplasms in Danish dogs--data from the Danish Veterinary Cancer Registry.

    Science.gov (United States)

    Brønden, Louise B; Eriksen, Thomas; Kristensen, Annemarie T

    2009-12-18

    Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign). In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans.Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a clinical model for OMM in humans.

  12. EMMPRIN promotes melanoma cells malignant properties through a HIF-2alpha mediated up-regulation of VEGF-receptor-2.

    Directory of Open Access Journals (Sweden)

    Faten Bougatef

    Full Text Available EMMPRIN's expression in melanoma tissue was reported to be predictive of poor prognosis. Here we demonstrate that EMMPRIN up-regulated VEGF receptor-2 (VEGFR-2 in two different primary melanoma cell lines and consequently increased migration and proliferation of these cells while inhibiting their apoptosis. SiRNA inhibition of VEGFR-2 expression abrogated these EMMPRIN effects. EMMPRIN regulation of VEGFR-2 was mediated through the over-expression of HIF-2alpha and its translocation to the nucleus where it forms heterodimers with HIF-1beta. These results were supported by an in vivo correlation between the expression of EMMPRIN with that of VEGFR-2 in human melanoma tissues as well as with the extent of HIF-2alpha localization in the nucleus. They demonstrate a novel mechanism by which EMMPRIN promotes tumor progression through HIF-2alpha/VEGFR-2 mediated mechanism, with an autocrine role in melanoma cell malignancy. The inhibition of EMMPRIN in cancer may thus simultaneously target both the VEGFR-2/VEGF system and the matrix degrading proteases to block tumor cell growth and invasion.

  13. Treatment efficacy and immune stimulation by AdCD40L gene therapy of spontaneous canine malignant melanoma.

    Science.gov (United States)

    Westberg, Sara; Sadeghi, Arian; Svensson, Emma; Segall, Thomas; Dimopoulou, Maria; Korsgren, Olle; Hemminki, Akseli; Loskog, Angelica S I; Tötterman, Thomas H; von Euler, Henrik

    2013-01-01

    Malignant melanoma is a serious disease in both humans and dogs, and the high metastatic potential results in poor prognosis for many patients. Its similarities with human melanoma make spontaneous canine melanoma an excellent model for comparative studies of novel therapies and tumor biology. We report a pilot study of local adenovector CD40L (AdCD40L) immunogene treatment in 19 cases of canine melanoma (14 oral, 4 cutaneous, and 1 conjunctival). Three patients were World Health Organization stage I, 2 were stage II, 10 stage III, and 4 stage IV. One to 6 intratumoral injections of AdCD40L were given every 7 days, followed by cytoreductive surgery in 9 cases and only immunotherapy in 10 cases. Tumor tissue was infiltrated with T and B lymphocytes after treatment, suggesting immune stimulation. The best overall response included 5 complete responses, 8 partial responses, and 4 stable and 2 progressive disease statuses according to the World Health Organization response criteria. Median survival was 160 days (range, 20-1141 d), with 3 dogs still alive at submission. Our results suggest that local AdCD40L therapy is safe and could have beneficial effects in dogs, supporting further treatment development. Clinical translation to human patients is in progress.

  14. Notch4 Signaling Induces a Mesenchymal–Epithelial–like Transition in Melanoma Cells to Suppress Malignant Behaviors

    Science.gov (United States)

    Rad, Ehsan Bonyadi; Hammerlindl, Heinz; Wels, Christian; Popper, Ulrich; Menon, Dinoop Ravindran; Breiteneder, Heimo; Kitzwoegerer, Melitta; Hafner, Christine; Herlyn, Meenhard; Bergler, Helmut; Schaider, Helmut

    2016-01-01

    The effects of Notch signaling are context-dependent and both oncogenic and tumor-suppressive functions have been described. Notch signaling in melanoma is considered oncogenic, but clinical trials testing Notch inhibition in this malignancy have not proved successful. Here, we report that expression of the constitutively active intracellular domain of Notch4 (N4ICD) in melanoma cells triggered a switch from a mesenchymal-like parental phenotype to an epithelial-like phenotype. The epithelial-like morphology was accompanied by strongly reduced invasive, migratory, and proliferative properties concomitant with the downregulation of epithelial–mesenchymal transition markers Snail2 (SNAI2), Twist1, vimentin (VIM), and MMP2 and the reexpression of E-cadherin (CDH1). The N4ICD-induced phenotypic switch also resulted in significantly reduced tumor growth in vivo. Immunohistochemical analysis of primary human melanomas and cutaneous metastases revealed a significant correlation between Notch4 and E-cadherin expression. Mechanistically, we demonstrate that N4ICD induced the expression of the transcription factors Hey1 and Hey2, which bound directly to the promoter regions of Snail2 and Twist1 and repressed gene transcription, as determined by EMSA and luciferase assays. Taken together, our findings indicate a role for Notch4 as a tumor suppressor in melanoma, uncovering a potential explanation for the poor clinical efficacy of Notch inhibitors observed in this setting. PMID:26801977

  15. Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Trude G. Simonsen

    2016-06-01

    Full Text Available INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.

  16. Cytoplasmic BRMS1 expression in malignant melanoma is associated with increased disease-free survival

    Directory of Open Access Journals (Sweden)

    Slipicevic Ana

    2012-02-01

    Full Text Available Abstract Background/aims Breast cancer metastasis suppressor 1 (BRMS1 blocks metastasis in melanoma xenografts; however, its usefulness as a biomarker in human melanomas has not been widely studied. The goal was to measure BRMS1 expression in benign nevi, primary and metastatic melanomas and evaluate its impact on disease progression and prognosis. Methods Paraffin-embedded tissue from 155 primary melanomas, 69 metastases and 15 nevi was examined for BRMS1 expression using immunohistochemistry. siRNA mediated BRMS1 down-regulation was used to study impact on invasion and migration in melanoma cell lines. Results A significantly higher percentage of nevi (87%, compared to primary melanomas (20% and metastases (48%, expressed BRMS1 in the nucelus (p Waf1/Cip1 (p = 0.009. Cytoplasmic score index was inversely associated with nuclear p-Akt (p = 0.013 and positively associated with cytoplasmic p-ERK1/2 expression (p = 0.033. Nuclear BRMS1 expression in ≥ 10% of primary melanoma cells was associated with thicker tumors (p = 0.016 and decreased relapse-free period (p = 0.043. Nuclear BRMS1 was associated with expression of fatty acid binding protein 7 (FABP7; p = 0.011, a marker of invasion in melanomas. In line with this, repression of BRMS1 expression reduced the ability of melanoma cells to migrate and invade in vitro. Conclusion Our data suggest that BRMS1 is localized in cytoplasm and nucleus of melanocytic cells and that cellular localization determines its in vivo effect. We hypothesize that cytoplasmic BRMS1 restricts melanoma progression while nuclear BRMS1 possibly promotes melanoma cell invasion. Please see related article: http://www.biomedcentral.com/1741-7015/10/19

  17. A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma.

    Science.gov (United States)

    Ottnod, J M; Smedley, R C; Walshaw, R; Hauptman, J G; Kiupel, M; Obradovich, J E

    2013-09-01

    Oral malignant melanoma (OMM) in the dog is often locally aggressive with a high metastatic potential and there are few treatment options that have been demonstrated to improve outcome of this disease. The purpose of this study was to determine whether adjunctive treatment with the Oncept melanoma vaccine affected the outcome of dogs with OMM that had achieved loco-regional cancer control. Medical records from 45 dogs that presented to the Animal Cancer and Imaging Center were reviewed, including 30 dogs with stage II and III disease. Dogs that received the vaccine did not achieve a greater progression-free survival, disease-free interval or median survival time than dogs that did not receive the vaccine. © 2013 John Wiley & Sons Ltd.

  18. Role of PET in the initial staging of cutaneous malignant melanoma: systematic review.

    Science.gov (United States)

    Krug, Bruno; Crott, Ralph; Lonneux, Max; Baurain, Jean-François; Pirson, Anne-Sophie; Vander Borght, Thierry

    2008-12-01

    To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC

  19. Efficacy and toxicity of whole brain radiotherapy in patients with multiple cerebral metastases from malignant melanoma

    Directory of Open Access Journals (Sweden)

    Hauswald Henrik

    2012-08-01

    Full Text Available Abstract Background To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT in patients with multiple brain metastases (BM from malignant melanoma (MM. Patients and methods Results of 87 patients (median age 58 years; 35 female, 52 male treated by WBRT for BM of MM between 2000 and 2011 were reviewed. Total dose applied was either 30 Gy in 10 fractions (n = 56 or 40 Gy in 20 fractions (n = 31. All but 9 patients suffered from extra-cerebral metastases. Prior surgical resection of BM was performed in 18 patients, salvage stereotactic radiosurgery in 13 patients. Results Mean follow-up was 8 months (range, 0–57 months, the 6- and 12-months overall-(OS survival rates were 29.2% and 16.5%, respectively. The median OS was 3.5 months. In cerebral follow-up imaging 6 (11 patients showed a complete (partial remission, while 11 (17 patients had stable disease (intra-cerebral tumor progression. In comparison of total dose, the group treated with 40 Gy in 20 fractions achieved a significant longer OS (p = 0.003, median 3.1 vs. 5.6 months. Furthermore, DS-GPA score (p  Conclusion Treatment of BM from MM with WBRT is tolerated well and some remissions of BM could be achieved. An advantage for higher treatment total doses was seen. However, outcome is non-satisfying, and further improvements in treatment of BM from MM are warranted.

  20. Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk: A Meta-Analysis Study.

    Directory of Open Access Journals (Sweden)

    Jibin Liu

    Full Text Available Several epidemiological studies have determined the associations between coffee intake level and skin cancer risk; however, the results were not yet conclusive. Herein, we conducted a systematic review and meta-analysis of the cohort and case-control studies for the association between coffee intake level and malignant melanoma (MM risk.Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015. Study-specific risk estimates were pooled under the random-effects model.Two case-control studies (846 MM patients and 843 controls and five cohort studies (including 844,246 participants and 5,737 MM cases were identified. For caffeinated coffee, the pooled relative risk (RR of MM was 0.81 [95% confidential interval (95% CI = 0.68-0.97; P-value for Q-test = 0.003; I2 = 63.5%] for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 (95% CI = 0.912-0.999 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found (P-value for nonlinearity = 0.326. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk (pooled RR = 0.92, 95% CI = 0.81-1.05; P-value for Q-test = 0.967; I2 = 0%; highest versus lowest quantity of intake.This meta-analysis suggested that caffeinated coffee might have chemo-preventive effects against MM but not decaffeinated coffee. However, larger prospective studies and the intervention studies are warranted to confirm these findings.

  1. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E)BRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to (V600E)BRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS......). Notably, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that (V600E)BRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes...

  2. Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the V600EBRAF oncogene

    DEFF Research Database (Denmark)

    Hall, Arnaldur; Meyle, Kathrine Damm; Lange, Marina Krarup

    2013-01-01

    basis for this addiction is largely unknown. Here we provide evidence for a metabolic rationale behind the addiction to V600EBRAF in two malignant melanoma cell lines. Both cell lines display a striking addiction to glycolysis due to underlying dysfunction of oxidative phosphorylation (OXPHOS). Notably......, even minor reductions in glycolytic activity lead to increased OXPHOS activity (reversed Warburg effect), however the mitochondria are unable to sustain ATP production. We show that V600EBRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to V...

  3. Facial resurfacing with a monoblock full-thickness skin graft after multiple malignant melanomas excision in xeroderma pigmentosum.

    Science.gov (United States)

    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.

  4. The burden of malignant melanoma--lessons to be learned from Austria.

    Science.gov (United States)

    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 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.

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

    Science.gov (United States)

    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.

  6. Malignant melanoma of the skin in black South Africans: A 15-year ...

    African Journals Online (AJOL)

    Trauma. 76. VOL 48, NO. 3, AUGUST 2010 SAJS. Acral lentiginous melanomas develop on palmar, plantar and subungual ... the mucous membranes of the face or anus and therefore not ..... inguinale veldefekte na radikale limfadenektomie.

  7. Estudo comparativo da flarefotometria em pacientes com melanoma maligno e nevo de coróide Comparative study of flare photometry in patients with choroidal malignant melanoma and choroidal nevus

    Directory of Open Access Journals (Sweden)

    Priscilla Luppi Ballalai

    2002-01-01

    Full Text Available Introdução: Os tumores malignos intra-oculares estão associados com um aumento do "flare" na câmara anterior, causado por uma quebra na barreira hemato-aquosa, que pode ocorrer por vários mecanismos. Estudos utilizando a flarefotometria confirmam o aumento do "flare" em olhos com tumores intra-oculares malignos e benignos. Objetivo: Avaliar a flarefotometria como auxiliar no diagnóstico diferencial de melanoma maligno e nevo de coróide, comparando-se com olhos contralaterais normais. Métodos: Foram avaliados olhos com melanoma maligno e olhos com nevo de coróide diagnosticados por meio de oftalmoscopia indireta e/ou ultra-sonografia. Os olhos normais contralaterais foram utilizados como controles. A flarefotometria foi realizada em todos os pacientes, sob midríase bilateral, utilizando equipamento Laser Flare Meter (FC 500, Kowa. Foram aplicados os testes de Wilcoxon, Mann-Whitney, e Spearman para análise estatística. Resultados: A média da flarefotometria nos olhos com melanoma maligno de coróide foi 17,1 ph/ms e nos olhos normais contralaterais foi 4,06 ph/ms. Nos olhos com nevo de coróide o valor da flarefotometria foi 6,12 ph/ms e nos olhos contralaterais normais foi 4,47 ph/ms. O valor da flarefotometria foi maior nos olhos com melanoma maligno e nevo quando comparado com os olhos contralaterais normais (pIntroduction: Malignant intraocular tumors are associated with an increase in the aqueous flare, caused by alterations of the blood-ocular barriers through various mechanisms. Several studies have demonstrated an ocular flare increase using flare photometry in eyes with benign and malignant tumors. Purpose: To evaluate flare photometry as an adjunct method in the differential diagnosis of choroidal malignant melanoma and choroidal nevus comparing to normal control eyes. Methods: Eyes with melanoma and nevus were diagnosed by indirect binocular ophthalmoscopy and/or ultrasound were evaluated. The fellow normal eyes were used

  8. Selective thermal neutron capture therapy of malignant melanoma using melanogenesis-seeking 10B-compounds

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1991-11-01

    This issue is the Part B of the Progress Report (III) which includes our latest research results focusing mainly on the successful treatment of the first human melanoma patient who had metastasis in the scalp region. We also include the subsequent clinical treatment of various types of human primary melanoma lesions and the additional basic investigations necessary to perform the treatment. (J.P.N.)

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

    Science.gov (United States)

    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

  10. Detection of sentinel lymph node in breast cancer and malignant melanoma - Influence of some factors on detection success rate

    International Nuclear Information System (INIS)

    Krafta, O.; Safarcika, K.; Stepien, A.

    2004-01-01

    Full text: The aim of this study was to compare three radiopharmaceuticals for sentinel lymph node detection in breast cancer and malignant melanoma patients. We examined 100 women and 2 men with breast cancer (average age 59.3 years) and 167 patients with malignant melanoma (69 men with mean age of 58.6 years and 98 women with mean age of 53.6 years). Lymphoscintigraphy was performed in all patients after injection of the radiotracer, either of the three: NANOCIS (average particle size 100 nm), SENTISCINT (particle size 100-600 nm), and NANOCOLL (particle size under 80 nm). Dynamic scintigraphy was performed in melanoma patients while breast cancer patients were subjected to stating imaging at 1-2 and 22 hours of injection. In patients with melanoma surgery was done on the same day, to remove the primary tumor, sentinel lymph node and other nodes, wherever required. In breast cancer patients, surgery, more or less, was done on the second day of radiotracer injection. In operation theatre isosulfan blue dye and gamma probe was used to detect sentinel lymph nodes. In breast cancer patients, scintigraphy detected a total of 231 lymph nodes but failed to show sentinel lymph node in 7 patients (success rate of lymphoscintigraphy 93.1 %). Using gamma probe 158 lymph nodes were detected in 89 patients but sentinel nodes were missed in 9 patients (success rate of probe was 89.9 %). 146 lymph nodes could be visualised using blue dye in 92 patients but were missed in 12 patients (detection rate by dye was 87 %). In 2 patients sentinel lymph node could not be detected by any method. In patients with melanoma, scintigraphy showed 304 lymph nodes. However, it did not detect sentinel lymph node in 9 patients (success rate of lymphoscintigraphy was 94.6 %). 104 patients were examined by means of gamma probe and 132 lymph nodes were detected and no lymph node was found in 13 patients (success rate of probe 87.5%). Using blue dye in 140 patients, 131 nodes were found but were

  11. Clinical value of FDG-PET in cutaneous malignant melanoma: First experience in Estonia

    International Nuclear Information System (INIS)

    Nazarenko, S.; Niin, M.; Paats, A.; Tonnov, A.

    2004-01-01

    Full text: In November 2002 first 18F-FDG-PET was performed in Estonia using a mobile truck-mounted scanning technology (Accel, Siemens) provided by the International Healthcare Group (IHG, Amersfoort, Netherlands). The FDG was provided by MAP Medical Technologies, Schering, (Helsinki, Finland). In 2003 this scheme was repeated for further scanning sessions. Evaluation of cutaneous malignant melanoma (CMM) using nuclear technique is of particular interest in Estonia as its incidence is on the rise. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) in CMM has a well-documented high diagnostic accuracy, especially in staging of the disease. The aim of the current study was to assess the impact of 18F-FDG-PET on detailed staging and clinical management in CMM. 30 patients of CMM, 16 males and 14 females, all non-diabetic, in the age range of 26 to 69 years were studied. Of these 30 patients, 12 were of high risk primary CMM, 7 had regional lymph node metastases and 11 had distant metastases. Patients were asked to consume a low-carbohydrate diet 3 days prior to the FDG-PET scan. 194 to 410 MBq (average 335 MBq) 18F-FDG was administered to the patients who were asked to come fasting for a minimum of 6 hours. Whole body scan was performed 40 to 65 minutes after the administration of FDG on the mobile PET. In 13 of the 30 patients (43%) 18F-FDG-PET changed the staging. In remaining 17 patients (57%) 18F-FDG-PET increased confidence level for the chosen treatment. Lymphadenectomy was planned in 2 patients showing lymph node involvement on FDG-PET. In other 2 patients, one with small pulmonary and other with a liver lesions found on PET but negative on radiological examination 'wait-and-watch' strategy was chosen. An unexpected hypermetabolic lesion seen in 1 case turned out to be a benign focus of connective tissue. One patient shown to have multiple distant metastases was started on chemotherapy. Finally in 8 of the 30 (27%) patients an immediate positive

  12. In vivo skin fluorescence imaging in young Caucasian adults with early malignant melanomas

    Directory of Open Access Journals (Sweden)

    Piérard GE

    2014-08-01

    Full Text Available Gérald E Piérard,1 Trinh Hermanns-Lê,2 Sébastien L Piérard,3 Lucas Dewalque,4 Corinne Charlier,4 Claudine Piérard-Franchimont,2 Philippe Delvenne2 1Laboratory of Skin Bioengineering and Imaging (LABIC, Department of Clinical Sciences, Liège University, 2Department of Dermatopathology, Unilab Lg, University Hospital of Liège, 3INTELSIG Laboratory, Montefiore Institute, University of Liège, 4Department of Clinical, Forensic and Environmental Toxicology, University Hospital of Liège, Liège, Belgium Background: Human cutaneous malignant melanoma (CMM is an aggressive cancer showing a dramatic worldwide increase in incidence over the past few decades. The most prominent relative epidemiological increase has been disclosed in young women. The aim of the study was to assess the effects of chronic sun exposures in order to rate the extend of melanocytic stimulations in the vicinity of CMM. Methods: The study was designed to evaluate the melanin distribution and density using ultraviolet light illumination. The present study was performed on surgical excision specimens of thin CMM lesion removed from the upper limbs of 55 Caucasian adults (37 women and 18 men. Two control groups comprised 23 men and 21 women of similar ages who had medium-size congenital melanocytic nevi, also present on the upper limbs. The peritumoral skin was scrutinized using a Visioscan® VC98 device, revealing the faint mosaic melanoderma (FMM pattern that grossly indicates early signs of chronic photodamage in epidermal melanin units. Results: The median extent of relative FMM was significantly higher in the CMM male group. By contrast, the CMM female group showed a reverse bimodal distribution in FMM size. Only 12/37 (32.5% of the CMM female group had an increased FMM size, whereas 25/37 (67.5% of females with CMM had a global FMM extent in the normal range, relative to the controls. Conclusion: Thin CMM supervening in young women appear unrelated to repeat

  13. An improved synthesis of [125I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma

    International Nuclear Information System (INIS)

    John, C.S.; Reba, R.C.; Varma, V.M.; McAfee, J.G.; Saga, T.; Kinuya, S.; Le, N.; Jeong, J.M.; Paik, C.H.

    1993-01-01

    To improve the radiolabeling yield and the specific activity of [ 125 I]N-(2-diethylaminoethyl)-4-iodobenzamide(DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [ 125 I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [ 125 I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma. (Author)

  14. An improved synthesis of [[sup 125]I]N-(diethylaminoethyl)-4-iodobenzamide: a potential ligand for imaging malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    John, C.S.; Reba, R.C.; Varma, V.M.; McAfee, J.G. (Georgetown Univ. Medical Center, Washington, DC (United States)); Saga, T.; Kinuya, S.; Le, N.; Jeong, J.M.; Paik, C.H. (National Insts. of Health, Bethesda, MD (United States))

    1993-01-01

    To improve the radiolabeling yield and the specific activity of [[sup 125]I]N-(2-diethylaminoethyl)-4-iodobenzamide(DAB), the aryltributyltin precursor was synthesized from the N-(2-diethylaminoethyl)-4-bromobenzamide derivative by palladium catalyzed stannylation using bis(tributyltin). The radiolabeled product, [[sup 125]I]DAB, was obtained by an iododestannylation reaction in high radiochemical yields (85-94%, radiochemical purity, > 98%) using chloramine-T as an oxidizing agent. The specific activity was greater than 1600 Ci/mmol. The biodistribution studies in nude mice implanted with human malignant melanoma xenograft showed a good tumor uptake (6.14% ID/g at 1 h, 2.81% ID/g at 6 h and 0.42% ID/g at 24 h) of [[sup 125]I]DAB. Unfortunately, a high uptake in the non-target organs, such as liver and lung was found. At 1 h post-injection the activity level in liver and lung was 11.76 and 7.58% ID/g, respectively. A slow clearance of activity from liver and lung was observed at 6 h (3.43 and 0.49% ID/g). These results demonstrate that iodinated IDAB is a potential radiopharmaceutical for the management of patients with malignant melanoma. (Author).

  15. Metastases in patients with malignant melanoma despite of negative sentinel lymph node: has the concept to be changed?

    International Nuclear Information System (INIS)

    Weiss, M.; Dresel, S.; Tatsch, K.; Hahn, K.; Konz, B.; Schmid-Wendtner, M.H.; Sander, C.; Volkenandt, M.

    2000-01-01

    The aim of the present study was to prove the prognostic value of the SLN-concept in these patients. Methods: So far the clinical follow-up of 162 patients with histologically proven malignant melanoma and metastatically uninvolved (negative) SLN was investigated. Histological examination included standard methods (HE-Test) and special histochemical techniques (S-100, HMB-45). All patients underwent clinical examination, ultrasonic diagnosis of the regional lymph nodes, and X-ray of the chest every 3 months. Results: Despite of negative SLN-findings in 8/162 patients metastases of the malignant melanoma were found after a time period of 5-27 months. Three patients presented with recurrence in the previously mapped (negative) SLN-basin. In another case the scintigraphically visualized SLN could not be identified intraoperatively by means of the hand-held gamma probe. One patient showed intransit-metastases or skin-metastases, respectively; another patient recurred in the scar area. One patient showed hematogenic dissemination (liver) which is not detectable by lymphoscintigraphy; in another patient metastases were found outside the primary lymphatic basin (cervical). Conclusion: In our patient group 4,9% presented with metastases despite negative SLN while published data report up to 11% (observation period 35 months), among them only 3 patients (1,9%) being real concept failures. Our results underline that there is no evidence to change this concept in patients with clinically early stage. (orig.) [de

  16. Depression, anxiety and quality of life in long-term survivors of malignant melanoma: a register-based cohort study.

    Directory of Open Access Journals (Sweden)

    Manfred E Beutel

    Full Text Available The purpose of the study was to determine anxiety and depression, quality of life, and their determinants in long-term survivors of malignant melanoma.In a state cancer registry a cohort of survivors of malignant melanoma was contacted via the physician registered. Of 1302 contactable patients, 689 (52.2% completed a questionnaire including the Patient Health Questionnaire with generalized anxiety (GAD-7 and depression (PHQ-9 and the EORTC Quality of Life Questionnaire (EORTC QLQ 30. Based on multiple regression analysis, predictors of quality of life and distress were identified. Comparison data were assessed in two waves of representative face-to-face household surveys of the adult German population.An average of 8.4 (5.7 to 12.2 years after diagnosis, distress was higher in women compared to men and in middle adulthood (vs. older patients. Symptoms were higher in women than in men, and there was a decline of functioning and increase of symptoms across the age range of both genders. Compared to the general population, there were slightly increased depression and anxiety (only women, but no impaired global quality of life. Yet, survivors evidenced functional decline and more physical symptoms. Distress and reduced quality of life were consistently predicted by lack of social support, fear of recurrence, pessimism and self-blame. Distress was increased by a family history of melanoma, and additional mental and somatic diseases.Overall, long-term survivors have adjusted well achieving a global quality of life comparable to the general population. Yet, compromised functional dimensions, physical symptoms and distress indicate the need for integrating psychooncological screening into oncological follow-up, which might be guided by predictors such as family history or social support. Further prospective study is needed to determine the course of adaptation to the disease and corroborate the risk factors identified.

  17. Treatment with Ipilimumab: A Case Report of Complete Response in a Metastatic Malignant Melanoma Patient

    Directory of Open Access Journals (Sweden)

    Alfredo Addeo

    2013-05-01

    Full Text Available Introduction: Over the past year, 3 agents have been approved for the treatment of melanoma by the Food and Drug Administration. These include pegylated interferon α-2b for stage III melanoma, vemurafenib for unresectable or metastatic melanoma with BRAF V600E mutation, and ipilimumab for unresectable or metastatic melanoma. Case Presentation: We present here the case of a 65-year-old Caucasian male diagnosed with advanced melanoma in April 2011 and treated with ipilimumab (Yervoy®, a monoclonal antibody targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4, as second-line treatment after progression with dacarbazine, for (wild-type BRAF metastatic melanoma. The patient was referred to us for several painful lumps on his right arm. A biopsy of one of them revealed melanoma. CT and PET scans did not show any other lesions or a primary site. The patient was started on first-line chemotherapy with dacarbazine 850 mg/m2 on day 1, every 3 weeks. After 3 cycles, the patient showed disease progression with an increase in size of the skin metastasis. Second-line treatment was started with ipilimumab 3 mg/kg on day 1, every 3 weeks. At the end of the treatment, after 4 cycles, we documented a complete clinical response with total resolution of the skin metastasis. At the time of writing this paper, our patient had finished his treatment more than 9 months earlier and is still in complete remission. Conclusion: This is a paradigmatic case where, despite extensive metastatic disease, treatment with ipilimumab has confirmed its efficacy. It is still an open question why only a minority of patients have such a remarkable response, and further trials are warranted to address this important question.

  18. Frequent Nuclear/Cytoplasmic Localization of β-Catenin without Exon 3 Mutations in Malignant Melanoma

    Science.gov (United States)

    Rimm, David L.; Caca, Karel; Hu, Gang; Harrison, Frank B.; Fearon, Eric R.

