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Sample records for advanced malignant melanoma

  1. New therapeutic options for advanced non-resectable malignant melanoma.

    Science.gov (United States)

    Stadler, Simone; Weina, Kasia; Gebhardt, Christoffer; Utikal, Jochen

    2015-03-01

    Melanoma is a malignant tumor which is inclined to metastasize promptly into the lymphatic system and other organs such as lung, liver, brain or bone. Therefore early diagnosis remains crucial for improving clinical outcome for melanoma patients. Current chemotherapy and chemo-immunotherapy regimes have shown little clinical benefit with no improvement in overall survival. However, new advances in melanoma biology such as the discovery of predisposed gene signatures and key somatic events have changed clinical practice. New therapeutic approaches are being tested or have been approved by the FDA/EMA recently including targeted therapies, such as BRAF- and MEK-inhibitors, and novel immunotherapies, such as anti-CTLA4 or anti-PD1 therapies. For these therapies an improvement of progression-free and overall survival has been seen in patients with advanced non-resectable melanoma. The following review summarizes recent therapeutic options after the ASCO and ESMO annual meetings 2014 for the treatment of malignant melanoma. PMID:25596540

  2. Malignant Melanoma of the Foot

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    ... Text Size Print Bookmark Malignant Melanoma of the Foot What is Malignant Melanoma? Melanoma is a cancer ... age groups, even the young. Melanoma in the Foot Melanoma that occurs in the foot or ankle ...

  3. Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Eshini Perera

    2013-12-01

    Full Text Available Melanomas are a major cause of premature death from cancer. The gradual decrease in rates of morbidity and mortality has occurred as a result of public health campaigns and improved rates of early diagnosis. Survival of melanoma has increased to over 90%. Management of melanoma involves a number of components: excision, tumor staging, re-excision with negative margins, adjuvant therapies (chemo, radiation or surgery, treatment of stage IV disease, follow-up examination for metastasis, lifestyle modification and counseling. Sentinel lymph node status is an important prognostic factor for survival in patients with a melanoma >1 mm. However, sentinel lymph node biopsies have received partial support due to the limited data regarding the survival advantage of complete lymph node dissection when a micrometastasis is detected in the lymph nodes. Functional mutations in the mitogen-activated pathways are commonly detected in melanomas and these influence the growth control. Therapies that target these pathways are rapidly emerging, and are being shown to increase survival rates in patients. Access to these newer agents can be gained by participation in clinical trials after referral to a multidisciplinary team for staging and re-excision of the scar.

  4. 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.

  5. Malignant melanoma of nose

    OpenAIRE

    Kundu, I. N.; Haldar, B.; Saha, A. K.

    2001-01-01

    Malignant melanoma (MM) is one of the uncommon malignancies of the nose. We present an unusually big proliferative like MM in the vestibule of the nose. Malignancy of nose constitutes less than 1% of all malignancies (3% of head & neck tumour). MM however contributes only 2% of all malignant neoplasms of the nose (Moore & Martin. 1955).

  6. Malignant melanoma - cutaneous metastases

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    Padmavathy L; Rao L; Ethirajan N; Swamy B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  7. Malignant melanoma - cutaneous metastases

    Directory of Open Access Journals (Sweden)

    Padmavathy L

    2008-01-01

    Full Text Available Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra. Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported.

  8. Malignant melanoma - cutaneous metastases.

    Science.gov (United States)

    L, Padmavathy; L, Lakshmana Rao; N, Ethirajan; B, Krishna Swamy

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  9. Malignant melanoma of the mandibular gingiva

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    Sandeep Fauzdar

    2010-04-01

    Full Text Available Oral malignant melanoma is an infrequent neoplasia making up less than 1% of all melanomas, which exhibits much more aggressive behavior than those found on the skin. We present an aggressive case of oral malignant melanoma located on the mandibular gingiva in a 24-year-old male patient, who developed metastases to not only the regional lymph nodes but also the lungs and liver. The advanced stage of the disease contraindicated any surgical intervention and palliative chemotherapy was planned.

  10. Malignant melanoma of choroid

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    Manohar S

    1991-01-01

    Full Text Available Four cases of malignant melanoma of the choroid are reported due to rarity of the condition in India. One of the cases presented with Naevus of Ota. All the cases had typical clinical and investigative features. All cases were enucleated. Histopathologically three of them were of mixed type and one was of the epithelioid type. Two of the cases were seen in patients below 40 years of age.

  11. MALIGNANT MELANOMA – CUTANEOUS METASTASES

    Science.gov (United States)

    Padmavathy, L; Lakshmana Rao, L; Ethirajan, N; Krishna Swamy, B

    2008-01-01

    Melanoma composed of melanocytes may arise in the skin or other tissues harboring melanocytes, such muco-cutaneous junctions, mucosa including the conjunctiva, iris, choroids and substantia nigra.1 Metastases to the skin and subcutaneous tissues from a malignant melanoma are less common. A case of multiple painless nodules on the body that revealed metastatic deposits of melanoma on histopathological examination is being reported. PMID:19882041

  12. METASTATIC MALIGNANT MELANOMA: CASE REPORT

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    Satish

    2015-06-01

    Full Text Available A 32 year s old man presented with well - defined lesion on the left sole 8 months back. Biopsy and FNAC from the lesion confirmed malignant melanoma left foot & the patient was advised excision. After 4 months patient gave h/o swelling on the medial aspect of the thigh. The patient was diagnosed to have fulminant metastatic malignant melanoma of the left foot with metastasis to femoral lymph node. This case report re - emphasizes the importance of the combined approach to ascertain diagnose early KEYWORDS : Melanoma .

  13. Current management and novel agents for malignant melanoma

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    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.

  14. Malignant melanoma of the vulva

    OpenAIRE

    Ragnarsson Olding, Boel

    1999-01-01

    From a consecutive, nationwide series of 219 females with primary vulvar malignant melanomas diagnosed in Sweden during 1960 to 1984 and followed up until 1994, we analyzed epidemiological, clinical, histopathological, prognostic and molecular genetic data. The age-standardized incidence among these patients, 75 % of whom were 60 years old or more, decreased by 3.2 % annually compared to an increase of almost 6 % for contemporary cutaneous melanomas in Sweden. Relative 5-and...

  15. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

    Science.gov (United States)

    Theurich, Sebastian; Rothschild, Sacha I; Hoffmann, Michael; Fabri, Mario; Sommer, Andrea; Garcia-Marquez, Maria; Thelen, Martin; Schill, Catherine; Merki, Ramona; Schmid, Thomas; Koeberle, Dieter; Zippelius, Alfred; Baues, Christian; Mauch, Cornelia; Tigges, Christian; Kreuter, Alexander; Borggrefe, Jan; von Bergwelt-Baildon, Michael; Schlaak, Max

    2016-09-01

    Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR. PMID:27466265

  16. Metastatic malignant melanoma of maxillary gingiva. A case report.

    OpenAIRE

    Srinivasan S; Pal K; Dayal P; Bastian T; Patil S

    1997-01-01

    Malignant melanoma of the oral cavity can be primary or secondary due to metastasis from distant site. Incidence of oral cavity by metastasis of melanoma is 1.85%. Most common oral sites involved are tongue, buccal mucosa and parotid gland. Oral lesions occur as a part of disseminated disease during the advanced stages and has poor prognosis. An unusual case of metastatic malignant melanoma of the maxillary gingiva is reported.

  17. Giant melanoacanthoma mimicking malignant melanoma

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    Vikas Shankar

    2011-01-01

    Full Text Available Melanoacanthoma denotes a rare variant of pigmented seborrheic keratosis. A 65-year-old male farmer had pigmented, verrucous, itchy, highly painful, progressively growing irregularly oval plaque on left side of lower back for the past five years. The indurated lesion, measuring maximum diameter 10 cm Χ 5 cm, had no discharge, bleeding, ulceration, or associated lymphadenopathy. Dermoscopy showed regular pigmentary network and cribiform pattern of ridges without any feature of malignant melanoma. Histopathology showed well-defined islands of basaloid cells interspersed with large and richly dendritic melanocytes. The lesion was totally excised followed by skin grafting. Our patient was unique in its massive size and clinical resemblance with malignant melanoma. The diagnosis was confirmed by dermoscopy and skin biopsy.

  18. 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....

  19. Molecular probes for malignant melanoma imaging.

    Science.gov (United States)

    Ren, Gang; Pan, Ying; Cheng, Zhen

    2010-09-01

    Malignant melanoma represents a serious public health problem and is a deadly disease when it is diagnosed at late stage. Though (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been widely used clinically for melanoma imaging, other approaches to specifically identify, characterize, monitor and guide therapeutics for malignant melanoma are still needed. Consequently, many probes targeting general molecular events including metabolism, angiogenesis, hypoxia and apoptosis in melanoma have been successfully developed. Furthermore, probes targeting melanoma associated targets such as melanocortin receptor 1 (MC1R), melanin, etc. have undergone active investigation and have demonstrated high melanoma specificity. In this review, these molecular probes targeting diverse melanoma biomarkers have been summarized. Some of them may eventually contribute to the improvement of personalized management of malignant melanoma. PMID:20497118

  20. Technique and outcomes of isolated limb infusion for locally advanced malignant melanoma - A radiological perspective

    Energy Technology Data Exchange (ETDEWEB)

    Chun, J.-Y., E-mail: drjyc78@gmail.com [Department of Radiology, St George' s Hospital, London (United Kingdom); Hussain, M.; Powell, B. [Plastic Surgery, St George' s Hospital, London (United Kingdom); Belli, A.-M. [Department of Radiology, St George' s Hospital, London (United Kingdom)

    2011-12-15

    Aim: Isolated limb infusion (ILI) is a novel, minimally invasive technique for delivering high-dose regional chemotherapy in patients with recurrent and in-transit melanoma. The aim of this study was to review our single-centre experience in treating eleven patients. We emphasize the role of radiologists in setting up this service, including pre-treatment workup and placement of vascular catheters. Materials and methods: A retrospective analysis of 11 patients who underwent 12 procedures between 2005 and 2009 was performed. Pre-procedural staging computed tomography (CT), CT angiography, and duplex studies were performed. All patients received a cytotoxic combination of melphalan and actinomycin-D via radiologically placed arterial and venous catheters in the affected limb under mild hyperthermic conditions. The outcome measures include response rates, limb toxicity, complications, and survival. Results: All patients were female with a mean age of 72 years. Three patients had American Joint Committee on Cancer (AJCC) stage IIIB melanoma, seven had stage IIIC melanoma, and one had a stage IIIB Merkel cell tumour. Complete response was seen in five patients (46%), partial response in four (36%), and progressive disease in two (18%). One patient developed grade 4 toxicity requiring a fasciotomy and another experienced systemic toxicity. Conclusion: These outcomes are comparable to previous studies and shows that ILI is effective in locoregional control of unresectable melanoma. It is a relatively safe procedure but not without risk. Our experience shows the importance of radiological input to ensure safe and effective delivery of services.

  1. 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

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

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    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.

  3. Unusual thoracic manifestation of metastatic malignant melanoma

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    Mohan K

    2010-01-01

    Full Text Available Massive pleural effusion due to metastatic malignant melanoma is rare. We report a case of bilateral (massive on left side pleural effusion as a metastatic manifestation of cutaneous malignant melanoma. In our case, successful outcome of pleurodesis with vincristine is significant as this agent is rarely used.

  4. 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 this...

  5. Primary malignant melanoma of the esophagus.

    Science.gov (United States)

    Jora, Charu; Pankaj, Promila; Verma, Ritu; Jain, Anjali; Belho, Ethel S

    2015-01-01

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography. PMID:25829739

  6. Primary malignant melanoma of the esophagus

    International Nuclear Information System (INIS)

    Primary malignant melanoma most commonly originates from the skin; other less common extra cutaneous sites include squamous mucous membranes, uvea, retina, leptomeninges, genitourinary tract, digestive tract, biliary tract, and upper respiratory tract. Primary melanoma of the gastrointestinal tract is exceedingly rare. We are reporting a histo-pathologically proven rare case of primary malignant melanoma of the esophagus and its findings on fluorodeoxyglucose positron emission tomography and computed tomography

  7. Malignant melanoma of breast: a case report

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    A. Bhagyalakshmi

    2014-04-01

    Full Text Available Malignant melanoma rarely affects the breast. Malignant melanoma of breast is divided into two categories: primary and metastatic lesions. Primary melanoma involves the skin and less commonly the glandular parenchyma of the breast. Differentiating them is very important in deciding on treatment strategies. This case report aims to increase awareness of unusual neoplasms of the breast which requires a different surgical and adjuvant therapeutic approach. [Int J Res Med Sci 2014; 2(2.000: 755-758

  8. Thigmotropism of Malignant Melanoma Cells

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    Pascale Quatresooz

    2012-01-01

    Full Text Available During malignant melanoma (MM progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape. These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called “accretive” growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread.

  9. Thigmotropism of malignant melanoma cells.

    Science.gov (United States)

    Quatresooz, Pascale; Piérard-Franchimont, Claudine; Noël, Fanchon; Piérard, Gérald E

    2012-01-01

    During malignant melanoma (MM) progression including incipient metastasis, neoplastic cells follow some specific migration paths inside the skin. In particular, they progress along the dermoepidermal basement membrane, the hair follicles, the sweat gland apparatus, nerves, and the near perivascular space. These features evoke the thigmotropism phenomenon defined as a contact-sensing growth of cells. This process is likely connected to modulation in cell tensegrity (control of the cell shape). These specifically located paucicellular aggregates of MM cells do not appear to be involved in the tumorigenic growth phase, but rather they participate in the so-called "accretive" growth model. These MM cell collections are often part of the primary neoplasm, but they may, however, correspond to MM micrometastases and predict further local overt metastasis spread. PMID:22203839

  10. CT findings of diffuse malignant leptomeningeal melanoma

    International Nuclear Information System (INIS)

    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. (Chiba, N.)

  11. Malignant melanoma of the oral cavity

    OpenAIRE

    M.S. Hashemi Pour

    2006-01-01

    Oral malignant melanoma is a rare disease. The common sites of its occurrence are the palate and gingiva with the maxillary arch being affected 80% of the time. Because of their presence at relatively obscure areas in the oral cavity, most of the malignant melanomas of the oral cavity are diagnosed at a late stage. These lesions are associated with poor prognosis. The dental clinician must therefore carefully examine the head, neck, and oral cavity, and any pigmented lesion that may ex...

  12. 20-year long-term results of the use of external beam radiotherapy for primary advanced, recurrent and metastatic malignant melanoma

    International Nuclear Information System (INIS)

    Purpose: The use of external beam radiotherapy (RT) is regarded only as 'last resort' approach in the multidisciplinary management of malignant melanoma (MM). We have analyzed the initial tumor response and the long-term local control, survival rate and relevant prognostic factors in patients with locally advanced, recurrent and metastatic MM who have been treated at our institution over the past 20 years. Methods: Between 1977 - 1995, a total of 2917 consecutive patients have been entered in the malignant melanoma registry of our university hospital. Just 121 (4%) out of these 2917 (4%) consecutive patients, i.e. 56 females and 65 males with histologically proven and clinically staged malignant melanoma (MM), have been selected during their disease process to receive external beam RT due to their advanced stage of the disease. The primary histology was nodular melanoma (NM) in 51 (47%) pts., superficial spreading melanoma (SSM) in 35 (32%) pts.; acral-lentiginous melanoma (ALM) in 8 (7%) pts. and lentigo maligna melanoma (LMM) in 4 (5%) pts.. The specific clinical indication for the application of RT was primarily for palliative reasons in the advanced clinical UICC stages II and IV: (a) 11 (9%) pts had residual disease (R1-2) after resection of a primary or recurrent MM (UICC II); (b) 57 (47%) pts suffered from regional lymph node metastases (33 pts.) or in-transit metastases (24 pts.) (UICC III); and (c) 53 (44%) pts had distant metastases at various body sites (7 pts. with M1a; 46 pts. with M1b) (UICC IV). The mean interval between the first diagnosis and actual application of the external beam radiotherapy (RT) was 19 months (range: 3 - 186 months). In most cases conventional RT and only in a few cases hypofractionated RT was applied with 2 - 6 Gy single dose fractions up to a median total RT dose of 48 Gy (range: 20 - 60 Gy). Results: The median follow-up of the patients (FU) was 9 years (range: 0.3 - 15.5 yrs.). With regard to UICC stages, an initial

  13. MALIGNANT MELANOMA OF THE ORAL CAVITY

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    Vishnu Prasad

    2016-02-01

    Full Text Available Oral malignant melanoma is a rare aggressive neoplasm commonly affects males and is more frequently seen at the level of the hard palate and gingiva. In many cases, melanoma has evolved from the pre-existing pigmented lesions. These neoplasms are biologically aggressive, but they often go unnoticed since they usually present merely as a hyperpigmented patch on the gingival surface. Performing biopsies of doubtful pigmented lesions helps in early treatment and better prognosis. The surgical excision combined with the chemotherapy is the treatment of choice. Here, we report a rare case of an elderly male patient with oral malignant melanoma with metastasis to vertebral column.

  14. Vaginal Primary Malignant Melanoma: A Rare and Aggressive Tumor

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    Georgios Androutsopoulos

    2013-01-01

    Full Text Available Vaginal primary malignant melanoma is a rare and very aggressive tumor. It most commonly occurs in postmenopausal women, with a mean age of 57 years. Our patient is an 80-year-old, postmenopausal Greek woman presented with a complaint of abnormal vaginal bleeding. On gynecologic examination there was a pigmented, raised, ulcerated, and irregular lesion  cm in the upper third of anterior vaginal wall. She underwent a wide local excision of the lesion. The histopathology revealed vaginal primary malignant melanoma with ulceration and no clear surgical margins. She denied any additional surgical interventions and underwent to postoperative adjuvant radiotherapy. Follow up 5 months after initial diagnosis revealed no evidence of local recurrence or distant metastasis. The prognosis of vaginal primary malignant melanoma is very poor despite treatment modality, because most of the cases are diagnosed at advanced stage. Particularly patients with no clear surgical margins and tumor size >3 cm needed postoperative adjuvant radiotherapy.

  15. Brain metastases from malignant melanoma.

    Science.gov (United States)

    Chiarion-Sileni, Vanna; Murr, Rita; Pigozzo, Jacopo; Sarti, Samanta; Tomassi, Ottaviano; Romanini, Antonella

    2003-01-01

    Metastatic spread of tumour cells detached from melanoma into the central nervous system (CNS) occurs haematogenously since lymphatic drainage is absent in the brain. CNS metastases occur in 10 to 40% of melanoma patients in clinical studies and up to 90% in autopsy studies. Headache is the most common presenting symptom, but brain metastases should be suspected in all melanoma patients with new neurologic findings. Magnetic resonance imaging is the best diagnostic technique for detecting CNS metastases. Median survival of melanoma patients with CNS metastases ranges between 2 and 8 months. The optimal treatment of melanoma patients with CNS metastases depends on the objective situation, often surgery, radiosurgery, whole brain radiotherapy and chemotherapy are used in combination to obtain longer remissions and optimal symptom relieve. PMID:14732883

  16. Screening for metastatic malignant melanoma of the uvea revisited

    DEFF Research Database (Denmark)

    Eskelin, Sebastian; Pyrhönen, Seppo; Summanen, Paula; Prause, J.U.; Kivelä, Tero

    ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases......ophthalmology, malignant uveal melanoma, metastasis, liver, screening, ultrasonography, X-ray, lactate dehydrogenase, alkaline phosphatase, aminotransferases...