    1999-01-01

    β-Catenin has a critical role in E-cadherin-mediated cell-cell adhesion, and it also functions as a downstream signaling molecule in the wnt pathway. Mutations in the putative glycogen synthase kinase 3β phosphorylation sites near the β-catenin amino terminus have been found in some cancers and cancer cell lines. The mutations render β-catenin resistant to regulation by a complex containing the glycogen synthase kinase 3β, adenomatous polyposis coli, and axin proteins. As a result, β-catenin accumulates in the cytosol and nucleus and activates T-cell factor/lymphoid enhancing factor transcription factors. Previously, 6 of 27 melanoma cell lines were found to have β-catenin exon 3 mutations affecting the N-terminal phosphorylation sites (Rubinfeld B, Robbins P, Elgamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science 1997, 275:1790–1792). To assess the role of β-catenin defects in primary melanomas, we undertook immunohistochemical and DNA sequencing studies in 65 melanoma specimens. Nuclear and/or cytoplasmic localization of β-catenin, a potential indicator of wnt pathway activation, was seen focally within roughly one third of the tumors, though a clonal somatic mutation in β-catenin was found in only one case (codon 45 Ser→Pro). Our findings demonstrate that β-catenin mutations are rare in primary melanoma, in contrast to the situation in melanoma cell lines. Nonetheless, activation of β-catenin, as indicated by its nuclear and/or cytoplasmic localization, appears to be frequent in melanoma, and in some cases, it may reflect focal and transient activation of the wnt pathway within the tumor. PMID:10027390

  19. Oral malignant melanomas and other head and neck neoplasms in Danish dogs - data from the Danish Veterinary Cancer Registry

    Science.gov (United States)

    2009-01-01

    Background Head and neck cancers (HNC) are relatively common and often very serious diseases in both dogs and humans. Neoplasms originating in the head and neck region are a heterogeneous group. HNC often has an unfavourable prognosis and the proximity of the tissue structures renders extirpation of tumours with sufficient margins almost incompatible with preservation of functionality. In humans oral malignant melanoma (OMM) is extremely rare, but represents a particular challenge since it is highly aggressive as is the canine counterpart, which thus may be of interest as a spontaneous animal model. Methods Canine cases entered in the Danish Veterinary Cancer Registry (DVCR) from May 15th 2005 through February 29th 2008 were included in this study. Fisher's exact test was used to compare proportions of HNC in dogs and humans as well as proportions of surgically treated cases of OMM and squamous cell carcinomas (SCC). Also the proportions of benign and malignant neoplasms of different locations in dogs were compared using Fisher's exact test. Results A total of 1768 cases of neoplasias (679 malignant, 826 benign, 263 unknown) were submitted. Of all neoplasias HNC accounted for 7.2% (n = 128). Of these, 64 (50%) were malignant and 44 (34%) benign. The most common types of malignant neoplasia were SCC (18; 28% of malignant), OMM (13; 20% of malignant), soft tissue sarcoma (11; 17% of malignant) and adenocarcinoma (5; 11% of malignant). The most common types of benign neoplasms were adenoma (7; 16% of benign), polyps (6; 14% of benign) and fibroma (5; 11% of benign). Conclusions In the current study, the proportion of neoplasia in the head and neck region in dogs in Denmark was similar to other canine studies and significantly more common than in humans with a large proportion of malignancies. Spontaneous HNC in dogs thus, may serve as a model for HNC in humans. Canine OMM is a spontaneous cancer in an outbred, immune-competent large mammal population and could be a

  20. Ultrasound-mediated interferon β gene transfection inhibits growth of malignant melanoma

    International Nuclear Information System (INIS)

    Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

    2011-01-01

    Highlights: → Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-β genes both in vitro and in vivo. → Ultrasound-mediated IFN-β transfection inhibited proliferation of melanoma cells in vitro. → Ultrasound-mediated IFN-β transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon β (IFN-β) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-β in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-β genes mixed with microbubbles. Successful sonotransfection with IFN-β gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-β 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.

  1. [Elective lymph node dissection in malignant melanoma--status of color Doppler findings].

    Science.gov (United States)

    Omlor, G; Dill-Müller, D; Gross, G; Kautz, G; Schüder, G; Zaun, H; Feifel, G

    1996-01-01

    Since there is still a controversial discussion about the ELND in melanoma patients, the purpose of this prospective study was to optimize the indication concerning ELND by ultrasound examinations. 144 patients with primary melanomas were checked every 3 months after excision. Echomorphologic pattern and intranodal vascularisation in the color-flow Doppler modus provide essential information for differential diagnosis. We found 47 patients (32.6%) with suspicious ultrasound lesions. 50% of these patients had no pathological clinical findings, the histological findings of excised lymph nodes were positive in all cases. It must be emphasized, however, that the group with lymph node metastases included 12 patients with low-risk-melanomas (2 x Tis, 10 x T1 historical control group (141 patients), where ELND was performed routinely in high-risk-patients ( > T2), the incidence of ELND in our hospital decreased more than 50%; at the same time the percentage of detected lymph node metastases increased (twice).

  2. Endolymphatic radionuclide therapy (ERT) in malignant melanomas and its immunological side effects

    International Nuclear Information System (INIS)

    Richter, G.; Heidenbluth, I.; Heidelbach, U.

    1982-01-01

    Doses of some thousands Gy affecting the retroperitoneal lymph nodes, but hardly causing reduction of subjective well-being, are interesting as to the endolymphatic instillation of 32 P tri-n-octylphosphate as an additional prophylactic therapy in operated stage 1 melanomas of the extremities. A real proof for its utility, however, has been missed till now, not only in our hitherto controlled 46 patients but also in the literature. On the other hand we found a significant lymphopenia for more than 1 year and reduced percentages of stimulated lymphocytes and rosette forming cells for 3 months. Compared to 3 control groups (melanomas before treatment, effect of operation and anaesthesia, patients without immunological alterations) these immunological changes proved to be caused by the ERT itself. They suggest a limitation of ERT to melanomas with a high likelihood of separating tumor cells or micrometastases as well as further immunological follow-up checks. (author)

  3. Clinical relevance of positron emission tomography for initial staging and follow-up of malignant melanoma

    International Nuclear Information System (INIS)

    Baum, R.P.; Rinne, D.; Kaufmann, R.

    2000-01-01

    The incidence of melanoma is rapidly increasing (at a rate of 5 percent per year) throughout the world. In Europe, the incidence is approximately 10-12 new cases of invasive melanoma per 100,000 inhabitants. The most important prognostic factor is the stage of disease (Clark Level and vertical tumor depth (TD) according to BRESLOW) at the time of presentation. Ten year survival is 90 percent with a TD of 1.5 mm; 5-year survival is 15-50 percent when there is regional lymph node involvement, and 5 percent when there is disseminated disease. Conventional diagnostic tests for staging include a chest X-ray, lymph node sonography and laboratory tests. Sentinel node biopsy is becoming an increasingly common procedure since melanoma usually metastasizes to regional lymph nodes before dissemination. CT scan of the thorax or abdomen, MRI of the brain and other tests are used only when signs or symptoms warrant. The results of a prospective study which we performed in 100 patients for staging of high risk melanoma (n=48) or for re-staging patients with suspected recurrence demonstrated that FDG whole-body PET is superior to conventional imaging techniques (X-ray, sonography, CT scan) except for the detection of brain metastases. The diagnostic accuracy of PET for the detection of metastases was 92.1% versus 55.7% for conventional imaging (p 1.5 mm); and 2) detection of occult metastases in patients with recurrent disease who are being considered for surgery. PET often changes the diagnostic evaluation and therapeutic management of patients with melanoma. PET has also shown to be cost effective in diagnosis and evaluation of patients with melanoma in the USA. (orig.) [de

  4. In vitro radiobiological evaluation of selective killing effects of 10B1-paraboronophenylalanine.HCl in the thermal neutron capture therapy of malignant melanoma cells

    International Nuclear Information System (INIS)

    Ichihashi, M.; Ueda, M.; Hayashibe, K.; Hatta, S.; Tsuji, M.; Mishima, Y.; Fukuda, H.; Kobayashi, T.; Kanda, K.

    1985-01-01

    In order to clarify the specific affinity of 10 B 1 -p-boronophenylalanine.HCl ( 10 B 1 -BPA) to melanoma cells, the killing effects of 10 B 1 -BPA in the thermal neutron capture treatment on both cultured melanotic and amelanotic melanoma cells were compared with those on non-melanoma cells, such as Alexander cells, HeLa cells and normal human fibroblasts. Cells in the plateau phase cultured in the usual medium for 4-7 days were incubated with the medium containing 50 μg/ml 10 B 1 -BPA for 20 hours until 2 hours before thermal neutron irradiation. After thermal neutron irradiation, the number of colonies consisting of more than 50 cells was counted to obtain the dose-survival curves. The melanotic cells pre-incubated with 10 B 1 -BPA had more enhanced killing sensitivity to thermal neutron irradiation than amelanotic melanoma cells pre-incubated similarly with 10 B 1 -BPA. 10 B 1 -BPA pre-incubation had no enhanced killing effects on Alexander cells, but had slightly enhanced killing effects on HeLa cells. These results indicate that 10 B 1 -BPA could be incorporated by a specific uptake mechanism of melanoma cells and accumulated within melanotic melanoma cells and that 10 B 1 -BPA at present could be the best chemical for the thermal neutron capture therapy of human malignant melanoma. (Namekawa, K.)

  5. Methyl DNA adducts, DNA repair, and hypoxanthine-guanine phosphoribosyl transferase mutations in peripheral white blood cells from patients with malignant melanoma treated with dacarbazine and hydroxyurea

    NARCIS (Netherlands)

    Philip, P.A.; Souliotis, V.L.; Harris, A.L.; Salisbury, A.; Tates, A.D.; Mitchell, K.; Delft, J.H.M. van; Ganesan, T.S.; Kyrtopoulos, S.A.

    1996-01-01

    Dacarbazine (DTIC) is a DNA-methylating drug used in the treatment of malignant melanoma. Among the DNA dducts induced by DTIC are N7-methylguanine (N7-meG) and O6-methylguamne (O6-meG). The latter adduct, in particular, may be important in the mutagenic as well as the cytotoxic activity of DTIC.

  6. Diagnosis of malignant melanoma and basal cell carcinoma by in vivo NIR-FT Raman spectroscopy is independent of skin pigmentation

    DEFF Research Database (Denmark)

    Philipsen, P A; Knudsen, L; Gniadecka, M

    2013-01-01

    and skin tumour diagnostics in vivo. We obtained Raman spectra in vivo from the normal skin of 55 healthy persons with different skin pigmentation (Fitzpatrick skin type I-VI) and in vivo from 25 basal cell carcinomas, 41 pigmented nevi and 15 malignant melanomas. Increased skin pigmentation resulted...

  7. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...

  8. The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1998-01-01

    In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients...

  9. Role of FDG-PET/CT in stage 1–4 malignant melanoma patients

    DEFF Research Database (Denmark)

    Eldon, Mai; Kjerkegaard, Ulrik Knap; Ørndrup, Mette Heisz

    2017-01-01

    /CT scanned in 2012 at a department of plastic surgery and to analyze the pattern of referral and outcome of PET/CT scans of these patients all back from early diagnosis of the patient in the period 2008–2012. Methods: All patients with MM stages 1–4 (AJCC stages) and melanoma of unknown primary (MUP) who...

  10. Phase II study of ipilimumab in adolescents with unresectable stage III or IV malignant melanoma

    DEFF Research Database (Denmark)

    Geoerger, Birgit; Bergeron, Christophe; Gore, Lia

    2017-01-01

    BACKGROUND: Ipilimumab is approved for the treatment of advanced melanoma in adults; however, little information on the efficacy and safety of ipilimumab in younger patients is available. METHODS: Patients aged 12 to <18 years with previously treated or untreated, unresectable stage III or IV mal...

  11. New diagnostic techniques in staging in the surgical treatment of cutaneous malignant melanoma

    NARCIS (Netherlands)

    Cobben, DCP; Koopal, S; Tiebosch, ATMG; Jager, PL; Elsinga, PH; Wobbes, T; Hoekstra, HJ

    2002-01-01

    The emphasis of the research on the surgical treatment of melanoma has been on the resection margins, the role of elective lymph node dissection. in high risk patients and the value of adjuvant regional treatment with hyperthermic isolated lymph perfusion with melphalan. Parallel to this research,

  12. The enigmatic role of nucleophosmin in malignant melanoma: Does it have an effect?

    Directory of Open Access Journals (Sweden)

    Aylin Orgen Calli

    2011-01-01

    Full Text Available Background: Melanoma is quite a heterogeneous group of diseases of the skin. Prognostic markers of tumor behavior are important to precisely assign individual patients for appropriate treatment protocols. Aim: The aim of our first study was to investigate nucleophosmin expression in melanoma patients and to determine its relationship with the tumor characterictics and patient prognosis. Materials and Methods: We analyzed the immunohistochemical expression of nucleophosmin in 55 melanoma patients. The immunostaining pattern was classified into two groups: Diffuse nuclear and nucleolar relocalization. We also investigated the relationship between the expression of nucleophosmin and the clinicopathological parameters sucssh as Clark level, tumor thickness, stage, histological type, location, and survey. Results: In all cases the neoplastic cells were strongly positive for nucleophosmin (14 cases diffuse nuclear, 41 cases nucleolar relocalization. No correlation was demonstrated between the expression pattern of nucleophosmin and the clinicopathological parameters and survey. Conclusions: The implications of our results, nevertheless, are that the immunohistochemical detection of nucleophosmin is not a valuable tool for predicting the outcome of patients with melanoma or identifying subgroups of patients who may be at a higher risk.

  13. Progressive Increase in Telomerase Activity From Benign Melanocytic Conditions to Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Ruben D. Ramirez

    1999-04-01

    Full Text Available The expression of telomerase activity and the in situ localization of the human telomerase RNA component (hTR in melanocytic skin lesions was evaluated in specimens from sixty-three patients. Specimens of melanocytic nevi, primary melanomas and subcutaneous metastases of melanoma were obtained from fifty-eight patients, whereas metastasized lymph nodes were obtained from five patients. Telomerase activity was determined in these specimens by using a Polymerase Chain Reaction—based assay (TRAP. High relative mean telomerase activity levels were detected in metastatic melanoma (subcutaneous metastasess = 54.5, lymph node metastasess = 56.5. Much lower levels were detected in primary melanomas, which increased with advancing levels of tumor cell penetration (Clark II = 0.02, Clark III = 1.1, and Clark IV = 1.9. Twenty-six formalin-fixed, paraffin-embedded melanocytic lesions were sectioned and analyzed for telomerase RNA with a radioactive in situ hybridization assay. In situ hybridization studies with a probe to the template RNA component of telomerase confirmed that expression was almost exclusively confined to tumor cells and not infiltrating lymphocytes. These results indicate that levels of telomerase activity and telomerase RNA in melanocytic lesions correlate well with clinical stage and could potentially assist in the diagnosis of borderline lesions.

  14. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P

    2008-01-01

    was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

  15. Immunohistochemical determination of HER-2/neu overexpression in malignant melanoma reveals no prognostic value, while c-Kit (CD117 overexpression exhibits potential therapeutic implications

    Directory of Open Access Journals (Sweden)

    Potti Anil

    2003-01-01

    Full Text Available Abstract Background HER-2/neu and c-kit (CD117 onco-protein are increasingly being recognized as targets for therapy in solid tumors, but data on their role in malignant melanoma is currently limited. We studied the prevalence of overexpression of HER-2/neu and c-Kit in 202 patients with malignant melanoma to evaluate a possible prognostic value of these molecular targets in malignant melanoma. Methods Overexpression of HER-2/neu and c-Kit was evaluated using immunohistochemical assays in 202 archival tissue specimens. Results Between 1991 and 2001, 202 subjects (109 males; 54% and 93 females; 46% with malignant melanoma were studied with a mean age of 57 years (age range: 15–101 years. The most common histologic type was amelanotic melanoma (n = 62; 30.7% followed by superficial spreading melanoma (n = 54; 26.7%. The depth of penetration of melanoma (Breslow thickness, pT Stage ranged from 0.4 mm (stage pT1 to 8.0 mm (stage pT4A. Mean thickness was 2.6 mm (stage pT3A. The ECOG performance scores ranged from 0 to 3. Only 2 patients (0.9% revealed HER-2/neu overexpression, whereas 46 (22.8% revealed c-Kit overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit positive and negative groups (p = 0.36. Interestingly, not only was c-Kit more likely to be overexpressed in the superficial spreading type, a preliminary association between the presence or absence of c-Kit overexpression and the existence of another second primary tumor was also observed. Conclusions The results of our large study indicate that the HER-2/neu onco-protein neither has a role in melanogenesis nor is a potential target for clinical trials with monoclonal antibody therapy. This indicates there is no role for its testing in patients with malignant melanoma. Although c-Kit, expressed preferentially in the superficial spreading type, may not have prognostic value, it does have significant therapeutic implications as a

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

    Science.gov (United States)

    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.

  17. Vanillin Suppresses Cell Motility by Inhibiting STAT3-Mediated HIF-1α mRNA Expression in Malignant Melanoma Cells.

    Science.gov (United States)

    Park, Eun-Ji; Lee, Yoon-Mi; Oh, Taek-In; Kim, Byeong Mo; Lim, Beong-Ou; Lim, Ji-Hong

    2017-03-01

    Recent studies have shown that vanillin has anti-cancer, anti-mutagenic, and anti-metastatic activity; however, the precise molecular mechanism whereby vanillin inhibits metastasis and cancer progression is not fully elucidated. In this study, we examined whether vanillin has anti-cancer and anti-metastatic activities via inhibition of hypoxia-inducible factor-1α (HIF-1α) in A2058 and A375 human malignant melanoma cells. Immunoblotting and quantitative real time (RT)-PCR analysis revealed that vanillin down-regulates HIF-1α protein accumulation and the transcripts of HIF-1α target genes related to cancer metastasis including fibronectin 1 ( FN1 ), lysyl oxidase-like 2 ( LOXL2 ), and urokinase plasminogen activator receptor ( uPAR ). It was also found that vanillin significantly suppresses HIF-1α mRNA expression and de novo HIF-1α protein synthesis. To understand the suppressive mechanism of vanillin on HIF-1α expression, chromatin immunoprecipitation was performed. Consequently, it was found that vanillin causes inhibition of promoter occupancy by signal transducer and activator of transcription 3 (STAT3), but not nuclear factor-κB (NF-κB), on HIF1A . Furthermore, an in vitro migration assay revealed that the motility of melanoma cells stimulated by hypoxia was attenuated by vanillin treatment. In conclusion, we demonstrate that vanillin might be a potential anti-metastatic agent that suppresses metastatic gene expression and migration activity under hypoxia via the STAT3-HIF-1α signaling pathway.

  18. A case of multiple metastatic malignant melanoma with the largest lesion in the ileum and no skin lesion

    Directory of Open Access Journals (Sweden)

    Shuji Suzuki

    2012-12-01

    Full Text Available We report the case of a 72-year-old woman with malignant melanoma and multiple metastases; the largest tumor was in the ileum. The patient experienced general fatigue and bloody feces for 1 month before consulting a nearby clinic. Blood tests revealed anemia, and fecal occult blood was positive, but no abnormalities were detected using gastrointestinal endoscopy and colonoscopy or the skin of the entire body. Computed tomography images of the chest, abdomen, and pelvic region, and positron emission tomography–computed tomography images of the entire body revealed multiple nodules in the ileum, left mammary gland, left thyroid, right inguinal lymph node, and on the fascia of the right thoracic area and right buttocks. The tumor in the left mammary gland was excised and immunohistochemical analysis revealed that the excised tissue was positive for HMB45, melan-A, and MITF, but negative for S-100 protein. Diagnosed with melanoma with multiple metastases, the patient underwent four cycles of dacarbazine, nimustine hydrochloride, and vincristine (DAV plus interferon beta chemotherapy and one cycle of dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen (DAC-Tam chemotherapy. Two series of embolizations of the artery feeding the ileum tumors, as well as a series of plasma and red blood cell transfusions, were performed for ileum tumor hemorrhage. The patient was hospitalized eight times, for a total of 204 days during the 1-year survival period before her death from respiratory failure.

  19. How gender, age, and geography influence the utilization of radiation therapy in the management of malignant melanoma

    International Nuclear Information System (INIS)

    French, John; McGahan, Colleen; Duncan, Graeme; Lengoc, Sonca; Soo, Jenny; Cannon, Jerry

    2006-01-01

    Purpose: Comparing radiation therapy utilization rates (RTUR) to those predicted by best evidence is a useful measure of the equity and accessibility of service delivery. In this study the RTUR for melanoma was established for British Columbia, Canada, and compared with the rate suggested by the evidence. Demographic variables, specifically age, gender, and geography that influenced the RTUR were examined with a view to identifying methods of improving underutilization. Methods and Materials: The RTUR in the management of malignant melanoma was taken from British Columbia Cancer registry data for 1986 to 1998. Variations in utilization based on age, gender, health authority, stage of disease, and referral patterns were analyzed. Results: An RTUR of 11% was identified. This was consistent over time. Referral rates decreased between 1986 and 1998. RT is used mostly for later stage disease. Males were more likely to receive RT than females, related to later stage of disease in men. Referral rates decreased, but RTUR for referred cases increased, in health authorities that did not have a cancer center. Conclusions: Use of RT is influenced by age and by stage of disease. Overall RTUR in British Columbia is lower than suggested by best evidence. Referral patterns are influenced by geography. RTUR was higher in males, consistent with a different pattern of disease in males compared with females

  20. Ultraviolet-induced formation of micronuclei and sister chromatid exchange in cultured fibroblasts of patients with cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Roser, M.; Boehm, A.O.; Oldigs, M.; Weichenthal, M.; Reimers, U.; Schmidt-Preuss, U.; Breitbart, E.W.; Ruediger, H.W.

    1989-01-01

    Genetically enhanced sensitivity to ultraviolet (UV) radiation may play an important role in the development of cutaneous malignant melanoma (CMM). This was studied in cultured fibroblasts of 26 CMM patients and controls by micronucleus (MN) test and sister chromatid exchange (SCE) after UV irradiation (375 J/m2). Sister chromatid exchange and MN formation were used as parameters to detect the UV-induced genotoxic damage in the individual cell strains. We found that the UV-induced level of MN was significantly increased in CMM patients (p = 0.0005), being most pronounced in the familial cases (p = 0.0001). Ultraviolet-induced SCE was also elevated in CMM patients (p = 0.001), but there was no difference between familial and nonfamilial cases. The present findings indicate that genetic predisposition contributes to the development of CMM in a subset of CMM patients and may be due to an enhanced susceptibility to UV light

  1. MR imaging of hepatic metastasis in patients with malignant melanoma: Evaluation of suspected lesions screened at contrast-enhanced CT

    International Nuclear Information System (INIS)

    Sofue, Keitaro; Tateishi, Ukihide; Tsurusaki, Masakatsu; Arai, Yasuaki; Yamazaki, Naoya; Sugimura, Kazuro

    2012-01-01

    Purpose: To evaluate the magnetic resonance (MR) imaging feature of suspected hepatic metastasis in patients with malignant melanoma which showed intermediate findings on screened contrast-enhanced computed tomography (CECT). Materials and methods: MR imaging was performed in 38 patients (22 men, 16 women; mean age, 58 years) whose CECT findings were intermediate. Hepatic metastases had been diagnosed on MR imaging in 23 of the 38 patients. Verification of hepatic metastasis was made by histological examination: ultrasonographic-guided needle biopsy (n = 3), autopsy (n = 3), and surgical resection (n = 1), or by an obvious progression in number and/or size of the lesions on follow-up MR imaging (n = 24). Two diagnostic radiologists reviewed MR images by consensus. The median follow-up duration was 14.2 months. Results: Abnormal findings were detected in 31 patients on MR images, and undetected in the remaining seven patients resulting in false-positive on CECT. The mean size of the lesion was 11.0 mm. False-positive results were obtained in two lesions which disappeared on follow-up MR imaging. In six patients, lesions were considered as hepatic cysts on MR images. As a result, a total of 35 hepatic metastases were detected on MR images. Of these, 18 patients demonstrated typical melanotic appearance on MR images which showed shortened T1 and T2 relaxation times, and five patients demonstrated atypical melanotic appearance. In 16 patients, extra-hepatic metastases were also developed. Conclusion: MR imaging could rule out hepatic metastasis in patients with malignant melanoma which showed intermediate findings on screened CECT, and could detect additional extra-hepatic metastases.

  2. MicroRNA-9 suppresses the growth, migration, and invasion of malignant melanoma cells via targeting NRP1

    Directory of Open Access Journals (Sweden)

    Xu D

    2016-11-01

    Full Text Available Dan Xu,1 Xiaofeng Chen,2 Quanyong He,1 Chengqun Luo1 1Department of Plastic Surgery, Third Xiangya Hospital of Central South University, 2Department of Neurosurgery, Brain Hospital of Hunan Province, Changsha, Hunan, People’s Republic of China Abstract: MicroRNAs (miRs are a class of small noncoding RNAs that negatively regulate the gene expression by directly binding to the 3' untranslated region of their target mRNA, thus resulting in mRNA degradation or translational repression. miR-9 has recently been demonstrated to play a role in the development and progression of malignant melanoma (MM, but the regulatory mechanism of miR-9 in the malignant phenotypes of MM still remains largely unknown. In this study, a total of 73 pairs of MM tissues and adjacent normal tissues were collected. Real-time reverse transcription polymerase chain reaction and Western blot were used to detect the mRNA and protein expression of miR-9. MTT assay, wound healing assay, and transwell assay were conducted to determine the cell proliferation, migration, and invasion. Luciferase reporter assay was used to determine the targeting relationship between miR-9 and NRP1. Our data demonstrated that miR-9 expression was significantly downregulated in MM tissues compared with that in adjacent normal tissues. The decreased miR-9 level was significantly associated with the tumor stage and metastasis of MM. We also found that the expression level of miR-9 was decreased in MM cell lines (G361, B16, A375, and HME1 compared with normal skin HACAT cells. Ectopic expression of miR-9 led to a significant decrease in the ability of proliferation, migration, and invasion in A375 cells. NRP1 was further identified as a direct target gene of miR-9, and the protein expression of NRP1 was negatively regulated by miR-9 in A375 cells. Furthermore, overexpression of NRP1 reversed the suppressive effects of miR-9 on the malignant phenotypes of A375 cells. In vivo study revealed that miR-9

  3. Generation of blood-derived dendritic cells in dogs with oral malignant melanoma.

    Science.gov (United States)

    Catchpole, B; Stell, A J; Dobson, J M

    2002-01-01

    Advances in treatment of human melanoma indicate that immunotherapy, particularly dendritic cell (DC) immunization, may prove useful. The aim of this study was to investigate whether blood-derived DCs could be generated from canine melanoma patients. Peripheral blood mononuclear cells were isolated from three such dogs and cultured with recombinant canine granulocyte-macrophage colony stimulating factor (GM-CSF), canine interleukin 4 and human Flt3-ligand for 7 days. The resulting cells demonstrated a typical dendritic morphology, and were enriched for cells expressing CD1a, CD11c and MHC II by flow cytometric analysis. Thus, canine blood-derived DCs can be generated in vitro and DC immunization should be feasible in dogs. Copyright Harcourt Publishers Ltd.

  4. Malignant melanoma arising in congenital melanocytic nevi: clinical and dermoscopic challenges

    Directory of Open Access Journals (Sweden)

    Fatma Pelin Cengiz

    2017-01-01

    Full Text Available Congenital melanocytic nevi (CMN are visible pigmented lesions in the skin that are present at birth. CMN are benign malformations resulting from defective development of melanocyte precursors in the embryo. Six MMs from six patients were analyzed by clinical and dermoscopic examination. Of the patients, 33.3% were female (N = 2 and 66.6% were male (N = 4. Of the MMs, four (66.6% were superficial spreading MM and two (33.3 % were in situ MM. A reticular pattern was present in the MMs of three patients (50%, a homogeneous pattern was present in the other patients (50% at the base of the MMs. Superficial spreading melanomas and in situ melanomas with atypical dots and globules and a blue-white veil were the most common dermoscopic features of MMs found in CMN.