  17. Malignant melanoma of the oral cavity

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    Ebenezer Jagadish

    2006-01-01

    Full Text Available Oral malignant melanoma is a rare disease. The common sites of its occurrence are the palate and gingiva with the maxillary arch being affected 80% of the time. Because of their presence at relatively obscure areas in the oral cavity, most of the malignant melanomas of the oral cavity are diagnosed at a late stage. These lesions are associated with poor prognosis. The dental clinician must therefore carefully examine the head, neck, and oral cavity, and any pigmented lesion that may exhibit growth potential must be biopsied. This article describes a case of malignant melanoma that was present in the oral cavity and briefly reviews the relevant literature that explains the nature of this lesion.

  18. MALIGNANT MELANOMA OF THE HEAD SKIN

    OpenAIRE

    Camelia Tamas; Doinita Radulescu; Lucian Popa; C. Tarasi; Cristina Stanescu; R. Nita

    2006-01-01

    Malignant melanoma (MM) is known as a tumor with high malignancy. The development of a melanoma on the head skin is even more severe, as prognosis, because of the limitted possibilities for large excision and high potential of diffusion in the wide vascular network. We treated 11 cases with MM head localisation in a period of 10 years. The rate of survival is very poor (6 months – 4 years after surgery). We used skin graft or fasciocutaneous flap for the regional reconstruction after exc...

  19. Malignant melanoma at a scientific laboratory

    International Nuclear Information System (INIS)

    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

  20. Veterinary researcher examines malignant melanoma in horses and people

    OpenAIRE

    Douglas, Jeffrey S.

    2006-01-01

    Malignant melanoma is a dangerous, aggressive form of cancer, and approximately 54,000 new cases are diagnosed every year, according to the American Cancer Society. Interestingly, there are many similarities between malignant melanoma in horses and malignant melanoma in people.

  1. 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...

  2. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: Clinicaltrials.gov NCT00356460.

  3. Intramuscular metastasis from malignant melanoma: MR findings

    International Nuclear Information System (INIS)

    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.)

  4. 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.

  5. Malignant Melanoma With Rhabdomyosarcomatous Differentiation: A Case Report.

    Science.gov (United States)

    Antonov, Nina K; Niedt, George W

    2016-06-01

    Malignant melanoma may exhibit morphologic characteristics of nonmelanocytic cell or tissue components, a phenomenon termed divergent differentiation. Melanoma with rhabdomyosarcomatous differentiation is rare, with 6 definite cases in adults reported in the literature. The authors describe a 75-year-old man with a cutaneous lesion of the right ear initially diagnosed as malignant melanoma. Three months later, biopsy of a right cervical lymph node showed changes suggestive of rhabdomyosarcoma. Reexamination of the initial skin biopsy with muscle markers confirmed a diagnosis of malignant melanoma with rhabdomyosarcomatous differentiation. This case serves to highlight the diagnostic challenges associated with this rare subtype of melanoma. PMID:27205908

  6. 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.

  7. 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...

  8. 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.

  9. 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...

  10. Malignant melanoma arising in mature cystic teratoma of the ovary

    OpenAIRE

    Heidi E Godoy; Kesterson, Joshua P.; Kasznica, John M.; Lele, Shashikant

    2011-01-01

    ► Teratomas are composed of elements of all three germ layers, all potentially capable of undergoing malignant transformation. ► A case of malignant melanoma arising in a mature teratoma is presented.

  11. A CASE OF LIMBAL MALIGNANT MELANOMA

    Directory of Open Access Journals (Sweden)

    Hansa H

    2015-05-01

    Full Text Available Conjunctival malignant melanoma is a rare pigmented tumor occurring during fifth and sixth decade typically involving limbus with high recurrence rate . A 65 yr male presented with complaints of slowly growing dark colored swelling in his left eye since 2 months . No systemic complaints . A black mass was seen on limbus with lobulated appearance . On USG ocular coats were normal . UBM shows 8*5 mm mass . Excision of mass was done and biopsy confirmed diagnosis . Mass excision was supplemented with cryotherapy . Now patient i s cosmetically and visually satisfied .

  12. UVB: suscetibilidade no melanoma maligno UVB: susceptibility in malignant melanoma

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2010-12-01

    Full Text Available FUNDAMENTOS: Está bem definido que a radiação ultravioleta provoca depleção imunológica na pele, permitindo o desenvolvimento de tumores cutâneos malignos. A maioria dos pacientes de cânceres da pele não melanomas são considerados UVB-suscetíveis. OBJETIVOS: Estudar a UVB-suscetibilidade nos pacientes com melanoma maligno e se este é um fator de risco para o desenvolvimento desse câncer. MÉTODOS: Foram selecionados 88 voluntários divididos em dois grupos: grupo-controle saudável (n=61 e grupo de portadores de melanoma (n=27, todos identificados de acordo com os critérios: tipo histológico, nível de invasão, fotótipos de pele, sexo e idade. A suscetibilidade à radiação ultravioleta B (UVB foi medida pela reação de hipersensibilidade ao contato com o difenciprone nos voluntários sensibilizados em áreas previamente irradiadas. RESULTADOS: A suscetibilidade à radiação UVB foi de 81,5% nos pacientes com melanoma maligno e de 31,2% no grupo-controle. O risco de um indivíduo desenvolver o melanoma maligno foi 9,7 vezes maior do que nos indivíduos UVB-resistentes. CONCLUSÕES: A UVB-suscetibilidade pode ser considerada um fator de risco importante para o desenvolvimento do melanoma maligno.BACKGROUND: It is well established that UV radiation provokes an immunological depletion in the skin, enabling the development of malignant cutaneous tumors. Most nonmelanoma skin cancer patients are considered to be UVB-susceptible. OBJECTIVE: To study the behavior of UVB- susceptibility in malignant melanoma (MM patients and whether this is a risk factor to the development of MM. METHODS: Eighty-eight volunteers were selected and divided into two groups: healthy control group (n = 61 and MM group (n = 27, which were identified according to the following clinical criteria: histopathological type, level of invasion, skin phototype, sex and age. Susceptibility to ultraviolet B (UVB radiation was measured by the onset of a contact

  13. Malignant melanoma of the oral cavity: A review of literature

    Directory of Open Access Journals (Sweden)

    Hashemi Pour M

    2008-01-01

    Full Text Available Oral malignant melanoma is a rare aggressive neoplasm of the middle age. This malignancy commonly affects male subjects and is more frequently seen at the level of the hard palate and gingiva. At present, the clinicopathological classification of oral melanoma is not yet clearly outlined; consequently, the skin form is often taken as a reference. In many cases (up to 30%, the diagnosis of melanoma is made on lesions, which have evolved from the pre-existing pigmented lesions. The poor prognosis of oral melanomas requires that pigmented lesions of undetermined origin be routinely biopsied. The surgical approach, combined with the chemotherapeutic one, is the first choice treatment. The purpose of this study is to review literature that has been published about malignant melanoma of the oral cavity. Materials and Methods: Thirty-eight published articles and 8 textbooks related to oral malignant melanoma and been published in the last two decades are reviewed. Conclusion: The review of literature in the field of malignant melanoma of the oral cavity show that this malignancy might be different from cutaneous malignant melanomas, and new criteria for diagnosis and therapy should be considered for this disease. Physicians and dentists who treat problems of the oral cavity should be aware of the need for early diagnosis of oral melanomas and performing biopsies of doubtful pigmented lesions.

  14. Malignant Melanoma Presenting as Superior Mediastinal Mass without Extrathoracic Primary Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    You, Myung Won; Sung, Dong Wook; Lee, Young Kyung [Dept. of Diagnostic Radiology, Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2013-03-15

    Malignant melanoma most commonly occurs in the skin, and other organs are secondarily involved. Malignant melanoma presenting in the mediastinum without an extrathoracic primary is very rare. Authors report a case of malignant melanoma of the superior mediastinum without clinical history of extrathoracic malignant melanoma primarily and discuss its radiologic findings. CT shows lobulated heterogenous enhanced mass. Magnetic resonance shows mild hyperintense mass on T1 and T2-weighted images contained focal hemorrhage and necrosis, and invasion to neural foramen. In addition, positron emission tomography/computed tomography shows high standard uptake values uptake of the mass.

  15. Malignant Melanoma Presenting as Superior Mediastinal Mass without Extrathoracic Primary Melanoma

    International Nuclear Information System (INIS)

    Malignant melanoma most commonly occurs in the skin, and other organs are secondarily involved. Malignant melanoma presenting in the mediastinum without an extrathoracic primary is very rare. Authors report a case of malignant melanoma of the superior mediastinum without clinical history of extrathoracic malignant melanoma primarily and discuss its radiologic findings. CT shows lobulated heterogenous enhanced mass. Magnetic resonance shows mild hyperintense mass on T1 and T2-weighted images contained focal hemorrhage and necrosis, and invasion to neural foramen. In addition, positron emission tomography/computed tomography shows high standard uptake values uptake of the mass.

  16. Metastatic Malignant Melanoma in an alpaca (Vicugna pacos)

    Science.gov (United States)

    Malignant melanoma in a 7-year old, intact male alpaca with a chronic, non-healing wound on the left nares, weight loss and inappetance is described. Malignant melanoma was diagnosed in punch biopsy specimens from a mass on the maxilla associated with the non-healing wound and from a mass in the su...

  17. Oral malignant melanoma: a rare case with unusual clinical presentation

    OpenAIRE

    Ali, Elneel Ahmed Mohamed; Karrar, Musadak Ali; El-Siddig, Abeer Abdalla; Zulfu, Azza

    2015-01-01

    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.

  18. Staging of cutaneous malignant melanoma by CT

    International Nuclear Information System (INIS)

    Malignant melanomas are a challenge in radiological imaging diagnostics as they may metastasize into every organ and tissue. Cross-sectional imaging, in particular positron emission tomography computed tomography (PET/CT) and whole body magnetic resonance imaging (MRI), are considered the standards in the staging of melanomas. Because of its excellent availability CT, however, remains a widely employed staging modality. Familiarity with the manifold CT morphology of metastasized melanomas as it is described here is essential when interpreting dedicated CT and in addition useful when interpreting PET/CT results. In individual cases CT can assist in the detection of transient metastases. In the detection of locoregional lymph node metastases CT has a median sensitivity and specificity in meta-analyses of at best 61 % and 97 %, respectively, which is inferior to the performance of ultrasound (96 % and 99 %, respectively). According to meta-analyses, in the assessment of systemic tumor spread CT can detect the majority of metastases with a sensitivity and specificity of 51-63 % and 69-78 %, respectively, which is inferior to MRI and PET/CT. Therefore, if an exact staging is required for critical management decisions, MRI or PET/CT should be employed whenever possible. (orig.)

  19. Primary oral malignant melanoma: Clinicopathological series of four cases

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2012-01-01

    Full Text Available Melanoma of the oral cavity is a rare malignant disease. On account of the presence at relatively obscure areas in the oral cavity, most of oral malignant melanomas are diagnosed at a late stage. Early diagnosis is essential for successful treatment and perhaps is the key factor in improving the prognosis of oral malignant melanoma. However, no large clinical series exist, and in fact, clinical cases are the sole key source of information. We hereby present a series of four cases of primary oral malignant melanoma of South-East Asian ethnic origin, with long-term, regular follow-up. The age of the patients ranged between 40 and 70 years, with equal sex predilection, and the gingiva was found to be the most common site of its occurrence. Based on clinical and histological parameters, all the cases were diagnosed as primary malignant melanoma, which were further confirmed by using immunohistochemical markers.

  20. Treatment with levodopa and risk for malignant melanoma

    DEFF Research Database (Denmark)

    Olsen, Jørgen H; Tangerud, Karina; Wermuth, Lene; Frederiksen, Kirsten; Friis, S.

    2007-01-01

    A large follow-up study in Denmark of 14,088 patients in whom Parkinson's disease was diagnosed at hospital showed a twofold higher incidence of malignant melanoma in these patients than in the general population. In a nested case-control study of 45 patients with malignant melanoma, 97 patients...... malignant melanoma in a subgroup of patients with a probable diagnosis of idiopathic Parkinson's disease as compared with other patients. There was apparently no effect of levodopa on the risk for malignant melanoma as indicated by an odds ratio of 1.0 (95% confidence interval, 0.8-1.3) per 1,000 g...... cumulative intake of the drug. We conclude that the increased rate of malignant melanoma observed in patients treated at hospital for Parkinson's disease is restricted to those with idiopathic Parkinson's disease, however, unrelated to the treatment with levodopa. (c) 2007 Movement Disorder Society....

  1. 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

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

    Science.gov (United States)

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

    2016-06-01

    Mucosal melanomas constitute 1.3% of all melanomas and they may develop in any mucosal membrane. Conjunctival melanomas (0.5/million/year) and melanomas in the sinonasal cavity (0.5/million/year) are the most common, followed by anorectal melanomas (0.4/million/year) and melanomas in the oral cavity (0.2/million/year). Anorectal melanoma occurs slightly more often in females, whereas oral melanoma has a male predilection. Mucosal melanoma most commonly develops in a patient's sixth or seventh decade of life, and no differences between races have been found except for sinonasal melanoma and conjunctival melanoma, which are very rare in Black people. The symptoms are not tumour-specific and are related to the organ system affected, and the disease is most often diagnosed at an advanced clinical stage. The diagnosis of a primary tumour is difficult, and metastatic cutaneous melanoma and choroidal melanoma must be excluded. Mutations in KIT are frequently found, while BRAF and NRAS mutations are rarely found - except in conjunctival melanomas that carry BRAF mutations. Mutations in the TERT promotor region are also found in mucosal melanomas. Complete surgical resection with free margins is the treatment of choice. The prognosis is poor, with the 5-year survival rate ranging from 0% (gastric melanoma) to 80% (conjunctival melanoma). PMID:27004972

  3. Oral malignant melanoma: A silent killer?

    Directory of Open Access Journals (Sweden)

    Ashvini Padhye

    2011-01-01

    Full Text Available Oral malignant melanomas are extremely rare lesions and occur commonly in the maxillary gingiva more frequently on the palate with fewer incidences in the mandibular gingiva. Though these lesions are biologically aggressive, they often go unnoticed since they are clinically asymptomatic in the early stages and usually present merely as a hyperpigmented patch on the gingival surface. These lesions if diagnosed at an early in situ stage are potentially curable and definitely have a better prognosis, but unfortunately as they are clinically asymptomatic, it results in delayed diagnosis thus making the prognosis extremely poor. This paper presents the case of a patient who visited our department with the complaint of darkened patches on the gums and his concern was purely aesthetic. There were no symptoms associated with the hyperpigmented lesions and hence the patient did not approach us earlier. When the lesions grew larger and were unsightly, the patient has seeked dental advice. Histopathologic investigation confirmed the diagnosis as ′Oral Malignant Melanoma′. Though aggressive therapy was instilled immediately, unfortunately, the patient succumbed to death within a few months after diagnosis as the lesion was highly invasive. Due to the biologically aggressive but clinically silent nature of progression of the lesion, the importance of maintaining a high index of suspicion and early detection and diagnosis for any pigmented gingival lesions cannot be overemphasised. Diagnosis must be based on thorough detailed history and valid histologic evidence.

  4. Malignant melanoma of the mandibular gingiva: A rare occurrence

    Directory of Open Access Journals (Sweden)

    Reddy BVR

    2010-01-01

    Full Text Available Primary mucosal malignant melanoma of the oral cavity is a rare tumor. It accounts for only 0.2-8% of all malignant melanomas. This malignancy commonly affects male subjects and is more frequently seen on the hard palate and maxillary gingiva. The peak age for diagnosis of oral melanoma is between 55 and 65 years. A biopsy is required to establish a diagnosis. Ablative surgery with tumor-free margins remains the treatment of choice. It has a much poorer prognosis than its counterpart on the skin. Here, we present a case of malignant melanoma of the mandibular lingual gingiva in a 55-year-old male patient. Immunohistochemistry and special stains were conducted for confirmatory diagnosis.

  5. Genetic determinants of cutaneous malignant melanoma in Sinclair swine.

    OpenAIRE

    Blangero, J; Tissot, R. G.; Beattie, C W; Amoss, M S

    1996-01-01

    The role of genetic factors involved in the determination of risk of cutaneous malignant melanoma (CMM) in humans remains unclear owing to genetic heterogeneity and reliance on simplistic models of inheritance. Here, we report a statistical genetic analysis of cutaneous malignant melanoma in Sinclair swine (SSCM), a unique animal model for human CMM. Using complex segregation analysis a two-locus model involving an unknown major locus and a second locus that lies within or close to the swine ...

  6. Primary malignant melanoma in the pineal region treated without chemotherapy

    OpenAIRE

    SHINSATO, Yoshinari; Hanada, Tomoko; Kisanuki, Takao; Yonezawa, Hajime; Yunoue, Shunji; Yoshioka, Takako; Hanaya, Ryosuke; Tokimura, Hiroshi; Hirano, Hirofumi; ARITA, Kazunori

    2012-01-01

    Background: Primary pineal malignant melanomas are uncommon intracranial tumor. Here we discuss and review a case of primary pineal malignant melanoma over its feature of imaging studies, pathological findings, and management. Case Description: A 49-year-old woman receiving renal dialysis underwent computed tomography due to a 4-month history of tinnitus and hearing disturbance. A high-density 35-mm diameter tumor was detected in the pineal region; there was obstructive hydrocephalus. The tum...

  7. Primary malignant melanoma of the vagina: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Ji Young; Kim, Do Kang; Lee, Eun Hee [College of Medicine, Catholic Univ., Seoul (Korea, Republic of); Kim, Jun Sang [College of Medicine, Chungnam National Univ., Daejeon (Korea, Republic of)

    2003-09-01

    A primary malignant melanoma of the vagina is a very rare gynecological malignant tumor. Its clinical behavior is more aggressive than that of cutaneous and vulvar melanomas. We present a case of a large sized primary melanoma of the lower third of the vagina, with a cervical lesion, in a 58-year-old postmenopausal woman. The patient was treated with conventional external radiation therapy and intracavitary radiotherapy (lCR), without surgical treatment. Although the primary lesion showed a partial response, the patient died of extensive metastases, which were found 4.5 months after the initial diagnosis. We suggest that shortening the treatment period, such as hypofractionated radiation therapy and surgical removal, and various systemic therapies for preventing early distant metastasis, are appropriate treatments for a primary malignant melanoma of the vagina, with a large tumor size.

  8. 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.

  9. Ability to self-detect malignant melanoma decreases with age

    DEFF Research Database (Denmark)

    Trolle, L; Henrik-Nielsen, R; Gniadecki, R

    2011-01-01

    The prognosis of malignant melanoma depends on the thickness of the tumour. In this study, we analysed the trends in Breslow thickness in 63 patients referred to our institution, a tertiary dermatology referral centre. The mean thickness of melanoma was 0.31 mm, which was lower than the national...... average of 1.10 mm. There was a significant trend towards increased melanoma thickness with increasing age, with a rate of 0.24 mm (95% CI 0.12-0.37) for each additional 10 years of age above the age of 20 years. This trend was only apparent in cases of self-diagnosed melanomas; the thickness of tumours...... diagnosed by a dermatologist did not show any dependence on patient age. As the mortality from melanoma increases with age, this study suggests that dermatologists should include older people in screening programmes for melanoma....

  10. Malignant uveal melanoma and similar lesions studied by computed tomography

    International Nuclear Information System (INIS)

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

  11. Psychoeducational intervention for patients with cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Boesen, Ellen H; Ross, Lone; Frederiksen, Kirsten;

    2005-01-01

    modifications in a randomized controlled trial among Danish patients with malignant melanoma and evaluated results on immediate and long-term effects on psychological distress and coping capacity. PATIENTS AND METHODS: A total of 262 patients with primary cutaneous malignant melanoma were randomly assigned to......, and they used significantly more active-behavioral and active-cognitive coping than the patients in the control group. The improvements were only significant at first follow-up. CONCLUSION: The findings of this study support the results of an earlier intervention study among patients with malignant...