  5. Chemotherapy of Malignant Melanoma with Dimethyl Triazeno Imidazole Carboxamide (DTIC) and Nitrosourea Derivatives (BCNU, CCNU)

    Science.gov (United States)

    Hill, George J.; Ruess, Robert; Berris, Robert; Philpott, Gordon W.; Parkin, Priscilla

    1974-01-01

    Chemotherapy for metastatic melanoma was performed in 80 consecutive evaluable patients. DTIC, BCNU and CCNU produced responses in 28% of patients, alone or in combination with each other. Three of 62 patients treated with DTIC remain free of tumor, off therapy at 18-36 months following objective regression of metastases. Chemotherapy with commercially available drugs continued to be uniformly unsuccessful. DTIC was used successfully in treatment of extensive extracranial disease, including one patient with metastatic melanoma during pregnancy. Cerebral metastases were the sole or major cause of death in 8/9 patients who relapsed following control with DTIC for nine months or longer, and one patient developed a carcinoma of the breast following therapy with DTIC and BCNU. Remission was induced in two patients with intralesional BCG, after prior attempts to control metastases with DTIC and combination chemotherapy. ImagesFig. 2.Fig. 2b.Fig. 2c. PMID:4601984

  6. Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions.

    Science.gov (United States)

    Eberle, Alex N; Rout, Bhimsen; Qi, Mei Bigliardi; Bigliardi, Paul L

    2017-01-01

    Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers. Special emphasis is given to different targeting options for the treatment of melanoma and melanotic lesions. Radionuclide Targeting: α-Melanocyte-stimulating hormone (α-MSH) is the most prominent peptide for targeting of melanoma tumors via the G protein-coupled melanocortin-1 receptor that is (over-)expressed by melanoma cells and melanocytes. More than 100 different linear and cyclic analogs of α-MSH containing chelators for 111In, 67/68Ga, 64Cu, 90Y, 212Pb, 99mTc, 188Re were synthesized and examined with experimental animals and in a few clinical studies. Linear Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 (NAP-amide) and Re-cyclized Cys- Cys-Glu-His-D-Phe-Arg-Trp-Cys-Arg-Pro-Val-NH2 (Re[Arg11]CCMSH) containing different chelators at the N- or C-terminus served as lead compounds for peptide drugs with further optimized characteristics. Alternatively, melanoma may be targeted with radiopeptides that bind to melanin granules occurring extracellularly in these tumors. Photosensitizer targeting: A more recent approach is the application of photosensitizers attached to the MSH molecule for targeted photodynamic therapy using LED or coherent laser light that specifically activates the photosensitizer. Experimental studies have demonstrated the feasibility of this approach as a more gentle and convenient alternative compared to radionuclides. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Pregnancy and melanoma.

    Science.gov (United States)

    Driscoll, Marcia S; Martires, Kathryn; Bieber, Amy Kalowitz; Pomeranz, Miriam Keltz; Grant-Kels, Jane M; Stein, Jennifer A

    2016-10-01

    Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  8. Combining chemotherapy and/or hyperthermia with radiation in the treatment of malignant melanoma

    International Nuclear Information System (INIS)

    Douple, E.B.

    1984-01-01

    Radiation survival curves for some but not all human melanoma cells show broad shoulders and recovery of potentially lethal radiation damage (PLD), both in vitro and in situ as xenografts in mice. Studies have also demonstrated a significant hypoxic melanoma cell population. Chemotherapy and/or hyperthermia with radiation offers the potential for additive cell killing plus modification of the terminal slope and/or shoulder as a result of supra-additive killing via radiosensitization of hypoxic cells and/or post-irradiation inhibition of cellular recovery from PLD. Such interactions should provide a therapeutic gain factor, expecially if the long-term normal tissue damage is not based on PLD repair. Higher radiation doses per fraction warrant use of PLD recovery inhibitors and would accommodate a practical consideration for the use of fewer drug/heat doses. Peak heat or drug concentrations should probably be present just before and immediately following irradiation. This paper reviews the radiobiological experiments to support the rationale for the addition of chemotherapy and/or hyperthermia to melanoma. The author stresses the problems which remain including the paucity of appropriate preclinical experiments as well as clinical problems of tumor heterogeneity, pharmacokinetics and anatomy

  9. Malignant melanoma of the nasal cavity: a case report with examination of KIT and platelet derived growth factor receptor-α (PDGFRA

    Directory of Open Access Journals (Sweden)

    Tadashi Terada

    2011-10-01

    Full Text Available Although several clinicopathological studies of malignant melanoma of the nasal cavity have been reported, there are no studies of the expression and gene mutation of KIT and platelet derived growth factor receptor-α (PDGFRA in melanoma of the nasal cavity. A 92-year-old Japanese woman consulted to our hospital because of right nasal obstruction and epistaxis. Physical examination and imaging modalities showed a tumor of the right nasal cavity. A biopsy was taken, and it showed malignant epithelioid cells with melanin deposition. Immunohistochemically, the tumor was positive for S100 protein, HMB45, p53, Ki-67 (labeling=20%, KIT and PDGFRA. The tumor was negative for cytokeratins (AE1/3 and CAM5.2. A genetic analysis using PCR-direct sequencing revealed no mutation of KIT gene (exons 9, 11, 13, and 17 or the PDGFRA gene (exons 12 and 18. The pathological diagnosis was primary malignant melanoma of the nasal cavity. The tumor was reduced in size by local resection and chemotherapy (Darthmose regimen: dacarbazine, carmustine, cisplatine, and tamoxifen, and the patient is now alive and free from metastasis 9 months after the first manifestation. In conclusion, the author reported a case of melanoma of the nasal cavity expressing KIT and PDGFRA without gene mutations of KIT and PDGFRA.

  10. An ethical dilemma: malignant melanoma in a 51-year-old patient awaiting simultaneous kidney and pancreas transplantation for type 1 diabetes.

    Science.gov (United States)

    Kirby, L C; Banerjee, A; Augustine, T; Douglas, J F

    2016-07-01

    Malignant melanoma is a high-risk skin cancer that, in potential transplant recipients, is considered a substantial contraindication to solid organ transplantation due to significant risk of recurrence with immunosuppression. Current guidelines stipulate waiting between 3 and 10 years after melanoma diagnosis. However, in young patients with end-stage organ failure and malignant melanoma, complex ethical and moral issues arise. Assessment of the true risk associated with transplantation in these patients is difficult due to lack of prospective data, but an autonomous patient can make a decision that clinicians may perceive to be high risk. The national and worldwide shortage of available organs also has to be incorporated into the decision to maximize the net benefit and minimize the risk of graft failure and mortality. The incidence of malignant melanoma worldwide is increasing faster than that of any other cancer and continues to pose ethically challenging decisions for transplant specialists evaluating recipients for solid organ transplantation. © 2016 British Association of Dermatologists.

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

    Science.gov (United States)

    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 Ptraditional VMI in patients with cutaneous malignant melanoma at thoracoabdominal DECT. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Rappa, Germana [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Mercapide, Javier; Anzanello, Fabio [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Le, Thuc T. [Nevada Cancer Institute, Las Vegas, NV 89135 (United States); Johlfs, Mary G. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Fiscus, Ronald R. [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Center for Diabetes and Obesity Prevention, Treatment, Research and Education, Roseman University of Health Sciences, Henderson, NV 89104 (United States); Wilsch-Bräuninger, Michaela [Max-Planck-Institute of Molecular Cell Biology and Genetics, Pfotenhauerstr. 108, 01307 Dresden (Germany); Corbeil, Denis [Tissue Engineering Laboratories (BIOTEC) and DFG Research Center and Cluster of Excellence for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, Tatzberg 47–49, 01307 Dresden, Germany Technische Universitat Dresden, Dresden (Germany); Lorico, Aurelio, E-mail: alorico@roseman.edu [Cancer Research Program, Roseman University of Health Sciences, 10530 Discovery Drive. Las Vegas, NV 89135 (United States); College of Pharmacy, Roseman University of Health Sciences, Henderson, NV 89104 (United States)

    2013-04-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  13. Wnt interaction and extracellular release of prominin-1/CD133 in human malignant melanoma cells

    International Nuclear Information System (INIS)

    Rappa, Germana; Mercapide, Javier; Anzanello, Fabio; Le, Thuc T.; Johlfs, Mary G.; Fiscus, Ronald R.; Wilsch-Bräuninger, Michaela; Corbeil, Denis; Lorico, Aurelio

    2013-01-01

    Prominin-1 (CD133) is the first identified gene of a novel class of pentaspan membrane glycoproteins. It is expressed by various epithelial and non-epithelial cells, and notably by stem and cancer stem cells. In non-cancerous cells such as neuro-epithelial and hematopoietic stem cells, prominin-1 is selectively concentrated in plasma membrane protrusions, and released into the extracellular milieu in association with small vesicles. Previously, we demonstrated that prominin-1 contributes to melanoma cells pro-metastatic properties and suggested that it may constitute a molecular target to prevent prominin-1-expressing melanomas from colonizing and growing in lymph nodes and distant organs. Here, we report that three distinct pools of prominin-1 co-exist in cultures of human FEMX-I metastatic melanoma. Morphologically, in addition to the plasma membrane localization, prominin-1 is found within the intracellular compartments, (e.g., Golgi apparatus) and in association with extracellular membrane vesicles. The latter prominin-1–positive structures appeared in three sizes (small, ≤40 nm; intermediates ∼40–80 nm, and large, >80 nm). Functionally, the down-regulation of prominin-1 in FEMX-I cells resulted in a significant reduction of number of lipid droplets as observed by coherent anti-Stokes Raman scattering image analysis and Oil red O staining, and surprisingly in a decrease in the nuclear localization of beta-catenin, a surrogate marker of Wnt activation. Moreover, the T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter activity was 2 to 4 times higher in parental than in prominin-1-knockdown cells. Collectively, our results point to Wnt signaling and/or release of prominin-1–containing membrane vesicles as mediators of the pro-metastatic activity of prominin-1 in FEMX-I melanoma. - Highlights: ► First report of release of prominin-1–containing microvesicles from cancer cells. ► Pro-metastatic role of prominin-1–containing microvesicles in

  14. Critérios histopatológicos para diagnóstico de melanoma maligno cutâneo: análise comparativa de sua freqüência em lesões benignas e melanomas de pequena espessura (< 2 mm Histopathological criteria for cutaneous malignant melanoma: comparative analysis between benign and thin malignant lesions (< 2 mm

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Veronese

    2007-10-01

    Full Text Available INTRODUÇÃO: A histopatologia convencional continua sendo o padrão-ouro no diagnóstico dos melanomas cutâneos, apesar do progresso da imuno-histoquímica e da biologia molecular. Os critérios microscópicos existentes para esse diagnóstico são numerosos, porém nenhum deles é específico para se afirmar que uma determinada lesão é maligna quando ele está presente, ou é benigna na sua ausência. Alguns critérios têm uma relevância maior para o diagnóstico em relação a outros. OBJETIVO: Este estudo propõe uma análise daqueles critérios considerados mais importantes, comparando sua presença em lesões melanocíticas benignas e melanomas. MATERIAL E MÉTODOS: Foram estudadas 33 lesões melanocíticas benignas (nevo de Spitz: 13; nevo de Reed: 6; nevo displásico: 6; nevo congênito: 3; nevo adquirido: 3; nevo combinado: 1; nevo recorrente: 1, bem como 101 casos de melanomas extensivo/superficiais: 25 intra-epidérmicos e 76 invasivos de pequena espessura (INTRODUCTION: Conventional histopathology has been considered as the gold standard in the diagnosis of cutaneous malignant melanoma, despite the progress of molecular biology and immunohistochemistry. There are many microscopic criteria for diagnosis of melanoma, however there is not a single one that can be useful to define malignancy. AIM: Our purpose is to analyse the criteria considered more important to the diagnosis of melanoma, comparing their presence in benign melanocytic lesions and melanomas. MATERIAL AND METHODS: We studied 33 benign melanocytic lesions (Spitz nevi, 13; Reed nevi, 6; dysplastic nevi, 6; congenital nevi, 3; acquired nevi, 3; combined nevus, 1; recurrent nevus, 1 and 101 extensive/superficial melanomas (25 in situ and 76 invasive up to 2 mm thickness. RESULTS: Some criteria showed high frequency in benign lesions, showing low-specificity, while others had low-positivity in the benign and high-frequency in malignant lesions, consequently high

  15. Cleaved CD147 shed from the surface of malignant melanoma cells activates MMP2 produced by fibroblasts.

    Science.gov (United States)

    Hatanaka, Miho; Higashi, Yuko; Fukushige, Tomoko; Baba, Naoko; Kawai, Kazuhiro; Hashiguchi, Teruto; Su, Juan; Zeng, Weiqi; Chen, Xiang; Kanekura, Takuro

    2014-12-01

    Cluster of differentiation 147 (CD147)/basigin on the malignant tumor cell surface is critical for tumor proliferation, invasiveness, metastasis, and angiogenesis. CD147 expressed on malignant melanoma cells can induce tumor cell invasion by stimulating the production of matrix metalloproteinases (MMPs) by surrounding fibroblasts. Membrane vesicles, microvesicles and exosomes have attracted attention, as vehicles of functional molecules and their association with CD147 has been reported. Cleaved CD147 fragments released from tumor cells were reported to interact with fibroblasts. We investigated the intercellular mechanisms by which CD147 stimulates fibroblasts to induce MMP2 activity. CD147 was knocked-down using short hairpin RNA (shRNA). The stimulatory effect of CD147 in cell culture supernatants, microvesicles, and exosomes on the enzymatic activity of MMP2 was examined by gelatin zymography. Supernatants from A375 control cells induced increased enzymatic activity of fibroblasts; such activity was significantly lower in CD147 knock-down cells. Cleaved CD147 plays a pivotal role in stimulating fibroblasts to induce MMP2 activity. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  16. Expression of microphthalmia transcription factor, S100 protein, and HMB-45 in malignant melanoma and pigmented nevi.

    Science.gov (United States)

    Xia, Jianxin; Wang, Yanlong; Li, Fuqiu; Wang, Jinfeng; Mu, Yan; Mei, Xianglin; Li, Xue; Zhu, Wenjing; Jin, Xianhua; Yu, Kai

    2016-09-01

    Malignant melanoma (MM) is a type of malignant tumor, which originates from neural crest melanocytes. MM progresses rapidly and results in a high mortality rate. The present study aims to investigate the expression of microphthalmia transcription factor (MITF), the S100 protein, and HMB-45 in MM and pigmented nevi. A total of 32 MM samples (including three skin metastasis, three lymph node metastasis and two spindle cell MM samples), two Spitz nevus samples, four pigmented nevus samples and two blue nevus samples were collected. The expression levels of S100 protein, HMB-45, and MITF were observed via immunostaining. The S100 protein exhibited high positive rates in MM and pigment disorders (96.7 and 100%, respectively), but with low specificity. The S100 protein was also expressed in fibroblasts, myoepithelial cells, histocytes and Langerhans cells in normal skin samples. HMB-45 had high specificity. Its positive expression was only confined to MM cells and junctional nevus cells. Furthermore, HMB-45 was not expressed in melanocytes in the normal tissue samples around the tumor or in the benign intradermal nevus cells. MITF exhibited high specificity and high sensitivity. It was expressed in the nuclei of melanocytes, MM cells and nevus cells. It was observed to be strongly expressed in metastatic MM and spindle cell MMs. Thus, MITF may present as a specific immunomarker for the diagnosis and differential diagnosis of MM.

  17. Correlation of histopathologic characteristics to protein expression and function in malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Charlotte Welinder

    Full Text Available Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information.Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease.In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor survival.In this feasibility

  18. Correlation of histopathologic characteristics to protein expression and function in malignant melanoma

    Science.gov (United States)

    Pawłowski, Krzysztof; Szasz, A. Marcell; Yakovleva, Maria; Sugihara, Yutaka; Malm, Johan; Jönsson, Göran; Ingvar, Christian; Lundgren, Lotta; Baldetorp, Bo; Olsson, Håkan; Rezeli, Melinda; Laurell, Thomas; Wieslander, Elisabet; Marko-Varga, György

    2017-01-01

    Background Metastatic melanoma is still one of the most prevalent skin cancers, which upon progression has neither a prognostic marker nor a specific and lasting treatment. Proteomic analysis is a versatile approach with high throughput data and results that can be used for characterizing tissue samples. However, such analysis is hampered by the complexity of the disease, heterogeneity of patients, tumors, and samples themselves. With the long term aim of quest for better diagnostics biomarkers, as well as predictive and prognostic markers, we focused on relating high resolution proteomics data to careful histopathological evaluation of the tumor samples and patient survival information. Patients and methods Regional lymph node metastases obtained from ten patients with metastatic melanoma (stage III) were analyzed by histopathology and proteomics using mass spectrometry. Out of the ten patients, six had clinical follow-up data. The protein deep mining mass spectrometry data was related to the histopathology tumor tissue sections adjacent to the area used for deep-mining. Clinical follow-up data provided information on disease progression which could be linked to protein expression aiming to identify tissue-based specific protein markers for metastatic melanoma and prognostic factors for prediction of progression of stage III disease. Results In this feasibility study, several proteins were identified that positively correlated to tumor tissue content including IF6, ARF4, MUC18, UBC12, CSPG4, PCNA, PMEL and MAGD2. The study also identified MYC, HNF4A and TGFB1 as top upstream regulators correlating to tumor tissue content. Other proteins were inversely correlated to tumor tissue content, the most significant being; TENX, EHD2, ZA2G, AOC3, FETUA and THRB. A number of proteins were significantly related to clinical outcome, among these, HEXB, PKM and GPNMB stood out, as hallmarks of processes involved in progression from stage III to stage IV disease and poor

  19. Marker Protein Expression Combined With Expression Heterogeneity is a Powerful Indicator of Malignancy in Acral Lentiginous Melanomas.

    Science.gov (United States)

    Cintra Lopes Carapeto, Fernando; Neves Comodo, Andréia; Germano, Andressa; Pereira Guimarães, Daiane; Barcelos, Denise; Fernandes, Mariana; Landman, Gilles

    2017-02-01

    Samples of acral lentiginous melanomas (ALMs) were obtained from the Department of Pathology at Escola Paulista de Medicina-Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. Demographic, clinical, and follow-up data were obtained from the charts of Hospital São Paulo. From 2 tissue microarrays containing 60 nevi and quadruplicate samples of ≥1.0-mm of 49 ALM, sections were stained to evaluate SCF, KIT, BRAF, CYCLIND1, MYC, and PTEN immunohistochemical protein expression. Nevi and ALM from 2006 to 2010 were reviewed and collected. All specimens were in the vertical growth phase, and histopathological parameters indicated that tumors were at an advanced stage at diagnosis. Average tumor thickness was 6.95 mm, 63% were ulcerated, average mitotic index was 5 mitotic cells per mm, and 43% were at Clark's level V. Compared with nevi, the χ test showed that ALM significantly correlated with SCF protein expression (P = 0.001) and expression heterogeneity (P < 0.000). Similar findings were observed for KIT (P = 0.005, P = 0.003, respectively), MYC (P < 0.000, P < 0.000), and PTEN (P = 0.005, P < 0.000). Malignancy did not correlate with BRAF and CYCLIN D1 expression (P = 0.053 and P = 0.259, respectively), but it did significantly correlate with their heterogeneous expression (P < 0.000, P = 0.024, respectively). Combined protein expression had an odds ratio of greater malignancy when BRAF and MYC were positive and/or heterogeneously expressed (OR of 78 and 95, respectively). We show that marker protein expression, when combined with heterogeneous expression as shown by immunohistochemistry, is a powerful indicator of malignancy in ALMs, especially, when protein pairs are combined.

  20. miR-125b induces cellular senescence in malignant melanoma

    DEFF Research Database (Denmark)

    Nyholm, Anne Marie; Lerche, Catharina M; Manfé, Valentina

    2014-01-01

    transfected melanoma cell line Mel-Juso and then investigated the effect of the presence of a stable overexpression of miR-125b on growth by western blotting, flow cytometry and β-galactosidase staining. The tumourogenicity of the transfected cells was tested using a murine model and the tumours were further...... examined with in-situ-hybridization. RESULTS: In primary human tumours and in lymph node metastases increased expression of miR-125b was found in single, large tumour cells with abundant cytoplasm. A stable overexpression of miR-125b in human melanoma cell line Mel-Juso resulted in a G0/G1 cell cycle block...... and emergence of large cells expressing senescence markers: senescence-associated beta-galactosidase, p21, p27 and p53. Mel-Juso cells overexpressing miR-125b were tumourigenic in mice, but the tumours exhibited higher level of cell senescence and decreased expression of proliferation markers, cyclin D1 and Ki...

  1. Functional Anorectal Disorders.

    Science.gov (United States)

    Rao, Satish Sc; Bharucha, Adil E; Chiarioni, Giuseppe; Felt-Bersma, Richelle; Knowles, Charles; Malcolm, Allison; Wald, Arnold

    2016-03-25

    This report defines criteria and reviews the epidemiology, pathophysiology, and management of common anorectal disorders: fecal incontinence (FI), functional anorectal pain and functional defecation disorders. FI is defined as the recurrent uncontrolled passage of fecal material for at least 3 months. The clinical features of FI are useful for guiding diagnostic testing and therapy. Anorectal manometry and imaging are useful for evaluating anal and pelvic floor structure and function. Education, antidiarrheals and biofeedback therapy are the mainstay of management; surgery may be useful in refractory cases. Functional anorectal pain syndromes are defined by clinical features and categorized into three subtypes. In proctalgia fugax, the pain is typically fleeting and lasts for seconds to minutes. In levator ani syndrome (LAS) and unspecified anorectal pain the pain lasts more than 30 minutes, but in LAS there is puborectalis tenderness. Functional defecation disorders are defined by >2 symptoms of chronic constipation or irritable bowel syndrome with constipation, and with >2 features of impaired evacuation i.e., abnormal evacuation pattern on manometry, abnormal balloon expulsion test or impaired rectal evacuation by imaging. It includes two subtypes; dyssynergic defecation and inadequate defecatory propulsion. Pelvic floor biofeedback therapy is effective for treating LAS and defecatory disorders. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  2. Spre[ing amelanotic malignant melanoma: A rare differential diagnosis with tumors of the glandula submandibularis

    International Nuclear Information System (INIS)

    Ehrenberg, C.; Helmberger, H.

    1998-01-01

    The case reported emphasizes the importance of immediate performance of imaging scans in case of the slightest suspicion that clinical symptoms might indicate malignancy of a detected lesion. Despite the superficially only marginal macroscopic findings, MR imaging as well as the CT scans revealed an [vanced, malignant process that h[ been spre[ing. Particularly the soft tissue differential diagnosis obtained with MRI yields the information required for diagnostic characterization of the space occupying tumor mass. It will however be necessary in any case to verify the diagnosis by biopsy or extirpation and cytologic examination of tissue, as the imaging methods do not always unambigiously reveal the malignant dignity of the tumor. (orig./CB) [de

  3. Do perinatal and early life exposures influence the risk of malignant melanoma? A Northern Ireland birth cohort analysis.

    Science.gov (United States)

    O'Rorke, M A; Black, C; Murray, L J; Cardwell, C R; Gavin, A T; Cantwell, M M

    2013-03-01

    Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (birth and both a higher birth order and greater household density OR 0.61 (95% CI 0.37-0.99) and OR 0.56 (95% CI 0.30-1.0) respectively. This large study of early onset melanoma supports a positive association with higher birth weight (imperatively gestational age adjusted) and CMM risk which may be related to factors which drive intrauterine foetal growth. Strong inverse associations observed with higher birth order and household density suggest that early-life immune modulation may confer protection; findings which warrant further investigation in prospective analyses. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. An Unusual Case of Metastatic Malignant Melanoma Presenting as Pseudomesothelioma with Intense Diffuse Pleural FDG Uptake Demonstrated on FDG PET/CT

    Directory of Open Access Journals (Sweden)

    Rosamma Bency

    2015-06-01

    Full Text Available A 75-year-old male, non-smoker with history of asbestos exposure, and excision of 2 mm Clark IV cutaneous malignant melanoma 15 months earlier, presented with rapidly progressive dyspnea, left pleuritic chest pain, and weight loss. CT Pulmonary Angiography (CTPA demonstrated bilateral pulmonary emboli and findings suspicious of mesothelioma. There was no evidence of infection or malignancy in the hemorrhagic pleural fluid aspirate. FDG PET-CT revealed extensive intense FDG uptake throughout the pleura of left hemi-thorax, bilateral hilar and mediastinal lymph nodes, bilateral adrenals and left gluteal musculature. Subsequent pleural biopsy was consistent with metastatic melanoma. The patient was referred for palliative therapy but died 10 days later

  5. Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study

    DEFF Research Database (Denmark)

    Lock-Andersen, J; Drzewiecki, K T; Wulf, H C

    1999-01-01

    To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell...... the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases...... were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair...

  6. Stereological estimation of nuclear volume in benign melanocytic lesions and cutaneous malignant melanomas

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    a favorable prognosis. No significant differences in vV could be demonstrated among different noninvasive tumor types. Two-dimensional estimates only distinguished benign from malignant tumors with considerable overlap and with significantly varying influence from other factors among different benign lesional...

  7. A retrospective study comparing the accuracy of prehistology diagnosis and surgical excision of malignant melanomas by general practitioners and hospital specialists.

    Science.gov (United States)

    Bakhai, M; Hopster, D; Wakeel, R

    2010-01-01

    A retrospective study was carried out to compare the overall standard of surgical excision of malignant melanomas (MMs) between general practitioners (GPs) and hospital specialists before and after the introduction of the UK melanoma guidelines between 1989 and 2006. In total, 213 melanoma excision reports were examined and surgical excision margins recorded. The results showed a significant difference in the rate of adequate surgical excision margins (at all levels of Breslow thickness) between GPs and hospital specialists, with hospital specialists excising melanomas with safe surgical excision margins at a significantly higher rate compared with GPs. Since the introduction of the guidelines in 2002, GPs showed a significant improvement in the completeness of melanoma excision but remained poor at prehistology diagnosis and in particular at taking adequate excision margins. Implementation of the guidelines has not produced significant improvements in adequacy of excision margins in both primary and secondary care. The results show that hospital specialists maintained a high standard of prehistological diagnosis and completeness of excision throughout the time of the study, performing at a significantly higher standard compared with GPs. Our conclusions concur with the UK melanoma guidelines and the National Institute for Health and Clinical Excellence guidelines, which suggest that lesions suspicious for melanoma should be urgently referred to a dermatologist or plastic surgeon for surgical excision and should not be surgically excised in primary care, particularly if lesions have a Breslow thickness > 2 mm. We suggest that the new guidelines need to be more aggressively implemented in primary care and guidance introduced to improve the accuracy of diagnosis, with better training provided for GPs.

  8. Concordance in BRAF V600E status over time in malignant melanoma and corresponding metastases

    DEFF Research Database (Denmark)

    Nielsen, Line Bjerrehave; Dabrosin, Nina; Sloth, Karen

    2017-01-01

    of inter-tumour heterogeneity between the primary tumour and the corresponding metastases, time as a factor was also investigated. METHODS: In total, 227 samples from 224 melanoma patients were analysed using both the Cobas® 4800 BRAF V600 Mutation test and IHC anti-BRAF V600E staining. In 82 primary......AIMS: The present study analysed the usability of an immunohistochemical (IHC) analysis compared to a frequently used mutation detection analysis and examined the extent of intra- and inter-tumour heterogeneity of BRAF V600E in primary tumours and their corresponding metastases. In the development...... tumours and 224 corresponding metastases, the extent of inter- and intra-tumour heterogeneity was investigated using IHC staining. RESULTS: In 15 cases, disagreement between IHC analysis and the Cobas test was seen. In all but one of the examined patients, homogeneity between the primary tumour...

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

    Science.gov (United States)

    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

  10. A comparison of high dose Ga-67 SPECT and FDG PET imaging in malignant melanoma

    International Nuclear Information System (INIS)

    Kaliff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A.