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

    International Nuclear Information System (INIS)

    125I-L-PC. Conclusions: 125I-PCA is a better substrate for tyrosinase and DNA polymerase and has higher uptake and longer retention in B16 melanoma cells when compared with 125I-L-PC. Therefore, 123/131I-PCA has good potential for diagnosis for malignant melanoma. Advance in Knowledge: 125I-PCA will be a specific diagnosis tool for malignant melanoma. Implications for Patient Care: 123/131I-PCA has good potential for the diagnosis of malignant melanoma when compared with other SPECT tracers, as well as anti-melanoma chemotherapeutic drugs

  13. Molecular biology of malignant melanoma and other cutaneous tumors.

    Science.gov (United States)

    Pons, M; Quintanilla, M

    2006-07-01

    Skin cancer is the most common cancer worldwide. Its incidence is doubling every 15-20 years likely because of an aging population, changes in behaviour towards sun exposure, and increased UV light fluency at the earth surface due to ozone depletion. In this review, we summarize the most important genetic changes contributing to the development of malignant melanoma, basal cell carcinoma and squamous cell carcinoma, the main tumor entities arising in the skin. While our understanding of the oncogenes and tumor suppressor genes involved in the development and progression of skin tumors is still fragmentary, recent advances have shown alterations affecting conserved signalling pathways that control cellular proliferation and viability. These pathways include INK4alpha/Rb, ARF/p53, RAS/MAPKs, and sonic hedgehog/Gli. PMID:16870533

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

    DEFF Research Database (Denmark)

    Boyle, Jenny L; Haupt, Helen M; Stern, Jere B; Multhaupt, Hinke A B

    2002-01-01

    CONTEXT: Pathologists may encounter problems in the differential diagnosis of malignant melanoma, spindle and epithelioid neoplasms of peripheral nerves, and fibrohistiocytic tumors. Tyrosinase has been demonstrated to be a sensitive marker for melanoma. OBJECTIVE: To determine the specificity 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...... melanotic), 13 malignant peripheral nerve sheath tumors; 10 schwannomas (1 pigmented), 12 neurofibromas (4 pigmented), and 20 fibrohistiocytic tumors (10 dermatofibrosarcoma protuberans and 10 dermatofibromas). Microwave-based antigen retrieval was performed in 10mM citrate buffer, pH 6.0, for 20 minutes at...

  15. Malignant melanoma metastatic to the larynx: treatment and functional outcome

    OpenAIRE

    Lanson, B.G.; Sanfilippo, N.; Wang, B; Grew, D.; DeLacure, M.D.

    2010-01-01

    The review considers management strategies for malignant melanoma metastatic to the larynx. This rare clinical entity lacks clear treatment recommendations because extirpative surgery can often result in severe functional debilitation in patients with limited life expectancy. Here, we report a case of melanoma metastatic to the larynx in a patient with a prior history of Hodgkin lymphoma. The patient was treated with partial laryngectomy and local radiation therapy. The rationale for treatmen...

  16. Rhabdomyosarcoma and late malignant melanoma of the orbit

    Energy Technology Data Exchange (ETDEWEB)

    Leff, S.R.; Henkind, P.

    1983-10-01

    Forty-five years following surgical excision and radiation for a childhood rhabdomyosarcoma of the left orbit, a patient with primary lymphedema developed an ipsilateral malignant melanoma of the anterior orbital tissue. This was excised, but a metastasis of the melanoma occurred in the contralateral upper lid. This is the first case report of treated rhabdomyosarcoma of the orbit followed by a second primary tumor occurring in the field of radiation.

  17. Rhabdomyosarcoma and late malignant melanoma of the orbit

    International Nuclear Information System (INIS)

    Forty-five years following surgical excision and radiation for a childhood rhabdomyosarcoma of the left orbit, a patient with primary lymphedema developed an ipsilateral malignant melanoma of the anterior orbital tissue. This was excised, but a metastasis of the melanoma occurred in the contralateral upper lid. This is the first case report of treated rhabdomyosarcoma of the orbit followed by a second primary tumor occurring in the field of radiation

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

    DEFF Research Database (Denmark)

    Kalialis, Louise V; Drzewiecki, Krzysztof T; Mohammadi, Mahin; Mehlsen, Anne-Birgitte; Klyver, Helle

    2008-01-01

    therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional...... factors. Our patient engaged in alternative therapies and was taking a number of different dietary supplements, none of which can be medically recommended, but the combination of which possibly strengthened the immune system and thereby the host defense against the melanoma metastases....

  19. Treatment side effects and follow-up of malignant melanoma

    International Nuclear Information System (INIS)

    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.)

  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 of...... therapy, which is considered inadequate to exert a significant influence on neoplastic disease. The incidence of spontaneous regression of metastases from malignant melanoma is approximately one per 400 patients, and possible mechanisms include immunologic, endocrine, inflammatory and tumour nutritional...

  1. Limbic encephalitis following immunotherapy against metastatic malignant melanoma.

    Science.gov (United States)

    Salam, Sharfaraz; Lavin, Timothy; Turan, Ayse

    2016-01-01

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

  2. [Is UV-A a cause of malignant melanoma?].

    Science.gov (United States)

    Moan, J

    1994-03-20

    The first action spectrum for cutaneous malignant melanoma was published recently (2). 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 melanomagnetic 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 filters (like titanium oxide) provide real protection against cutaneous malignant melanoma, at least if they are photochemically inert. PMID:8191472

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

    International Nuclear Information System (INIS)

    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

  4. MALIGNANT MELANOMA WITH MULTIPLE METASTASES ON THE SMALL BOWEL - CASE REPORT

    OpenAIRE

    V.T. Grigorean; M.A. Iacobini; Popescu, M.; C.M. Neacşu; A-R. Stoian; Corina Roxana Buf; Violeta Elena Radu; Aurelia Mihaela Sandu

    2010-01-01

    BACKGROUND: Malignant melanomas often cause intestinal metastasis.Metastases of malignant melanoma are the most common secondary tumors of the gastrointestinal tract.The incidence of intestinal metastasis of malignant melanomas is 1.5-4.4% in clinical studies, reaching upto 35.6-58% in necroptic studies. AIM: We present a clinical case of multiple metastases to the smallbowel with point of departure right retroauricular malignant melanoma. METHODS: Patient T.I., 76years old, is admitted in ou...

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

    International Nuclear Information System (INIS)

    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 10B chlorpromazine compounds and 10B1-para-boronophenylalanine (10B1-BPA) as tumor-seeking 10B 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 10B1-BPA in the thermal neutron capture treatment of melanoma is provided: 1) in vitro studies on specific enhanced melanoma cell killing effects of 10B1-BPA; 2) in vivo studies on therapeutic effects of 10B1-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.)

  6. Malignant melanoma of the cerebello-pontine angle region

    Directory of Open Access Journals (Sweden)

    F. Menezes Braga

    1989-12-01

    Full Text Available A case of malignant melanoma in the cerebello-pontine angle region is presented in a 72 years old female patient, who had neurological examination and CT scan suggestive of acoustic neuroma. The surgical finding and the histological examination provided the diagnosis. As a primary focus was not found on clinical examination and although autopsy was not carried out, there is a possibility of the diagnosis being a primary malignant melanoma in CNS. This specific location for this kind of tumor was found to be rare when literature is looked up.

  7. Malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously: A case report.

    Science.gov (United States)

    Ozgun, Alpaslan; Tuncel, Tolga; Emirzeoglu, Levent; Celik, Serkan; Bilgi, Oguz; Haholu, Abdullah; Urhan, Muammer; Karagoz, Bulent

    2015-01-01

    Malignant melanoma can be successfully treated when it is identified in its early stages, but the disease is associated with a poor prognosis when it is detected in an advanced stage. Papillary thyroid carcinoma is a thyroid cancer that has a good prognosis. The present study reports a rare case of malignant melanoma and papillary thyroid carcinoma that were diagnosed concurrently and treated simultaneously. The present patient was a 37-year-old male, in whom examination of a skin biopsy that was obtained from a lesion in the right retroauricular region revealed the lesion to be consistent with malignant melanoma. The patient underwent radical neck dissection upon the detection of malignant melanoma metastasis to the sentinel lymph node. Metastases of papillary thyroid carcinoma were detected in four out of 38 lymph nodes. The patient was then diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. The patient was administered with high-dose followed by moderate-dose interferon-α therapy for the treatment of malignant melanoma. The patient also received concurrent radioactive iodine therapy for the treatment of papillary thyroid carcinoma, at the same time as the interferon therapy. The two primary tumors of the patient were treated successfully. During therapy, no serious side-effects were observed, with the exception of fever caused by high-dose interferon therapy. Malignant melanoma and papillary thyroid carcinoma may occur concurrently, although this is rarely observed. The present study reports a rare case that demonstrates that the two tumors can be successfully treated simultaneously. PMID:25436010

  8. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options.

    Science.gov (United States)

    Metcalfe, Lucy Va; O'Brien, Peter J; Papakonstantinou, Stratos; Cahalan, Stephen D; McAllister, Hester; Duggan, Vivienne E

    2013-01-01

    A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thoracic radiography, cytological examination of the pleural fluid and a fine needle aspirate of a thoracic mass led to a presumptive diagnosis of malignant melanoma and this was confirmed at post mortem examination. Further metastatic spread to the central nervous system and right guttural pouch was also identified. In conclusion this case manifests the potential malignant behaviour of equine melanomas, and a review of proposed therapies for melanoma treatment highlights the therapeutic options and current areas of research. PMID:24196087

  9. Malignant cutaneous melanoma in patients from Las Tunas province

    Directory of Open Access Journals (Sweden)

    Alicia María Yabor Palomo

    2015-11-01

    Full Text Available Background: malignant melanoma is a highly aggressive skin neoplasia, whose incidence shows a constant and rapid increase.Objective: to characterize variables in patients diagnosed with cutaneous melanoma, whose biopsies were analyzed in the pathologic anatomy department of "Dr. Ernesto Guevara de la Serna" General Teaching Hospital from January, 2008 to December, 2014.Methods: a descriptive and cross-sectional study was performed in 31 patients treated in the place and period of time mentioned above. The official form of biopsy was used as a secondary source of collecting information and it was processed using descriptive statistics.Results: the 10,6 % of the biopsies analyzed corresponded with cutaneous melanoma, its frequency prevailed in 2011 and 2010, with a 25,8 % and 19,3 % respectively. It was evident a higher percentage in males (67,7 % and in the age group between 60 and 69 years old, with a 35,4 %. Caucasian patients were the most affected ones, with a 90,3 % and the predominant location was in the lower limbs in 45,1 % of the cases. The prevailing Clark invasion level was IV, evident by the 32,2 % of the sample, and the most frequent histological variety was the malignant nodular melanoma in 19 patients, for a 61,2 %.Conclusions: cutaneous melanoma prevailed in lower extremities in males and it had a belated diagnosis, since there was prevalence of IV Clark invasion level and nodular melanoma as the most frequent histological type.

  10. MR imaging of mucocutaneous malignant melanoma in head and neck

    International Nuclear Information System (INIS)

    MR imaging was performed in three patients with mucocutaneous malignant melanoma of the head and neck, and surgical specimens were investigated in MR-pathological correlation. Two of 3 cases were revealed to be melanotic melanoma; one arised in the maxillary sinus, and another in the bulbar conjunctiva. The remaining one was amelanotic melanoma originated in the nasal cavity. Two cases of melanotic melanoma showed different intensity on T1WI according to the melanin concentration; the more the melanin-producing process existed, the higher intensity in the tumor was shown. On T2WI there were also some differences in signal intensity; the case having more concentration of melanin changed lower partially in the areas where very high intensity was noted on T1WI, while another case remained unchanged. These findings are based on the inherent paramagnetic effect mostly compatible with the previous reports. On the other hand, the amelanotic melanoma was demonstrated as an intermediate intensity both on T1- and T2WI. Because of the higher incidence of hemorrhage in/around the tumor, it is an important diagnostic clue to this tumor, as in our case of amelanotic type. On reviewing the three cases, we consider that MR imaging offers a useful adjunct in the diagnosis of malignant melanoma. (author)

  11. Ensemble approach for differentiation of malignant melanoma

    Science.gov (United States)

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

    2015-04-01

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

  12. Treatment of malignant melanoma by selective thermal neutron capture therapy using melanoma-seeking compound

    International Nuclear Information System (INIS)

    As pigment cells undergo melanoma genesis, accentuated melanogenesis concurrently occurs in principle. Subsequent to the understanding of intrinsic factors controlling both processes, we found our selective melanoma neutron capture therapy (NCT) using 10B-dopa (melanin substrate) analogue, 10B1-p-boronophenylalanine (10B1-BPA), followed by 10B(n, alpha)7Li reaction, induced by essentially harmless thermal neutrons, which releases energy of 2.33 MeV to 14 mu, the diameter of melanoma cells. In vitro/in vivo radiobiological analysis revealed the highly enhanced melanoma killing effect of 10B1-BPA. Chemical and prompt gamma ray spectrometry assays of 10B accumulated within melanoma cells after 10B1-BPA administration in vitro and in vivo show high affinity, e.g., 10B melanoma/blood ratio of 11.5. After successfully eradicating melanoma transplanted into hamsters with NCT, we advanced to preclinical studies using spontaneously occurring melanoma in Duroc pig skin. We cured three melanoma cases, 4.6 to 12 cm in diameter, by single neutron capture treatment. Complete disappearance of melanoma was obtained without substantial side effects. Acute and subacute toxicity as well as pharmacodynamics of 10B1-BPA have been studied in relation to therapeutic dosage requirements. Clinical radiation dosimetry using human phantom has been carried out. Further preclinical studies using human melanoma transplanted into nude mouse have been a useful model for obtaining optimal results for each melanoma type. We recently treated the first human melanoma patient with our NCT, using essentially the method for Duroc pig melanoma, and obtained similar regression time course leading to cure

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-03-01

    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.

  14. Malignant melanoma of the vagina: a report of 2 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ok Bae; Kim, Jin Hee; Jung, Young Yeon; Cho, Chi Heum; Choi, Tae Jin [Dongsan Medical Center, School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    2005-06-15

    Primary malignant melanoma of the vagina is an extremely rare genital neoplasm occurring mainly in postmenopausal women. It has a worse prognosis than cutaneous melanomas, because of the high rate of locoregional recurrences and rapid systemic dissemination. In the past, radical surgical extirpation as the primary management had been recommended to improve loco-regional control, and possibly overall survival. However, the prognosis was poor in spite of such a radical approach. Recently, more conservative treatment such as wide local excision combined with adjuvant high-dose fraction radiotherapy seems to have promising results. Primary radiation therapy could be served as an alternative to surgery for patients with lesion less than 3 cm in diameter. We report 2 cases of primary vaginal malignant melanoma treated with radiotherapy.

  15. Malignant melanoma in an area of chronic radiodermatitis. Case report

    Energy Technology Data Exchange (ETDEWEB)

    Shono, Yoshitaka [Matsuyama Red Cross Hospital (Japan); Nakanishi, Hideki; Hashimoto, Ichiro

    2000-02-01

    This is a case report of malignant melanoma that occurred in an area of chronic radiodermatitis on the sole of the foot. A 55-year-old woman was irradiated for corns on the soles of both feet in 1967. Dermatoplasty was performed for hyperkeratosis of the sole of the right foot in 1988, but a tumor developed on the right heel in 1998, and grew larger. The histological findings suggested malignant melanoma, and the tumor including the periosteum, was removed. The patient was treated with four cycles of adjuvant chemotherapy (dacarbazine, nimustine hydrochloride, and vincristine), and no signs of recurrence one year after surgery. Based on a review of the literature, there appears to be little relation between melanoma and irradiation, and this is only the second case ever reported in Japan. (K.H.)

  16. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R

    2013-01-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical......-RAF-MEK-ERK pathway, the p16(INK4A) -CDK4-RB pathway, the PIK3-AKT pathway and the MITF pathway....... play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...

  17. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    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)

  18. Subungual malignant melanoma – re-learning the lesson

    OpenAIRE

    Amin, Kavit; Edmonds, Katy; Fleming, Andrew; Powell, Barry

    2011-01-01

    The authors present two patients referred by colleagues after traumatic hand injury. However, upon closer inspection, both patients had pigmented lesions under the nail bed, which upon biopsy showed proven subungual malignant melanoma. The authors wish to emphasise the importance of this diagnosis, especially in emergency care.

  19. 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...

  20. Immunological consequences of selective BRAF inhibitors in malignant melanoma

    OpenAIRE

    Schilling, Bastian; Paschen, Annette

    2013-01-01

    Myeloid-derived suppressor cells (MDSC) potently repress antitumor immunity. The amount of MDSC in the blood of melanoma patients declines in response to vemurafenib, an inhibitor of oncogenic BRAF signaling that abrogates the ability of malignant cells to induce MDSC. This suggests that vemurafenib may be used in combination with various immunotherapeutic agents for the induction of long-lasting tumor regression.

  1. Cerebral MR imaging of malignant melanoma

    International Nuclear Information System (INIS)

    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

  2. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    International Nuclear Information System (INIS)

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS 240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care

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

    Science.gov (United States)

    Jaworek-Korjakowska, Joanna

    2016-01-01

    Background. One of the fatal disorders causing death is malignant melanoma, the deadliest form of skin cancer. The aim of the modern dermatology is the early detection of skin cancer, which usually results in reducing the mortality rate and less extensive treatment. This paper presents a study on classification of melanoma in the early stage of development using SVMs as a useful technique for data classification. Method. In this paper an automatic algorithm for the classification of melanomas in their early stage, with a diameter under 5 mm, has been presented. The system contains the following steps: image enhancement, lesion segmentation, feature calculation and selection, and classification stage using SVMs. Results. The algorithm has been tested on 200 images including 70 melanomas and 130 benign lesions. The SVM classifier achieved sensitivity of 90% and specificity of 96%. The results indicate that the proposed approach captured most of the malignant cases and could provide reliable information for effective skin mole examination. Conclusions. Micro-melanomas due to the small size and low advancement of development create enormous difficulties during the diagnosis even for experts. The use of advanced equipment and sophisticated computer systems can help in the early diagnosis of skin lesions. PMID:27382567

  4. 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.

  5. Primary Malignant Melanoma of the Mediastinum: Radiologic and Pathologic Correlation in Two Case

    OpenAIRE

    Park, Sun-Young; Kim, Mi Young; Chae, Eun Jin

    2012-01-01

    Primary malignant melanoma of the anterior mediastinum is extremely rare, accounting for 0.1-0.5% of all primary malignant neoplasms. These tumors may be mistakenly diagnosed as lymphomas, thymic carcinomas and malignant germ-cell tumors of the mediastinum. We describe two cases of primary malignant melanomas of the anterior mediastinum and report their CT and pathology findings.

  6. Nevoid malignant melanoma in an albino woman

    OpenAIRE

    Binesh, F; Akhavan, A; Navabii, H

    2010-01-01

    Albinism is a disorder of hypopigmentation affecting the skin, hair and eyes. Ultraviolet light induced cutaneous tumours are common in patients with albinism due to reduced or absent protection from melanin, with squamous cell carcinoma being the most common. Although non-melanomatous skin cancers are more frequent in patients with albinism, dysplastic nevi and melanoma present a greater diagnostic challenge in this group because of their hypopigmented appearance. Here the authors report a c...

  7. Nivolumab-Based Treatments for Advanced Melanoma

    Science.gov (United States)

    A summary of results from an international, double-blind, randomized phase III trial testing the combination of nivolumab (Opdivo®) and ipilimumab (Yervoy®) against nivolumab alone and ipilimumab alone in patients with advanced melanoma.