    1998-01-01

    Full text: Ga-67 imaging for tumour localisation lost favour in the 1970's. With improvement in technology and use of higher doses, it has now found an important role in lymphoma. A similar phenomenon may be possible in the staging of melanoma. This study therefore compares high dose (370 MBq) Ga-67 imaging using a day 5 and 7 whole-body and comprehensive SPECT protocol, with (100 MBq) F-18 fluorodeoxyglucose (FDG) imaging using positron emission tomography (PET): a technique recently shown to be highly accurate in this condition. 85 patients; 46 males, mean age 52+17 yrs: range 22-83 yrs, underwent both studies within 9±16 days (max-91 days). Scans were judged as positive (+ve), negative (-ve) or equivocal (EQ) for local, regional and distant disease. Clinical follow-up resolved discordant scan findings. PET and Ga-67 results were concordant in 61 (70%) patients (19 with +ve, 37 -ve and 5 EQ scans). None of the 9 ps with one EQ and one eye scan had disease on follow-up. Follow-up was available in 4/5 patients with discordantly +ve (3 patients) or more extensive Ga-67 abnormality: 3 patients had disease confirmed, 1 patient false +ve (asymmetric lung hilum). Follow-up was available in 9/10 patients with discordantly +ve (3 patients) or more extensive PET abnormality: 4 patients had confirmed disease, l pt false +ve (bladder diverticulum). A further 4 patients had second primaries (2 rectal carcinomas, 1 plasmacytoma, 1 basal cell carcinoma). High dose Ga-67 scanning incorporating SPECT appears to be a reasonable alternative to FDG PET for screening patients with melanoma. In this series PET's main advantages were in the detection of other occult tumours, greater patient convenience and lower radiation dosimetry

  11. Identification of the sentinel lymph node in patients with malignant melanoma: what are the reasons for mistakes?

    International Nuclear Information System (INIS)

    Vidal-Sicart, Sergi; Pons, Francesca; Puig, Susana; Vilalta, Antonio; Palou, J.M.; Castel, Teresa; Ortega, Marisa; Martin, Francisco; Rull, Ramon

    2003-01-01

    Scintigraphic identification of the sentinel lymph node is achievable in nearly all patients with malignant melanoma. However, in a very small number of cases the sentinel node fails to be detected, and sometimes recurrence appears during follow-up in patients who had previously tested negative for metastatic disease. The purpose of this study was to review our experience in order to isolate the reasons for erroneous sentinel lymph node identification. The evaluation involved 435 consecutive malignant melanoma patients with AJCC stages I and II (clinically negative nodes) and Breslow thickness >0.76 mm. Lymphoscintigraphy was performed the day before surgery by intradermal administration of technetium-99m labelled nanocolloid. Dynamic and static images were obtained. The sentinel node was intraoperatively identified with the aid of patent blue dye and a hand-held gamma probe. After removal, routine histopathological examination with haematoxylin-eosin (H-E) and immunohistochemistry with S 100 and HMB45 (IHC) were performed. In those patients who developed regional recurrences during follow-up, sentinel nodes were further evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR). Lymphoscintigraphy visualised at least one sentinel node in 434 out of 435 patients (99.8%). Uptake in in-transit sentinel lymph nodes was observed in 32 patients (7.4%). During surgery, localisation and removal of sentinel nodes was successful in 430/435 patients (98.8%). A total of 790 sentinel lymph nodes were harvested, with a mean of 1.8 per patient. Routine histopathological examination with H-E or IHC revealed metastatic disease in 72 patients (16.8%). During a mean follow-up of 26 months, seven of those patients with a negative sentinel node developed regional lymph node metastases. In five of them RT-PCR was positive for micrometastases within the sentinel node. In conclusion, erroneous sentinel lymph node identification can be due to changes in the surgical team

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

    Science.gov (United States)

    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.

  13. Burden of Melanoma

    NARCIS (Netherlands)

    C. Holterhues (Cynthia)

    2011-01-01

    markdownabstract__Abstract__ Melanoma is a type of skin cancer that arises from melanocytes. More than 95% of all melanomas occur in the skin, but rarely in the pigmented cells of the eye, meninges or mucosa. This thesis will only regard the invasive cutaneous malignant melanomas.

  14. Acne in late adolescence is not associated with a raised risk of subsequent malignant melanoma among men.

    Science.gov (United States)

    Mota Garcia, Teresa; Hiyoshi, Ayako; Udumyan, Ruzan; Sjöqvist, Hugo; Fall, Katja; Montgomery, Scott

    2017-12-01

    To evaluate the association of acne in late adolescence with the risk for subsequent malignant melanoma (MM) in men. Swedish register-based cohort study of 242,096 males born between 1952 and 1956, who took part in compulsory assessments for Swedish military conscription in late adolescence between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December 31, 2009. Covariates included measures of childhood circumstances and information from adolescence on presence of acne, physical fitness, cognitive function, body mass index (BMI), and a summary of diagnoses. Cox regression was used for the analysis. In total 1,058 men were diagnosed with MM. Acne was not associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers, and men who lived in northern Sweden, had lower physical fitness, or lower cognitive function had a lower risk of MM. Overweight and obesity was associated with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71). Acne in late adolescence is unlikely to represent a raised risk for subsequent MM in men. Overweight or obesity was identified as a raised risk for MM, possibly due to the associated increased skin surface area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Effect of single-dose x irradiation on the growth curves of a human malignant melanoma transplanted into nude mice

    International Nuclear Information System (INIS)

    Spang-Thomsen, M.; Visfeldt, J.; Nielsen, A.

    1981-01-01

    A human malignant melanoma transplanted into nude mice was exposed to single-dose x irradiation. Experimental growth data described mathematically according to a transformed Gompertz function were used to determine the effect of irradiation on growth delay, growth rate, and tumor shrinkage. The radiation-induced changes in the histology of the tumors were also described. The results showed that irradiation induced a dose-dependent growth delay; this parameter was therefore found suitable for the assessment of relative therapeutic effect. The treatment also induced a dose-dependent reduction in growth rate during regrowth. As a result of this effect on growth rate, extrapolation of tumor shrinkage to the time of treatment became directly misleading as a measure of the effect of the treatment. From this it can be deduced that in therapeutic studies where treatment induces nonparallel posttherapeutic growth curves, growth delay for various tumors and therapies cannot be compared directly. The transformed Gompertz function proved to be extremely well suited for evaluating these conditions

  16. High-dose proton beam therapy for sinonasal mucosal malignant melanoma

    International Nuclear Information System (INIS)

    Fuji, Hiroshi; Yoshikawa, Shusuke; Kasami, Masako; Murayama, Shigeyuki; Onitsuka, Tetsuro; Kashiwagi, Hiroya; Kiyohara, Yoshio

    2014-01-01

    The significance of definitive radiotherapy for sinonasal mucosal melanoma (SMM) is sill controvertial. This study was to evaluate the role of high-dose proton beam therapy (PBT) in patients with SMM. The cases of 20 patients with SMM localized to the primary site who were treated by PBT between 2006 and 2012 were retrospectively analyzed. The patterns of overall survival and morbidity were assessed. The median follow-up time was 35 months (range, 6–77 months). The 5-year overall and disease-free survival rates were 51% and 38%, respectively. Four patients showed local failure, 2 showed regrowth of the primary tumor, and 2 showed new sinonasal tumors beyond the primary site. The 5-year local control rate after PBT was 62%. Nodal and distant failure was seen in 7 patients. Three grade 4 late toxicities were observed in tumor-involved optic nerve. Our findings suggested that high-dose PBT is an effective local treatment that is less invasive than surgery but with comparable outcomes

  17. Retrospective analysis of drug utilization, health care resource use, and costs associated with IFN therapy for adjuvant treatment of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Zhang Y

    2015-07-01

    Full Text Available ≥Ying Zhang,1 Trong Kim Le,1 James W Shaw,2 Srividya Kotapati31Center for Observational Research and Data Sciences, Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Hopewell, NJ, USA; 2Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Princeton, NJ, USA; 3Worldwide Health Economics and Outcomes Research, Bristol-Myers Squibb Research and Development, Wallingford Center, CT, USABackground: This study examines real-world drug utilization patterns, health care resource use, and costs among patients receiving adjuvant treatment with IFN versus patients receiving no treatment ("observation" for malignant melanoma following surgery.Methods: A retrospective cohort study was conducted using administrative claims from Truven Health Analytics (MarketScan® to identify all adjuvant melanoma patients (aged ≥18 years diagnosed between June 2007 and June 2011 who had a lymph node dissection (ie, index surgery and were treated with IFN or subsequently observed. Health care resource use and costs of services were converted to 2012 US dollars and were evaluated and compared using multivariable regression.Results: Of 1,999 eligible subjects with melanoma surgery claims, 179 (9.0% were treated with IFN and 1,820 (91.0% were observed. The median duration (days and number of doses of IFN therapy were 73 and 36, respectively. Among IFN-treated patients, only 10.6% completed ≥80% of maintenance therapy. The total average cost for patients treated with IFN was US$60,755±$3,972 (n=179; significantly higher than for patients undergoing observation ($31,641±$2,471; P<0.0001. Similar trends were observed when evaluating total cost components, including melanoma-related and non-melanoma–related medical costs. Among the melanoma-related medical costs, outpatient services, including office visits and laboratory testing, represented between 33% and 53% of total costs and

  18. Metastatic melanoma of mesentery

    International Nuclear Information System (INIS)

    Shamim, M. S.; Ali, S.A.; Shirazi, B.; Shamim, M.

    2004-01-01

    A case of malignant melanoma metastatic to small bowel mesentery in an old female is reported. Her primary malignant melanoma of nasal mucosa was already treated. She presented with intestinal obstruction, underwent surgical excision of the tumour and was tumour-free postoperatively. (author)

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Naoya Maekawa

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  2. Clear Cell Sarcoma (Malignant Melanoma of Soft Parts: A Clinicopathologic Study of 52 Cases

    Directory of Open Access Journals (Sweden)

    O. Hocar

    2012-01-01

    Full Text Available Clear cell sarcomas are aggressive, rare soft tissue tumors and their classification among melanoma or sarcoma is still undetermined due to their clinical, pathologic, and molecular properties found in both types of tumors. This is a retrospective study of 52 patients with CCS seen between April 1979 and April 2005 in two institutions. The EWS-ATF-1 fusion transcript was studied in 31 patients and an activating mutation of the BRAF or NRAS gene was researched in 22 patients. 30 men and 22 women, with a mean age of 33 were studied. Forty-three tumors (82.69% were located in the extremities, specially the foot (19 tumors. Median initial tumor size was 4.8 cm (1 to 15 cm. Necrosis involving more than 50% of the tumor cells was found in 14 cases (26.92%. High mitotic rate (>10 was found in 25 cases (48.07%. The EWS/ATF-1 translocation was found in 28 (53.84% of 31 patients studied, and mutation of BRAF or NRAS was found in only 2 of 22 patients analyzed cases (3.84%. Among the tumor-associated parameters, only tumor size (>4 cm emerged as a significant prognostic factor. Forty-nine patients had a localized disease at diagnosis (94.23% and underwent surgical resection immediately (90% or after neoadjuvant chemotherapy (CT (10%. Various CT regimens were used in 37 patients (71.15% with no significant efficacy. The 5- and 10-year OS rates were 59% and 41%, respectively. Tumor size was the only emerging prognosis factor in our series. Complete surgical resection remains the optimal treatment for this aggressive chemoresistant tumor.

  3. TAPIOCA MELANOMA OF THE IRIS

    NARCIS (Netherlands)

    DEKEIZER, RJW; OOSTERHUIS, JA; HOUTMAN, WA; DEWOLFFROUENDAAL, D

    Clinical identification of tapioca melanoma of the iris is important because its medical treatment may differ from that of other malignant iris melanomas. The characteristic iris nodules must be differentiated from granulomatous uveitis, metastases, and Lisch nodules (neurofibromatosis). We will

  4. Pharmacokinetics of 111In-labeled anti-p97 monoclonal antibody in patients with metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Rosenblum, M.G.; Murray, J.L.; Haynie, T.P.; Glenn, H.J.; Jahns, M.F.; Benjamin, R.S.; Frincke, J.M.; Carlo, D.J.; Hersh, E.M.

    1985-01-01

    Twenty-eight patients with metastatic malignant melanoma received anti-p97 murine monoclonal antibody (96.5) infused over 2 h at doses between 1 and 20 mg coupled to either 2.5 or 5.0 mCi of 111 In by the bifunctional chelating agent diethyltriaminepentaacetic acid. Clearance of 111 In from plasma closely fit an open, one-compartment mathematical model (r2 greater than 0.90). The overall half-life of 111 In plasma was approximately 31 h and did not appear to be dependent on the total dose of antibody administered. The apparent volume of distribution of the 111 In label approximated the total blood volume (7.8 +/- 0.7 liters) at the 1-mg dose and decreased to 3.0 +/- 0.14 liters at the 20-mg dose, suggesting saturation of antigenic or other extravascular binding sites at higher antibody doses. The clearance of the murine monoclonal antibody itself from plasma was measured by an enzyme-linked immunosorbent assay. The pharmacokinetics for the murine antibody in plasma also fit an open, one-compartment mathematical model. All pharmacokinetic parameters for unlabeled antibody closely paralleled those found for 111 In-labeled antibody pharmacokinetics. This suggests that the 111 In radiolabel remains complexed to the monoclonal antibody after in vivo administration. The cumulative urinary excretion of the 111 In label over 48 h was between 12 and 23% of the total administered dose and is assumed to represent 111 In-labeled chelate complex unattached to antibody. Analysis of the 111 In label in spleen, liver, heart, and kidney showed that the concentration of label in liver tissue was reduced with increasing antibody doses and coincided with changes in the apparent volume of distribution

  5. CSPG4-specific immunity and survival prolongation in dogs with oral malignant melanoma immunized with human CSPG4 DNA.

    Science.gov (United States)

    Riccardo, Federica; Iussich, Selina; Maniscalco, Lorella; Lorda Mayayo, Saray; La Rosa, Giuseppe; Arigoni, Maddalena; De Maria, Raffaella; Gattino, Francesca; Lanzardo, Stefania; Lardone, Elena; Martano, Marina; Morello, Emanuela; Prestigio, Simone; Fiore, Alessandra; Quaglino, Elena; Zabarino, Sara; Ferrone, Soldano; Buracco, Paolo; Cavallo, Federica

    2014-07-15

    Due to the many similarities with its human counterpart, canine malignant melanoma (cMM) is a valuable model in which to assess the efficacy of novel therapeutic strategies. The model is herein used to evaluate the immunogenicity, safety, and therapeutic efficacy of a human chondroitin sulfate proteoglycan-4 (hCSPG4) DNA-based vaccine. The fact that homology between hCSPG4 and cCSPG4 amino-acidic sequences stands at more than 80% provides the rationale for using an hCSPG4 DNA vaccine in the cMM model. Dogs with stage II-III surgically resected CSPG4-positive oral MM were subjected to monthly intramuscular plasmid administration, which was followed immediately by electroporation (electrovaccination) for at least 6, and up to 20, months. The immunogenicity, safety, and therapeutic efficacy of the vaccine have been evaluated. hCSPG4 electrovaccination caused no clinically relevant local or systemic side effects and resulted in significantly longer overall and disease-free survival times in 14 vaccinated dogs as compared with 13 nonvaccinated controls. All vaccinated dogs developed antibodies against both hCSPG4 and cCSPG4. Seven vaccinated dogs were also tested for a cCSPG4-specific T-cell response and only two gave a detectable interferon (IFN)γ response. Xenogeneic electrovaccination against CSPG4 is able to overcome host unresponsiveness to the "self" antigen and seems to be effective in treating cMM, laying the foundation for its translation to a human clinical setting. ©2014 American Association for Cancer Research.

  6. Evaluation of cisplatin combined with piroxicam for the treatment of oral malignant melanoma and oral squamous cell carcinoma in dogs.

    Science.gov (United States)

    Boria, Pedro A; Murry, Daryl J; Bennett, Peter F; Glickman, Nita W; Snyder, Paul W; Merkel, Brenna L; Schlittler, Deborah L; Mutsaers, Anthony J; Thomas, Rose M; Knapp, Deborah W

    2004-02-01

    To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors. Prospective nonrandomized clinical trial. 25 dogs. Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone. 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam. Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

  7. Anorectal and Pelvic Pain.

    Science.gov (United States)

    Bharucha, Adil E; Lee, Tae Hee

    2016-10-01

    Although pelvic pain is a symptom of several structural anorectal and pelvic disorders (eg, anal fissure, endometriosis, and pelvic inflammatory disease), this comprehensive review will focus on the 3 most common nonstructural, or functional, disorders associated with pelvic pain: functional anorectal pain (ie, levator ani syndrome, unspecified anorectal pain, and proctalgia fugax), interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. The first 2 conditions occur in both sexes, while the latter occurs only in men. They are defined by symptoms, supplemented with levator tenderness (levator ani syndrome) and bladder mucosal inflammation (interstitial cystitis). Although distinct, these conditions share several similarities, including associations with dysfunctional voiding or defecation, comorbid conditions (eg, fibromyalgia, depression), impaired quality of life, and increased health care utilization. Several factors, including pelvic floor muscle tension, peripheral inflammation, peripheral and central sensitization, and psychosocial factors, have been implicated in the pathogenesis. The management is tailored to symptoms, is partly supported by clinical trials, and includes multidisciplinary approaches such as lifestyle modifications and pharmacological, behavioral, and physical therapy. Opioids should be avoided, and surgical treatment has a limited role, primarily in refractory interstitial cystitis. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. Insights into the therapeutic potential of hypoxia-inducible factor-1α small interfering RNA in malignant melanoma delivered via folate-decorated cationic liposomes

    Directory of Open Access Journals (Sweden)

    Chen Z

    2016-03-01

    Full Text Available Zhongjian Chen,1,* Tianpeng Zhang,2,* Baojian Wu,2 Xingwang Zhang2 1Department of Pharmaceutics, Shanghai Dermatology Hospital, 2Division of Pharmaceutics, College of Pharmacy, Jinan University, Gangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Malignant melanoma (MM represents the most dangerous form of skin cancer, and its incidence is expected to rise in the coming time. However, therapy for MM is limited by low topical drug concentration and multidrug resistance. This article aimed to develop folate-decorated cationic liposomes (fc-LPs for hypoxia-inducible factor-1α (HIF-1α small interfering (siRNA delivery, and to evaluate the potential of such siRNA/liposome complexes in MM therapy. HIF-1α siRNA-loaded fc-LPs (siRNA-fc-LPs were prepared by a film hydration method followed by siRNA incubation. Folate decoration of liposomes was achieved by incorporation of folate/oleic acid-diacylated oligochitosans. The resulting siRNA-fc-LPs were 95.3 nm in size with a ζ potential of 2.41 mV. The liposomal vectors exhibited excellent loading capacity and protective effect toward siRNA. The in vitro cell transfection efficiency was almost parallel to the commercially available Lipofectamine™ 2000. Moreover, the anti-melanoma activity of HIF-1α siRNA was significantly enhanced through fc-LPs. Western blot analysis and apoptosis test demonstrated that siRNA-fc-LPs substantially reduced the production of HIF-1α-associated protein and induced the apoptosis of hypoxia-tolerant melanoma cells. Our designed liposomal vectors might be applicable as siRNA delivery vehicle to systemically or topically treat MM. Keywords: malignant melanoma, HIF-1α siRNA, chitosan, cationic liposomes, gene therapy

  9. A canine chimeric monoclonal antibody targeting PD-L1 and its clinical efficacy in canine oral malignant melanoma or undifferentiated sarcoma.

    Science.gov (United States)

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

    2017-08-21

    Immunotherapy targeting immune checkpoint molecules, programmed cell death 1 (PD-1) and PD-ligand 1 (PD-L1), using therapeutic antibodies has been widely used for some human malignancies in the last 5 years. A costimulatory receptor, PD-1, is expressed on T cells and suppresses effector functions when it binds to its ligand, PD-L1. Aberrant PD-L1 expression is reported in various human cancers and is considered an immune escape mechanism. Antibodies blocking the PD-1/PD-L1 axis induce antitumour responses in patients with malignant melanoma and other cancers. In dogs, no such clinical studies have been performed to date because of the lack of therapeutic antibodies that can be used in dogs. In this study, the immunomodulatory effects of c4G12, a canine-chimerised anti-PD-L1 monoclonal antibody, were evaluated in vitro, demonstrating significantly enhanced cytokine production and proliferation of dog peripheral blood mononuclear cells. A pilot clinical study was performed on seven dogs with oral malignant melanoma (OMM) and two with undifferentiated sarcoma. Objective antitumour responses were observed in one dog with OMM (14.3%, 1/7) and one with undifferentiated sarcoma (50.0%, 1/2) when c4G12 was given at 2 or 5 mg/kg, every 2 weeks. c4G12 could be a safe and effective treatment option for canine cancers.

  10. In vitro and in vivo cytotoxic activity of human lactoferricin derived antitumor peptide R-DIM-P-LF11-334 on human malignant melanoma.

    Science.gov (United States)

    Riedl, Sabrina; Rinner, Beate; Schaider, Helmut; Liegl-Atzwanger, Bernadette; Meditz, Katharina; Preishuber-Pflügl, Julia; Grissenberger, Sarah; Lohner, Karl; Zweytick, Dagmar

    2017-09-22

    Di-peptides derived from the human host defense peptide lactoferricin were previously described to specifically interact with the negatively charged lipid phosphatidylserine exposed by cancer cells. In this study one further derivative, namely R-DIM-P-LF11-334 is shown to exhibit even increased cancer toxicity in vitro and in vivo while non-neoplastic cells are not harmed. In liposomal model systems composed of phosphatidylserine mimicking cancerous and phosphatidylcholine mimicking non-cancerous membranes the specific interaction with the cancer marker PS was confirmed by specific induction of membrane perturbation and permeabilization in presence of the peptide. In vitro studies with cell lines of human malignant melanoma, such as A375, or primary cells of human melanoma metastases to the brain, as MUG Mel1, and non-neoplastic human dermal fibroblasts NHDF revealed high cytotoxic effect of R-DIM-P-LF11-334 on melanoma cells of A375 and MUG Mel1, whereas only minor effect on the dermal fibroblasts NHDF was observed, yielding an about 20-fold killing-specificity for A375 and MUG-Mel1. The LC 50 values for melanoma A375 and MUG Mel1 were about 10 μM. Analysis of secondary structure of the peptide revealed an increase in the proportion of β-sheets exclusively in presence of the cancer mimic. Stability studies further indicated a potential adequate stability in blood or under stringent conditions. Importantly the cytotoxic effect on cancer cells was also proven in vivo in mouse xenografts of human melanoma, where peptide treatment induced strong tumor regression and in average a tumor area reduction of 85% compared to tumors of control mice without peptide treatment.

  11. Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Smith, P.J.; Greene, M.H.; Adams, D.; Paterson, M.C.

    1983-01-01

    The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. An extension of these studies is reported in which we have examined the invitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. The data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients

  12. The evaluaton of prevalence rate of p53 antigen expression in cutaneous malignant melanoma and it′s relation to tumor thickness

    Directory of Open Access Journals (Sweden)

    Faghihi Gita

    2005-01-01

    Full Text Available P53 tumor suppressor gene mutation is one of the most common genetic alteration in human malignancies. This study was done to determine the prevalence of the P53 antigen expression by sex, age, type of melanoma, thickness of the lesion and site of the antigen expression either cytoplasmic or nuclear. Paraffin embeded block of 50 patients (45 primary and metastaticwith documented diagnosis of melanoma deparaffinized and immuno stained with DO-7 monoclonal antibody. The lesions were divided depending on the degree of the staining as follow: 1. no staining, 2. mild (less than 10%, 3. moderate (10%-50% staining, 4. severe (more than 50%. Fifty four percent of evaluated patients were female and 46% were male. Forty percent of lesions were graded as no staining, 36% of lesions showed mild staining, 14% moderate and 10% severe staining site of expression was excusively in the cytoplasm. There was no meaningful statistical deference between severity of staining and the age group, sex, type and thickness of melanoma. (p value was 0.532, 0.488, 0.626, 0.954 respectively.

  13. Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Stoffels, Ingo; Leyh, Julia; Schadendorf, Dirk; Klode, Joachim [University of Duisburg-Essen, Department of Dermatology, Venerology and Allergology, University-Hospital Essen, Essen (Germany); Mueller, Markus [University of Duisburg-Essen, Department of Medical controlling, University-Hospital Essen, Essen (Germany); Geisel, Marie Henrike [University of Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, University-Hospital Essen, Essen (Germany); Poeppel, Thorsten [University of Duisburg-Essen, Department of Nuclear Medicine, University-Hospital Essen, Essen (Germany)

    2014-09-15

    Malignant melanoma has become a major growing interdisciplinary problem in public health worldwide. Sentinel lymph node excision (SLNE) in conjunction with preoperative SPECT/CT is considered the most sensitive and specific staging test for the detection of micrometastatic melanoma in regional lymph nodes. Among patients with clinically lymph node-negative melanoma, the use of SPECT/CT-aided SLNE compared with SLNE alone has been found to be associated with a higher frequency of metastatic involvement and a higher rate of disease-free survival. The aim of this study was to analyse the cost-effectiveness of SLNE with preoperative SPECT/CT for detecting sentinel lymph nodes versus that of standard SLNE with preoperative lymphoscintigraphy from a single-institution database. Cost-effectiveness analysis of two surgical approaches for SLNE for malignant melanoma at the University Hospital Essen, Skin Cancer Center in Essen, Germany. Between March 2003 and April 2011 464 patients eligible for SLNE were identified. Of these patients, 403 with clinically negative lymph nodes who underwent SLNE with or without preoperative SPECT/CT qualified for subsequent analysis. Between March 2003 and October 2008, 254 patients were operated upon with the standard technique. From November 2008, 149 patients underwent the SPECT/CT technique. Cost analysis showed a mean cost saving of EUR 710.50 when SPECT/CT was added to preoperative imaging. This was achieved by a reduction in operative time (median, Q1;Q3, 40 min, 40;50 min, vs. 45 min, 35;60 min; p = 0.002), hospital stay duration (5 days, 3;8 days, vs. 8 days, 4.5;14.5 days; p < 0.001) and more frequent use of local anaesthesia (90.6 % vs. 70.5 %; p < 0.001). The median cost of SLNE using SPECT/CT was EUR 1,619.7 (Q1;Q3 EUR 1,317.0;2,603.4) and of SLNE without SPECT/CT was EUR 2,330.2 (EUR 1,468.3;4,058.1; p < 0.001), a cost saving of 30.5 %. In patients with cutaneous melanoma, the use of preoperative SPECT/CT-aided SLNE compared

  14. NAD(P)H:Quinone Oxidoreductase-1 Expression Sensitizes Malignant Melanoma Cells to the HSP90 Inhibitor 17-AAG.

    Science.gov (United States)

    Kasai, Shuya; Arakawa, Nobuyuki; Okubo, Ayaka; Shigeeda, Wataru; Yasuhira, Shinji; Masuda, Tomoyuki; Akasaka, Toshihide; Shibazaki, Masahiko; Maesawa, Chihaya

    2016-01-01

    The KEAP1-NRF2 pathway regulates cellular redox homeostasis by transcriptional induction of genes associated with antioxidant synthesis and detoxification in response to oxidative stress. Previously, we reported that KEAP1 mutation elicits constitutive NRF2 activation and resistance to cisplatin (CDDP) and dacarbazine (DTIC) in human melanomas. The present study was conducted to clarify whether an HSP90 inhibitor, 17-AAG, efficiently eliminates melanoma with KEAP1 mutation, as the NRF2 target gene, NQO1, is a key enzyme in 17-AAG bioactivation. In melanoma and non-small cell lung carcinoma cell lines with or without KEAP1 mutations, NQO1 expression and 17-AAG sensitivity are inversely correlated. NQO1 is highly expressed in normal melanocytes and in several melanoma cell lines despite the presence of wild-type KEAP1, and the NQO1 expression is dependent on NRF2 activation. Because either CDDP or DTIC produces reactive oxygen species that activate NRF2, we determined whether these agents would sensitize NQO1-low melanoma cells to 17-AAG. Synergistic cytotoxicity of the 17-AAG and CDDP combination was detected in four out of five NQO1-low cell lines, but not in the cell line with KEAP1 mutation. These data indicate that 17-AAG could be a potential chemotherapeutic agent for melanoma with KEAP1 mutation or NQO1 expression.