  8. MicroRNAs in the pathogenesis of malignant melanoma.

    Science.gov (United States)

    Glud, M; Gniadecki, R

    2013-02-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS-RAF-MEK-ERK pathway, the p16(INK4A) -CDK4-RB pathway, the PIK3-AKT pathway and the MITF pathway. PMID:22621697

  9. Karnofsky Performance Status and Lactate Dehydrogenase Predict the Benefit of Palliative Whole-Brain Irradiation in Patients With Advanced Intra- and Extracranial Metastases From Malignant Melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Partl, Richard, E-mail: richard.partl@medunigraz.at [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria); Richtig, Erika [Department of Dermatology, Medical University of Graz, Graz (Austria); Avian, Alexander; Berghold, Andrea [Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz (Austria); Kapp, Karin S. [Department of Therapeutic Radiology and Oncology, Medical University of Graz, Graz (Austria)

    2013-03-01

    Purpose: To determine prognostic factors that allow the selection of melanoma patients with advanced intra- and extracerebral metastatic disease for palliative whole-brain radiation therapy (WBRT) or best supportive care. Methods and Materials: This was a retrospective study of 87 patients who underwent palliative WBRT between 1988 and 2009 for progressive or multiple cerebral metastases at presentation. Uni- and multivariate analysis took into account the following patient- and tumor-associated factors: gender and age, Karnofsky performance status (KPS), neurologic symptoms, serum lactate dehydrogenase (LDH) level, number of intracranial metastases, previous resection or stereotactic radiosurgery of brain metastases, number of extracranial metastasis sites, and local recurrences as well as regional lymph node metastases at the time of WBRT. Results: In univariate analysis, KPS, LDH, number of intracranial metastases, and neurologic symptoms had a significant influence on overall survival. In multivariate survival analysis, KPS and LDH remained as significant prognostic factors, with hazard ratios of 3.3 (95% confidence interval [CI] 1.6-6.5) and 2.8 (95% CI 1.6-4.9), respectively. Patients with KPS ≥70 and LDH ≤240 U/L had a median survival of 191 days; patients with KPS ≥70 and LDH >240 U/L, 96 days; patients with KPS <70 and LDH ≤240 U/L, 47 days; and patients with KPS <70 and LDH >240 U/L, only 34 days. Conclusions: Karnofsky performance status and serum LDH values indicate whether patients with advanced intra- and extracranial tumor manifestations are candidates for palliative WBRT or best supportive care.

  10. Primary anorectal malignant melanoma treated with neoadjuvant chemoradiotherapy and sphincter-sparing surgery: A case report

    OpenAIRE

    Su, Meng; ZHU, LUCHENG; Luo, Wenhua; WEI, HANGPING; ZOU, CHANGLIN

    2014-01-01

    Primary anorectal (PA) malignant melanoma (MM) is a rare disease associated with a high mortality rate. The most appropriate treatment strategy for PAMM remains controversial. A 55-year-old female patient, who was misdiagnosed with locally advanced rectal carcinoma, was treated with preoperative radiotherapy and concurrent oral capecitabine. During the therapy, grade 1 leukopenia occurred, however, there was no interruption to treatment. Following chemoradiotherapy, a computer tomography scan...

  11. FDG PET in early stage cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    Fluorodeoxyglucose positron emission tomography (FDG PET) is not recommended in early stage melanoma; however, a significant number of cases are referred to our institution for FDG PET. We refer to early stage disease as American Joint Committee on Cancer (AJCC) stage I and II, which includes all cases without metastases. A retrospective review was undertaken to determine the clinical utility of FDG PET in this patient group. A retrospective study of FDG scans on all patients presenting to the WA PET Centre with early stage melanoma over a 5½ year period was undertaken. The positivity rate of the initial study for detection of malignant melanoma was determined. In patients with an initially negative FDG PET, the time from initial diagnosis to a positive surveillance study was determined. Both the initial positivity rate and time to a positive study were correlated with Breslow staging. Three hundred twenty-two patients were included in the study, of which 74 had initial positive FDG PET scans (23%). Adequate follow-up was available in 51 patients with the PET result confirmed as true positive in 37 (positive predictive value 73%). One hundred eight of 248 patients initially negative had follow-up scans during the follow-up period, of which 48 became positive. The 73% of recurrences were over 12 months post-diagnosis. No correlation with Breslow thickness was demonstrated. Despite FDG PET not being recommended for early cutaneous malignant melanoma, 27% of melanoma cases referred for FDG PET during the study period were AJCC stage I or II. Our results suggest FDG PET in early stage melanoma demonstrates occult disease in 17% of cases.

  12. Symptomatic malignant melanoma presenting as multiple gastrointestinal polyps.

    Science.gov (United States)

    Casey, Shauna; Dvorkin, Lee; Alsanjari, Nazar; Dezso, Balazs

    2011-01-01

    We report on a 66-year-old man with a past medical history of gout who presented to his general practitioner (GP) in July 2009 with a history of nausea and intermittent diarrhoea. He had lost 6 kg in weight over 6 months. His GP found he was anaemic and referred him to a gastrointestinal outpatient clinic. He went on to have a gastroscopy and colonoscopy, which revealed multiple polyps in the stomach, duodenum and colon. Histology revealed that all the polyps were malignant melanoma. He had no known history of malignant melanoma. A staging CT scan revealed multiple lung metastases and he was referred for palliative care. The patient died 4 months after diagnosis. PMID:22715248

  13. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    International Nuclear Information System (INIS)

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid

  14. Cataract extraction after brachytherapy for malignant melanoma of the choroid

    Energy Technology Data Exchange (ETDEWEB)

    Fish, G.E.; Jost, B.F.; Snyder, W.I.; Fuller, D.G.; Birch, D.G. (Texas Retina Associates, Dallas (USA))

    1991-05-01

    Thirteen eyes of 55 consecutive patients treated with brachytherapy for malignant melanoma of the choroid developed postirradiation cataracts. Cataract development was more common in older patients and in patients with larger and more anterior tumors. Eleven eyes had extracapsular cataract extraction and intraocular lens implantation. Initial visual improvement occurred in 91% of eyes, with an average improvement of 5.5 lines. Visual acuity was maintained at 20/60 or better in 55% of the eyes over an average period of follow-up of 24 months (range, 6 to 40 months). These data suggest that, visually, cataract extraction can be helpful in selected patients who develop a cataract after brachytherapy for malignant melanoma of the choroid.

  15. 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.

  16. Sentinel lymph node biopsy for conjunctival malignant melanoma: surgical techniques

    Directory of Open Access Journals (Sweden)

    Wainstein AJA

    2014-12-01

    Full Text Available Alberto JA Wainstein,1,2 Ana P Drummond-Lage,1 Milhem JM Kansaon,2 Gustavo O Bretas,2 Rodrigo F Almeida,3 Ana LF Gloria,3 Ana RP Figueiredo3 1Faculty of Medical Sciences of Minas Gerais, 2Oncad Surgical Oncology, 3Ophthalmology Department, Federal University of Minas Gerais, Belo Horizonte, Brazil Background: The purpose of this report is to examine the viability and safety of preoperative lymphoscintigraphy and radio guided sentinel lymph node (SLN biopsy for conjunctival melanoma, and to identify the best technique to perform this procedure.Methods: Three patients diagnosed with malignant melanoma of the conjunctiva underwent lymphoscintigraphy and SLN biopsy using a dual technique comprising isosulfan blue dye and technetium Tc 99m sulfur colloid. Each patient was anesthetized and the conjunctival melanoma was excised. SLNs were localized by a gamma probe, identified according to radioactivity and sentinel blue printing, and dissected, along with drainage of the associated lymphatic basins. The SLNs were evaluated by a pathologist using hematoxylin-eosin staining following serial sectioning and immunohistochemistry using a triple melanoma cocktail (S-100, Melan-A, and HMB-45 antigens.Results: Two SLNs were stained in the jugular chain during preoperative lymphoscintigraphy in the first patient, two SLNs were identified in the preauricular and submandibular areas in the second patient, and two SLNs were identified in the submandibular and parotid areas in the third patient. All lymph nodes identified by lymphoscintigraphy were dissected and identified at surgery with 100% accuracy in all three patients. All SLNs were histologically and immunohistochemically negative. Patients had good cosmetic and functional results, and maintained their visual acuity and ocular motility.Conclusion: Patients with conjunctival melanoma can undergo preoperative lymphoscintigraphy and SLN biopsy safely using radioactive technetium and isosulfan blue dye. Keywords

  17. Video comparator system for early detection of cutaneous malignant melanoma

    Science.gov (United States)

    Craine, Eric R.; Craine, Brian L.

    1992-05-01

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

  18. Oral malignant melanoma detected after resection of amelanotic pulmonary metastasis ☆

    OpenAIRE

    Matsuoka, Katsunari

    2013-01-01

    INTRODUCTION Solitary pulmonary metastasis from oral malignant melanoma is very rare. PRESENTATION OF CASE We demonstrated a 84-year-old patient with a lung nodule that was diagnosed as malignant melanoma by video-assisted thoracoscopic resection. Because primary pulmonary malignant melanoma was extremely rare, the tumor was thought to be a metastasized from an occult primary lesion. A detailed physical examination revealed a black tumor in the oral cavity, and this was suspected to have been...

  19. 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.

  20. Updates in Therapy for Advanced Melanoma

    Directory of Open Access Journals (Sweden)

    Bhavana P. Singh

    2016-01-01

    Full Text Available Cutaneous melanoma is one of the most aggressive forms of skin cancer, and is correlated with a large proportion of skin cancer-related deaths. Therapy for cutaneous melanoma has advanced greatly through careful identification of therapeutic targets and the development of novel immunotherapeutic approaches. The identification of BRAF as well as other driver mutations, have allowed for a specialized approach to treatment. In addition, immune checkpoint inhibition has dramatically changed the treatment landscape over the past 5–10 years. The successful targeting of CTLA-4, as well as PD-1/PD-L1, has been translated into meaningful clinical benefit for patients, with multiple other potential agents in development. Systemic therapy for cutaneous melanoma is becoming more nuanced and often takes a multifaceted strategy. This review aims to discuss the benefits and limitations of current therapies in systemic melanoma treatment as well as areas of future development.

  1. Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

    Institute of Scientific and Technical Information of China (English)

    BaocunSun; ShiwuZhang; XiulanZhao; YanxueLiu; ChunshengNi; DanfangZhang; HongQi; ZhiyongLiu; XishanHao

    2004-01-01

    OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

  2. 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....

  3. 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.

  4. Sunlight exposure as risk factor for intraocular malignant melanoma

    International Nuclear Information System (INIS)

    In a case-control study, the authors compared 444 patients with intraocular malignant melanoma with matched controls to evaluate the role of exposure to ultraviolet radiation and other risk factors in the pathogenesis of this tumor. Persons born in the southern United States had a relative risk of 2.7 (95 per cent confidence interval, 1.3 to 5.9) as compared with those born in the North. Subjects with brown eyes were protected as compared with those with blue eyes (relative risk, 0.6; 95 per cent confidence interval, 0.4 to 0.8), but complexion and hair color were not important risk factors. Patients with intraocular malignant melanoma were also more likely to have spent time outdoors in their gardens, to have sunbathed, and to have used sunlamps. Rarely wearing hats, visors, or sunglasses while in the sun was a risk factor for the disease (relative risk, 1.9; 95 per cent confidence interval, 1.6 to 2.2). These data suggest that sunlight exposure is an important risk factor for intraocular melanoma

  5. Some interesting prognostic factors related to cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    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)

  6. Malignant melanoma of nasal fossae, a propos of a case

    Directory of Open Access Journals (Sweden)

    Gómez-González JL

    2012-07-01

    Full Text Available Introduction: The melanoma of the nasal fossae represents a 4% of all sinonasal malignant tumors. The symptoms are unspecific, thus delaying diagnosis. We present a case of a woman of 80 years of age. She has hypertension and a degenerative heart disease, and presents nasal respiratory insufficiency, left otalgia and epistaxis of 8 months of evolution. Examination revealed a dark, polypoidal, fleshy mass. The CT revealed a mass that occupied that space, without bone erosion. A biopsy of the mass revealed that it was an amelanotic melanoma. Due to the age of the patient and her general pathology, endoscopic sinonasal surgery was applied. The pathological anatomic analysis confirmed that it was a malignant round cell melanoma with the following phenotype: positive for Vimentin, positive for nuclear S-100, focal positive for HMB-45, negative, melan A+ negative for HMB-45 with heterogeneous intensity, and negative for ENE and ALC. The patient did not present symptoms until a year later, when she discovered a small laterocervical adenopathy. A FNAP confirmed that the melanoma had metastatized. The patient underwent a radical neck dissection and remained 15 months without symptoms. She is currently going through monthly revisions. Discussion: The treatment of choice is surgery. Selective neck dissection is not justified. This tumor is radioresistant. Active immunotherapy (a combination of Interferon and Cimetidine and targeted chemotherapy have also been used, mainly in inoperable cases. Five-year survival ranges between 6.5% and 34%.Conclusion: We propose endoscopic surgery for non-infiltrating tumors or for patients who cannot undergo very aggressive surgery due to their general condition.

  7. 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.

  8. Primary Malignant Melanoma of Maxilla: Report of a Case with Discussion

    Directory of Open Access Journals (Sweden)

    G. Shirisha Rani

    2014-01-01

    Full Text Available Primary oral malignant melanoma, very rare neoplasm of melanocytic origin, usually presents as a bluish black to tan-brown colored lesion Which is accounting for 0.2 to 8% of all melanomas, 1.6% of all head and neck malignancies, and 0.5% of all oral neoplasia. In general, the prognosis of oral melanoma is poor and worse than that of cutaneous melanoma. Here a case of oral malignant melanoma is presented, which was undetected during the first visit to a dental clinic. When a simple oral surgical treatment was carried out in that region, it resulted in the appearance of a massive pigmented lesion which was histopathologically diagnosed as malignant melanoma. This paper is presented to reemphasize the fact that any pigmented lesion in the oral cavity should be viewed with suspicion and proper investigation (biopsy should be carried out to rule out any untoward experiences later.

  9. 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.

  10. Primary malignant melanoma of the lung in the elderly: case report and literature review

    Institute of Scientific and Technical Information of China (English)

    PAN Xu-dong; ZHANG Bin; GUO Ling-chuan; GU Dong-mei; MAO Yan-qing; LI Jie; XIE Yan; WANG Ling

    2010-01-01

    @@ Malignant melanoma involving the respiratory tract, which is predominantly found in the skin, is nearly metastatic and true primary tumours are very rare.1 To date, only 32 cases have been reported in English literature and 22 cases of primary malignant melanoma of the lung have been reported in Chinese literature.

  11. Recurrence and massive extraocular extension of choroidal malignant melanoma after vitrectomy and endoresection

    Directory of Open Access Journals (Sweden)

    Mehdi Modarres

    2014-01-01

    Full Text Available Vitrectomy and endoresection is an alternative to enucleation for the treatment of large malignant choroidal melanoma. We report a rare case of extensive recurrence of choroidal malignant melanoma with extraocular extension 11 years after surgical endoresection without adjuvant treatment.

  12. Utility of chest X-ray and abdominal ultrasound for stage III cutaneous malignant melanoma

    DEFF Research Database (Denmark)

    Breitenbauch, M. T. W.; Holm, J.; Rødgaard, J. C.;

    2015-01-01

    -ray and abdominal ultrasound in excluding lung and liver metastases in stage III cutaneous malignant melanoma disease. Methods: A retrospective study was conducted on stage III malignant melanoma patients who underwent wide local excision and complete lymph node dissection from 1 January 2009 to 31 December 2012...

  13. 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.

  14. 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.

  15. 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.

  16. Impact of sentinel lymph node management in malignant melanoma

    International Nuclear Information System (INIS)

    Malignant melanoma initially metastasises to regional lymph nodes and belongs to the ''leading candidates'' for sentinel lymph node (SLN) management. In newly diagnosed melanoma stage Ib to IIIa, today the SLN diagnostics is classified as the staging method of first choice. The technique of the SLN diagnostics is described thoroughly, including multimodal imaging if this is required for selective SLN biopsy. The evaluation of the diagnostic results, documentation and classification encompasses an important part. In approximately 2/3 of the melanoma patients there is no presence of metastases in SLN and non-SLN, one of five patients has metastases in SLN with negative non-SLN, every sixth to tenth patient has positive SLN and non SLN. Every thirtieth patient with tumour free SLN exhibits pathological findings in the non-SLN by using conventional examination methods only, every fifteenth if using molecular-genetic methods in addition. Among the prognostic parameters the SLN status has the most significant impact on disease-free and disease-specific survival. (orig.)

  17. Primary Oral Malignant Melanoma: Two Case Reports and Review of Literature

    Directory of Open Access Journals (Sweden)

    Neeraj Sharma

    2012-01-01

    Full Text Available Primary malignant melanoma of the oral cavity is a rare neoplasm. The tumors tend to metastasize or locally invade tissue more readily than other malignant tumors in the oral region. The survival of patients with mucosal melanomas is less than for those with cutaneous melanomas. Tumor size and metastases are related to the prognosis of the disease. Early detection, therefore, is important.

  18. Recurrent malignant melanoma of the palate successfully treated by gamma knife radiosurgery

    OpenAIRE

    YAMADA, SHIN-ICHI; Yanamoto, Souichi; Kawakita, Akiko; Kawasaki, Goro; Fujita, Shuichi; Ikeda, Tohru; Matsuo, Takemitsu; UMEDA, MASAHIRO

    2013-01-01

    The prognosis of oral malignant melanoma is reported to be extremely poor. In this report, a patient with recurrent oral melanoma in the skull base that was successfully treated by gamma knife radiosurgery (GKS) is described. A 53-year-old man was referred with a chief complaint of a mass of the hard palate. The histological diagnosis of a biopsy specimen was malignant melanoma. He underwent a wide local resection with bilateral neck dissection, followed by immunochemotherapy with DAV-Feron. ...

  19. Treating advanced melanoma: current insights and opportunities

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    Tronnier M

    2014-09-01

    Full Text Available Michael Tronnier, Christina Mitteldorf Department of Dermatology, Klinikum Hildesheim GmbH, Hildesheim, Germany Abstract: Whereas thin melanomas have an excellent prognosis after sufficient surgical treatment, melanoma disease in advanced stages is still a therapeutic challenge. After decades of frustrating studies, new therapeutic strategies have come up in the past few years. On the one hand, increasing insights into the molecular aberrations in melanoma have led to specific "targeted" therapies to affect only the mutated tumor cells, as in many other types of cancers. Today there are few "targeted" substances which are already approved and successfully used for single or combination therapy, but many others are under development. While on the other hand, nonpersonalized strategy substances have been developed successfully inducing an immunologic tumor response. Both kinds of therapy have been found to result in an improvement not only of the response rate, but also of the overall survival in metastatic disease, which represents a milestone in melanoma therapy. However, using these therapies there is still much to learn regarding the effects, the side effects, and the limitations of these promising substances. Keywords: melanoma, treatment, targeted therapy, immunotherapy, BRAF, CTLA-4

  20. Nevus of the Eyelid Margin Mimicking a Malignant Melanoma

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    A. Echchaoui

    2016-06-01

    Full Text Available Nevi are a benign skin lesions commonly found on the eyelid margin, these tumors are usually pigmented and have thickness. Nevi are not typically visible at birth; they appear during childhood and often exhibit a more rapid increase in pigmentation about the time of puberty. Most eyelid nevi can be diagnosed by clinical examination; suspicious lesions should be biopsied when rapid growth, loss of eyelashes or discoloration of the nevus is noted. Eyelid nevi require treatment if malignant transformation and/or cosmetically bothersome to the patient. We report a case of a 37-year-old female patient exhibited a single cutaneous tumor at the free margin of the lower left eyelid, she noticed a dark spot on their eyelid since childhood. It was a brown, fleshy, thickened, and nodular well-circumscribed exophytic mass, measuring 6 mm in diameter; its clinical appearance argued for a possible nodular melanoma. Excisional-biopsy was performed using a full-thickness pentagonal wedge excision technique. Histopathology showed that the lesion was a benign melanocytic nevocellular nevus. The postoperative courses were uneventful with excellent cosmetic and functional result. Preventive measures (cap, sunglasses... and regular monitoring of the lesion by assessing ABCDE criteria (asymmetry, irregular borders, multiple colors, diameter ≥ 6 mm, and enlargement remain necessary to detect and rule out a possible risk of malignant melanoma.