  15. Advanced malignant melanoma during pregnancy: technical description of sentinel lymph node biopsy followed by radical lymph node dissection

    Directory of Open Access Journals (Sweden)

    Alberto Julius Alves Wainstein

    2015-12-01

    Full Text Available Abstract Introduction: melanoma is a very aggressive cancer, with increasing incidence, and is currently the fifth most common cancer in men and the sixth most common in women in the United States. Melanoma is not unusual in pregnancy, with an estimated occur-rence rate of 1:1.000. Although not the most common cancer in pregnancy, melanoma is the tumor with the highest incidence ofplacenta and fetus metastases. Description: a 29-year-old lady, 4 weeks after conception underwent resection of an atypical pigmented lesion after a diagnosis of stage T4b melanoma. At 16 weeks she underwent a broad local excision and sentinel lymph node (SLN biopsy. SLN was evaluated histologically and tested positive for melanoma. A radical axillary lymphadenectomy was performed on the patient without evidence of metas-tasis in any other LN. In the 40th week of pregnancy, labor was induced and a healthy newborn was deli-vered via cesarean. Discussion: melanoma management in pregnancy is more complex and requires multidisciplinary coor-dination, as well as extensive discussion with the patient and her family. We present a case report description in which treatment recommendations are established according to no pregnancy experience.

  16. The electronics in fluorescent bulbs and light emitting diodes (LED), rather than ultraviolet radiation, cause increased malignant melanoma incidence in indoor office workers and tanning bed users.

    Science.gov (United States)

    Milham, Samuel; Stetzer, Dave

    2018-07-01

    The epidemiology of cutaneous malignant melanoma (CMM) has a number of facets that do not fit with sunlight and ultraviolet light as the primary etiologic agents. Indoor workers have higher incidence and mortality rates of CMM than outdoor workers; CMM occurs in body locations never exposed to sunlight; CMM incidence is increasing in spite of use of UV blocking agents and small changes in solar radiation. Installation of two new fluorescent lights in the milking parlor holding area of a Minnesota dairy farm in 2015 caused an immediate drop in milk production. This lead to measurement of body amperage in humans exposed to modern non-incandescent lighting. People exposed to old and new fluorescent lights, light emitting diodes (LED) and compact fluorescent lights (CFL) had body amperage levels above those considered carcinogenic. We hypothesize that modern electric lighting is a significant health hazard, a carcinogen, and is causing increasing CMM incidence in indoor office workers and tanning bed users. These lights generate dirty electricity (high frequency voltage transients), radio frequency (RF) radiation, and increase body amperage, all of which have been shown to be carcinogenic. This could explain the failure of ultraviolet blockers to stem the malignant melanoma pandemic. Tanning beds and non-incandescent lighting could be made safe by incorporating a grounded Faraday cage which allows passage of ultraviolet and visible light frequencies and blocks other frequencies. Modern electric lighting should be fabricated to be electrically clean. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Adaptable pattern recognition system for discriminating Melanocytic Nevi from Malignant Melanomas using plain photography images from different image databases.

    Science.gov (United States)

    Kostopoulos, Spiros A; Asvestas, Pantelis A; Kalatzis, Ioannis K; Sakellaropoulos, George C; Sakkis, Theofilos H; Cavouras, Dionisis A; Glotsos, Dimitris T

    2017-09-01

    The aim of this study was to propose features that evaluate pictorial differences between melanocytic nevus (mole) and melanoma lesions by computer-based analysis of plain photography images and to design a cross-platform, tunable, decision support system to discriminate with high accuracy moles from melanomas in different publicly available image databases. Digital plain photography images of verified mole and melanoma lesions were downloaded from (i) Edinburgh University Hospital, UK, (Dermofit, 330moles/70 melanomas, under signed agreement), from 5 different centers (Multicenter, 63moles/25 melanomas, publicly available), and from the Groningen University, Netherlands (Groningen, 100moles/70 melanomas, publicly available). Images were processed for outlining the lesion-border and isolating the lesion from the surrounding background. Fourteen features were generated from each lesion evaluating texture (4), structure (5), shape (4) and color (1). Features were subjected to statistical analysis for determining differences in pictorial properties between moles and melanomas. The Probabilistic Neural Network (PNN) classifier, the exhaustive search features selection, the leave-one-out (LOO), and the external cross-validation (ECV) methods were used to design the PR-system for discriminating between moles and melanomas. Statistical analysis revealed that melanomas as compared to moles were of lower intensity, of less homogenous surface, had more dark pixels with intensities spanning larger spectra of gray-values, contained more objects of different sizes and gray-levels, had more asymmetrical shapes and irregular outlines, had abrupt intensity transitions from lesion to background tissue, and had more distinct colors. The PR-system designed by the Dermofit images scored on the Dermofit images, using the ECV, 94.1%, 82.9%, 96.5% for overall accuracy, sensitivity, specificity, on the Multicenter Images 92.0%, 88%, 93.7% and on the Groningen Images 76.2%, 73.9%, 77

  18. Differential inhibition of ex-vivo tumor kinase activity by vemurafenib in BRAF(V600E and BRAF wild-type metastatic malignant melanoma.

    Directory of Open Access Journals (Sweden)

    Andliena Tahiri

    Full Text Available Treatment of metastatic malignant melanoma patients harboring BRAF(V600E has improved drastically after the discovery of the BRAF inhibitor, vemurafenib. However, drug resistance is a recurring problem, and prognoses are still very bad for patients harboring BRAF wild-type. Better markers for targeted therapy are therefore urgently needed.In this study, we assessed the individual kinase activity profiles in 26 tumor samples obtained from patients with metastatic malignant melanoma using peptide arrays with 144 kinase substrates. In addition, we studied the overall ex-vivo inhibitory effects of vemurafenib and sunitinib on kinase activity status.Overall kinase activity was significantly higher in lysates from melanoma tumors compared to normal skin tissue. Furthermore, ex-vivo incubation with both vemurafenib and sunitinib caused significant decrease in phosphorylation of kinase substrates, i.e kinase activity. While basal phosphorylation profiles were similar in BRAF wild-type and BRAF(V600E tumors, analysis with ex-vivo vemurafenib treatment identified a subset of 40 kinase substrates showing stronger inhibition in BRAF(V600E tumor lysates, distinguishing the BRAF wild-type and BRAF(V600E tumors. Interestingly, a few BRAF wild-type tumors showed inhibition profiles similar to BRAF(V600E tumors. The kinase inhibitory effect of vemurafenib was subsequently analyzed in cell lines harboring different BRAF mutational status with various vemurafenib sensitivity in-vitro.Our findings suggest that multiplex kinase substrate array analysis give valuable information about overall tumor kinase activity. Furthermore, intra-assay exposure to kinase inhibiting drugs may provide a useful tool to study mechanisms of resistance, as well as to identify predictive markers.

  19. The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma.

    Science.gov (United States)

    Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

    2015-01-01

    Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation.

  20. The Added Value of a Single-photon Emission Computed Tomography-Computed Tomography in Sentinel Lymph Node Mapping in Patients with Breast Cancer and Malignant Melanoma

    International Nuclear Information System (INIS)

    Bennie, George; Vorster, Mariza; Buscombe, John; Sathekge, Mike

    2015-01-01

    Single-photon emission computed tomography-computed tomography (SPECT-CT) allows for physiological and anatomical co-registration in sentinel lymph node (SLN) mapping and offers additional benefits over conventional planar imaging. However, the clinical relevance when considering added costs and radiation burden of these reported benefits remains somewhat uncertain. This study aimed to evaluate the possible added value of SPECT-CT and intra-operative gamma-probe use over planar imaging alone in the South African setting. 80 patients with breast cancer or malignant melanoma underwent both planar and SPECT-CT imaging for SLN mapping. We assessed and compared the number of nodes detected on each study, false positive and negative findings, changes in surgical approach and or patient management. In all cases where a sentinel node was identified, SPECT-CT was more accurate anatomically. There was a significant change in surgical approach in 30 cases - breast cancer (n = 13; P 0.001) and malignant melanoma (n = 17; P 0.0002). In 4 cases a node not identified on planar imaging was seen on SPECT-CT. In 16 cases additional echelon nodes were identified. False positives were excluded by SPECT-CT in 12 cases. The addition of SPECT-CT and use of intra-operative gamma-probe to planar imaging offers important benefits in patients who present with breast cancer and melanoma. These benefits include increased nodal detection, elimination of false positives and negatives and improved anatomical localization that ultimately aids and expedites surgical management. This has been demonstrated in the context of industrialized country previously and has now also been confirmed in the setting of a emerging-market nation

  1. Pancreatic metastases from ocular malignant melanoma: the use of endoscopic ultrasound-guided fine-needle aspiration to establish a definitive cytologic diagnosis: a case report

    Directory of Open Access Journals (Sweden)

    Diogo Turiani Hourneaux De Moura

    2016-12-01

    Full Text Available Abstract Background When encountering solid pancreatic lesions, nonpancreatic primary metastases are rare and differentiating a metastasis from a primary neoplastic lesion is challenging. The clinical presentation and radiologic features can be similar and the possibility of a pancreatic metastasis should be considered when the patient refers to a history of a different primary cancer. Endoscopic ultrasound offers a key anatomical advantage in accessing the pancreas and endoscopic ultrasound-guided fine-needle aspiration has become the gold standard method for diagnosing pancreatic lesions. Case presentation A 58-year-old white Hispanic woman with a history of uveal malignant melanoma, presented with abdominal pain and jaundice. On admission, laboratory tests were performed (her total bilirubin was 6.37 mg/dL with a direct fraction of 5.30 mg/dL. Cross-sectional, abdominal computed tomography with contrast, showed a low-attenuating lesion localized in the pancreatic head (measuring 4 × 3 cm and a thinner section of the distal bile duct suspicious for compression. Our patient was scheduled for an endoscopic ultrasound-guided fine-needle aspiration to establish a diagnosis. Endoscopic ultrasound showed a solid, hypoechoic, well-defined lesion with regular contours (measuring 3.17 × 2.61 cm, localized between the head and neck of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration was performed with a 22G needle and cytology confirmed the diagnosis of metastatic melanoma. Our patient subsequently underwent right orbital exenteration, followed by duodenopancreatectomy without complications. At the moment our patient is receiving adjuvant chemotherapy at an outside oncology clinic. Conclusions To the best of our knowledge, this is a very rare presentation of an ocular malignant melanoma with an isolated pancreatic metastasis causing symptomatic biliary obstruction. Endoscopic ultrasound-guided fine-needle aspiration has

  2. Long Noncoding RNA Taurine-Upregulated Gene1 (TUG1) Promotes Tumor Growth and Metastasis Through TUG1/Mir-129-5p/Astrocyte-Elevated Gene-1 (AEG-1) Axis in Malignant Melanoma.

    Science.gov (United States)

    Long, Jianwen; Menggen, Qiqige; Wuren, Qimige; Shi, Quan; Pi, Xianming

    2018-03-15

    BACKGROUND Malignant melanoma is a class of malignant tumors derived from melanocytes. lncRNAs have been considered as pro-/anti-tumor factors in progression of cancers. The function of lncRNA TUG1 on growth of melanoma was investigated in this study. MATERIAL AND METHODS The TUG1 and miR-129-5p expression were examined via qRT-PCR. The protein expression was investigated by Western blotting assay. Luciferase reporter assay was used to assess if lncRNA TUG1 can bind to miR-129-5p and if miR-129-5p can target AEG1 mRNA. CCK-8 and apoptosis assay were used to detect cell growth and apoptosis. The metastasis of melanoma cells was detected by wound-healing and Transwell assays. The effects of TUG1 on growth of melanoma in vivo and cell chemoresistance were investigated via xenograft animal experiment and CCK-8 assay. RESULTS The expression of TUG1 and AEG1 was elevated and the miR-129-5p level was decreased in melanoma specimens and cell lines. Downregulation of either TUG1 or AEG1 suppressed cell growth and metastasis. miR-129-5p can bind directly to AEG1 and TUG1 can directly sponge miR-129-5p. Inhibition of TUG1 expression suppressed the expression of Bcl-2, MMP-9, and cyclin D1, and raised the level of cleaved caspase3 by modulating AEG1 level in melanoma cells. Inhibition of TUG1 reduced the growth of tumors in vivo and improved the chemosensitivity of A375 cells to cisplatin and 5-FU. CONCLUSIONS Reduction of TUG1 level suppressed cell growth and metastasis by regulating AEG1 expression mediated by targeting miR-129-5p. Suppression of lnc TUG1 may be a promising therapeutic strategy in the treatment of malignant melanoma.

  3. Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP in Patients with Malignant Melanoma.

    Directory of Open Access Journals (Sweden)

    Ruth Heise

    Full Text Available Interferon alpha (IFNα is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1 is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling.We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment.We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in 'silent' metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and monitor therapeutic

  4. Interferon Alpha Signalling and Its Relevance for the Upregulatory Effect of Transporter Proteins Associated with Antigen Processing (TAP) in Patients with Malignant Melanoma

    Science.gov (United States)

    Ensslen, Silke; Marquardt, Yvonne; Czaja, Katharina; Joussen, Sylvia; Beer, Daniel; Abele, Rupert; Plewnia, Gabriele; Tampé, Robert; Merk, Hans F.; Hermanns, Heike M.; Baron, Jens M.

    2016-01-01

    Introduction Interferon alpha (IFNα) is routinely used in the clinical practice for adjuvant systemic melanoma therapy. Understanding the molecular mechanism of IFNα effects and prediction of response in the IFNα therapy regime allows initiation and continuation of IFNα treatment for responder and exclusion of non-responder to avoid therapy inefficacy and side-effects. The transporter protein associated with antigen processing-1 (TAP1) is part of the MHC class I peptide-loading complex, and important for antigen presentation in tumor and antigen presenting cells. In the context of personalized medicine, we address this potential biomarker TAP1 as a target of IFNα signalling. Results We could show that IFNα upregulates TAP1 expression in peripheral blood mononuclear cells (PBMCs) of patients with malignant melanoma receiving adjuvant high-dose immunotherapy. IFNα also induced expression of TAP1 in mouse blood and tumor tissue and suppressed the formation of melanoma metastasis in an in vivo B16 tumor model. Besides its expression, TAP binding affinity and transport activity is induced by IFNα in human monocytic THP1 cells. Furthermore, our data revealed that IFNα clearly activates phosphorylation of STAT1 and STAT3 in THP1 and A375 melanoma cells. Inhibition of Janus kinases abrogates the IFNα-induced TAP1 expression. These results suggest that the JAK/STAT pathway is a crucial mediator for TAP1 expression elicited by IFNα treatment. Conclusion We suppose that silencing of TAP1 expression provides tumor cells with a mechanism to escape cytotoxic T-lymphocyte recognition. The observed benefit of IFNα treatment could be mediated by the shown dual effect of TAP1 upregulation in antigen presenting cells on the one hand, and of TAP1 upregulation in ‘silent’ metastatic melanoma cells on the other hand. In conclusion, this work contributes to a better understanding of the mode of action of IFNα which is essential to identify markers to predict, assess and

  5. Cutaneous metastasis in anorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Krishnendra Varma

    2015-01-01

    Full Text Available Cutaneous metastasis in anorectal adenocarcinoma is a rare entity. Here, we report the case of a 40-year-old female who presented with yellowish-brown, irregular, solid, elevated rashes over the pubis with a recent history off palliative colostomy for anorectal adenocarcinoma. Clinically, we suspected metastasis that was proved on biopsy. We report this case due to the rare presenting site (i.e., perineum of a metastatic adenocarcinoma.

  6. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

    DEFF Research Database (Denmark)

    Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina

    2014-01-01

    -dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1...

  7. HLA class Ia and Ib molecules and FOXP3+ TILs in relation to the prognosis of malignant melanoma patients

    DEFF Research Database (Denmark)

    Melsted, Wenna Nascimento; Johansen, Lasse Lindholm; Lock-Andersen, Jørgen

    2017-01-01

    HLA class Ia (HLA-ABC) and HLA class Ib (HLA-E, -F and -G) molecules and FOXP3+ tumor-infiltrating lymphocytes (TILs) are often reported as relevant factors of tumor immune regulation. We investigated their expression as prognostic factors in 200 patients with primary cutaneous melanoma (PCM...

  8. Protein expression changes induced in a malignant melanoma cell line by the curcumin analogue compound D6

    International Nuclear Information System (INIS)

    Pisano, Marina; Palomba, Antonio; Tanca, Alessandro; Pagnozzi, Daniela; Uzzau, Sergio; Addis, Maria Filippa; Dettori, Maria Antonietta; Fabbri, Davide; Palmieri, Giuseppe; Rozzo, Carla

    2016-01-01

    We have previously demonstrated that the hydroxylated biphenyl compound D6 (3E,3′E)-4,4′-(5,5′,6,6′-tetramethoxy-[1,1′-biphenyl]-3,3′-diyl)bis (but-3-en-2-one), a structural analogue of curcumin, exerts a strong antitumor activity on melanoma cells both in vitro and in vivo. Although the mechanism of action of D6 is yet to be clarified, this compound is thought to inhibit cancer cell growth by arresting the cell cycle in G2/M phase, and to induce apoptosis through the mitochondrial intrinsic pathway. To investigate the changes in protein expression induced by exposure of melanoma cells to D6, a differential proteomic study was carried out on D6-treated and untreated primary melanoma LB24Dagi cells. Proteins were fractionated by SDS-PAGE and subjected to in gel digestion. The peptide mixtures were analyzed by liquid chromatography coupled with tandem mass spectrometry. Proteins were identified and quantified using database search and spectral counting. Proteomic data were finally uploaded into the Ingenuity Pathway Analysis software to find significantly modulated networks and pathways. Analysis of the differentially expressed protein profiles revealed the activation of a strong cellular stress response, with overexpression of several HSPs and stimulation of ubiquitin-proteasome pathways. These were accompanied by a decrease of protein synthesis, evidenced by downregulation of proteins involved in mRNA processing and translation. These findings are consistent with our previous results on gene expression profiling in melanoma cells treated with D6. Our findings confirm that the curcumin analogue D6 triggers a strong stress response in melanoma cells, turning down majority of cell functions and finally driving cells to apoptosis. The online version of this article (doi:10.1186/s12885-016-2362-6) contains supplementary material, which is available to authorized users

  9. Melanoma maligno cutâneo: sistema de pontos (scoring system para auxílio no diagnóstico histopatológico Cutaneous malignant melanoma: scoring system to assist in the histopathologic diagnosis

    Directory of Open Access Journals (Sweden)

    Luiz Alberto Veronese

    2006-10-01

    . A total of 101 cases of extensive-superficial melanoma less than 2mm thick were comparatively analysed with 33 benign melanocytic lesions (thirteen Spitz nevi, six Reed nevi, six dysplastic nevi, three congenital nevi, three acquired nevi, one combined nevus and one recurrent nevus. RESULTS: The total amount of values obtained on histopathological criteria (scores pointed out significant statistical differences between benign and malignant lesions, what makes this method useful for surgical pathologist in daily routines. CONCLUSION: The objective and systematic application of histopathological criteria by means of the scoring system may be helpful in the differential diagnosis between benign and malignant melanocytic neoplasms, but the approach was not able to distinguish melanocytic lesions of unknown biological behavior.

  10. Phase I study of GC1008 (fresolimumab: a human anti-transforming growth factor-beta (TGFβ monoclonal antibody in patients with advanced malignant melanoma or renal cell carcinoma.

    Directory of Open Access Journals (Sweden)

    John C Morris

    Full Text Available In advanced cancers, transforming growth factor-beta (TGFβ promotes tumor growth and metastases and suppresses host antitumor immunity. GC1008 is a human anti-TGFβ monoclonal antibody that neutralizes all isoforms of TGFβ. Here, the safety and activity of GC1008 was evaluated in patients with advanced malignant melanoma and renal cell carcinoma.In this multi-center phase I trial, cohorts of patients with previously treated malignant melanoma or renal cell carcinoma received intravenous GC1008 at 0.1, 0.3, 1, 3, 10, or 15 mg/kg on days 0, 28, 42, and 56. Patients achieving at least stable disease were eligible to receive Extended Treatment consisting of 4 doses of GC1008 every 2 weeks for up to 2 additional courses. Pharmacokinetic and exploratory biomarker assessments were performed.Twenty-nine patients, 28 with malignant melanoma and 1 with renal cell carcinoma, were enrolled and treated, 22 in the dose-escalation part and 7 in a safety cohort expansion. No dose-limiting toxicity was observed, and the maximum dose, 15 mg/kg, was determined to be safe. The development of reversible cutaneous keratoacanthomas/squamous-cell carcinomas (4 patients and hyperkeratosis was the major adverse event observed. One malignant melanoma patient achieved a partial response, and six had stable disease with a median progression-free survival of 24 weeks for these 7 patients (range, 16.4-44.4 weeks.GC1008 had no dose-limiting toxicity up to 15 mg/kg. In patients with advanced malignant melanoma and renal cell carcinoma, multiple doses of GC1008 demonstrated acceptable safety and preliminary evidence of antitumor activity, warranting further studies of single agent and combination treatments.Clinicaltrials.gov NCT00356460.

  11. A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma.

    Science.gov (United States)

    Treggiari, Elisabetta; Grant, Jessica Pauline; North, Susan Margaret

    2016-06-01

    A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301-540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132-232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma.

  12. A prospective phase II study of adjuvant postoperative radiation therapy following nodal surgery in malignant melanoma-Trans Tasman Radiation Oncology Group (TROG) Study 96.06

    International Nuclear Information System (INIS)

    Burmeister, Bryan H.; Mark Smithers, B.; Burmeister, Elizabeth; Baumann, Kathryn; Davis, Sidney; Krawitz, Hedley; Johnson, Carol; Spry, Nigel

    2006-01-01

    Background: The role of adjuvant postoperative therapy after resection of localised malignant melanoma involving regional lymph nodes remains controversial. There are no randomised trials that confirm that postoperative radiation conveys a benefit in terms of regional control or survival. Methods: Two hundred and thirty-four patients with melanoma involving lymph nodes were registered on a prospective study to evaluate the effect of postoperative radiation therapy. The regimen consisted of 48 Gy in 20 fractions to the nodal basin using recommended treatment guidelines for each of the major node sites. The primary endpoints were regional in-field relapse and late toxicity. Secondary endpoints were adjacent relapse, distant relapse, overall survival, progression-free survival and time to in-field progression. Results: Adjuvant radiation therapy was well tolerated by all of the patients. As the first site of relapse, regional in-field relapses occurred in 16/234 patients (6.8%). The overall survival was 36% at 5 years. The progression-free survival and regional control rates were 27% and 91%, respectively, at 5 years. Patients with more than 2 nodes involved had a significantly worse outcome in terms of distant relapse, overall and progression-free survival. Conclusion: We believe that adjuvant radiation therapy following nodal surgery could offer a possible benefit in terms of regional control. These results require confirmation in a randomised trial

  13. Direct comparison of [18F]FDG PET/CT with PET alone and with side-by-side PET and CT in patients with malignant melanoma

    International Nuclear Information System (INIS)

    Mottaghy, Felix M.; Wohlfart, Petra; Blumstein, Norbert M.; Neumaier, Bernd; Glatting, Gerhard; Buck, Andreas K.; Reske, Sven N.; Sunderkoetter, Cord; Schubert, Roland; Oezdemir, Cueneyt; Scharfetter-Kochanek, Karin

    2007-01-01

    The purpose of this retrospective, blinded study was to evaluate the additional value of [ 18 F]FDG PET/CT in comparison with PET alone and with side-by-side PET and CT in patients with malignant melanoma (MM). A total of 127 consecutive studies of patients with known MM referred for a whole-body PET/CT examination were included in this study. PET alone, side-by-side PET and CT and integrated PET/CT study were independently and separately interpreted without awareness of the clinical information. One score each was applied for certainty of lesion localisation and for certainty of lesion characterisation. Verification of the findings was subsequently performed using all available clinical, pathological (n = 30) and follow-up information. The number of lesions with an uncertain localisation was significantly (p 18 F]FDG. (orig.)

  14. Preoperative 18F-FDG-PET/CT imaging and sentinel node biopsy in the detection of regional lymph node metastases in malignant melanoma.

    Science.gov (United States)

    Singh, Baljinder; Ezziddin, Samer; Palmedo, Holger; Reinhardt, Michael; Strunk, Holger; Tüting, Thomas; Biersack, Hans-Jürgen; Ahmadzadehfar, Hojjat

    2008-10-01

    The objective of this study was to evaluate the role of preoperative 18F-fluorodeoxyglucose-positron emission tomography/computed tomography scanning, preoperative lymphoscintigraphy (LS), and sentinel lymph node biopsy in patients with malignant melanoma. Fifty-two patients (36 men: 16 women; mean age 55.0+/-13.0 years; median age 61 years; range 17-76 years) with malignant melanoma were selected. According to the latest version of the American Joint Committee on Cancer staging system, the disease in the study patients was initially classified as either stage I or II. The other primary tumor characteristics were mean Breslow depth=2.87 mm and median=2 mm; range 1-12.0 mm and Clarks levels III-V. None of the study patients had clinical or radiological evidence of regional lymph node metastatic disease. At least one sentinel node was identified in all patients. Preoperative LS detected a total of 111 sentinel lymph nodes (average 2.13 sentinel lymph node per patient) and demonstrated a single nodal draining basin in 38 (73%) patients and multiple (2-3 draining basins) in the remaining 14 (27%) patients. Fourteen out of the 52 patients (27%) had at least one involved sentinel node. Positron emission tomography was true positive in two patients with a sentinel node greater than 1 cm and false positive in two other patients. In this study, the detection of sentinel lymph node by LS and gamma probe had a sensitivity of 100%. In contrast, 18F-FDG-PET imaging demonstrated very low sensitivity (14.3%; 95% CI, 2.5 to 44%) and positive predictive value (50%; 95% CI, 9 to 90%) for localizing the subclinical nodal metastases. The specificity, net present value, and diagnostic accuracy were 94.7, 75, and 73%, respectively. Preoperative fluorodeoxyglucose-positron emission tomography/computed tomography imaging is not able to substitute LS/sentinel lymph node biopsy in patients at stage I or II.

  15. siRNA - Mediated LRP/LR knock-down reduces cellular viability of malignant melanoma cells through the activation of apoptotic caspases.

    Science.gov (United States)

    Rebelo, Thalia M; Vania, Leila; Ferreira, Eloise; Weiss, Stefan F T

    2018-07-01

    The 37 kDa/67 kDa laminin receptor (LRP/LR) is over-expressed in tumor cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively. In order to determine the effect of LRP/LR on cell viability and apoptosis, LRP was down-regulated via siRNA technology. MTT assays revealed that LRP knock-down led to significant reductions in the viability of A375 and A375SM cells. Confocal microscopy indicated nuclear morphological changes suggestive of apoptotic induction in both cell lines and Annexin-V FITC/PI assays confirmed this observation. Additionally, caspase-3 activity assays revealed that apoptosis was induced in both cell lines after siRNA-mediated down-regulation of LRP. Caspase-8 and -9 activity assays suggested that post LRP knock-down; A375 cells undergo apoptosis solely via the extrinsic pathway, while A375SM cells undergo apoptosis via the intrinsic pathway. siRNAs mediated LRP knock-down might represent a powerful alternative therapeutic strategy for the treatment of malignant melanoma through the induction of apoptosis. Copyright © 2018. Published by Elsevier Inc.

  16. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    International Nuclear Information System (INIS)

    Fukumoto, Shinya; Hanazono, Kiwamu; Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi; Iwano, Hidetomo; Uchide, Tsuyoshi

    2013-01-01

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P 3 H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM. These findings suggest that LAT1 could be a new therapeutic target for MM

  17. Changes in visual acuity in patients with malignant melanoma of the uvea treated with stereotactic radiosurgery (presentation)

    International Nuclear Information System (INIS)

    Mackova, K.; Waczultkova, I.; Furdova, Ad.; Furdova, Al.