  1. Sunlight, vitamin D and malignant melanoma: an update.

    Science.gov (United States)

    Reichrath, Jörg; Reichrath, Sandra

    2014-01-01

    Solar radiation represents an essential requirement for life, not only by spending the thermal energy for photosynthesis in plants, which provides our atmosphere with oxygen, but also by facilitating the cutaneous synthesis of vitamin D in vertebrates and many other organisms. It is well known that humans and most vertebrates have to obtain an adequate source of vitamin D, in order to develop and maintain a healthy mineralized skeleton and in order to be protected against cancer and a broad variety of other diseases. On the other hand, solar UV radiation can be assumed to be the most relevant environmental carcinogen causing melanoma and nonmelanoma skin cancer with increasing incidences. During the last decades, epidemiological studies and experimental animal models, including genetically engineered mice, the Xiphophorus hybrid fish, the south american oppossum and human skin xenografts, have further elucidated the multi-step process of UV-induced melanomagenesis. It has to be emphasized that, in contrast to intermittent, short-term high-dose solar UV-exposure, more chronic less intense exposure (which is recommended by many experts in the field to obtain a sufficient vitamin D status) has not been found to be a risk factor for the development of melanoma and in fact has been found in several studies to be protective. Interestingly, several independent lines of investigation have demonstrated convincing evidence that vitamin D and/or analogs may be effective in the prevention and treatment of melanoma. This essay summarizes our present understanding about the pathogenic role of UV radiation and of vitamin D for malignant melanoma. PMID:25207378

  2. 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.

  3. The dysplastic naevus syndrome in patients with cutaneous malignant melanoma in Western Australia.

    Science.gov (United States)

    English, D R; Menz, J; Heenan, P J; Elder, D E; Watt, J D; Armstrong, B K

    1986-09-01

    One hundred and three patients with cutaneous malignant melanoma responded to an invitation to attend a dermatology outpatient clinic. All patients with a family history of melanoma, a history of multiple melanomas, or histological evidence of a dysplastic naevus that was associated with their melanoma were invited. A random sample of other patients with cutaneous malignant melanoma was also invited to attend. First-degree relatives of patients with the dysplastic naevus syndrome (DNS) were invited for a similar examination. DNS was found in 27% of the patients with a family history of melanoma, multiple melanomas, or histological evidence of a dysplastic naevus in association with their melanoma, and in 6% of the remaining patients who were selected at random. DNS was estimated to be present in 12.8% of 17- to 55-year-old patients with cutaneous malignant melanoma in the Perth region, while familial DNS was present in 4.5%. Patients with melanomas with DNS were more likely to be young men and to have numerous naevi, particularly on the lateral surfaces of the arms, shoulders and trunk, than were patients with melanomas without the syndrome. PMID:3747894

  4. Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

    International Nuclear Information System (INIS)

    Purpose/Objective: This course will (a) review the epidemiology, clinical presentation, staging, radiobiology, and radiation treatment of malignant melanoma and (b) review the etiology, epidemiology, clinical presentation, staging, and therapy of cutaneous T-cell lymphoma. I. Malignant Melanoma (MM): The incidence of MM has one of the fastest growth rates in the world. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for stage I-II cutaneous MM. Five-year survival rates depend on (a) sex: female-63%, male-40%; (b) tumor thickness: † 4mm-25%; (c) location: extremity-60%, trunk-41%; and (d) regional lymph node status: negative-77%, positive-31%. Despite adequate surgery, 45%-50% of MM patients will develop metastatic disease. Both the multi-target model and the linear quadratic model predict a possible benefit for high dose per fraction (> 400 cGy) radiation therapy for some MM cell lines. Other radiobiologic factors (repair of potentially lethal damage, hypoxia, reoxygenation, and repopulation) predict a wide variety of clinical responses to different time-dose prescriptions including high dose per fraction (> 400 cGy), low dose per fraction (200-300 cGy), or b.i.d. therapy. Based on a review of the radiobiology of MM, no single therapeutic strategy emerges which could be expected to be successful for all tumors. A review of all of the clinical trials evaluating various time-dose prescriptions for MM reveals that MM is a radiosensitive tumor over a very wide range of time-dose prescriptions. RT is the single most effective therapy for local palliation metastatic disease. Complete response (CR) rates range from 24%-75% and overall response (OR) rates are 59%-98% with RT compared with CR rates of 3%-10% and OR rates of only 15%-36% with either chemotherapy or immunotherapy. In addition, postoperative RT for residual microscopic/macroscopic disease produces long term local control rates of 75%-88%. II

  5. Role of 18F-FDG PET/CT in restaging of patients with recurrent malignant melanoma

    International Nuclear Information System (INIS)

    The incidence of malignant melanoma has increased in recent years. Patients with familial melanoma and a personal history of melanoma have a very high risk for the development of recurrence at other sites even after adequate treatment which demands a non invasive imaging modality for the early and accurate restaging of the recurrence of melanoma. We evaluated the role of 18F-FDG PET/CT in restaging of patients with recurrent malignant melanoma. It is found to be an sensitive tool for restaging recurrent malignant melanoma

  6. Adjuvant irradiation for axillary metastases from malignant melanoma

    International Nuclear Information System (INIS)

    Purpose: To evaluate the outcome and treatment-related toxicity for patients with axillary lymph node metastases from malignant melanoma treated with surgery and radiation, with or without systemic therapy. Methods and Materials: The medical records of 89 consecutive patients with axillary lymph node metastases from malignant melanoma were retrospectively reviewed. All patients underwent axillary dissection and postoperative radiation to a median dose of 30 Gy at 6 Gy/fraction delivered twice weekly. In 3 patients referred with microscopic residual disease, a single boost (4-6 Gy) was given to a reduced field. All but 2 patients were referred because their axillary dissections revealed features believed to predict a 30-50% risk of subsequent axillary recurrence: lymph nodes ≥3 cm in size (54 patients), ≥4 lymph nodes positive (44), the presence of extracapsular extension (69), recurrent disease after initial surgical resection (23), or multiple risk factors (77). Fifty-one patients received systemic therapy before or after radiation therapy. Results: At a median follow-up of 63 months, 47 patients had relapsed and 43 patients had died. The actuarial overall and disease-free survival rates at 5 years were 50% and 46%, respectively. The actuarial axillary control and distant metastasis-free survival rates at 5 years were 87% and 49%, respectively. Univariate analysis revealed that the probability of axillary control was inferior when the axillary disease measured >6 cm in size (72% vs. 93%, p=0.02), the location of the primary tumor was unknown (74% vs. 93%, p=0.02), the axillary failure occurred within 18 months from diagnosis of the primary melanoma (84% vs. 100%, p = 0.04), or the Breslow thickness was >4 mm (80% vs. 96%, p = 0.04). Additionally, there was an inferior distant metastasis-free and disease-free survival when there were >2 nodes positive for metastatic disease, the primary lesion had a Breslow thickness >4 mm, or the axillary failure occurred

  7. Malignant epibulbar melanoma: natural history and treatment by radiotherapy

    International Nuclear Information System (INIS)

    One hundred and eighty-four cases of malignant melanoma of the lids and epibulbar region were seen in the Radiotherapy Department of the Royal Marsden Hospital during the period 1943-74. Some of these tumours were radiosensitive and could thus be treated by radiotherapy without loss of the affected eye. Their clinical and histological features are described. The treatment policy adopted was based on radiotherapy first, and surgery reserved for the failures. A policy of observation is advised for precancerous melanosis, and active treatment should be undertaken only if malignancy supervenes. The contraindications for radiotherapy, the factors governing radiosensitivity, and the incidence and site of metastases are reported, and the possible effect on the metastatic and survival rates of leaving the eye are discussed. Active treatment of the node-free neck is not advised. Results are given according to site, histology, and treatment method, and the frequency with which the eye was lost is shown, since the sole advantage of radiotherapy over surgery is the possibility of saving the eye without worsening the prognosis for survival. (author)

  8. Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report

    Science.gov (United States)

    Gogakos, Apostolos S; Paliouras, Dimitrios; Asteriou, Christos; Rallis, Thomas; Lazopoulos, Achilleas; Chatzinikolaou, Fotios; Zissimopoulos, Athanassios; Tsavlis, Drosos; Tsirgogianni, Katerina; Zarogoulidis, Konstantinos; Porpodis, Konstantinos; Tsakiridis, Kosmas; Pitsiou, Georgia; Kioumis, Ioannis; Karapantzos, Ilias; Karapantzou, Chrysanthi; Sachpekidis, Nikos; Zarogoulidis, Paul; Barbetakis, Nikolaos

    2016-01-01

    Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient’s history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival. PMID:26848270

  9. Lymph node dissection in patients with malignant melanoma is associated with high risk of morbidity

    DEFF Research Database (Denmark)

    Ul-Mulk, Jamshaid; Hölmich, Lisbet Rosenkrantz

    2012-01-01

    Malignant melanoma is one of the most rapidly increasing cancer types globally, and it is by far the most serious skin cancer. Patients with a melanoma ≥ 1 mm in Breslow thickness are offered sentinel node (SN) biopsy and subsequent radical lymph node dissection if the biopsy is positive. The obj...

  10. Primary malignant melanoma of the ovary: case report and review of the literature.

    Science.gov (United States)

    Gök, Nazlı Demır; Yildiz, Kürşat; Corakçi, Aydın

    2011-05-01

    Ovarian malignant melanomas are extremely rare tumors. Most of them are secondary tumors and disseminated metastases are recognized at the time of diagnosis. Primary tumors are even more rare and usually associated with a teratoma. A 67-year-old female had a pelvic mass that was recognized on ultrasonography (USG) and physical examination. Intraoperative pathological consultation was reported as "pigmented solid ovarian tumor, probably compatible with malignant melanoma". Paraffin sections, and histochemical (Masson Fontana and Prussia blue) and immunohistochemical examination (S-100 and HMB-45) were also consistent with "malignant melanoma". This case was accepted as "Probably primary ovarian malignant melanoma" in lack of any other tumor focus on detailed clinical and radiological investigation, skin biopsies or pigmented lesions in medical history. It is reported for being an extremely rare tumor and its distinctive characteristics for differential diagnosis are emphasized. PMID:21630207

  11. Linear accelerator-based stereotactic radiosurgery in 140 brain metastases from malignant melanoma

    OpenAIRE

    Hauswald, Henrik; Stenke, Alina; Debus, Jürgen; Combs, Stephanie E

    2015-01-01

    Background: To retrospectively access outcome and prognostic parameters of linear accelerator-based stereotactic radiosurgery in brain metastases from malignant melanoma. Methods: Between 1990 and 2011 140 brain metastases in 84 patients with malignant melanoma (median age 56 years) were treated with stereotactic radiosurgery. At initial stereotactic radiosurgery 48 % of patients showed extracerebral control. The median count of brain metastases in a single patient was 1, the median diamete...

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

    OpenAIRE

    Pablo Fernandez-Crehuet Serrano; Jose Luis Fernandez-Crehuet Serrano; Mohamed Farouk Allam; Rafael Fernandez-Crehuet Navajas

    2016-01-01

    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 datab...

  13. Diffuse Interstitial Infiltrative Lung Metastasis of Malignant Melanoma: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Na young; Hong, Yoo Jin; Kim, Ah Hyun; Shim, Hyo Sub; Nam, Ji Eun; Lee, Hye Jeong; Kim, Myung Joon [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2011-04-15

    A diffuse interstitial infiltrative pattern of lung metastasis in a patient with malignant melanoma is rare and can be confused with benign conditions such as pulmonary edema or drug-induced pneumonitis. We experienced a case of diffuse interstitial infiltrative lung metastasis in malignant melanoma in a 37-year-old man. This case was confirmed by a transbronchial lung biopsy. We herein describe the findings on CT and positron emission tomography scan

  14. CHEK2*1100delC and risk of malignant melanoma

    DEFF Research Database (Denmark)

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

    2012-01-01

    It is possible that reduced function of DNA repair and cell-cycle control genes increases the individual susceptibility to malignant melanoma. As CHEK2 is a cell-cycle master controller, we tested the hypothesis that heterozygosity for the frameshift alteration CHEK2*1100delC is associated with...... increased risk of malignant melanoma. First, we performed case-control studies of 1,152 Danish and 752 German individuals with malignant melanoma compared with 9,142 Danish and 3,718 German controls. Second, we performed a meta-analysis of CHEK2*1100delC and malignant melanoma, involving 2,619 cases and 17......,481 controls. Third, we examined the risk of malignant melanoma associated with CHEK2*1100delC heterozygosity in an analysis stratified for sun exposure, as well as for subtype and location on the body. The odds ratios for malignant melanoma for CHEK2(*)1100del heterozygotes compared with those for noncarriers...

  15. Importance of glycolysis and oxidative phosphorylation in advanced melanoma

    Directory of Open Access Journals (Sweden)

    Ho Jonhan

    2012-10-01

    Full Text Available Abstract Serum lactate dehydrogenase (LDH is a prognostic factor for patients with stage IV melanoma. To gain insights into the biology underlying this prognostic factor, we analyzed total serum LDH, serum LDH isoenzymes, and serum lactate in up to 49 patients with metastatic melanoma. Our data demonstrate that high serum LDH is associated with a significant increase in LDH isoenzymes 3 and 4, and a decrease in LDH isoenzymes 1 and 2. Since LDH isoenzymes play a role in both glycolysis and oxidative phosphorylation (OXPHOS, we subsequently determined using tissue microarray (TMA analysis that the levels of proteins associated with mitochondrial function, lactate metabolism, and regulators of glycolysis were all elevated in advanced melanomas compared with nevic melanocytes. To investigate whether in advanced melanoma, the glycolysis and OXPHOS pathways might be linked, we determined expression of the monocarboxylate transporters (MCT 1 and 4. Analysis of a nevus-to-melanoma progression TMA revealed that MCT4, and to a lesser extend MCT1, were elevated with progression to advanced melanoma. Further analysis of human melanoma specimens using the Seahorse XF24 extracellular flux analyzer indicated that metastatic melanoma tumors derived a large fraction of energy from OXPHOS. Taken together, these findings suggest that in stage IV melanomas with normal serum LDH, glycolysis and OXPHOS may provide metabolic symbiosis within the same tumor, whereas in stage IV melanomas with high serum LDH glycolysis is the principle source of energy.

  16. Small Molecules Antagonise the MIA-Fibronectin Interaction in Malignant Melanoma.

    Science.gov (United States)

    Yip, King Tuo; Zhong, Xue Yin; Seibel, Nadia; Pütz, Stefanie; Autzen, Jasmin; Gasper, Raphael; Hofmann, Eckhard; Scherkenbeck, Jürgen; Stoll, Raphael

    2016-01-01

    Melanoma inhibitory activity (MIA), an extracellular protein highly expressed by malignant melanoma cells, plays an important functional role in melanoma development, progression, and metastasis. After its secretion, MIA directly interacts with extracellular matrix proteins, such as fibronectin (FN). By this mechanism, MIA actively facilitates focal cell detachment from surrounding structures and strongly promotes tumour cell invasion and migration. Hence, the molecular understanding of MIA's function provides a promising target for the development of new strategies in malignant melanoma therapy. Here, we describe for the first time the discovery of small molecules that are able to disrupt the MIA-FN complex by selectively binding to a new druggable pocket, which we could identify on MIA by structural analysis and fragment-based screening. Our findings may inspire novel drug discovery efforts aiming at a therapeutically effective treatment of melanoma by targeting MIA. PMID:27151361

  17. Experience with Ruthenium /sup 106/-treatment of uveal malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Laatikainen, L.; Tarkkanen, A.

    1987-01-01

    In 1981-1986, 25 eyes with malignant melanoma of the uvea were treated with beta irradiation using ruthenium/sup 106/ plaques. In 21 cases the tumour originated in the choriod, in 4 cases in the ciliary body. In 12 eyes it was within 3 mm from the optic disc or the fovea, and the mean height (+-SEM) was 5.2+-0.4 mm. Three eyes received two sets of irradiation with 1.1 - 1.7 years' interval. After a mean followup of 1.6 years (range 0,5 - 5.6) the tumour had decreased in size in 12, was unchanged in 6, and had progressed in 7 eyes, 4 of the latter were enucleated. In 3 patients metastases were diagnosed (2.0 -2.9 years after irradiation), and 1 patient has died (3.3 years after the first irradiation). Twelve eyes have retained useful vision (0.05 or better), but in some of them a tendency to deterioration was observed 3-5 years after treatment due to radiation maculopathy. Other causes of visual loss were the centrally located tumour itself, exudative detachment of the retina, and persistent vitreous haemorrhage.

  18. Experience with Ruthenium 106-treatment of uveal malignant melanoma

    International Nuclear Information System (INIS)

    In 1981-1986, 25 eyes with malignant melanoma of the uvea were treated with beta irradiation using ruthenium106 plaques. In 21 cases the tumour originated in the choriod, in 4 cases in the ciliary body. In 12 eyes it was within 3 mm from the optic disc or the fovea, and the mean height (±SEM) was 5.2±0.4 mm. Three eyes received two sets of irradiation with 1.1 - 1.7 years' interval. After a mean followup of 1.6 years (range 0,5 - 5.6) the tumour had decreased in size in 12, was unchanged in 6, and had progressed in 7 eyes, 4 of the latter were enucleated. In 3 patients metastases were diagnosed (2.0 -2.9 years after irradiation), and 1 patient has died (3.3 years after the first irradiation). Twelve eyes have retained useful vision (0.05 or better), but in some of them a tendency to deterioration was observed 3-5 years after treatment due to radiation maculopathy. Other causes of visual loss were the centrally located tumour itself, exudative detachment of the retina, and persistent vitreous haemorrhage. (author)

  19. 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.

  20. Priapism in a stallion with generalized malignant melanoma.

    Science.gov (United States)

    Blanchard, T L; Schumacher, J; Edwards, J F; Varner, D D; Lewis, R D; Everett, K; Joyce, J R

    1991-03-15

    A Thoroughbred stallion developed priapism that was unresponsive to medical treatment and lavage of the corpus cavernosum penis with heparinized 0.9% NaCl solution. Three weeks after onset of priapism, the penis was firm and noncompliant, and penile pain sensation and ability to retract the penis were lost. Ultrasonography confirmed thrombosis of the corpus cavernosum penis. The stallion was euthanatized because of poor prognosis for return to breeding soundness. Necropsy revealed enlargement of numerous lymph nodes. The dorsal penile nerves were demyelinated distal to the crura of the penis. A diagnosis of generalized malignant melanoma was made; however, neither metastasis to the vertebral canal nor compression of spinal nerve roots as they exited the vertebral foramen was found. Priapism is a persistent erection without sexual arousal and is initially unassociated with penile paralysis, but if prolonged, leads to irreversible venous occlusion where collecting veins join the cavernous spaces. Damage to the dorsal penile nerves may explain the long-term penile paralysis and loss of sensation that accompanied priapism in this stallion. Priapism unassociated with the use of phenothiazine-derivative tranquilizers is uncommon in horses. PMID:2032912

  1. Brain metastases of malignant melanoma in Chinese:report of 23 cases

    Institute of Scientific and Technical Information of China (English)

    WANG Yi-chou; LEE Shih-tseng

    2007-01-01

    Background Patients with melanoma metastasized to the central nervous system have a poor prognosis. Because the incidence of malignant melanoma in the Oriental is lower than that in the Caucasian population, brain metastases of malignant melanoma are rarely reported in Asia. Here we present our experience of brain metastasis of melanoma in an Asian perspective.Methods From 1990 to 2003, 369 patients with melanoma were treated in our hospital, 26 of them were diagnosed as having central nervous system involvement. Of the 26 cases, the clinical history, image, and pathologic findings of 23 patients were analyzed; the other 3 were excluded because of incomplete clinical data.Results Among the 369 patients with melanoma, 45% (167/369) developed lower extremity melanoma, and 27.1%(100/369) had acral lentiginous melanoma (ALM); while in the 23 patients with brain metastases, 34.7% (8/23) had lower extremity melanoma, and 34.7% (8/23) had ALM. Among the 23 patients, 17 had acute hemorrhage into the tumor,8 initially presented with a single cerebral metastatic lesion, and 15 had multiple brain lesions. Ten of them received surgery, 3 underwent stereotactic radiosurgery, and 16 received whole brain radiation. During follow-up, only 2 patients survived for more than 1 year, the median survival period was 5 months. The longest follow-up period was 11 years.Conclusions Compared with the Caucasian, Chinese patients with melanoma have a different proportion of melanoma subtype and higher incidence rates of lower extremities melanoma and ALM. However, their clinical presentation and prognosis are similar. The patients, who have excisable single or multiple brain lesions or limited extracranial disease and who are actively treated, may survive longer.

  2. Homeopathic treatment of malignant melanoma in a dog. Tratamiento homeopático de melanoma maligno en un perro. Tratamiento homeopático de melanoma maligno num cachorro.

    Directory of Open Access Journals (Sweden)

    Priscilla A. Melville

    2003-01-01

    Full Text Available Malignant melanoma is the most frequently diagnosed of canine’s oral tumors. Conventional treatment’s efficacy – surgical excision, radio and chemotherapy – is very low and the prognostics are very reserved. The present article presents a case of homeopathically treated malignant melanoma in a dog, with successful results. It may be concluded that following the guidelines suggested by Hahnemann for Psora cases might heal the homeopathic treatment of canine malignant melanoma.

  3. MALIGNANT MELANOMA WITH MULTIPLE METASTASES ON THE SMALL BOWEL - CASE REPORT

    Directory of Open Access Journals (Sweden)

    V.T. Grigorean

    2010-08-01

    Full Text Available BACKGROUND: Malignant melanomas often cause intestinal metastasis.Metastases of malignant melanoma are the most common secondary tumors of the gastrointestinal tract.The incidence of intestinal metastasis of malignant melanomas is 1.5-4.4% in clinical studies, reaching upto 35.6-58% in necroptic studies. AIM: We present a clinical case of multiple metastases to the smallbowel with point of departure right retroauricular malignant melanoma. METHODS: Patient T.I., 76years old, is admitted in our clinic with occlusion clinical features installed by approximately 2-3 days.From anamnesis we retain a subocclusion clinical feature installed by approximately 1-2 months, withgradual overheating. On clinical examination a right supraclavicular tumoral formation is found, sizing2.5-3cm, suggestive for malignant melanoma. The abdominal CT shows multiple tumoral formations inthe small bowel, with no other secondary determinations in the other organs. RESULTS: Intraoperatorywe have found six secondary lesions on the jejunum, two on the ileum and two mesenteric metastases. Itwas done partial enterectomy on the jejunal segment with latero-lateral jejuno-jejunal anastomoses andpartial enterectomy on the ileum segment with ileostoma. Postoperatory short-term outcome, at six andtwelve months was favorable. CONCLUSIONS: Small bowel metastases of malignant melanoma is thefirst suspected diagnosis in a patient with oclusive/suboclusive intestinal manifestations and clinicallesions suggestive of malignant melanoma. The patient presentes for acute complications (occlusion,intestinal perforation or chronic complications (chronic digestive bleeding, anemic syndrome. Oftennon-specific symptoms are present, which delay the diagnosis. Surgical treatment is the first therapeuticoption, even in case of multiple secondary determinations.

  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. A Case of Pediatric Melanoma: Treatment Considerations in Advanced Disease

    OpenAIRE

    Albino, Frank P; Wood, Benjamin C.; Oh, Albert; Rogers, Gary F.; Sauerhammer, Tina

    2015-01-01

    Summary: We document a 3-year-old healthy African American girl who developed malignant melanoma on her lower extremity. The clinical appearance offered little indication of the lesion’s severity (T4), and only the history of de novo presentation and disproportionate growth raised clinical suspicion. This case report highlights the subtle clinical findings of this condition and presents controversies related to surgical management of pediatric melanoma.

  6. Clear Cell Sarcoma of Gluteal Region Malignant Melanoma of Soft Parts

    Directory of Open Access Journals (Sweden)

    Haren V. Oza

    2013-04-01

    Full Text Available Clear cell sarcoma (CCS is described as variant of sarcoma characterized by prominent clear cells showing features similar to malignant melanoma of soft parts. This neoplasm was first described by Dr. Franz m. Enzinger. Primary CCS usually arises in deeper soft tissues, in association with fascia, tendons, or aponeuroses. Clear cell sarcoma (CCS is a rare malignant tumor with a propensity for slow progressive invasion. It is a tumor derived from Melanoblast like cell. They occur most commonly in the extremities, with a predilection for young females. Clear cell sarcoma of tendons and aponeuroses (malignant melanoma of soft parts and conventional malignant melanoma may demonstrate significant morphologic overlap at the light microscopic and ultra structural level. The tumor is very rare and can pose clinical challenges in early diagnosis. This case report demonstrates an unusual site of occurrence for clear cell sarcoma. [Natl J Med Res 2013; 3(2.000: 193-195

  7. Primary leptomeningeal malignant melanoma in posterior fossa and upper cervical canal: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Kyu Ran; Kim, Jung Hyuk; Shin, Bong Kyung; Lee, Nam Joon [Korea Univ. Hospital, Seoul (Korea, Republic of)

    2001-11-01

    The term 'primary melanocytic neoplasm' covers a wide disease spectrum, from well differentiated meningeal melanocytoma to malignant melanoma, its most aggressive malignant counterpart. Previous reports have shown that due to the paramagnetic effect of melanin, melanocytic neoplasms show high signal intensity on T1-weighted images and very low signal intensity on T2-weighted images, with relatively homogeneous contrast enhancement. The differentiation of leptomeningeal malignant melanoma from benign melanocytoma is important because of their different prognosis but on the basis of imaging findings alone is difficult. Ultrastructural immunohistochemical analysis is a possible alternative. We report the imaging findings of rare primary malignant melanoma, revealed by noncontrast-enhanced CT as a high-density mass, and demonstrating high signal intensity on T1-weighted images, and very low signal intensity on T2WI, with relatively good contrast enhancement.

  8. Primary leptomeningeal malignant melanoma in posterior fossa and upper cervical canal: a case report

    International Nuclear Information System (INIS)

    The term 'primary melanocytic neoplasm' covers a wide disease spectrum, from well differentiated meningeal melanocytoma to malignant melanoma, its most aggressive malignant counterpart. Previous reports have shown that due to the paramagnetic effect of melanin, melanocytic neoplasms show high signal intensity on T1-weighted images and very low signal intensity on T2-weighted images, with relatively homogeneous contrast enhancement. The differentiation of leptomeningeal malignant melanoma from benign melanocytoma is important because of their different prognosis but on the basis of imaging findings alone is difficult. Ultrastructural immunohistochemical analysis is a possible alternative. We report the imaging findings of rare primary malignant melanoma, revealed by noncontrast-enhanced CT as a high-density mass, and demonstrating high signal intensity on T1-weighted images, and very low signal intensity on T2WI, with relatively good contrast enhancement

  9. Metastatic malignant melanoma representing a multiple mesenteric cystic tumor: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Lim; Woo, Ji Young [Kangnam Sacred Heart, College of Medicine, Hallym University, Seoul (Korea, Republic of)

    2008-05-15

    A metastatic malignant melanoma is a malignant tumor which can involve virtually every organ system. It has variable radiographic findings which mostly indicate solid masses in the mesentery. We report here on a case of a metastatic malignant melanoma, which is made up of multiple mesenteric cystic tumors that need to differentiate from the mesenteric cystic tumor. These include the cystic spindle cell tumor, cystic teratoma, cystic mesothelioma as well as the mesenteric cystic and the solid tumor, which in turn comprises the gastrointestinal stromal tumor, lymphoma and metastatic lesion. The metastatic malignant melanoma can offer a differential diagnosis when the image findings indicate multiple mesenteric cystic masses, multiple organic metastases, and subcutaneous nodules.

  10. Malignant melanoma cure by selective thermal neutron capture therapy

    International Nuclear Information System (INIS)

    Thermal neutrons are easily absorbed by the nonradioactive isotope 10B, resulting in the emission of alpha particles and lithium atoms, which release an energy of 2.33 MeV for up to a 14-μm-diam melanoma cell. Thus, if 10B can be selectively accumulated in melanoma, it can be destroyed without injury to the surrounding normal tissues by concentrating high linear energy transfer particles. The authors have synthesized seven melanoma-seeking 10B compounds, two of which, 10B12-chlorpromazine(10B12-CPZ) and 10B1-p-boronophenylalanine(10B1-BPA), are found to be highly effective. The enhanced melanoma-killing effect of the 10B compounds is found by in vitro radiobiological analysis. A chemical assay and alpha-track analysis 28 h after systemic administration to melanoma-bearing hamsters reveals a 10B melanoma/blood ratio of 11.5 and a melanoma/liver ratio of 15. Establishment of a clinical therapeutic method for curing human melanoma without failure is underway by correlating biophysical, biochemical, biological, and therapeutic data analysis. Recently, the authors have also been working to develop neutron capture therapy using 10B-monoclonal antibodies for melanoma and were able to make some 10B conjugates with the specific m259-0 antibody

  11. Malignant skin diseases: Malignant melanoma and cutaneous T-cell lymphoma

    International Nuclear Information System (INIS)

    Purpose/Objective: This course will (a) review the epidemiology, clinical presentation, staging, radiobiology, and radiation treatment of malignant melanoma and (b) review the epidemiology, clinical presentation, staging, and therapy of cutaneous T-cell lymphoma with an emphasis on radiotherapy based studies. I. Malignant Melanoma (MM): The incidence of MM has one of the fastest growth rates in the world. By the year 2000, one of every 90 Americans will develop MM. Wide local excision is the treatment of choice for stage I-II cutaneous MM. Five-year survival rates depend on (a) sex: female-63%, male-40%; (b) tumor thickness: t 4mm-25%; (c) location: extremity-60%, trunk-41%; and (d) regional lymph node status: negative-77%, positive-31%. Despite adequate surgery, 45%-50% of MM patients will develop metastatic disease. Both the multi-target model and the linear quadratic model predict a possible benefit for high dose per fraction (> 400 cGy) radiation therapy for some MM cell lines. Other radiobiologic factors (repair of potentially lethal damage, hypoxia, reoxygenation, and repopulation) predict a wide variety of clinical responses to different time-dose prescriptions including high dose per fraction (> 400 cGy), low dose per fraction (200-300 cGy), or b.i.d. therapy. Based on a review of the radiobiology of MM, no single therapeutic strategy emerges which could be expected to be successful for all tumors. A review of all of the clinical trials evaluating various time-dose prescriptions for MM reveals that MM is a radiosensitive tumor over a very wide range of time-dose prescriptions. RT is the single most effective therapy for local palliation of metastatic disease. Complete response (CR) rates range from 24%-75% and overall response (OR) rates are 59%-98% with RT compared with CR rates of 3%-10% and OR rates of only 15%-36% with either chemotherapy or immunotherapy. In addition, postoperative RT for residual microscopic/macroscopic disease produces long term

  12. Staging of cutaneous malignant melanoma by CT; CT-Staging kutaner maligner Melanome

    Energy Technology Data Exchange (ETDEWEB)

    Hoffend, J. [Klinikum der Stadt Ludwigshafen gGmbH, Zentralinstitut fuer diagnostische und interventionelle Radiologie, Ludwigshafen (Germany)

    2015-01-30

    Malignant melanomas are a challenge in radiological imaging diagnostics as they may metastasize into every organ and tissue. Cross-sectional imaging, in particular positron emission tomography computed tomography (PET/CT) and whole body magnetic resonance imaging (MRI), are considered the standards in the staging of melanomas. Because of its excellent availability CT, however, remains a widely employed staging modality. Familiarity with the manifold CT morphology of metastasized melanomas as it is described here is essential when interpreting dedicated CT and in addition useful when interpreting PET/CT results. In individual cases CT can assist in the detection of transient metastases. In the detection of locoregional lymph node metastases CT has a median sensitivity and specificity in meta-analyses of at best 61 % and 97 %, respectively, which is inferior to the performance of ultrasound (96 % and 99 %, respectively). According to meta-analyses, in the assessment of systemic tumor spread CT can detect the majority of metastases with a sensitivity and specificity of 51-63 % and 69-78 %, respectively, which is inferior to MRI and PET/CT. Therefore, if an exact staging is required for critical management decisions, MRI or PET/CT should be employed whenever possible. (orig.) [German] Maligne Melanome koennen in praktisch jedes Organ und Gewebe metastasieren und stellen daher eine Herausforderung fuer die radiologische Diagnostik dar. Schnittbildverfahren, bevorzugt PET/CT und MRT, werden heute als Standard in der Ausbreitungsdiagnostik von Melanomen angesehen. Wegen ihrer ubiquitaeren Verfuegbarkeit bleibt jedoch die CT ein vielfach genutztes Staginginstrument. Die Kenntnis der vielfaeltigen CT-Morphologie von Melanommetastasen, wie sie in diesem Beitrag beschrieben wird, ist ueber die dedizierte CT hinaus uebertragbar auf die von der aktuellen Leitlinie bevorzugte Bildgebung mit der PET/CT. Im Einzelfall kann die CT hilfreich bei der Detektion von In

  13. Biologic correlation between glucose transporters, hexokinase-II, Ki-67 and FDG uptake in malignant melanoma

    International Nuclear Information System (INIS)

    Introduction: The purpose of this study was to investigate the correlative association between tumoral 2-deoxy-2-[18 F]-fluoro-D-glucose (FDG) uptake, and the expressions of glucose transporter 1 (GLUT-1), glucose transporter 3 (GLUT-3), hexokinase II (HK-2), and Ki-67 expression in malignant melanoma. Methods: Nineteen patients with histologically proven malignant melanoma and pretreatment FDG PET/CT performance were involved in this preliminary study. For semi-quantitative analysis of FDG PET/CT, maximal standardized uptake values (SUVmax) were estimated. Immunohistochemical staining of tumor sections was performed for GLUT-1, GLUT-3, and HK-2, and for the cell proliferation maker Ki-67. Especially, by combining proportions and intensity of immunochemical staining, we evaluated modified immunohistologic scores of GLUT-1 and GLUT-3. Results: The SUVmax of malignant melanoma lesions ranged from 2 to 18.7 (average; 9.1 ± 5.4). Comparison between nodal and extranodal lesions revealed no significant difference of SUVmax (p = 0.97). GLUT-1 staining showed the most positive expression level (89.5%, 17/19) among the diverse immunohistochemical markers. There were significant relationships between FDG uptake of malignant melanoma and GLUT-1 proportion (p < 0.0001), GLUT-1 intensity (p < 0.0001), GLUT-3 proportion (p = 0.031), GLUT-3 intensity (p = 0.009), GLUT-1 immunohistologic scores (p < 0.0001), and GLUT-3 immunohistologic scores (p = 0.028). HK-2 was not expressed in all melanoma samples. Although Ki-67 expression showed a high grade in all staining, there was no significant link between FDG uptake and Ki-67 grades (p = 0.38). Conclusions: The data in this preliminary study indicate that FDG uptake in malignant melanoma is determined by GLUT-1 and GLUT-3, whereas HK-2 and Ki-67 play no role in FDG uptake of malignant melanoma.

  14. A RARE CASE OF PRIMARY MALIGNANT MELANOMA OF THE VAGINA IN A YOUNG LADY: A REPOR

    Directory of Open Access Journals (Sweden)

    Sangeeta

    2013-10-01

    Full Text Available ABSTRACT : Malignant melanoma of vagina is a rare tumor with incidence rate of only 0.46 c ases per one million women per year and less than 250 cases have been reported in medical literature till date. It has a notoriously aggressive behavior and is associated with a high risk of local recurrence and distant metastasis. At present, there are va rious treatment options for this disease but no standard guideline. It accounts for less than 1% of all malignant melanoma and less than 3% of all primary malignant tumors of the vagina. Conventional imaging techniques i.e. computed tomography, may be sub - optimal in evaluating a small volume of tumor, which may lead to inaccurate staging of a loco - regional tumor . The optimal treatment for vaginal melanoma is a subject of debate. Malignant melanoma of the vagina is a disease of postmenopausal women, with 75 % of women being more than 50 years of age . Here, we present a case of primary vaginal malignant melanoma in a 35 year woman located in lower 1/3 rd of the vagina

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

    Directory of Open Access Journals (Sweden)

    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.

  16. 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 no...

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

    International Nuclear Information System (INIS)

    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

  18. Sunitinib in malignant melanoma: a treatment option only for KIT-mutated patients?

    Science.gov (United States)

    Santini, Daniele; Vincenzi, Bruno; Venditti, Olga; Dell'Aquila, Emanuela; Frezza, Anna Maria; Silletta, Marianna; Guida, Francesco Maria; Grasso, Rosario Francesco; Silvestris, Nicola; Lanzetta, Gaetano; Tonini, Giuseppe

    2013-12-01

    Sunitinib has previously been reported to be potentially effective in the treatment of malignant melanomas expressing c-KIT. Here we report on the case of a 77-year-old gentleman affected by a metastatic clear cell carcinoma of the kidney and a metastatic malignant melanoma with liver and lung metastases. Despite the negativity for CD117 and the absence of KIT amplification or mutations in the melanoma specimen, he achieved a partial response both in the lungs and in the liver while on sunitinib (50 mg once/day, 4 weeks on/2 weeks off) for the treatment of kidney cancer. To our knowledge, this represents the first evidence of sunitinib activity in KIT wild-type melanoma. Further studies should be performed to confirm these preliminary data. PMID:24295410

  19. Cataract surgery following cobalt-60 plaque radiotherapy for posterior uveal malignant melanoma

    International Nuclear Information System (INIS)

    The authors reviewed the records of thirteen patients with posterior uveal malignant melanoma who had developed a mature radiation cataract following cobalt-60 plaque radiotherapy. Cataract extraction had been performed in seven of these patients as of the survey date of this investigation. The authors attempted to determine if cataract extraction increased the risk of metastatic melanoma, improved or worsened visual function, or resulted in any consistent intraoperative or postoperative complications that did not occur if the cataract was retained. This analysis showed that removing the cataract did not appear to increase the risk of death from metastatic melanoma, but it also indicated that cataract extraction did not seem to improve the visual function of the irradiated eye. On the basis of this experience to date, the authors offer suggested guidelines for the management of patients who develop a mature cataract following cobalt-60 plaque radiotherapy of a posterior uveal malignant melanoma

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

    International Nuclear Information System (INIS)

    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

  1. 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...... of primary 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....

  2. Malignant Amelanotic Melanoma of the Pleura without Primary Skin Lesion:An Autopsy Case Report

    Directory of Open Access Journals (Sweden)

    Nakanishi,Kuniaki

    2009-12-01

    Full Text Available Melanoma metastasizing to the lungs is common, but primary pulmonary or pleural melanoma is extremely rare. We present an autopsy case of malignant melanoma of the pleura without primary skin lesion in a 49-year-old man. A mass found in the right chest was diagnosed as spindle cell sarcoma by antemortem fine-needle aspiration cytology. At autopsy, a yellow-white tumor located primarily in the right visceral pleura (diagnosed as an amelanotic melanoma was found to have invaded into the right lung, right parietal pleura, and right diaphragm, and to have metastasized into the left lung and visceral pleura, thyroid, and left adrenal gland. No primary site was found. The tumor cells were positive for S100 and focally positive for HMB-45, but negative for other markers. Immuno-histochemical examination for S100 and HMB-45 would thus appear to be useful for the diagnosis of an amelanotic melanoma.