    2013-01-01

    The goal was to assess the changes in visual acuity before and after 6 months of treatment, depending on the dose in risk structures (lens, optic nerve). This is a retrospective study of 19 patients group treated in 2011. The average age of the group was (57.3 ± 12.4) years (31-73 years). The analysis of the studied group did not demonstrate dependence of the tumour presence on gender. Higher prevalence of tumours was observed in the elderly population. Considered relationship of worse diagnosis with higher age (r = 0.39; p = 0.13) we could not prove to be significant due to the small group of patients. The median of melanoma volume was 0.77 cm 3 (0.11 to 1.76 cubic centimetres). The mean dose applied to melanoma was 37.34 Gy (Gy 36.74 to 44.65).

  18. [Combined use of irradiation and DNA tumor vaccine to treat canine oral malignant melanoma: a pilot study].

    Science.gov (United States)

    Herzog, A; Buchholz, J; Ruess-Melzer, K; Lang, J; Kaser-Hotz, B

    2013-02-01

    Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

  19. [Hypofractionated radiation therapy for the treatment of malignant melanoma and squamous cell carcinoma in dogs and cats].

    Science.gov (United States)

    Kinzel, Sylvia; Hein, Sven; Stopinski, Thaddeus; Koch, Johannes; Buecker, Arno; Treusacher, Hans-Peter; Schmachtenberg, Axel; Jansen, Thomas; Eble, Michael; Küpper, Wernen

    2003-01-01

    This study describes the experience with hypofractionated radiation therapy of squamous cell carcinoma and melanoma in dogs and cats. A total dose of 32-48 Gray (Gy) was delivered once a week in 8 Gy fractions. 34 animals in which a complete surgical excision was impossible were treated. There was no tumor detectable macroscopically in 14 patients at the beginning of radiation therapy. In 20 animals the median volume of the tumor was 9.9 cm3. The median survival times and the local tumor control of squamous cell carcinoma of the oral and nasal cavities and of the body are comparable to results which were reached with a Monday-Wednesday-Friday scheme. For the treatment of Melanoma the hypofractionated radiation therapy is first choice. There are no significant side effects. Late side effects did not occur. 88% of the owners are satisfied with this kind of treatment and would choose it again.

  20. An optimization study for radioiodination of a new synthesized benzamide derivative as an analogue tracer for malignant melanoma imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kandil, Shaban A.; Aglan, Hany; Seddik, Usama [Atomic Energy Authority, Cairo (Egypt). Nuclear Research Center; EL-Kafrawy, Ahmed F. [Ain Shams Univ., Cairo (Egypt). Faculty of Science

    2017-03-01

    Iodobenzamides are reported to possess some affinity for melanoma. This study describes the synthesis of a new benzamide analogue, N-(2-diethylamino-ethyl)-4-(4-chloro-nicotinamido)-5-[{sup 125}I]iodo-2 -methoxybenz amide ([{sup 125}I]H4) designed to target melanoma. The synthesis was simply achieved in four steps. There were two PyCIU/DIPEA amide condensations and a transfer hydrogenation using an ammonium formate hydrogen donor. The radioiodination step was carried out with {sup 125}I via an electrophilic substitution reaction. The reaction conditions were optimized. The labeled compound was purified by HPLC. The maximum radiochemical yield was found to be 78% at a radiochemical purity of 98%. All compounds were characterized by MS and NMR techniques. The log P value for [{sup 125}I]H4 was found as 3.96±0.5.

  1. Inhibitory effect of live-attenuated Listeria monocytogenes-based vaccines expressing MIA gene on malignant melanoma.

    Science.gov (United States)

    Qian, Yue; Zhang, Na; Jiang, Ping; Chen, Siyuan; Chu, Shujuan; Hamze, Firas; Wu, Yan; Luo, Qin; Feng, Aiping

    2012-08-01

    Listeria monocytogenes (LM), a Gram-positive facultative intracellular bacterium, can be used as an effective exogenous antigen expression vector in tumor-target therapy. But for successful clinical application, it is necessary to construct attenuated LM stain that is safe yet retains the potency of LM based on the full virulent pathogen. In this study, attenuated LM and recombinants of LM expressing melanoma inhibitory activity (MIA) were constructed successfully. The median lethal dose (LD(50)) and invasion efficiency of attenuated LM strains were detected. The recombinants were utilized for immunotherapy of animal model of B16F10 melanoma. The level of MIA mRNA expression in tumor tissue was detected by using real-time polymerase chain reaction (PCR) with specific sequence, meanwhile the anti-tumor immune response was assayed by flow cytometric analysis and enzyme-linked immunosorbent spot (ELISPOT) assay. The results showed the toxicity and invasiveness of attenuated LM were decreased as compared with LM, and attenuated LM expressing MIA, especially the double-genes attenuated LM recombinant, could significantly induce anti-tumor immune response and inhibit tumor growth. This study implicates attenuated LM may be a safer and more effective vector for immunotherapy of melanoma.

  2. Killing malignant melanoma cells with protoporphyrin IX-loaded polymersome-mediated photodynamic therapy and cold atmospheric plasma

    Directory of Open Access Journals (Sweden)

    Wang M

    2017-05-01

    Full Text Available Mian Wang,1 Benjamin M Geilich,2 Michael Keidar,3 Thomas J Webster1,4 1Department of Chemical Engineering, 2Department of Bioengineering, Northeastern University, Boston, MA, 3Department of Mechanical and Aerospace Engineering, George Washington University, Washington, DC, USA; 4Wenzhou Institute of Biomaterials and Engineering, Wenzhou Medical University, Wenzhou, People’s Republic of China Abstract: Traditional cancer treatments contain several limitations such as incomplete ablation and multidrug resistance. It is known that photodynamic therapy (PDT is an effective treatment for several tumor types especially melanoma cells. During the PDT process, protoporphyrin IX (PpIX, an effective photosensitizer, can selectively kill cancer cells by activating a special light source. When tumor cells encapsulate a photosensitizer, they can be easily excited into an excited state by a light source. In this study, cold atmospheric plasma (CAP was used as a novel light source. Results of some studies have showed that cancer cells can be effectively killed by using either a light source or an individual treatment due to the generation of reactive oxygen species and electrons from a wide range of wavelengths, which suggest that CAP can act as a potential light source for anticancer applications compared with UV light sources. Results of the present in vitro study indicated for the first time that PpIX can be successfully loaded into polymersomes. Most importantly, cell viability studies revealed that PpIX-loaded polymersomes had a low toxicity to healthy fibroblasts (20% were killed at a concentration of 400 µg/mL, but they showed a great potential to selectively kill melanoma cells (almost 50% were killed. With the application of CAP posttreatment, melanoma cell viability significantly decreased (80% were killed compared to not using a light source (45% were killed or using a UV light source (65% were killed. In summary, these results indicated for the

  3. 2008 update of standards, options: recommendations for management of patients with salivary gland malignant tumours (excluding lymphoma, sarcoma and melanoma), summary report

    International Nuclear Information System (INIS)

    Bensadoun, R.J.; Dassonville, O.; Rousmans, S.

    2008-01-01

    Context: An update of the S.O.R.-C.P.G. for management of patients with salivary gland malignant tumours has been initiated by the French National Federation of Cancer Centres (F.N.C.L.C.C.) in collaboration with French league against cancer, specialists from university or general hospitals and private clinics, and with the French National Cancer Institute. This work performed is based on the methodology developed and used in the 'Standards, Options: Recommendations' program (S.O.R.). Objectives. To update the S.O.R. guideline for the management of patients with salivary gland malignant tumors (excluding lymphoma, sarcoma and melanoma) previously validated in 1997 and 2003. Method: The guideline development process is based on literature review and critical appraisal by a multidisciplinary group of experts. The methodological approach combines systematic review with expert judgement. Recommendations take into account the effectiveness and toxicity of the different therapeutic alternatives and the levels of evidence. Following their development and prior to publication, S.O.R.-guidelines are reviewed by independent practitioners in cancer care delivery. Results: This paper is a summary version of the full clinical practice guideline presenting the updated recommendations. Recommendations on radiotherapy have been updated to underline new Options on more and more accessible emerging techniques including 'intensity-modulated radiotherapy', '3-D conformational radiotherapy', 'Cyber-knife', 'Tomotherapy', 'Proton therapy' and 'particle accelerators producing carbon ions' (e.g. last generation hadron therapy). Therapeutical modalities have also been specified. (authors)

  4. MELDOQ - astrophysical image and pattern analysis in medicine: early recognition of malignant melanomas of the skin by digital image analysis. Final report

    International Nuclear Information System (INIS)

    Bunk, W.; Pompl, R.; Morfill, G.; Stolz, W.; Abmayr, W.

    1999-01-01

    Dermatoscopy is at present the most powerful clinical method for early detection of malignant melanomas. However, the application requires a lot of expertise and experience. Therefore, a quantitative image analysis system has been developed in order to assist dermatologists in 'on site diagnosis' and to improve the detection efficiency. Based on a very extensive dataset of dermatoscopic images, recorded in a standardized manner, a number of features for quantitative characterization of complex patterns in melanocytic skin lesions has been developed. The derived classifier improved the detection rate of malignant and benign melanocytic lesions to over 90% (sensitivity =91.5% and specificity =93.4% in the test set), using only six measures. A distinguishing feature of the system is the visualization of the quantified characteristics that are based on the dermatoscopic ABCD-rule. The developed prototype of a dermatoscopic workplace consists of defined procedures for standardized image acquisition and documentation, components of a necessary data pre-processing (e.g. shading- and colour-correction, removal of artefacts), quantification algorithms (evaluating asymmetry properties, border characteristics, the content of colours and structural components) and classification routines. In 2000 an industrial partner will begin marketing the digital imaging system including the specialized software for the early detection of skin cancer, which is suitable for clinicians and practitioners. The primary used nonlinear analysis techniques (e.g. scaling index method and others) can identify and characterize complex patterns in images and have a diagnostic potential in many other applications. (orig.) [de

  5. Malignant melanoma and radiotherapy: past myths, excellent local control in 146 studied lesions at Georgetown University, and improving future management

    International Nuclear Information System (INIS)

    Jahanshahi, Pooya; Nasr, Nadim; Unger, Keith; Batouli, Ali; Gagnon, Gregory J.

    2012-01-01

    Introduction: Once thought to be radioresistant, emerging cellular and clinical evidence now suggests melanoma can respond to large radiation doses per fraction. Materials and Methods: We conducted a retrospective study of all patients treated with stereotactic radiosurgery and stereotactic body radiotherapy at Georgetown University Hospital from May 2002 through November 2008 and studied the classic extrapolated total dose corrected for volume (ETD vol ) model for predicting melanoma tumor response. Region-specific tumor outcomes were categorized by RECIST criteria and local control curves were estimated and analyzed when stratified by ETD vol thresholds by use of the Kaplan–Meier method. Results: Follow-up information was available for 78 lesions (49 intracranial, 8 spinal, and 21 body) with mean follow-up period of 9.2 (range, 2–36) months. 1-year local control rates for intracranial, spinal, and body tumors were 84, 100, and 72%, respectively. Treatments in general were well-tolerated. Increased ETD vol (p < 0.001) among intracranial sites resulted from larger (p < 0.001) doses per fraction combined with smaller (p < 0.001) tumor diameters. Intracranial 6-, 12-, and 24-month local control rates when treated above ETD vol threshold of 230 Gy were all 90 vs. 89, 80, and 53% below this threshold. Body 6- and 12-month local control rates when treated above ETD vol threshold of 100 Gy were 100 and 80% vs. 74 and 59% below this threshold. Discussion: By tailoring to melanoma’s unique radiobiology with large radiation doses per fraction, favorable local control was safely achieved. The ETD vol model combines the important factor of dose per fraction in melanoma treatment with a volume correction factor to predict tumor response. Although limited sample size may have prevented reaching statistical significance for local control improvements using ETD vol thresholds, optimal thresholds may exist to improve future tumor responses and further research is required.

  6. Anorectal smear in the diagnosis of anorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    D Demirel

    2013-01-01

    Full Text Available The purpose of this case report is to point out the diagnostic value of cytologic smears in patients presenting with anorectal complaints, such as bleeding, pain or discomfort, which may suggest a neoplastic lesion. We present a case of a 64-year-old man with a 3 months′ history of anal bleeding and pain during defecation. He was diagnosed as having hemorrhoids and a hemorrhoidectomy was performed. The patient developed an anal stricture postoperatively that required operative dilation. He continued to complain about anorectal pain for 2 months and a subsequent rectoscopy revealed the presence of tumor 5 to 7 cm above the dentate line. The tumor was resected laparoscopically and was reported as an adenocarcinoma. Rectal bleeding recurred 18 months postoperatively and a smear was procured from the anorectal mucosal surface for cytologic evaluation. A definitive diagnosis of adenocarcinoma was rendered based on cytologic and histologic examination of the material. To the best of our knowledge, this is the first case report of anorectal adenocarcinoma diagnosed by cytologic smear in the English literature.

  7. Common anorectal disorders: diagnosis and treatment.

    Science.gov (United States)

    Lacy, Brian E; Weiser, Kirsten

    2009-10-01

    Anorectal disorders affect men and women of all ages. Their management is not limited to the evaluation and treatment of hemorrhoids. Rather, a spectrum of anorectal disorders ranges from benign and irritating (pruritus ani) to potentially life-threatening (anorectal cancer). Symptoms are nonspecific, which can make the evaluation of patients difficult. In addition, treatment can be frustrating because clinicians are hamstrung by a lack of well-designed, prospective, clinical trials. Some of the most common anorectal disorders include fecal incontinence, pelvic floor dyssynergia, anal fissures, pruritus ani, proctalgia fugax, and solitary rectal ulcer syndrome. This article provides an update on the evaluation and treatment of common anorectal disorders.

  8. Uveal melanoma: Estimating prognosis

    Directory of Open Access Journals (Sweden)

    Swathi Kaliki

    2015-01-01

    Full Text Available Uveal melanoma is the most common primary malignant tumor of the eye in adults, predominantly found in Caucasians. Local tumor control of uveal melanoma is excellent, yet this malignancy is associated with relatively high mortality secondary to metastasis. Various clinical, histopathological, cytogenetic features and gene expression features help in estimating the prognosis of uveal melanoma. The clinical features associated with poor prognosis in patients with uveal melanoma include older age at presentation, male gender, larger tumor basal diameter and thickness, ciliary body location, diffuse tumor configuration, association with ocular/oculodermal melanocytosis, extraocular tumor extension, and advanced tumor staging by American Joint Committee on Cancer classification. Histopathological features suggestive of poor prognosis include epithelioid cell type, high mitotic activity, higher values of mean diameter of ten largest nucleoli, higher microvascular density, extravascular matrix patterns, tumor-infiltrating lymphocytes, tumor-infiltrating macrophages, higher expression of insulin-like growth factor-1 receptor, and higher expression of human leukocyte antigen Class I and II. Monosomy 3, 1p loss, 6q loss, and 8q and those classified as Class II by gene expression are predictive of poor prognosis of uveal melanoma. In this review, we discuss the prognostic factors of uveal melanoma. A database search was performed on PubMed, using the terms "uvea," "iris," "ciliary body," "choroid," "melanoma," "uveal melanoma" and "prognosis," "metastasis," "genetic testing," "gene expression profiling." Relevant English language articles were extracted, reviewed, and referenced appropriately.

  9. Canine oral melanoma.

    Science.gov (United States)

    Bergman, Philip J

    2007-05-01

    Melanoma is the most common oral malignancy in the dog. Oral and/or mucosal melanoma has been routinely considered an extremely malignant tumor with a high degree of local invasiveness and high metastatic propensity. Primary tumor size has been found to be extremely prognostic. The World Health Organization staging scheme for dogs with oral melanoma is based on size, with stage I = or = 4cm tumor and/or lymph node metastasis, and stage IV = distant metastasis. Median survival times for dogs with oral melanoma treated with surgery are approximately 17 to 18, 5 to 6, and 3 months with stage I, II, and III disease, respectively. Significant negative prognostic factors include stage, size, evidence of metastasis, and a variety of histologic criteria. Standardized treatments such as surgery, coarse-fractionation radiation therapy, and chemotherapy have afforded minimal to modest stage-dependent clinical benefits and death is usually due to systemic metastasis. Numerous immunotherapeutic strategies have been employed to date with limited clinical efficacy; however, the use of xenogeneic DNA vaccines may represent a leap forward in clinical efficacy. Oral melanoma is a spontaneous syngeneic cancer occurring in outbred, immunocompetent dogs and appears to be a more clinically faithful therapeutic model for human melanoma; further use of canine melanoma as a therapeutic model for human melanoma is strongly encouraged. In addition, the development of an expanded but clinically relevant staging system incorporating the aforementioned prognostic factors is also strongly encouraged.

  10. Photodynamic Treatment of Cultured Human Malignant Melanoma cells and Assessment of Resultant Cell Death and Inflicted Bio molecular Damage As Determined by Synchrotron I.R. Radiations

    International Nuclear Information System (INIS)

    Mamoon, A.; Ruppel, M.; Miller, L.M.; Smith, S.; Tsang, T.; Miller, L.M.

    2008-01-01

    Malignant melanoma is a very serious skin cancer that if not discovered early and treated by surgery can become fatal. Photodynamic treatment involves the use of a photosensitive dye that is not toxic by itself and is taken up by all cells normal and tumor cells. However it is released from normal cells in a short time while it is kept inside tumor cells for a longer time. A laser light of wave length that is maximally absorbed by the used dye is then used to illuminate tumor cells, still having the dye, and a reaction takes place resulting in the liberation of s inglet oxygen , a very active form of oxygen that damages important biomolecules and results eventually in cell death. The photosensitive dye I ndocyanine green a nd a Ti - Sapphire laser (780 nm wave length ) and power density of 55 m Watt/ cm 2 were used. The percentage of cell death increased slowly with the strength of the PDT until it reached 75% death of the exposed cells at a net dye concentration of 150 u M and laser exposure dose of 60 minute duration.Synchrotron infrared imaging was carried out on control and experimental cultures at the national synchrotron light source (BNL) using FTIR spectro microscopy to reveal the I.R. absorption characteristics of protein, lipids and nucleic acids biomolecules. It was found that increasing the strength of the PDT had an increasingly damaging effect on the concentration of cellular biomolecules, the largest effect being in the protein, lipids and nucleic acid components of the cell. More experiments are planned involving changes in the strengths of the PDT treatments for eventually reaching 100% melanoma cell death

  11. Early phase II study on BNCT in metastatic malignant melanoma using the boron carrier BPA (EORTC protocol 11011)

    International Nuclear Information System (INIS)

    Wittig, Andrea; Sauerwein, Wolfgang; Moss, Raymond

    2006-01-01

    The aim of the trial is to examine the clinical response of metastatic melanoma following BNCT with BPA. The trial contains an optional biodistribution sub-study, which is done if operable metastases are removed prior BNCT. BNCT is applied in 2 fractions at the HFR in Petten. In cases of diffuse brain metastases the whole brain is irradiated homogeneously using 5 irradiation beams from different directions. Up to now 4 patients suffering from multiple brain metastases (more than 20) have been included. In all cases we observed a partial response or no change in the irradiated volume. However, none of the patients survived more than 3 months. The pharmacokinetic of the BPA can be predicted very precisely using a two-compartment model. The treatment can be performed safety. (author)

  12. The use of positron emission tomography in BNCT treatment planning for metastatic malignant melanoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Kabalka, G.; Nichols, T.; Smith, G.; Miller, L.; Kahn, M.

    2000-01-01

    Positron emission tomography (PET) evaluations of six glioblastoma multiforme (GBM) and one metastatic melanoma (MM) patient have been carried out utilizing fluorine-18 labeled p-boronophenylalanine. Four of the GBM patients were imaged both prior to and post BNCT. In one GBM patient, biopsy derived boron distribution data compared favorably to the PET derived data. The PET data have been used as input to dosimetry calculations and the results vary from those obtained using current protocols. In addition, PET images of the thorax would indicate that the utility of PET for staging tumors for BNCT may extend beyond the brain. However, higher than anticipated levels of activity in the lungs (as also seen in salivary glands) indicate the more effective BNCT agents will be required. (author)

  13. A new treatment for human malignant melanoma targeting L-type amino acid transporter 1 (LAT1): A pilot study in a canine model

    Energy Technology Data Exchange (ETDEWEB)

    Fukumoto, Shinya; Hanazono, Kiwamu [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Fu, Dah-Renn; Endo, Yoshifumi; Kadosawa, Tsuyoshi [Veterinary Oncology, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Iwano, Hidetomo [Veterinary Biochemistry, Department of Basic Veterinary Medicine, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan); Uchide, Tsuyoshi, E-mail: uchide@rakuno.ac.jp [Veterinary Internal Medicine, Department of Small Animal Clinical Sciences, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501 (Japan)

    2013-09-13

    Highlights: •LAT1 is highly expressed in tumors but at low levels in normal tissues. •We examine LAT1 expression and function in malignant melanoma (MM). •LAT1 expression in MM tissues and cell lines is higher than those in normal tissues. •LAT1 selective inhibitors inhibit amino acid uptake and cell growth in MM cells. •New chemotherapeutic protocols including LAT1 inhibitors are effective for treatment. -- Abstract: L-type amino acid transporter 1 (LAT1), an isoform of amino acid transport system L, transports branched or aromatic amino acids essential for fundamental cellular activities such as cellular growth, proliferation and maintenance. This amino acid transporter recently has received attention because of its preferential and up-regulated expression in a variety of human tumors in contrast to its limited distribution and low-level expression in normal tissues. In this study, we explored the feasibility of using LAT1 inhibitor as a new therapeutic agent for human malignant melanomas (MM) using canine spontaneous MM as a model for human MM. A comparative study of LAT expression was performed in 48 normal tissues, 25 MM tissues and five cell lines established from MM. The study observed LAT1 mRNA levels from MM tissues and cell lines that were significantly (P < 0.01) higher than in normal tissues. Additionally, MM with distant metastasis showed a higher expression than those without distant metastasis. Functional analysis of LAT1 was performed on one of the five cell lines, CMeC-1. [{sup 3}H]L-Leucine uptake and cellular growth activities in CMeC-1 were inhibited in a dose-dependent manner by selective LAT1 inhibitors (2-amino-2-norbornane-carboxylic acid, BCH and melphalan, LPM). Inhibitory growth activities of various conventional anti-cancer drugs, including carboplatin, cyclophosphamide, dacarbazine, doxorubicin, mitoxantrone, nimustine, vinblastine and vincristine, were significantly (P < 0.05) enhanced by combination use with BCH or LPM

  14. Hemorrhagic cystitis in a patient receiving conventional doses of dacarbazine for metastatic malignant melanoma: case report and review of the literature.

    Science.gov (United States)

    Mohammadianpanah, Mohammad; Shirazi, Mehdi; Mosalaei, Ahmad; Omidvari, Shapour; Ahmadloo, Niloofar

    2007-06-01

    Hemorrhagic cystitis is a potentially life-threatening complication in patients receiving cancer therapy. This urologic emergency is commonly associated with the chemotherapeutic use of oxazaphosphorine alkylating agents. This report describes a case of hemorrhagic cystitis associated with dacarbazine treatment. A 63-year-old man with asymptomatic metastatic malignant melanoma received 3 cycles of dacarbazine (600-850 mg/m2) monochemotherapy, each 3 weeks apart. Two weeks after the third cycle, he presented with gross hematuria and mild dysuria. Physical examination revealed no significant finding. Hematuria was confirmed by urinalysis, and urinary infection was excluded by repeated urine cultures. Ultrasonography revealed diffuse bladder wall thickening with no discrete mass or ulceration. Cystoscopy findings revealed generalized inflammation and edema of the mucosa of the bladder, confirming the diagnosis of hemorrhagic cystitis. The patient's gross hematuria continued for 2 weeks and then completely resolved with supportive care. Two weeks after complete resolution, the patient experienced 2 transient episodes of gross hematuria that lasted a few hours and subsided spontaneously. Dacarbazine is currently considered the standard first-line treatment in patients with advanced malignant melanoma. At standard prescribed doses (a single dose of 850-1000 mg/m2 or 250 mg/m2 for 5 days per cycle), dacarbazine is a reasonably well tolerated chemotherapeutic drug; nausea, vomiting, and myelosuppression are the most common adverse effects. Association of dacarbazine with hemorrhagic cystitis has not been reported previously (in a PubMed literature search from 1950-2006), and only 1 case report associates temozolomide (an analog of dacarbazine) with hemorrhagic cystitis. Based on the Naranjo adverse drug reactions probability scale, an objective assessment revealed dacarbazine to be a probable cause of hemorrhagic cystitis in this case. This case report suggests that

  15. CD147-targeting siRNA inhibits cell-matrix adhesion of human malignant melanoma cells by phosphorylating focal adhesion kinase.

    Science.gov (United States)

    Nishibaba, Rie; Higashi, Yuko; Su, Juan; Furukawa, Tatsuhiko; Kawai, Kazuhiro; Kanekura, Takuro

    2012-01-01

    CD147/basigin, highly expressed on the surface of malignant tumor cells including malignant melanoma (MM) cells, plays a critical role in the invasiveness and metastasis of MM. Metastasis is an orchestrated process comprised of multiple steps including adhesion and invasion. Integrin, a major adhesion molecule, co-localizes with CD147/basigin on the cell surface. Using the human MM cell line A375 that highly expresses CD147/basigin, we investigated whether CD147/basigin is involved in adhesion in association with integrin. CD147/basigin was knocked-down using siRNA targeting CD147 to elucidate the role of CD147/basigin. Cell adhesion was evaluated by adhesion assay on matrix-coated plates. The localization of integrin was inspected under a confocal microscope and the expression and phosphorylation of focal adhesion kinase (FAK), a downstream kinase of integrin, were examined by western blot analysis. Silencing of CD147/basigin in A375 cells by siRNA induced the phosphorylation of FAK at Y397. Integrin identified on the surface of parental cells was distributed in a speckled fashion in the cytoplasm of CD147 knockdown cells, resulting in morphological changes from a round to a polygonal shape with pseudopodial protrusions. Silencing of CD147/basigin in A375 cells clearly weakened their adhesiveness to collagen I and IV. Our results suggest that CD147/basigin regulates the adhesion of MM cells to extracellular matrices and of integrin β1 signaling via the phosphorylation of FAK. © 2011 Japanese Dermatological Association.

  16. iDermatoPath - a novel software tool for mitosis detection in H&E-stained tissue sections of malignant melanoma.

    Science.gov (United States)

    Andres, C; Andres-Belloni, B; Hein, R; Biedermann, T; Schäpe, A; Brieu, N; Schönmeyer, R; Yigitsoy, M; Ring, J; Schmidt, G; Harder, N

    2017-07-01

    Malignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well-defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter- and intra-individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer-assisted method. The objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support. We developed a computer-aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing. A quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%. On the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist. © 2017 European Academy of Dermatology and Venereology.

  17. Synthesis and biodistribution study of 3-iodo-4-hydroxyphenyl-cysteamine for detection of malignant melanoma based on specific enzyme of melanin formation

    International Nuclear Information System (INIS)

    Nishii, R.; Nagamachi, S.; Tamura, S.; Kawai, K.; Nishimura, K.; Kinuya, S.; Uehara, T.; Tonami, N.; Arano, Y.

    2002-01-01

    min after injection. It was higher than those of 125 I-L-PC; 6.5 ± 0.8 and 67 Ga-citrate; 4.6 ± 0.4. It indicated specific retention of the tracer in the melanoma. Conclusions: The results suggested that I-PCA achieved the desired affinity for melanin formation. That is, I-PCA has high potentiality for diagnosis of malignant melanoma. Moreover, because I-PCA accumulated low in normal tissue and showed rapid clearance, it might be applied as a therapeutic radiopharmaceutical when labeled with I-131

  18. Characterization of Melanin Radicals in Paraffin-embedded Malignant Melanoma and Nevus Pigmentosus Using X-band EPR and EPR Imaging.