  3. Analysis of Alpha-Synuclein in Malignant Melanoma – Development of a SRM Quantification Assay

    Science.gov (United States)

    Welinder, Charlotte; Jönsson, Göran B.; Ingvar, Christian; Lundgren, Lotta; Baldetorp, Bo; Olsson, Håkan; Breslin, Thomas; Rezeli, Melinda; Jansson, Bo; Fehniger, Thomas E.; Laurell, Thomas; Wieslander, Elisabet; Pawlowski, Krzysztof; Marko-Varga, György

    2014-01-01

    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. PMID:25333933

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

    Science.gov (United States)

    Welinder, Charlotte; Jönsson, Göran B; Ingvar, Christian; Lundgren, Lotta; Baldetorp, Bo; Olsson, Håkan; Breslin, Thomas; Rezeli, Melinda; Jansson, Bo; Fehniger, Thomas E; Laurell, Thomas; Wieslander, Elisabet; Pawlowski, Krzysztof; Marko-Varga, György

    2014-01-01

    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. PMID:25333933

  5. 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.

  6. Metastatic Malignant Melanoma of the Inguinal Lymph Node with Unknown Primary Lesion

    Directory of Open Access Journals (Sweden)

    Sherif Ali Eltawansy

    2015-01-01

    Full Text Available Background. Malignant melanoma could present with metastasis with unknown primary (MUP and this happens in 2-3% according to the studies. Around 90% of melanomas have cutaneous origin, but still there are melanomas that could be found in visceral organs or lymph nodes with unknown primary site. Spontaneous regression of the primary site could be an explanation. Case Report. We report a 58-year-old Caucasian male who presented with a right sided swelling in the inguinal region. Surgery was performed and biopsy showed metastatic malignant melanoma. No cutaneous lesions were identified by history or physical examination. Work up could not detect the primary lesion and patient was started on radiotherapy and immunotherapy. Conclusion. We present a case of malignant melanoma of unknown primary presenting in an unusual place which is the inguinal lymph node. Theories try to explain the pathway of development of such tumors and one of the theories mentions that it could be a spontaneous regression of the primary cutaneous lesion. Another theory is that it could be from transformation of aberrant melanocyte within the lymph node. Prognosis is postulated to be better in this case than in melanoma with a known primary.

  7. Amelanotic corneally displaced malignant conjunctival melanoma: a case report evaluated with impression cytology

    Directory of Open Access Journals (Sweden)

    Jeison de Nadai Barros

    2014-01-01

    Full Text Available Here we describe the case of a 65-year-old Caucasian female who presented with an amelanotic malignant conjunctival melanoma and highlight the clinical and pathological features of this rare entity that displayed exclusive corneal invasive growth without evidence of conjunctival tumors other than primary acquired melanosis. Impression cytology aided in the initial diagnosis. The patient underwent surgical treatment. Histopathology and immunohistochemistry revealed an invasive amelanotic melanoma limited to the cornea and exhibiting S-100, Melan A, and HMB-45 positivity. The absence of pigmentation delayed early clinical detection and treatment. Awareness of this nonpigmented melanoma is important for early recognition and appropriate management.

  8. 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.

    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...

  9. 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

    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 and......The purpose of this study was to develop a suitable animal model for the investigation of the pathogenesis and therapy of uveal malignant melanoma. Eight choroidal malignant melanomas from eight patients were transplanted into nude mice in an attempt to establish a serially transplantable tumour...... electron microscopy. Only one of the eight transplanted primary tumours (13%) was established as a xenograft in nude mice. Furthermore, the take rate of the transplantable tumour was low (13%). The growth of the tumour fitted a Gompertz function, and the calculated tumour volume doubling time was 54 days...

  10. Expression and prognostic significance of Cathepsin L in early cutaneous malignant melanoma.

    Science.gov (United States)

    Stabuc, B; Mrevlje, Z; Markovic, J; Stabuc-Silih, M

    2006-01-01

    Cathepsins are papain-like lysosome cysteine proteases involved in tumor growth, invasiveness and spread, angiogenesis and alteration in immune and inflammatory responses. We investigated the differences in cathepsin L (CatL) concentrations in primary cutaneous malignant melanoma stage I and normal skin and correlated these values with well-established malignant melanoma prognostic factors. The study was performed on 36 patients (17 men and 19 women; mean age 54 years; range 21-84 years) with histological confirmed primary malignant melanomas less than 1.5 mm thick. The CatL concentrations were measured in 36 pairs of triton extracts of cytosols prepared from the tumor and adjacent normal tissue samples (matched pairs). The CatL concentrations were determined by commercially available enzyme-liked immunosorbent (ELISA) assay from KRKA (Novo Mesto, Slovenia). Significantly higher concentrations of CatL were detected in malignant melanomas than in normal surrounding skin (6.73 vs. 1.42 ng/mg total protein (mgp), pskin concentrations for CatL were found. The malignant melanoma CatL concentrations correlated significantly with normal skin (r=0.38; p=0.021). CatL concentrations were significantly lower (p0.75 mm, Clark invasion of >or=II and malignant melanomas indicate its possible involvement in the processes of early metastatic spread and its association with poor prognosis. PMID:16652198

  11. O6-methylguanine-DNA-methyltransferase and DNA mismatch repair in relation to drug resistance in malignant melanoma

    OpenAIRE

    Ma, Shuhua

    2004-01-01

    Although the survival rate of patients with malignant melanoma has improved, treatment of the disease poses large problems since disseminated melanoma frequently shows primary resistance to chemotherapy. Resistance to chemotherapy is thus a major clinical problem and a cause of failure in the treatment of metastatic malignant melanoma. The primary aim of this thesis was to investigate whether the DNA repair protein 06-methylguanineDNA-metbyltransferase (MGMT) and the post...

  12. Socioeconomic status, sunlight exposure, and risk of malignant melanoma: the Western Canada Melanoma Study.

    Science.gov (United States)

    Gallagher, R P; Elwood, J M; Threlfall, W J; Spinelli, J J; Fincham, S; Hill, G B

    1987-10-01

    In a study of 261 male melanoma patients and age-and sex-matched controls, a strong positive univariate association between socioeconomic status, as determined by usual occupation, and risk of melanoma was detected. This association, however, was substantially explained by host constitutional factors and occupational, recreational, and vacation sunlight exposure. The study demonstrated an increased risk of melanoma in draftsmen and surveyors and a reduced risk of melanoma in construction workers and individuals employed in the finance, insurance, and real estate industry even after control for the effect of host factors and sunlight exposure. PMID:3116308

  13. PATHOLOGICAL FRACTURE TIBIA DUE TO METASTATIC LESION FROM MALIGNANT MELANOMA OF FOOT: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Kunal R

    2016-03-01

    Full Text Available There is considerable variation in the reported incidence of skeletal metastasis from malignant melanoma. Metastasis to axial skeleton is almost four times more common than to appendicular skeleton.1 In long bones, the metastasis is usually located symmetrically at diaphysis.1 Patients with skeletal metastasis have grave prognosis with mean survival of 3.6 months.2 We report a case of malignant melanoma of foot with symmetrical metastasis to tibial diaphysis and pathological fracture on one side with 18 months’ survival.

  14. Development of Malignant Melanoma of the Orbit in Previous Radiation Field.

    Science.gov (United States)

    Ahmed, Shamima; McDonald, Nicholas; Lowder, Lindsey; Mahoney, Bruce

    2015-11-01

    We present a case of a 40-year-old woman with a history of retinoblastoma in the left eye treated with enucleation and radiation therapy as an infant who recently developed worsening pain and exophthalmos in her right eye. Multimodality imaging demonstrated an enhancing, FDG-avid mass in the medial right orbit with associated bone destruction and extension into the ethmoid sinus. Pathologic analysis after excision showed a highly undifferentiated tumor consistent with melanoma. Although development of malignant melanoma in an irradiated field is rare, it should be considered in the differential, especially in childhood cancer survivors at increased risk of second malignant neoplasms. PMID:26053723

  15. Imaging Finding of Malignant Melanoma of Eustachian Tube with Extension to Middle Ear Cavity: Case Report

    International Nuclear Information System (INIS)

    We report a case of malignant melanoma of Eustachian tube with extension to the middle ear cavity and nasopharynx in a 51-year-old woman who presented with right ear fullness. Computed tomography showed a soft tissue mass in the middle ear cavity and caused the widening and eroding of the bony eustachian tube. Magnetic resonance imaging showed well enhancing mass in eustachian tube extending nasopharynx to middle ear cavity. A biopsy of the middle ear cavity mass revealed a malignant amelanotic melanoma.

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

    Energy Technology Data Exchange (ETDEWEB)

    Moan, J.; Setlow, R.; Cicarma, E.; Porojnicu, A. C.; Grant, W. B.; Juzeniene, A.

    2010-01-01

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

  17. The metastatic microenvironment: Claudin-1 suppresses the malignant phenotype of melanoma brain metastasis.

    Science.gov (United States)

    Izraely, Sivan; Sagi-Assif, Orit; Klein, Anat; Meshel, Tsipi; Ben-Menachem, Shlomit; Zaritsky, Assaf; Ehrlich, Marcelo; Prieto, Victor G; Bar-Eli, Menashe; Pirker, Christine; Berger, Walter; Nahmias, Clara; Couraud, Pierre-Olivier; Hoon, Dave S B; Witz, Isaac P

    2015-03-15

    Brain metastases occur frequently in melanoma patients with advanced disease whereby the prognosis is dismal. The underlying mechanisms of melanoma brain metastasis development are not well understood. Identification of molecular determinants regulating melanoma brain metastasis would advance the development of prevention and therapy strategies for this disease. Gene expression profiles of cutaneous and brain-metastasizing melanoma variants from three xenograft tumor models established in our laboratory revealed that expression of tight junction component CLDN1 was lower in the brain-metastasizing variants than in cutaneous variants from the same melanoma. The objective of our study was to determine the significance of CLDN1 downregulation/loss in metastatic melanoma and its role in melanoma brain metastasis. An immunohistochemical analysis of human cells of the melanocyte lineage indicated a significant CLDN1 downregulation in metastatic melanomas. Transduction of melanoma brain metastatic cells expressing low levels of CLDN1 with a CLDN1 retrovirus suppressed their metastatic phenotype. CLDN1-overexpressing melanoma cells expressed a lower ability to migrate and adhere to extracellular matrix, reduced tumor aggressiveness in nude mice and, most importantly, eliminated the formation of micrometastases in the brain. In sharp contrast, the ability of the CLDN1-overexpressing cells to form lung micrometastases was not impaired. CLDN1-mediated interactions between these cells and brain endothelial cells constitute the mechanism underlying these results. Taken together, we demonstrated that downregulation or loss of CLDN1 supports the formation of melanoma brain metastasis, and that CLDN1 expression could be a useful prognostic predictor for melanoma patients with a high risk of brain metastasis. PMID:25046141

  18. A clinicopathological study of malignant melanoma with special reference to atypical presentation

    Directory of Open Access Journals (Sweden)

    Mukhopadhyay Subhalakshmi

    2008-10-01

    Full Text Available Malignant melanoma is a tumor of melanocytic origin. Lymphatic and hematogenous metastases are common in this condition. Retrospective analysis was performed in 16 consecutive cases diagnosed histopathologically as malignant melanoma at the pathology department of a medial college in eastern India. 75% of the patients were male; majority of them was in their sixth decade. All (100% the lesions were pigmented. The primary site was known in all cases, except two (12.5%. Out of the 14 cases with known primary site 11 (78.57% were cutaneous melanomas, including one arising in labia minora, two (14.29% were ocular and one (7.14% was vaginal in origin. Among cutaneous melanomas, superficial spreading type was the commonest variety and mixed population of epithelioid and spindle cell was the commonest histopathological pattern. The commonest grade of invasion was grade III (Clark′s. The clinical presentation of the case of vaginal melanoma and the two cases of secondary melanomas, including the one with obscure primary tumor, were bewildering and hence are discussed separately.

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

    International Nuclear Information System (INIS)

    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 18F-fluordeoxyglucose (FDG) positron emission tomography (PET)/CT. In total, 50 18F-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, 18F-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 18F-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.)

  20. 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.

  1. Primary Malignant Melanoma of the Ovary: Case Report and Review of the Literature

    OpenAIRE

    Nazlı DEMİR GÖK; YILDIZ, Kürşat; ÇORAKÇI, Aydın

    2011-01-01

    Ovarian malignant melanomas are extremely rare tumors. Most of them are secondary tumors and disseminated metastases are recognized at the time of diagnosis. Primary tumors are even more rare and usually associated with a teratoma. A 67-year-old female had a pelvic mass that was recognized on ultrasonography (USG) and physical examination. Intraoperative pathological consultation was reported as “pigmented solid ovarian tumor, probably compatible with malignant melanoma”. Paraffin sections, a...

  2. Malignant Melanoma in the Elderly: Different Regional Disease and Poorer Prognosis

    Directory of Open Access Journals (Sweden)

    James B. Macdonald, Amylou C. Dueck, Richard J. Gray, Nabil Wasif, David L. Swanson, Aleksandar Sekulic, Barbara A. Pockaj

    2011-01-01

    Full Text Available Purpose: Age is a poor prognostic factor in melanoma patients. Elderly melanoma patients have a different presentation and clinical course than younger patients. We evaluated the impact of age ≥70 years (yrs on the diagnosis and natural history of melanoma.Methods: Retrospective review of 610 patients with malignant melanoma entered into a prospective sentinel lymph node (SLN database, treated from June 1997 to June 2010. Disease characteristics and clinical outcomes were compared between patients ≥70 yrs vs. <70 yrs of age.Results: 237 patients (39% were ≥70 yrs. Elderly patients had a higher proportion of head and neck melanomas (34% vs. 20%, p<0.001, and greater mean tumor thickness (2.4mm vs. 1.8mm, p<0.001. A greater proportion of T3 or T4 melanoma was seen in the elderly (p<0.001 as well as a greater mean number of mitotic figures: 3.6/mm2 vs. 2.7/mm2 (p=0.005. Despite greater mean thickness, the incidence of SLN metastases was less in the ≥70 yrs group with T3/T4 melanomas (18% vs. 33%, p=0.02. The elderly had a higher rate of local and in-transit recurrences, 14.5% vs. 3.4% at 5 yrs (p<0.001. 5 yr disease-specific mortality and overall mortality were worse for those ≥70 yrs: 16% vs. 8% (p=0.004, and 30% vs. 12% (p<0.001, respectively.Conclusions: Elderly (≥70 yrs melanoma patients present with thicker melanomas and a higher mitotic rate but have fewer SLN metastases. Melanoma in the elderly is more common on the head and neck. Higher incidence of local/in-transit metastases is seen among the elderly. Five-year disease-specific mortality and overall mortality are both worse for these patients.

  3. PET of Malignant Melanoma Using 18F-Labeled Metallopeptides

    OpenAIRE

    Ren, Gang; Liu, Zhe; Miao, Zheng; Liu, Hongguang; Subbarayan, Murugesan; Chin, Frederick T.; Zhang, Lan; Sanjiv S Gambhir; CHENG Zhen

    2009-01-01

    Melanocortin type 1 receptor (MC1R), also known as α-melanocyte–stimulating hormone (α-MSH) receptor, is an attractive molecular target for melanoma imaging and therapy. An 18F-labeled linear α-MSH peptide (18F-FB-Ac-Nle-Asp-His-D-Phe-Arg-Trp-Gly-Lys-NH2 [NAPamide]) shows promising melanoma imaging properties but with only moderate tumor uptake and retention. A transition metal rhenium-cyclized α-MSH peptide, ReO[Cys3,4,10,D-Phe7,Arg11] α-MSH3–13 (ReCCMSH(Arg11)), has shown high in vitro bind...

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

    Science.gov (United States)

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

    2006-06-01

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

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

    International Nuclear Information System (INIS)

    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 D2O 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.)

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Dirk Schadendorf

    2012-04-01

    Full Text Available 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.

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

    International Nuclear Information System (INIS)

    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

  9. 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.

  10. Successful non-typical radiotherapy of a recurrent and metastasizing malignant melanoma of the vulva

    Energy Technology Data Exchange (ETDEWEB)

    Dietz, W.; Dietz, R.

    1982-02-01

    A report is given about the successful, ambulatory, non-typical radiotherapy of a malignant vulvar melanoma producing recurrences and metastases after surgery. The problems of radiotherapy are discussed under special consideration of this case. With regard to the communications found in literature, the author underlines the efficiency of radiotherapy, especially if it is fractionated into high individual doses.

  11. Successful non-typical radiotherapy of a recurrent and metastasizing malignant melanoma of the vulva

    International Nuclear Information System (INIS)

    A report is given about the successful, ambulatory, non-typical radiotherapy of a malignant vulvar melanoma producing recurrences and metastases after surgery. The problems of radiotherapy are discussed under special consideration of this case. With regard to the communications found in literature, the author underlines the efficiency of radiotherapy, especially if it is fractionated into high individual doses. (orig.)

  12. 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; Ross, Lone; Dahlstrøm, Karin; Schmidt, Grethe; Naested, Jesper; Krag, Christen; Johansen, Christoffer

    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...

  13. Amelanotic Malignant Melanoma Mimicking Hemangioma of the Hand: One Case Report and Literature Review

    Institute of Scientific and Technical Information of China (English)

    Lei Ma; Xinghua Gao

    2009-01-01

    @@ Introduction Malignant melanoma (MM) is one of the most deadly cancers[1]. Although the disease accounts for only about 4% of skin cancer related cases, it is responsible for about 79% of skin cancer deaths[2]. Early diagnosis of MM is, therefore, essential for appropriate treatment decision and, in turn, may give patients the best chance for prolonged survival[3-5].

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

    International Nuclear Information System (INIS)

    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.)