    Science.gov (United States)

    Nakagawa, Kouichi; Minakawa, Satoko; Sawamura, Daisuke; Hara, Hideyuki

    2017-01-01

    Continuous wave electron paramagnetic resonance (CW EPR) and X-band (9 GHz) EPR imaging (EPRI) were used to nondestructively investigate the possible differentiation between malignant melanoma (MM) and nevus pigmentosus (NP) melanin radicals in paraffin-embedded specimens. The EPR spectra of both samples were analyzed using linewidth, spectral pattern, and X-band EPRI. The CW-EPR spectra of the MM showed an additional signal overlap. Eumelanin- and pheomelanin-related radicals were observed in the MM specimens. The EPR results revealed that the peak-to-peak linewidths (ΔH pp ) of paraffin-embedded MM and NP samples were 0.65 ± 0.01 and 0.69 ± 0.01 mT, respectively. The g-value was 2.005 for both samples. Moreover, the two-dimensional (2D) EPRI of the MM showed different signal intensities at the different tumor stages, unlike the NP, which displayed fewer variations in signal intensity. Thus, the present results suggest that EPR and 2D EPRI can be useful for characterization of the two melanin radicals in the MM and for determination of their size and concentration.

  19. Semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma stage III/IV-A feasibility study

    International Nuclear Information System (INIS)

    Fabel, M.; Tengg-Kobligk, H. von; Giesel, F.L.; Delorme, S.; Kauczor, H.-U.; Bornemann, L.; Dicken, V.; Kopp-Schneider, A.; Moser, C.

    2008-01-01

    Therapy monitoring in oncological patient care requires accurate and reliable imaging and post-processing methods. RECIST criteria are the current standard, with inherent disadvantages. The aim of this study was to investigate the feasibility of semi-automated volumetric analysis of lymph node metastases in patients with malignant melanoma compared to manual volumetric analysis and RECIST. Multislice CT was performed in 47 patients, covering the chest, abdomen and pelvis. In total, 227 suspicious, enlarged lymph nodes were evaluated retrospectively by two radiologists regarding diameters (RECIST), manually measured volume by placement of ROIs and semi-automated volumetric analysis. Volume (ml), quality of segmentation (++/-) and time effort (s) were evaluated in the study. The semi-automated volumetric analysis software tool was rated acceptable to excellent in 81% of all cases (reader 1) and 79% (reader 2). Median time for the entire segmentation process and necessary corrections was shorter with the semi-automated software than by manual segmentation. Bland-Altman plots showed a significantly lower interobserver variability for semi-automated volumetric than for RECIST measurements. The study demonstrated feasibility of volumetric analysis of lymph node metastases. The software allows a fast and robust segmentation in up to 80% of all cases. Ease of use and time needed are acceptable for application in the clinical routine. Variability and interuser bias were reduced to about one third of the values found for RECIST measurements. (orig.)

  20. Safety and efficacy of a xenogeneic DNA vaccine encoding for human tyrosinase as adjunctive treatment for oral malignant melanoma in dogs following surgical excision of the primary tumor.

    Science.gov (United States)

    Grosenbaugh, Deborah A; Leard, A Timothy; Bergman, Philip J; Klein, Mary K; Meleo, Karri; Susaneck, Steven; Hess, Paul R; Jankowski, Monika K; Jones, Pamela D; Leibman, Nicole F; Johnson, Maribeth H; Kurzman, Ilene D; Wolchok, Jedd D

    2011-12-01

    To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs. 111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved. 58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death. Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because dogs as adjunctive treatment for oral MM. Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

  1. Efficacy and side effects of radiation therapy in comparison with radiation therapy and temozolomide in the treatment of measurable canine malignant melanoma.

    Science.gov (United States)

    Cancedda, S; Rohrer Bley, C; Aresu, L; Dacasto, M; Leone, V F; Pizzoni, S; Gracis, M; Marconato, L

    2016-12-01

    Prognosis for unresectable canine malignant melanoma (MM) is typically poor, and therapeutic approaches remain largely palliative. A bi-institutional trial was conducted to compare efficacy and safety of radiation therapy (RT) and RT with post-radiation temozolomide in dogs with chemotherapy-naïve, measurable MM. RT consisted of 5 × 6 Gy fractions over 2.5 weeks. Dogs whose owners wished to pursue chemotherapy received adjuvant oral temozolomide (60 mg m -2 for 5 days every 28 days). Fifteen dogs were treated with RT only (Group 1) and 12 dogs subsequently received temozolomide (Group 2). Overall response rate was similar between Group 1 (86.7%) and Group 2 (81.1%). Median time to progression (TTP) was significantly longer in Group 2 (205 days) compared to Group 1 (110 days; p = 0.046). Survival time was not significantly different between groups. Both treatments were well tolerated. Post-radiation temozolomide has a good safety profile, and may improve TTP in MM when compared to coarse fractionated RT. © 2014 John Wiley & Sons Ltd.

  2. Metastases radiotherapy of malignant melanomas in soft tissues: analysis of sixty patients series treated between the 1. of january 1990 and the 31. december of 1996

    International Nuclear Information System (INIS)

    Meunier-Olympie, O

    1998-01-01

    The radiotherapy efficiency is still undervalued in the therapeutic taking charge of the malignant melanoma. Our series with its heterogeneity has authorized an only mono factorial analysis. The data in literature and our personal experience give a better efficiency of the strong unitary doses in term of local control. The accuracy of irradiation must allow to reduce the importance of after-effects that can be necessary to the local control and then to the survival. for the future, an increasing of of the applied unitary doses, by taking into account the localisation, the tumoral volume and the therapeutic objective, would allow to improve the efficiency of this treatment. In The particular indication of inoperable Dubreuilh melanosis, it could be an alternative to the surgery. The results of a complementary radiotherapy, after a radical surgery of secondary localisation are very encouraging. Its contribution in adjuvant treatment of recurrence or primitive lesions with high risks would deserve to be evaluated in the frame of well defined and randomized tests. (N.C.)

  3. Role of the technologist in the lymphoscintigraphy and the identification of sentinel node in malignant skin melanoma

    International Nuclear Information System (INIS)

    Barbier, D.

    2002-01-01

    The biopsy of the first tumor-draining lymph node (sentinel node) is bound to become the procedure of choice in regional staging of skin melanoma patients. In our department, we do successively: lymphoscintigraphy; identification of sentinel node by γ probe before surgery; identification during surgery of sentinel node with γ probe. During those different steps, the technologist has an important role. The different steps of the technologist's work are: Preparation of radiopharmaceutical Tc 99m Nanocolloides (Nanocis Cis Bio Int); Control of radio chemical purity(RCP) by thin-layer chromatography (TLC); Programming of acquisition protocol on the γ camera; Acquisition of dynamic and static images; Identification percutaneous of the sentinel node with the γ probe and Co 57 pencil; Processing of scintigraphic images; At least identification with surgeon of the sentinel node. After excision of the lymph node, we have to verify the disappearing of radioactivity. Those steps will be illustrated by different clinical cases. Conclusion: Sentinel node identification is: New useful technique for patient: not very much invasive; screening of patients with high risk factors; great parameters of prognosis; Interest for technologist: narrow collaboration with nuclearist and surgeon; psychological role close to the patient; various competency of technologist; diagnostic and therapeutic participations

  4. Boronated monoclonal antibody 225.28S for potential use in neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    Tamat, S.R.; Moore, D.E.; Patwardhan, A.; Hersey, P.

    1989-01-01

    The concept of conjugating boron cluster compounds to monoclonal antibodies has been examined by several groups of research workers in boron neutron capture therapy (BNCT). The procedures reported to date for boronation of monoclonal antibodies resulted in either an inadequate level of boron incorporation, the precipitation of the conjugates, or a loss of immunological activity. The present report describes the conjugation of dicesium-mercapto-undecahydrododecaborate (Cs2B12H11SH) to 225.28S monoclonal antibody directed against high molecular weight melanoma-associated antigens (HMW-MAA), using poly-L-ornithine as a bridge to increase the carrying capacity of the antibody and to minimize change in the conformational structure of antibody. The method produces a boron content of 1,300 to 1,700 B atoms per molecule 225.28S while retaining the immunoreactivity. Characterization in terms of the homogeneity of the conjugation of the boron-monoclonal antibody conjugates has been studied by gel electrophoresis and ion-exchange HPLC

  5. Prevalence and correlates of sun protection and skin self-examination practices among cutaneous malignant melanoma survivors.

    Science.gov (United States)

    Manne, Sharon; Lessin, Stuart

    2006-10-01

    Little is known about the level of engagement and correlates of sun protection and skin self-exam among individuals diagnosed with melanoma. Participants (N = 229) completed measures of skin self-exam and sun protection practice and knowledge and attitudes. Approximately eighty-four percent of patients reported engaging in skin self-examination at least once in the past year. Engagement in sun protection practices was moderate. Self-exam practice was associated with gender, physician recommendation about self-exam, and perceived benefits and barriers of self-exam. Sun protection was associated with gender, age, medical status and health care access, physician recommendation, knowledge, and a number of psychological factors. Behavioral interventions to improve skin surveillance and sun protection may benefit from an emphasis on physician education regarding self-exam and sun protection, education regarding the efficacy of sunscreen and the risks associated with sunbathing, reducing perceived barriers to self-exam and sun protection, and reducing reliance on social influences on sun protection practices.

  6. Germline rearrangements in families with strong family history of glioma and malignant melanoma, colon, and breast cancer

    Science.gov (United States)

    Andersson, Ulrika; Wibom, Carl; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Armstrong, Georgina N.; Shete, Sanjay; Lau, Ching C.; Bainbridge, Matthew N.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Lai, Rose; Il'yasova, Dora; Houlston, Richard S.; Schildkraut, Joellen; Bernstein, Jonine L.; Olson, Sara H.; Jenkins, Robert B.; Lachance, Daniel H.; Wrensch, Margaret; Davis, Faith G.; Merrell, Ryan; Johansen, Christoffer; Sadetzki, Siegal; Bondy, Melissa L.; Melin, Beatrice S.; Adatto, Phyllis; Morice, Fabian; Payen, Sam; McQuinn, Lacey; McGaha, Rebecca; Guerra, Sandra; Paith, Leslie; Roth, Katherine; Zeng, Dong; Zhang, Hui; Yung, Alfred; Aldape, Kenneth; Gilbert, Mark; Weinberger, Jeffrey; Colman, Howard; Conrad, Charles; de Groot, John; Forman, Arthur; Groves, Morris; Levin, Victor; Loghin, Monica; Puduvalli, Vinay; Sawaya, Raymond; Heimberger, Amy; Lang, Frederick; Levine, Nicholas; Tolentino, Lori; Saunders, Kate; Thach, Thu-Trang; Iacono, Donna Dello; Sloan, Andrew; Gerson, Stanton; Selman, Warren; Bambakidis, Nicholas; Hart, David; Miller, Jonathan; Hoffer, Alan; Cohen, Mark; Rogers, Lisa; Nock, Charles J; Wolinsky, Yingli; Devine, Karen; Fulop, Jordonna; Barrett, Wendi; Shimmel, Kristen; Ostrom, Quinn; Barnett, Gene; Rosenfeld, Steven; Vogelbaum, Michael; Weil, Robert; Ahluwalia, Manmeet; Peereboom, David; Staugaitis, Susan; Schilero, Cathy; Brewer, Cathy; Smolenski, Kathy; McGraw, Mary; Naska, Theresa; Rosenfeld, Steven; Ram, Zvi; Blumenthal, Deborah T.; Bokstein, Felix; Umansky, Felix; Zaaroor, Menashe; Cohen, Avi; Tzuk-Shina, Tzeela; Voldby, Bo; Laursen, René; Andersen, Claus; Brennum, Jannick; Henriksen, Matilde Bille; Marzouk, Maya; Davis, Mary Elizabeth; Boland, Eamon; Smith, Marcel; Eze, Ogechukwu; Way, Mahalia; Lada, Pat; Miedzianowski, Nancy; Frechette, Michelle; Paleologos, Nina; Byström, Gudrun; Svedberg, Eva; Huggert, Sara; Kimdal, Mikael; Sandström, Monica; Brännström, Nikolina; Hayat, Amina; Tihan, Tarik; Zheng, Shichun; Berger, Mitchel; Butowski, Nicholas; Chang, Susan; Clarke, Jennifer; Prados, Michael; Rice, Terri; Sison, Jeannette; Kivett, Valerie; Duo, Xiaoqin; Hansen, Helen; Hsuang, George; Lamela, Rosito; Ramos, Christian; Patoka, Joe; Wagenman, Katherine; Zhou, Mi; Klein, Adam; McGee, Nora; Pfefferle, Jon; Wilson, Callie; Morris, Pagan; Hughes, Mary; Britt-Williams, Marlin; Foft, Jessica; Madsen, Julia; Polony, Csaba; McCarthy, Bridget; Zahora, Candice; Villano, John; Engelhard, Herbert; Borg, Ake; Chanock, Stephen K; Collins, Peter; Elston, Robert; Kleihues, Paul; Kruchko, Carol; Petersen, Gloria; Plon, Sharon; Thompson, Patricia; Johansen, C.; Sadetzki, S.; Melin, B.; Bondy, Melissa L.; Lau, Ching C.; Scheurer, Michael E.; Armstrong, Georgina N.; Liu, Yanhong; Shete, Sanjay; Yu, Robert K.; Aldape, Kenneth D.; Gilbert, Mark R.; Weinberg, Jeffrey; Houlston, Richard S.; Hosking, Fay J.; Robertson, Lindsay; Papaemmanuil, Elli; Claus, Elizabeth B.; Claus, Elizabeth B.; Barnholtz-Sloan, Jill; Sloan, Andrew E.; Barnett, Gene; Devine, Karen; Wolinsky, Yingli; Lai, Rose; McKean-Cowdin, Roberta; Il'yasova, Dora; Schildkraut, Joellen; Sadetzki, Siegal; Yechezkel, Galit Hirsh; Bruchim, Revital Bar-Sade; Aslanov, Lili; Sadetzki, Siegal; Johansen, Christoffer; Kosteljanetz, Michael; Broholm, Helle; Bernstein, Jonine L.; Olson, Sara H.; Schubert, Erica; DeAngelis, Lisa; Jenkins, Robert B.; Yang, Ping; Rynearson, Amanda; Andersson, Ulrika; Wibom, Carl; Henriksson, Roger; Melin, Beatrice S.; Cederquist, Kristina; Aradottir, Steina; Borg, Åke; Merrell, Ryan; Lada, Patricia; Wrensch, Margaret; Wiencke, John; Wiemels, Joe; McCoy, Lucie; McCarthy, Bridget J.; Davis, Faith G.

    2014-01-01

    Background Although familial susceptibility to glioma is known, the genetic basis for this susceptibility remains unidentified in the majority of glioma-specific families. An alternative approach to identifying such genes is to examine cancer pedigrees, which include glioma as one of several cancer phenotypes, to determine whether common chromosomal modifications might account for the familial aggregation of glioma and other cancers. Methods Germline rearrangements in 146 glioma families (from the Gliogene Consortium; http://www.gliogene.org/) were examined using multiplex ligation-dependent probe amplification. These families all had at least 2 verified glioma cases and a third reported or verified glioma case in the same family or 2 glioma cases in the family with at least one family member affected with melanoma, colon, or breast cancer.The genomic areas covering TP53, CDKN2A, MLH1, and MSH2 were selected because these genes have been previously reported to be associated with cancer pedigrees known to include glioma. Results We detected a single structural rearrangement, a deletion of exons 1-6 in MSH2, in the proband of one family with 3 cases with glioma and one relative with colon cancer. Conclusions Large deletions and duplications are rare events in familial glioma cases, even in families with a strong family history of cancers that may be involved in known cancer syndromes. PMID:24723567

  7. Second-line chemotherapy of disseminated malignant melanoma with cystemustine at 60 mg/m2: a phase II trial.

    Science.gov (United States)

    Thivat, Emilie; Durando, Xavier; D'Incan, Michel; Cure, Hervé; Mouret-Reynier, Marie-Ange; Madelmont, Jean-Claude; Souteyrand, Pierre; Chollet, Philippe

    2005-10-01

    Nitrosoureas possess some anti-tumor activity as a single agent in metastatic melanoma (MM). In a phase II trial, we evaluated the anti-tumor effects of cystemustine chemotherapy, a new nitrosourea, as a second-line treatment. Patients were required to have histologic evidence of disseminated MM and had failed in first-line chemotherapy. Treatment comprised cystemustine given at a dose of 60 mg/m every 2 weeks by a 15-min infusion. From February 1997 to September 1999, 22 patients (median age 66 years) were enrolled and were assessable. Two complete responses, one partial response, three stable diseases and 16 progressions were observed, giving an overall response rate of 13.6%. Median duration of response was 10 months (range 4-63). Median survival of responders and non-responders was 11 and 4 months, respectively. However, hematological toxicity, particularly thrombopenia, was a limiting factor for one-third of patients. We conclude that cystemustine at 60 mg/m is active in patients who progressed after one line of chemotherapy in advanced disease, and offers the possibility of complete responses and long durations of these responses.

  8. Spontaneous ileal perforation complicating low anorectal malformation

    Directory of Open Access Journals (Sweden)

    TiJesuni Olatunji

    2015-01-01

    Full Text Available Anorectal malformation is a common anomaly in neonates. Although colorectal perforations have been reported as a complication, ileal perforation is rarely encountered. This is a report of a 2-day-old boy presenting with a low anorectal malformation, complicated with ileal perforation, necessitating laparotomy and ileal repair. Anoplasty was done for the low anomaly. Early presentation and prompt treatment of anorectal malformations is important to prevent such potential life threatening complication.

  9. Downregulation of reversion-inducing cysteine-rich protein with Kazal motifs in malignant melanoma: inverse correlation with membrane-type 1-matrix metalloproteinase and tissue inhibitor of metalloproteinase 2.

    Science.gov (United States)

    Jacomasso, Thiago; Trombetta-Lima, Marina; Sogayar, Mari C; Winnischofer, Sheila M B

    2014-02-01

    The invasive phenotype of many tumors is associated with an imbalance between the matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), and the membrane-anchored reversion-inducing cysteine-rich protein with Kazal motifs (RECK). RECK inhibits MMP-2, MMP-9, and MT1-MMP, and has been linked to patient survival and better prognosis in several types of tumors. However, despite the wide implication of these MMPs in melanoma establishment and progression, the role of RECK in this type of tumor is still unknown. Here, we analyzed the expression of RECK, TIMP1, TIMP2, TIMP3, MT1MMP, MMP2, and MMP9 in two publicly available melanoma microarray datasets and in a panel of human melanoma cell lines. We found that RECK is downregulated in malignant melanoma, accompanied by upregulation of MT1MMP and TIMP2. In both datasets, we observed that the group of samples displaying higher RECK levels show lower median expression levels of MT1MMP and TIMP2 and higher levels of TIMP3. When tested in a sample-wise manner, these correlations were statistically significant. Inverse correlations between RECK, MT1MMP, and TIMP2 were verified in a panel of human melanoma cell lines and in a further reduced model that includes a pair of matched primary tumor-derived and metastasis-derived cell lines. Taken together, our data indicate a consistent correlation between RECK, MT1MMP, and TIMP2 across different models of clinical samples and cell lines and suggest evidence of the potential use of this subset of genes as a gene signature for diagnosing melanoma.

  10. Utility of magnetic resonance imaging in anorectal disease

    Institute of Scientific and Technical Information of China (English)

    Loren Berman; Gary M Israel; Shirley M McCarthy; Jeffrey C Weinreb; Walter E Longo

    2007-01-01

    Imaging of both benign and malignant anorectal diseases has traditionally posed a challenge to clinicians, and as a result history and physical exam have been relied on heavily. CT scanning and endorectal ultrasound have become popular in assessment of anatomy and staging of tumors, but have limitations. Magnetic resonance imaging(MRI) has the capability to fill in the gaps left open by more conventional imaging modalities and continues to be promising as the definitive imaging technique in the pelvis, especially with advancement of emerging technologies in this field. A comprehensive review of this topic has been undertaken. Anorectal disease is divided into three broad categories: cancer, fistula/abscess,and pelvic floor disorders. A review of the literature is performed to evaluate the use of MRI and other imaging modalities in these three areas. Preoperative imaging is useful in the evaluation of all three areas of anorectal disease. MRI is an effective tool in delineating anatomy and, when correlating with the specific clinical scenario,is an effective adjunct in clinical decision-making in order to optimize outcome. MRI continues to be a promising and novel approach to imaging various afflictions of the anorectum and the pelvic floor. Its role is more wellestablished in some areas than in others, and there are still significant limitations. As technology advances, MRI will shed more light on a complex anatomical area.

  11. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

    International Nuclear Information System (INIS)

    Liu, Hao; Zhang, Yikai; Zheng, Shanyuan; Weng, Zeping; Ma, Jun; Li, Yangqiu; Xie, Xinyuan; Zheng, Wenjie

    2016-01-01

    Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities

  12. Detention of copper by sulfur nanoparticles inhibits the proliferation of A375 malignant melanoma and MCF-7 breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hao [Department of Chemistry, Jinan University, Guangzhou (China); Zhang, Yikai [Institute of Hematology, Jinan University, Guangzhou (China); Zheng, Shanyuan [School of Life Sciences, The Chinese University of Hong Kong, Hong Kong (China); Weng, Zeping; Ma, Jun [First Affiliated Hospital, Jinan University, Guangzhou (China); Li, Yangqiu [Institute of Hematology, Jinan University, Guangzhou (China); First Affiliated Hospital, Jinan University, Guangzhou (China); Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632 (China); Xie, Xinyuan [Department of Chemistry, Jinan University, Guangzhou (China); Zheng, Wenjie, E-mail: tzhwj@jnu.edu.cn [Department of Chemistry, Jinan University, Guangzhou (China)

    2016-09-02

    Selective induction of cell death or growth inhibition of cancer cells is the future of chemotherapy. Clinical trials have found that cancer tissues are enriched with copper. Based on this finding, many copper-containing compounds and complexes have been designed to “copper” cancer cells using copper as bait. However, recent studies have demonstrated that copper boosts tumor development, and copper deprivation from serum was shown to effectively inhibit the promotion of cancer. Mechanistically, copper is an essential cofactor for mitogen-activated protein kinase (MAPK)/extracellular activating kinase (ERK) kinase (MEK), a central molecule in the BRAF/MEK/ERK pathway. Therefore, depleting copper from cancer cells by directly sequestering copper has a wider field for research and potential for combination therapy. Based on the affinity between sulfur and copper, we therefore designed sulfur nanoparticles (Nano-S) that detain copper, achieving tumor growth restriction. We found that spherical Nano-S could effectively bind copper and form a tighter surficial structure. Moreover, this Nano-S detention of copper effectively inhibited the proliferation of A375 melanoma and MCF-7 breast cancer cells with minimum toxicity to normal cells. Mechanistic studies revealed that Nano-S triggered inactivation of the MEK-ERK pathway followed by inhibition of the proliferation of the A375 and MCF-7 cells. In addition, lower Nano-S concentrations and shorter exposure stimulated the expression of a copper transporter as compensation, which further increased the cellular uptake and anticancer activities of cisplatin. Collectively, our results highlight the potential of Nano-S as an anticancer agent or adjuvant through its detention of copper. - Highlights: • Nano-S selectively inhibited the mitosis of A375 and MCF-7 cells by depleting copper. • Nano-S inactivated MEK/ERK pathway through the detention of copper. • Nano-S improved the cellular uptake and anticancer activities

  13. Calreticulin Fragment 39-272 Promotes B16 Melanoma Malignancy through Myeloid-Derived Suppressor Cells In Vivo

    Directory of Open Access Journals (Sweden)

    Xiao-Yan He

    2017-10-01

    Full Text Available Calreticulin (CRT, a multifunctional Ca2+-binding glycoprotein mainly located in the endoplasmic reticulum, is a tumor-associated antigen that has been shown to play protective roles in angiogenesis suppression and anti-tumor immunity. We previously reported that soluble CRT (sCRT was functionally similar to heat shock proteins or damage-associated molecular patterns in terms of ability to activate myeloid cells and elicit strong inflammatory cytokine production. In the present study, B16 melanoma cell lines expressing recombinant CRT fragment 39-272 (sCRT/39-272 in secreted form (B16-CRT, or recombinant enhanced green fluorescence protein (rEGFP (B16-EGFP, were constructed for investigation on the roles of sCRT in tumor development. When s.c. inoculated into C57BL/6 mice, the B16-CRT cells were significantly more aggressive (in terms of solid tumor growth rate than B16-EGFP controls in a TLR4- and myeloid-derived suppressor cells (MDSC-dependent manner. The B16-CRT-bearing mice showed increased Gr1+ MDSC infiltration in tumor tissues, accelerated proliferation of CD11b+Ly6G+Ly6Clow (G-MDSC precursors in bone marrow, and higher percentages of G-MDSCs in spleen and blood, which was mirrored by decreased percentage of dendritic cells (DC in periphery. In in vitro studies, recombinant sCRT/39-272 was able to promote migration and survival of tumor-derived MDSCs via interaction with TLR4, inhibit MDSC differentiation into DC, and also elicit expression of inflammatory proteins S100A8 and S100A9 which are essential for functional maturation and chemotactic migration of MDSCs. Our data provide solid evidence for CRT as a double-edged sword in tumor development.

  14. Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary metastases from malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Krug, Bruno; Pirson, Anne-Sophie; Borght Thierry Vander (Nuclear Medicine Division, Mont-Godinne Univ. Hospital, Yvoir (Belgium)), E-mail: bruno.krug@uclouvain.be; Crott, Ralph (Public Health, Saint-Luc Univ. Hospital, Brussels (Belgium)); Roch, Isabelle (Public Health School, Univ. Catholique de Louvain, Brussels (Belgium)); Lonneux, Max (Nuclear Medicine Division, Saint-Luc Univ. Hospital, Brussels (Belgium)); Beguin, Claire (Medical Information and Statistics, Saint-Luc Univ. Hospital, Brussels (Belgium)); Baurain, Jean-Francois (Dept. of Oncology, Saint-Luc Univ. Hospital, Brussels (Belgium))

    2010-02-15

    Objectives. Most guidelines consider FDG PET-CT to detect occult extra-pulmonary disease prior to lung metastasectomy. A cost-effectiveness analysis, using a Markov model over a 10 year period, was performed to compare two different surveillance programs, either PET-CT or whole-body CT, in patients with suspected pulmonary metastasised melanoma. Methods. Data from published studies provided probabilities for the model. Complication and care costs were obtained from standardised administrative databases from 19 hospitals identified by DRG codes (reported in 2009 Euros). For the cost calculation of PET-CT we performed a microcosting analysis. All costs and benefits were yearly discounted at respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. Results. The PET-CT strategy provided 86.29 LMG (95% CI: 81.50-90.88 LMG) at a discounted cost of Euro 3 974 (95% CI: Euro 1 339-12 303), while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a discounted cost of Euro 5 022 (95% CI: Euro 1 378-16 018). This PET-CT strategy resulted in a net saving of Euro 1 048 with a gain of 0.2 LMG. Based on PET-CT findings, 20% of futile surgeries could be avoided. Conclusion. Integrating PET-CT in the management of patients with high risk MM appears to be less costly and more accurate by avoiding futile thoracotomies in one of five patients as well as by providing a small survival benefit at 10 years

  15. Anesthesia for ambulatory anorectal surgery.

    Science.gov (United States)

    Gudaityte, Jūrate; Marchertiene, Irena; Pavalkis, Dainius

    2004-01-01

    The prevalence of minor anorectal diseases is 4-5% of adult Western population. Operations are performed on ambulatory or 24-hour stay basis. Requirements for ambulatory anesthesia are: rapid onset and recovery, ability to provide quick adjustments during maintenance, lack of intraoperative and postoperative side effects, and cost-effectiveness. Anorectal surgery requires deep levels of anesthesia. The aim is achieved with 1) regional blocks alone or in combination with monitored anesthesia care or 2) deep general anesthesia, usually with muscle relaxants and tracheal intubation. Modern general anesthetics provide smooth, quickly adjustable anesthesia and are a good choice for ambulatory surgery. Popular regional methods are: spinal anesthesia, caudal blockade, posterior perineal blockade and local anesthesia. The trend in regional anesthesia is lowering the dose of local anesthetic, providing selective segmental block. Adjuvants potentiating analgesia are recommended. Postoperative period may be complicated by: 1) severe pain, 2) urinary retention due to common nerve supply, and 3) surgical bleeding. Complications may lead to hospital admission. In conclusion, novel general anesthetics are recommended for ambulatory anorectal surgery. Further studies to determine an optimal dose and method are needed in the group of regional anesthesia.

  16. Worldwide cutaneous malignant melanoma incidences analyzed by sex, age, and skin type over time (1955–2007): Is HPV infection of androgenic hair follicular melanocytes a risk factor for developing melanoma exclusively in people of European-ancestry?

    Science.gov (United States)

    Merrill, Stephen J.; Subramanian, Madhan; Godar, Dianne E.

    2016-01-01

    ABSTRACT The cutaneous malignant melanoma (CMM) incidence has been increasing in an exponential manner in certain populations around the world for over 7 decades. To help illuminate the etiology, we performed worldwide temporal (1955–2007) CMM incidence analysis by sex, age (0–14, 15–29, 30–49, 50–69, 70–85+), and skin type on 6 continents using data from the International Agency for Research on Cancer. We observe an exponential increase in the CMM incidence over time and an increase of about 2 orders of magnitude between age groups 0–14 and 15–29 exclusively in European-ancestry populations around the world independent of skin type (I–III or III–IV). Other populations like the Chinese (III-IV) had much lower CMM incidences that either remained stable or temporally decreased but did not display a dramatic increase between the youngest age groups. The dramatic increase in the incidence between the youngest age groups found only in European-ancestry populations suggests one of the most important risk factors for CMM may be developing androgenic hair, the occurrence of which appears to correlate with the distribution of CMM over male and female body sites. Besides that potential new risk factor, the increasing CMM incidence with increasing age, known not to be from cumulative UV doses, may be associated with age-related changes to skin, i.e., thinning epidermis causing lower vitamin D3 levels, and hair, i.e., whitening from higher reactive oxygen species. The temporal exponential increasing CMM incidence in European-ancestry populations may be due to Human Papilloma Virus infection of follicular hair melanocytes, found in CMM biopsies. PMID:27588159

  17. Oral Amelanotic Melanoma | Adisa | Annals of Ibadan Postgraduate ...

    African Journals Online (AJOL)

    Malignant melanomas of the mucosal regions of the head and neck are extremely rare neoplasms accounting for less than 1% of all melanomas. Approximately half of all head and neck melanomas occur in the oral cavity. Less than 2% of all melanomas lack pigmentation, in the oral mucosa however, up to 75% of cases ...

  18. Sunnier European countries have lower melanoma mortality.

    Science.gov (United States)

    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.

  19. Seven Non-melanoma Features to Rule Out Facial Melanoma

    Directory of Open Access Journals (Sweden)

    Philipp Tschandl

    2017-08-01

    Full Text Available Facial melanoma is difficult to diagnose and dermatoscopic features are often subtle. Dermatoscopic non-melanoma patterns may have a comparable diagnostic value. In this pilot study, facial lesions were collected retrospectively, resulting in a case set of 339 melanomas and 308 non-melanomas. Lesions were evaluated for the prevalence (> 50% of lesional surface of 7 dermatoscopic non-melanoma features: scales, white follicles, erythema/reticular vessels, reticular and/or curved lines/fingerprints, structureless brown colour, sharp demarcation, and classic criteria of seborrhoeic keratosis. Melanomas had a lower number of non-melanoma patterns (p < 0.001. Scoring a lesion suspicious when no prevalent non-melanoma pattern is found resulted in a sensitivity of 88.5% and a specificity of 66.9% for the diagnosis of melanoma. Specificity was higher for solar lentigo (78.8% and seborrhoeic keratosis (74.3% and lower for actinic keratosis (61.4% and lichenoid keratosis (25.6%. Evaluation of prevalent non-melanoma patterns can provide slightly lower sensitivity and higher specificity in detecting facial melanoma compared with already known malignant features.

  20. [Melanoma in organ transplant patients].

    Science.gov (United States)

    Lévêque, L; Dalac, S; Dompmartin, A; Louvet, S; Euvrard, S; Catteau, B; Hazan, M; Schollhamer, M; Aubin, F; Dreno, B; Daguin, P; Chevrant-Breton, J; Frances, C; Bismuth, M J; Tanter, Y; Lambert, D

    2000-02-01

    The incidence of cutaneous melanoma has rapidly increased in the white population over the last decades. It has been estimated that the incidence doubles world-wide every 10 years. Different risk factors have been identified, including immunosuppression. The aim of our study-was to determine the relative risk of developing melanoma in the organ transplant population and the clinical and histological features of their melanomas. This retrospective study was conducted with the collaboration of 9 University Hospital Centers: Besançon, Brest, Caen, Dijon, Lille, Lyon, Nantes, Paris (Pitié-Salpétrière) and Rennes. A questionnaire was sent to the different departments of dermatology of these hospitals to obtain information on patients who had presented a melanoma after a transplantation between 1971 and 1997. During this period, there were 12,477 organ transplant recipients in the transplantation units of these 9 hospitals. Average follow-up for these patients was about 5 years and the average duration of immunosuppressive therapy was about 4.5 years. Among 12,477 organ transplant recipients, we found 17 cases of melanoma but no data could be obtain on one case: 14 occurred in renal transplant recipients and 3 in cardiac transplant recipients. Clinical and histological data were only available in 16 patients. The average time between transplantation and diagnosis of melanoma was 63 months, but it was 5 times shorter for 2 patients who had a past history of melanoma before transplantation. Two patients had a mucosal melanoma; for the cutaneous melanomas, 2 appeared on Dubreuilh melanosis, 2 were in situ melanomas, 7 were superficial spreading melanomas and 3 were nodular melanomas. The histological review of 11 cutaneous melanomas revealed a precursor nevus in 6 cases and a weak or no stroma reaction in 7/7 cases. Complete excision of the melanoma was performed in all patients except one with anorectal melanoma. Four patients died of visceral metastasis within a mean

  1. Choroidal melanoma

    International Nuclear Information System (INIS)

    Hernandez Quesada, Flora

    2013-01-01

    A useful and practical guide is developed to better track to the uveal melanoma, due to its highly malignant character. Melanoma of the uveal tract (choroid, iris, ciliary body) has been the intraocular tumor most frequent in adults. The biopsy has been inaccessible, due to its location; therefore, the diagnostic should be based on clinical examination and the correct utilization of the diagnostic procedures (ultrasound, fluorescent angiography, computed axial tomography and magnetic resonance). The cases are diagnosed in the histological examination of the operatory piece post-enucleation for other causes. Epidemiological research has been key to determine the associated factors and better to understand the mechanisms of onset of the disease. Anatomopathological studies of choroidal melanoma have permitted to know the natural history of the disease. The decrease of the visual acuity, pain or inflammation are presented as a defect in the visual field. Different techniques to diagnose the disease are explained. Ultrasound in mode A and B, computed axial tomography and magnetic resonance are the diagnostic method of election. Ultrasound has been the primary method of diagnostic, giving the size and vascularisation, useful in tracking, when they are treated in shape conservatively, showing changes in echogenicity and less vascularisation as good response to treatment. The treatments of choroidal melanoma are specified. The correct interpretation of the clinical symptoms and early utilization of diagnostic imaging methods, have permitted to establish the adequate therapeutic and to avoid local and distant metastasis. The uveal melanoma, depending on their size and location, traditionally has been treated by enucleation. Data from the literature and authors, have promoted the conservation of the ocular globe, depending on the size of the tumor. Transpupillary thermotherapy has been an available alternative for small tumors in Costa Rica and level of social security

  2. Exponentially increasing incidences of cutaneous malignant melanoma in Europe correlate with low personal annual UV doses and suggests 2 major risk factors.

    Science.gov (United States)

    Merrill, Stephen J; Ashrafi, Samira; Subramanian, Madhan; Godar, Dianne E

    2015-01-01

    For several decades the incidence of cutaneous malignant melanoma (CMM) steadily increased in fair-skinned, indoor-working people around the world. Scientists think poor tanning ability resulting in sunburns initiate CMM, but they do not understand why the incidence continues to increase despite the increased use of sunscreens and formulations offering more protection. This paradox, along with lower incidences of CMM in outdoor workers, although they have significantly higher annual UV doses than indoor workers have, perplexes scientists. We found a temporal exponential increase in the CMM incidence indicating second-order reaction kinetics revealing the existence of 2 major risk factors. From epidemiology studies, we know one major risk factor for getting CMM is poor tanning ability and we now propose the other major risk factor may be the Human Papilloma Virus (HPV) because clinicians find β HPVs in over half the biopsies. Moreover, we uncovered yet another paradox; the increasing CMM incidences significantly correlate with decreasing personal annual UV dose, a proxy for low vitamin D3 levels. We also discovered the incidence of CMM significantly increased with decreasing personal annual UV dose from 1960, when it was almost insignificant, to 2000. UV and other DNA-damaging agents can activate viruses, and UV-induced cytokines can hide HPV from immune surveillance, which may explain why CMM also occurs in anatomical locations where the sun does not shine. Thus, we propose the 2 major risk factors for getting CMM are intermittent UV exposures that result in low cutaneous levels of vitamin D3 and possibly viral infection.

  3. Prolongation of survival of dogs with oral malignant melanoma treated by en bloc surgical resection and adjuvant CSPG4-antigen electrovaccination.

    Science.gov (United States)

    Piras, L A; Riccardo, F; Iussich, S; Maniscalco, L; Gattino, F; Martano, M; Morello, E; Lorda Mayayo, S; Rolih, V; Garavaglia, F; De Maria, R; Lardone, E; Collivignarelli, F; Mignacca, D; Giacobino, D; Ferrone, S; Cavallo, F; Buracco, P

    2017-09-01

    Reported post-surgery 1-year survival rate for oral canine malignant melanoma (cMM) is around 30%; novel treatments are needed as the role of adjuvant chemotherapy is unclear. This prospective study regards adjuvant electrovaccination with human chondroitin sulfate proteoglycan-4 (hCSPG4)-encoded plasmid in 23 dogs with resected II/III-staged CSPG4-positive oral cMM compared with 19 dogs with resected only II/III-staged CSPG4-positive oral cMM. Vaccination resulted in 6-, 12-, 18- and 24-month survival rate of 95.6, 73.9, 47.8 and 30.4%, respectively [median survival time (MST) 684 days, range 78-1694, 8 of 23 dogs alive] and 6-, 12-, 18- and 24-month disease-free interval (DFI) rate of 82.6, 47.8, 26.1 and 17.4%, respectively (DFI 477 days, range 50-1694). Non-vaccinated dogs showed 6-, 12-, 18- and 24-month survival rate of 63.2, 26.3, 15.8 and 5.3%, respectively (MST 200 days, range 75-1507, 1 of 19 dogs alive) and 6-, 12-, 18- and 24-month DFI rate of 52.6, 26.3, 10.5 and 5.3%, respectively (DFI 180 days, range 38-1250). Overall survival and DFI of vaccinated dogs was longer in those dogs local recurrence rate was 34.8 and 42%, respectively while lung metastatic rate was 39 and 79%, respectively. © 2016 John Wiley & Sons Ltd.

  4. MR imaging of clear cell sarcoma (malignant melanoma of the soft parts): a multicenter correlative MRI-pathology study of 21 cases and literature review

    International Nuclear Information System (INIS)

    Beuckeleer, L.H. de; Schepper, A.M. de; Vandevenne, J.E.; Bloem, J.L.; Davies, A.M.; Oudkerk, M.; Hauben, E.; Marck, E. van; Somville, J.; Vanel, D.; Steinbach, L.S.; Guinebretiere, J.M.; Hogendoorn, P.C.W.; Mooi, W.J.; Verstraete, K.; Zaloudek, C.; Jones, H.

    2000-01-01

    Objective. To evaluate MR imaging and pathology findings in order to define the characteristic features of clear cell sarcoma of the soft tissues (malignant melanoma of the soft parts).Design and patients. MR examinations of 21 patients with histologically proven clear cell sarcoma of the musculoskeletal system were retrospectively reviewed and assessed for shape, homogeneity, delineation, signal intensities on T1- and T2-weighted images, contrast enhancement, relationship with adjacent fascia or tendon, secondary bone involvement, and intratumoral necrosis. In 19 cases the pathology findings were available for review and for a comparative MR-pathology study.Results. On T1-weighted images, lesions were isointense (n=3), hypointense (n=7) or slightly hyperintense to muscle (n=11). Immunohistochemical examination was performed in 17 patients. All 17 specimens showed positivity for HMB-45 antibody. In nine of 11 lesions with slightly increased signal intensity on T1-weighted images, a correlative MR imaging-pathology study was possible. All nine were positive to HMB-45 antibody.Conclusions. Clear cell sarcoma of the musculoskeletal system often has a benign-looking appearance on MR images. In up to 52% of patients, this lesion with melanocytic differentiation has slightly increased signal intensity on T1-weighted images compared with muscle. As the presence of this relative higher signal intensity on T1-weighted images is rather specific for tumors displaying melanocytic differentiation, radiologists should familiarize themselves with this rare entity and include it in their differential diagnosis when confronted with a well-defined, homogeneous, strongly enhancing mass with slightly higher signal intensity compared with muscle on native T1-weighted images. (orig.)

  5. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  6. Anorectal injury in pelvic blast.

    Science.gov (United States)

    Brogden, Tom G; Garner, J P

    2013-03-01

    The signature injury of the Afghanistan campaign has, amongst other things, included an increased incidence of destructive anorectal injury. There is no significant body of evidence about this type of injury on which to base management strategies. This review examines the historical military data, later civilian reports, many of which have challenged the military dogmas of Vietnam, and the spartan contemporaneous military data which does not particularly address pelviperineal blast injury. There is no evidence to support a move away from the doctrine of the four D's (diversion, distal washout, drainage and direct repair), but sound surgical judgement remains the mainstay of managing these challenging and highly morbid injuries.

  7. 21 CFR 346.50 - Labeling of anorectal drug products.

    Science.gov (United States)

    2010-04-01

    ... the following: “hemorrhoids,” “anorectal disorders,” “inflamed hemorrhoidal tissues,” “anorectal inflammation,” “hemorrhoidal tissues,” or “piles (hemorrhoids).”)] (2) Additional indications. Indications... and other anorectal disorders” or “irritation in hemorrhoids and other anorectal disorders”). (B...

  8. Melanoma em cavidade anoftálmica secundária a evisceração: relato de 2 casos e revisão da literatura Malignant melanoma in anophthalmic socket post-evisceration: case reports and literature review

    Directory of Open Access Journals (Sweden)

    Patricia Mitiko Santello Akaishi

    2004-12-01

    Full Text Available Os autores relatam 2 casos de pacientes com melanoma em cavidade anoftálmica secundária a eviscerações ocorridas há 30 e 60 anos. Em ambos os casos a análise histopatológica mostrou que o tumor estava aderido a remanescentes esclerais. A implicação desses casos foi discutida no contexto das indicações de evisceração e enucleação.We report 2 cases of malignant melanoma in anophthalmic sockets of patients who had undergone eviscerations 30 and 60 years ago. The histopathologic analysis showed that the tumors were adherent to scleral remnants. The implications of these cases were discussed in the context of the indications of evisceration and enucleation.

  9. Ocular Melanoma

    Science.gov (United States)

    ... is Ocular Melanoma? Leer en Español: ¿Qué es el melanoma ocular? Written By: Daniel Porter Reviewed By: Robert H Janigian Jr MD Sep. 01, 2017 Ocular melanoma (melanoma in or around the eye) is a type of cancer that develops in the cells that produce pigment. ...

  10. MR findings of congenital anorectal malformation

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Kyung; Kim, Hyae Young; Kwag, Hyon Joo; Chung, Eun Chul; Lee, Jung Sik; Suh, Jeong Soo [Ewha Womens University, medical College, Seoul (Korea, Republic of)

    1995-05-15

    To assess the usefulness of MRI in preoperative diagnosis of congenital anorectal malformation. MR findings of 11 cases with surgically proved anorectal malformations were retrospectively reviewed and compared with operative findings, according to the level of atresia, the development of sphincter muscle, fistula and associated anomalies of other organs. Four of 11 cases were low type of anorectal atresia, 3 cases were intermediate type, and 3 cases were high type. There was one case of Currarino triad with low type of anorectal stenosis. MRI demonstrated the levels of atresia correctly in all cases and revealed fistulas in all high type of anomalies. Degrees of the development of the sphincter muscles were good in all cases of low types and fair in a case of intermediate type and an anorectal stenosis, whereas the development was poor in 2 cases of intermediate type and all 4 cases of high type. The associated anomalies in anorectal malformation were renal agenesis, congenital hip dysplasia and sacral defect with presacral teratoma in Currarino triad. MRI was a simple and useful study to confirm the level of atresia, fistula and associated anomalies in the diagnosis of the congenital anorectal malformation.

  11. MR findings of congenital anorectal malformation

    International Nuclear Information System (INIS)

    Kim, Yoo Kyung; Kim, Hyae Young; Kwag, Hyon Joo; Chung, Eun Chul; Lee, Jung Sik; Suh, Jeong Soo

    1995-01-01

    To assess the usefulness of MRI in preoperative diagnosis of congenital anorectal malformation. MR findings of 11 cases with surgically proved anorectal malformations were retrospectively reviewed and compared with operative findings, according to the level of atresia, the development of sphincter muscle, fistula and associated anomalies of other organs. Four of 11 cases were low type of anorectal atresia, 3 cases were intermediate type, and 3 cases were high type. There was one case of Currarino triad with low type of anorectal stenosis. MRI demonstrated the levels of atresia correctly in all cases and revealed fistulas in all high type of anomalies. Degrees of the development of the sphincter muscles were good in all cases of low types and fair in a case of intermediate type and an anorectal stenosis, whereas the development was poor in 2 cases of intermediate type and all 4 cases of high type. The associated anomalies in anorectal malformation were renal agenesis, congenital hip dysplasia and sacral defect with presacral teratoma in Currarino triad. MRI was a simple and useful study to confirm the level of atresia, fistula and associated anomalies in the diagnosis of the congenital anorectal malformation

  12. Anticancer effects of kaempferol in A375 human malignant melanoma cells are mediated via induction of apoptosis, cell cycle arrest, inhibition of cell migration and downregulation of m-TOR/PI3K/AKT pathway.

    Science.gov (United States)

    Yang, Jia; Xiao, Peng; Sun, Jiaming; Guo, Liang

    2018-01-01

    Melanoma is an aggressive form of human cancer with limited treatment options currently available. The present study was aimed to evaluate the anticancer activity of kaempferol (KAM) against the human malignant melanoma A375 cell line along with evaluation of its effects on apoptosis, cell cycle, cell migration and m-TOR/PI3K/AKT pathway. Effects on cell viability were assessed by MTT assay while clonogenic assay measured the effects of KAM on colony formation. Annexin V assay evaluated the apoptotic effects of KAM in these cells using flow cytometry. Effects on cell cycle were determined by using flow cytometry with propidium iodide (PI) as probe. The effects of KAM on m-TOR/ PI3K/AKT signalling pathway were evaluated by western blot assay. MTT assay indicated that KAM exhibits a significant anticancer activity against A375 cells with an IC50 of 20 μM. These antiproliferative effects of KAM were also supported by the colony formation assay wherein KAM reduced the colony formation in a dose-dependent manner. The anticancer effect of KAM was found to be due to the initiation of apoptosis in human malignant melanoma A375 cells. Additionally, KAM also exhibited the capacity to trigger G2/M cell cycle arrest and to inhibit the cell migratory potential of A375 cells. KAM caused significant downregulation of m-TOR, phosphorylated (p) m-TOR, PI3K, p-PI3K and Akt protein levels in A375 malignantmelanoma cells. KAM exerts potent anticancer effects via induction of apoptosis, G2/M cell cycle arrest, cell migration inhibition and downregulation of m-TOR, pm-TOR, PI3K, p-PI3K and Akt protein levels.

  13. Immunohistochemical detection of XIAP in melanoma.

    Science.gov (United States)

    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). 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.

  14. Immunoscintigraphy in ocular melanoma

    International Nuclear Information System (INIS)

    Scheidhauer, K.; Scober, O.; Scheidler, J.; Leinsinger, G.; Scheiffarth, O.; Riedel, K.; Schumacher, U.

    1990-01-01

    Immunoscintigraphy (IS) of malignant tumors has become an encouraging tool in nuclear medicine. Early diagnosis of small lesions is mandatory for successful cancer therapy generally. The scintigraphic detectability of small lesions ( 2 fragments of the anti-melanoma monoclonal antibody 225.28S; this antibody recognizes the high-molecular-weight melanoma-associated antigen. No adverse effects were observed. In terms of true positive results, Single Photon Emission CT proved to be superior compared to planar scans (81 versus 46 percent true positive results). (author). 30 refs

  15. Gingival osteogenic melanoma in two dogs.

    Science.gov (United States)

    Ellis, Angela E; Harmon, Barry G; Miller, Debra L; Northrup, Nicole C; Latimer, Kenneth S; Uhl, Elizabeth W

    2010-01-01

    Osteogenic melanoma is a rare variant of metaplastic malignant melanoma in human medicine and appears to be a similarly rare variant in dogs. Two dogs with oral malignant melanoma with neoplastic bone formation are reported in this study. Both tumors were characterized by malignant melanocytes that transitioned into neoplastic bone at the deep margins of the neoplasm. Immunohistochemical analysis revealed S100- and Melan-A-positive neoplastic cells adjacent to, and occasionally embedded within, an osteoid and chondroblastic matrix. Scattered clusters of neoplastic cells were also positive for osteocalcin. The findings indicate that in dogs, as in humans, neoplastic melanocytes have metaplastic potential and can be osteogenic.

  16. Eumycetoma Masquerading As Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Janaki C

    1999-01-01

    Full Text Available Eumycetoma of the right foot caused by madurella mycetomatis with infection to regional inguinal lymph nodes has been described in a male patient along with the clinical, mycological and mycopathological features. The lesions never recurred in the follow up period of four years, after the excision of the sole lesions along with block dissection of the involved lymph nodes.

  17. Long-term Survival after Metastatic Childhood Melanoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; Bybjerg Jensen, Mette; Krag, Christen

    2014-01-01

    SUMMARY: Malignant melanoma in children is very rare and accounts for only 1-3% of all melanomas. A congenital melanocytic nevus depending on the size of the lesion is one of the risk factors for developing childhood melanoma because of the possible malignant transformation. Childhood malignant...... of malign melanoma must be in mind when evaluating a pigmented lesion in a pediatric patient. We present a case of a patient born with a congenital nevus diagnosed with metastatic childhood malignant scalp melanoma at the age of 6 years. The patient underwent surgical ablation and reconstruction and has...... survived 26 years without recurrence, thus representing an uplifting case of long-term survival of childhood melanoma....

  18. Melanoma genetics

    DEFF Research Database (Denmark)

    Read, Jazlyn; Wadt, Karin A W; Hayward, Nicholas K

    2015-01-01

    Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence of herita......Approximately 10% of melanoma cases report a relative affected with melanoma, and a positive family history is associated with an increased risk of developing melanoma. Although the majority of genetic alterations associated with melanoma development are somatic, the underlying presence...... in a combined total of approximately 50% of familial melanoma cases, the underlying genetic basis is unexplained for the remainder of high-density melanoma families. Aside from the possibility of extremely rare mutations in a few additional high penetrance genes yet to be discovered, this suggests a likely...... polygenic component to susceptibility, and a unique level of personal melanoma risk influenced by multiple low-risk alleles and genetic modifiers. In addition to conferring a risk of cutaneous melanoma, some 'melanoma' predisposition genes have been linked to other cancers, with cancer clustering observed...

  19. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography

    DEFF Research Database (Denmark)

    Boone, M A L M; Suppa, M; Dhaenens, F.

    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 op......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...

  20. Ocular melanoma: Detection using iodine-123-iodoamphetamine and SPECT imaging

    International Nuclear Information System (INIS)

    Dewey, S.H.; Leonard, J.C.

    1990-01-01

    Uptake of iodine-123-iodoamphetamine has been demonstrated in malignant melanoma using planar imaging techniques and has been used to detect an ocular melanoma at 12 hr postinjection. Using SPECT technique, an ocular melanoma is identified in a 64-yr-old male at 1 hr postinjection

  1. Development of primary malignant melanoma during treatment with a TNF-α antagonist for severe Crohn’s disease: a case report and review of the hypothetical association between TNF-α blockers and cancer

    Directory of Open Access Journals (Sweden)

    Kouklakis G

    2013-03-01

    Full Text Available George Kouklakis,1 Eleni I Efremidou,2 Michael Pitiakoudis,3 Nikolaos Liratzopoulos,2 Alexandros Ch Polychronidis2 1Endoscopy Unit, 2First Surgical Department, 3Second Surgical Department, Medical School, Democritus University of Thrace, University Hospital of Alexandroupolis, Alexandroupolis, Greece Abstract: It is recognized that immunosuppression may lead to reduced immune surveillance and tumor formation. Because of the immunosuppressive properties of tumor necrosis factor (TNF-alpha (TNF-α antagonists, it is plausible that these biologics may increase the risk of the occurrence of malignancies or the reactivation of latent malignancies. TNF-α antagonists have gained momentum in the field of dermatology for treating rheumatoid arthritis and psoriasis, and they have revolutionized the treatment of other inflammatory autoimmune diseases such as refractory Crohn's disease. However, there is accumulating evidence that TNF-α inhibitors slightly increase the risk of cancer, including malignant melanoma (MM. The authors herein report the case of a 54-year-old female patient who developed a primary MM during treatment with adalimumab for severe Crohn’s disease resistant to successive medical therapies. The patient had been receiving this TNF-α blocker therapy for 3 years before the occurrence of MM. After wide surgical excision of the lesion and staging (based on Breslow thickness and Clark level, evaluation with a whole-body computed tomography scan was negative for metastatic disease. The long duration of the adalimumab therapy and the patient's lack of a predisposition to skin cancer suggest an association between anti-TNF-α drugs and melanocytic proliferation. The authors also review the literature on the potential association between anti-TNF regimens and the occurrence of malignancies such as melanocytic proliferations. There is a substantial hypothetical link between anti-TNF-α regimens such as adalimumab and the potential for cancers

  2. Paraneoplastic ophthalmoplegia and subacute motor axonal neuropathy associated with anti-GQ1b antibodies in a patient with malignant melanoma

    NARCIS (Netherlands)

    L. Kloos; C.W. Ang (Wim); W.H.J. Kruit (Wim); G. Stoter (Gerrit); P.A.E. Sillevis Smitt (Peter)

    2003-01-01

    textabstractA 68 year old woman developed oculomotor paresis shortly after metastatic progression of her melanoma was discovered. She was then immunised with the tumour antigen MAGE-3 in combination with an immunological adjuvant. During immunisation her symptoms worsened and she

  3. Anorectal function and outcomes after transanal minimally invasive surgery for rectal tumors

    Directory of Open Access Journals (Sweden)

    Feza Y Karakayali

    2015-01-01

    Full Text Available Background: Transanal endoscopic microsurgery is a minimally invasive technique that allows full-thickness resection and suture closure of the defect for large rectal adenomas, selected low-risk rectal cancers, or small cancers in patients who have a high risk for major surgery. Our aim, in the given prospective study was to report our initial clinical experience with TAMIS, and to evaluate its effects on postoperative anorectal functions. Materials and Methods: In 10 patients treated with TAMIS for benign and malignant rectal tumors, preoperative and postoperative anorectal function was evaluated with anorectal manometry and Cleveland Clinic Incontinence Score. Results: The mean distance of the tumors from the anal verge was 5.6 cm, and mean tumor diameter was 2.6 cm. All resection margins were tumor free. There was no difference in preoperative and 3-week postoperative anorectalmanometry findings; only mean minimum rectal sensory volume was lower at 3 weeks after surgery. The Cleveland Clinic Incontinence Score was normal in all patients except one which resolved by 6 weeks after surgery.The mean postoperative follow-up w