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

    Science.gov (United States)

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

    2016-08-01

    Immunotherapy has attracted attention as a novel treatment modality for malignant melanoma. Although the use of immunotherapy in metastatic melanoma has shown promising results, there remains a lack of predictive biomarkers indicating treatment benefit from immunotherapy. There is growing evidence suggesting that microsatellite instability (MSI) as a product of DNA mismatch repair deficiency, may be one of possible predictive markers in malignant melanoma. It has been proposed that the immunogenicity of some tumors might be determined by mutational heterogeneity and could be the key to the success of immune therapies. This is also supported by the fact that tumors with the highest amount of somatic mutations, such as malignant melanoma have showed positive results with immune checkpoint inhibitors. There are promising data regarding the association between MSI status and immunogenicity from studies with colorectal cancer, where MSI is linked to improved prognosis compared to microsatellite stable cancers. MSI in colon cancer is linked to a significant increase of immunocompetent cells responsible for the antitumor activity - CD3(+), CD8(+), CD45RO(+), and T-bet(+) lymphocytes and decrease of inhibition factors such as Foxp3, IL-6, IL-17, and TGF-β. On the other hand, taking into account the progression-dependent accumulation of somatic mutations in MSI tumors and consequent high levels of neo-antigens, the possible drug resistance of MSI tumors to traditional treatment, and the presence of inhibition checkpoints within the MSI tumors, there is a solid rationale for the use of novel therapeutic strategies such as immunotherapy in MSI melanomas. We presume that the MSI phenotype in malignant melanoma might be helpful to identify patients, who would be more likely to profit from immunotherapy than from conventional therapy. PMID:27372860

  16. Thermal neutron capture therapy: The Japanese-Australian clinical trial for malignant melanoma

    International Nuclear Information System (INIS)

    Following the first NCT treatment for melanoma last year in Japan, it is planned to treat at least 12 patients during 1988, from Australia and Japan. Patients will be selected from those having evaluable superficial or subcutaneous local recurrence or isolated metastasis. In addition, selected Japanese patients with thick primary acral-lentiginous melanoma or superficially spreading melanoma that have poor prognosis with conventional therapy will be treated with NCT. Australian patients will be selected from those attending the Sydney Melanoma Unit at Royal Prince Alfred Hospital. They will have no detectable deep-seated distant metastases and should have an estimated life expectancy of at least 6 months. Locally recurrent or advanced melanoma are rare conditions, thanks to the increased awareness of the public and general practitioners and to the more stringent procedures adopted by surgeons

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

    Science.gov (United States)

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

    2016-05-01

    Recent studies cite β2-adrenergic receptor (β2AR) antagonists as novel therapeutic agents for melanoma, as they may reduce the disease progression. The β2AR has shown to be expressed in malignant melanoma. However, it remains unclear whether the β2AR expression has a clinical and pathological significance in patients with cutaneous malignant melanoma. We herein conducted a clinicopathological study to investigate the protein expression of β2AR in malignant melanoma of the skin and its prognostic significance. One hundred thirty-three patients with surgically resected cutaneous malignant melanoma were evaluated. Tumor sections were stained by immunohistochemistry for β2AR, Ki-67, the microvessel density (MVD) determined by CD34, and p53. β2AR was highly expressed in 44.4 % (59 out of 133) of the patients. The expression of β2AR was significantly associated with the tumor thickness, ulceration, T factor, N factor, disease stage, tumor size, cell proliferation (Ki-67), and MVD (CD34). Using Spearman's rank test, the β2AR expression was correlated with Ki-67 (r = 0.278; 95 % CI, 0.108 to 0.432; P = 0.001), CD34 (r = 0.445; 95 %CI, 0.293 to 0.575; P < 0.001), and the tumor size (r = 0.226; 95 % CI, 0.053 to 0.386; P = 0.008). Using a univariate analysis, the tumor thickness, ulceration, disease stage, β2AR, Ki-67, and CD34 had a significant relationship with the overall and progression-free survivals. A multivariable analysis confirmed that β2AR was an independent prognostic factor for predicting a poor overall survival (HR 1.730; 95 % CI 1.221-2.515) and progression-free survival (HR 1.576; 95 % CI 1.176-2.143) of malignant melanoma of the skin. β2AR can serve as a promising prognostic factor for predicting a worse outcome after surgical treatment and may play an important role in the development and aggressiveness of malignant melanoma. PMID:26596834

  18. Chemovirotherapy of malignant melanoma with a targeted and armed oncolytic measles virus.

    Science.gov (United States)

    Kaufmann, Johanna K; Bossow, Sascha; Grossardt, Christian; Sawall, Stefanie; Kupsch, Jörg; Erbs, Philippe; Hassel, Jessica C; von Kalle, Christof; Enk, Alexander H; Nettelbeck, Dirk M; Ungerechts, Guy

    2013-04-01

    Effective treatment modalities for advanced melanoma are desperately needed. An innovative approach is virotherapy, in which viruses are engineered to infect cancer cells, resulting in tumor cell lysis and an amplification effect by viral replication and spread. Ideally, tumor selectivity of these oncolytic viruses is already determined during viral cell binding and entry, which has not been reported for melanoma. We engineered an oncolytic measles virus entering melanoma cells through the high molecular weight melanoma-associated antigen (HMWMAA) and proved highly specific infection and spread in melanoma cells. We further enhanced this oncolytic virus by inserting the FCU1 gene encoding the yeast-derived prodrug convertases cytosine deaminase and uracil phosphoribosyltransferase. Combination treatment with armed and retargeted MV-FCU1-αHMWMAA and the prodrug 5-fluorocytosine (5-FC) led to effective prodrug conversion to 5-fluorouracil, extensive cytotoxicity to melanoma cells, and excessive bystander killing of noninfected cells. Importantly, HMWMAA-retargeted MV showed antitumor activity in a human xenograft mouse model, which was further increased by the FCU1/5-FC prodrug activation system. Finally, we demonstrated susceptibility of melanoma skin metastasis biopsies to HMWMAA-retargeted MV. The highly selective, entry-targeted and armed oncolytic virus MV-FCU1-αHMWMAA may become a potent building block of future melanoma therapies. PMID:23223133

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

    Science.gov (United States)

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

    2016-07-01

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

  20. Malignant melanoma S3-guideline "diagnosis, therapy and follow-up of melanoma".

    Science.gov (United States)

    Pflugfelder, Annette; Kochs, Corinna; Blum, Andreas; Capellaro, Marcus; Czeschik, Christina; Dettenborn, Therese; Dill, Dorothee; Dippel, Edgar; Eigentler, Thomas; Feyer, Petra; Follmann, Markus; Frerich, Bernhard; Ganten, Maria-Katharina; Gärtner, Jan; Gutzmer, Ralf; Hassel, Jessica; Hauschild, Axel; Hohenberger, Peter; Hübner, Jutta; Kaatz, Martin; Kleeberg, Ulrich R; Kölbl, Oliver; Kortmann, Rolf-Dieter; Krause-Bergmann, Albrecht; Kurschat, Peter; Leiter, Ulrike; Link, Hartmut; Loquai, Carmen; Löser, Christoph; Mackensen, Andreas; Meier, Friedegund; Mohr, Peter; Möhrle, Matthias; Nashan, Dorothee; Reske, Sven; Rose, Christian; Sander, Christian; Satzger, Imke; Schiller, Meinhard; Schlemmer, Heinz-Peter; Strittmatter, Gerhard; Sunderkötter, Cord; Swoboda, Lothar; Trefzer, Uwe; Voltz, Raymond; Vordermark, Dirk; Weichenthal, Michael; Werner, Andreas; Wesselmann, Simone; Weyergraf, Ansgar J; Wick, Wolfgang; Garbe, Claus; Schadendorf, Dirk

    2013-08-01

    This first German evidence-based guideline for cutaneous melanoma was developed under the auspices of the German Dermatological Society (DDG) and the Dermatologic Cooperative Oncology Group (DeCOG) and funded by the German Guideline Program in Oncology. The recommendations are based on a systematic literature search, and on the consensus of 32 medical societies, working groups and patient representatives. This guideline contains recommendations concerning diagnosis, therapy and follow-up of melanoma. The diagnosis of primary melanoma based on clinical features and dermoscopic criteria. It is confirmed by histopathologic examination after complete excision with a small margin. For the staging of melanoma, the AJCC classification of 2009 is used. The definitive excision margins are 0.5 cm for in situ melanomas, 1 cm for melanomas with up to 2 mm tumor thickness and 2 cm for thicker melanomas, they are reached in a secondary excision. From 1 mm tumor thickness, sentinel lymph node biopsy is recommended. For stages II and III, adjuvant therapy with interferon-alpha should be considered after careful analysis of the benefits and possible risks. In the stage of locoregional metastasis surgical treatment with complete lymphadenectomy is the treatment of choice. In the presence of distant metastasis mutational screening should be performed for BRAF mutation, and eventually for CKIT and NRAS mutations. In the presence of mutations in case of inoperable metastases targeted therapies should be applied. Furthermore, in addition to standard chemotherapies, new immunotherapies such as the CTLA-4 antibody ipilimumab are available. Regular follow-up examinations are recommended for a period of 10 years, with an intensified schedule for the first three years. PMID:24028775

  1. Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. PMID:26701857

  2. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature

    Science.gov (United States)

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5–29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10–15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

  3. Oral malignant melanoma: An aggressive clinical entity - Report of a rare case with review of literature.

    Science.gov (United States)

    Hasan, Shamimul; Jamdar, Sami Faisal; Jangra, Jogender; Al Beaiji, Sadun Mohammad Al Ageel

    2016-01-01

    Melanomais one of the most dreaded and aggressive neoplasms, being derived from epidermal melanocytes. The majority of melanomas are seen to involve the skin, and primary mucosal melanomas account for less than 1% of all melanomas. Oral malignant melanomas (OMM) are asymptomatic at the initial presentation, but later they become painful with growth and expansion. In the late stages, the patient may present with ulceration, bleeding, tooth mobility, paresthesia, ill-fitting prosthesis, and delayed healing of the extraction sockets. Diagnosis is often delayed due to asymptomatic clinical presentation, with silent progression of the lesion. OMM are associated with poor prognosis due to their invasive and metastasizing tendencies. The condition has poor survival rates, and metastatic melanomas show even worse prognosis. The 5-year survival rate for OMM ranges 4.5-29%, with 18.5 months being the mean survival rate. The tumor is best managed by wide surgical resection; however, consideration should also be made for adjunctive therapies such as chemotherapy, immunotherapy, and radiotherapy. Recurrences may be seen even 10-15 years after the primary therapy. This paper aims to present an interesting report of aggressive OMM in a 50-year-old male patient and emphasizes the role of dental professionals in maintaining a high degree of vigilance for the pigmented lesions of the oral cavity. Pigmented lesions of uncertain origin should be routinely biopsied to rule out malignancy. Early diagnosis of this dreadful entity entails thorough history taking, physical examination, and radiographic features coupled with histopathology. PMID:27114959

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

    Science.gov (United States)

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

    2016-07-01

    As an oncogene, aurora kinase A (AURKA) is overexpressed in various types of human cancers. However, the expression and roles of AURKA in malignant melanoma are largely unknown. In this study, a miR-137-AURKA axis was revealed to regulate melanoma growth. We found a significant increase in levels of AURKA in melanoma. Both genetic knockdown and pharmacologic inhibition of AURKA decreased tumor cell growth in vitro and in vivo. Further found that miR-137 reduced AURKA expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 was negatively correlated with AURKA expression in melanoma specimens. Overexpression of miR-137 decreased cell proliferation and colony formation in vitro. Notably, re-expression of AURKA significantly rescued miR-137-mediated suppression of cell growth and clonality. In summary, these results reveal that miR-137 functions as a tumor suppressor by targeting AURKA, providing new insights into investigation of therapeutic strategies against malignant melanoma. PMID:27233613

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

    International Nuclear Information System (INIS)

    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

  6. Melanoma

    Science.gov (United States)

    Melanoma is the most serious type of skin cancer. Often the first sign of melanoma is a change in the size, shape, color, or feel of a mole. Most melanomas have a black or black-blue area. Melanoma ...

  7. Clinical utility of nivolumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Asmar R

    2016-02-01

    Full Text Available Ramsey Asmar,1 Jessica Yang,1 Richard D Carvajal1,2 1Department of Medicine, College of Physicians and Surgeons, 2Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA Abstract: Melanomas are highly immunogenic tumors that evade the immune system by exploiting innate checkpoint pathways, rendering effector T-cells anergic. The immunotherapeutic approach of checkpoint inhibition can restore and invigorate endogenous antitumor T-cell responses and has become an important treatment option for patients with advanced melanoma. The CTLA-4 inhibitor ipilimumab and the PD-1 inhibitors nivolumab and pembrolizumab have been shown to induce durable responses and improve overall survival in metastatic, refractory melanoma. Optimization and validation of pretreatment biomarkers to predict response to these agents is a crucial area of ongoing research. Combination immunotherapy has recently demonstrated superior response rates compared to monotherapy; further investigation is needed to refine combinatorial strategies. Keywords: nivolumab, immune checkpoint inhibitors, PD-1, melanoma

  8. [The humoral immunity indices of patients with malignant skin melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Heisele, O G; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of a viral immunomodulator rigvir on humoral immunity was studied in patients with skin malignant melanoma. Peripheral blood levels of B-lymphocytes, IgA, G and M and circulating immune complexes were assayed and immunoglobulin/B-cell ratio (Ig/B) calculated. Preoperative treatment with rigvir brought the indexes of humoral immunity to normal. Response of melanoma patients to rigvir treatment was different from that seen in healthy subjects and was determined by the course of disease. PMID:1300751

  9. 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

    determined by flow cytometry in adjacent sections from the same paraffin-embedded tumours. Only a poor correlation was found between nuclear vv and DI (Kendall's tau = +0.21). The variability of nuclear vv among metastatic lesions was increased as compared to primary melanomas, whereas averaged mean values...... obtained objectively by point-sampled intercepts. Using this approach, the volume-weighted mean nuclear volume, nuclear vv, was estimated in ordinary histological sections from 34 primary cutaneous malignant melanomas and their corresponding 62 metastatic lesions. For comparison, DNA-indices (DI) were...

  10. 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...

  11. Dabrafenib Plus Trametinib for Advanced Melanoma

    Science.gov (United States)

    A summary of results from two phase III trials show that patients with metastatic melanoma whose tumors have specific mutations in the BRAF gene lived longer following treatment with dabrafenib (Tafinlar®), a BRAF inhibitor, plus trametinib (Mekinist®), a

  12. Testing Adjuvant Ipilimumab in Advanced Melanoma

    Science.gov (United States)

    In this clinical trial, patients with stage III or stage IV melanoma that has been completely resected will be randomly assigned to receive post-surgical treatment with either ipilimumab or high-dose interferon alfa-2b, the current standard of care.

  13. 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.

  14. Primary cerebral malignant melanoma: an unusual cause of dyspraxia.

    Science.gov (United States)

    Farnsworth, T A

    1998-09-01

    Primary intracranial melanomas are rare and occur mainly in young adults. Originating from leptomeningeal melanoblasts and extending into the parenchyma, the tumours closely resemble meningiomas, from which they are radiologically difficult to distinguish despite progress in neuroimaging. Definitive diagnosis is usually made on histopathological examination, though confirmed only after post-mortem examination in some cases. Prolonged disease-free periods, and in rare cases long-term survival, are possible following successful total surgical excision. This case presented with typical clinical features but, at 79 years old, an unusual age. PMID:9894390

  15. 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

  16. Uveal and conjunctival malignant melanoma in denmark 1943-97: observed and relative survival of patients followed through 2002

    DEFF Research Database (Denmark)

    Isager, Peter; Engholm, G.; Overgaard, Jens;

    2006-01-01

    PURPOSE: To evaluate the observed and relative survival of patients diagnosed with a malignant melanoma in the ocular region in Denmark during the period 1943-97. METHODS: The study included 2,504 patients (1,292 men and 1,212 women) diagnosed with a melanoma in the ocular region, of which 2,434 ...

  17. Amelanotic malignant melanoma of the uterine cervix diagnosed by cervical smear.

    Science.gov (United States)

    Arık, Deniz; Öge, Tufan; Kabukçuoğlu, Sare; Yalçın, Ömer Tarık; Özalp, Sinan

    2016-06-01

    The melanocytic cells of the cervical epithelium are capable of forming the complete spectrum of melanocytic lesions, from benign lentigines to melanoma. Primary malignant melanoma of the uterine cervix is a rare neoplasm with aggressive behavior. The absence of melanin pigment can lead to misdiagnosis as carcinomas, sarcomas, or lymphoma. Immunohistochemical studies should be used for confirmation. In order to consent the cervix as a primary site, exclusion of any other probable primary sites of melanoma is needed. Here, we present a 61-year-old female patient with postmenopausal vaginal bleeding. After cervical smear, diagnosis was confirmed by cervical punch biopsy. Diagn. Cytopathol. 2016;44:535-537. © 2016 Wiley Periodicals, Inc. PMID:26991516

  18. The role of radiation therapy in the treatment of malignant melanoma in the nasal cavity and nasopharynx-case report

    International Nuclear Information System (INIS)

    Purpose: Primary mucosal malignant melanoma of the nasal cavity, paranasal sinuses, and nasopharynx (hereinafter referred to collectively as the sinonasal tract, i.e., sinonasal tract mucosal malignant melanomas [SNMMs]) is rare, accounting for between 0.3% and 2% of all malignant melanomas and about 4% of head and neck melanomas. Surgery is the treatment of choice for sinonasal mucosal malignant melanomas, especially complete resection of the tumor with sufficient free margins. Radiotherapy has controversial role in the treatment. Melanoma cells are traditionally considered as radioresistant because they have a high capacity for repair of sublethal damages, in particular when we used a conventional fractionation. Therefore, hypo fractionation considered as a reasonable treatment regimen for this disease. Case: In this paper, we have reported the patient with intranasal cavity malignant melanoma. Functional endoscopic sinus surgery was performed to excise the nasal cavity tumor. However, using positron emission tomography/computed tomography scan with fluorodeoxyglucose was diagnosed residual nasopharyngeal tumor. Then, intracavitary brachytherapy for nasopharynx was further administered. Solitary metastatic cervical nodal involvement which was completely removed has been occurred 6 months after the end of brachytherapy. Even with the regional disease progression, we used external radiation therapy, as a modality of treatment. Conclusion: We decided to show this case report because of its rarity and the possible use of radiotherapy. (author)

  19. [The reaction of the T-immunity system in patients with malignant skin melanoma and stomach cancer to active nonspecific immunotherapy].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh

    1992-01-01

    Changes in E-receptor-bearing T-lymphocyte level (total and that of active T-lymphocytes) were studied in peripheral blood and resected material obtained from skin malignant melanoma and gastric cancer patients treated with rigvir, an original immunomodulator of the viral origin. Injection of rigvir into peripheral blood was followed by an increase in active T-lymphocyte level and stimulated their migration into tumor. The latter was determined by stage and rate of tumor advancement. PMID:1300766

  20. Advances in diffuse malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Tristan D. Yan

    2011-12-01

    Full Text Available Malignant mesothelioma is a highly aggressive neoplasm. The incidence of malignant mesothelioma is increasing worldwide. Diffuse malignant peritoneal mesothelioma (DMPM represents one-fourth of all mesotheliomas. Association of asbestos exposure with DMPM has been observed, especially in males. A great majority of patients present with abdominal pain and distension, caused by accumulation of tumors and ascitic fluid. In the past, DMPM was considered a pre-terminal condition; therefore attracted little attention. Patients invariably died from their disease within a year. Recently, several prospective trials have demonstrated median survival of 40 to 90 months and 5-year survival of 30% to 60% after the combined treatment using cytoreductive surgery and perioperative intraperitoneal chemotherapy. This improvement in survival has prompted new searches into the medical science related to DMPM, a disease previously ignored as uninteresting. This review article focuses on the key advances in the epidemiology, diagnosis, staging, treatments and prognosis of DMPM that have occurred in the past decade.

  1. Liquid biopsy utility for the surveillance of cutaneous malignant melanoma patients.

    Science.gov (United States)

    Huang, Sharon K; Hoon, Dave S B

    2016-03-01

    Cutaneous melanoma is one of the highest incident-rate cancers with increasing prevalence in Western societies. Despite the advent of new approved therapeutics, the 5-year overall survival rate of stage IV melanoma patients remains below 15%. Current treatments for late stage disease have shown higher efficacy when treated at a lower disease burden. Thus, blood-based biomarkers capable of detecting melanoma prior to clinically evident distant metastasis, will improve the treatment and outcomes for melanoma patients. To that end, effective treatment of melanoma necessitates identification of patients at risk for developing distant metastases. Furthermore, employing blood biomarkers that monitor cancer progression over the course of treatment is a promising solution to post-treatment drug resistance often developed in melanoma patients. Non-invasive blood biomarker assays allow for regular dynamic monitoring of disease. "Liquid Biopsy" of blood, which exploits circulating tumor cells (CTCs), cell-free circulating tumor DNA (ctDNA) and cell-free circulating microRNA (cmiRNA), has been shown to detect prognostic factors for relapse in AJCC stage III and stage IV melanoma patients. Moreover, molecular characterization of CTC and analysis of various forms of ctDNA present promising potential in development of individualized therapy for melanoma patients. New approaches such as massive parallel sequencing (MPS) provide a comprehensive view of the disease progression, allowing for the selection of therapeutic options for individual patients. With advancements of improving molecular assays, liquid biopsy analysis as a powerful, routine clinical assay for melanoma patients, is highly promising prospective. PMID:26778792

  2. 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.

  3. 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.

  4. 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.

  5. Guiding the Killer and Bringing in Accomplices: Bispecific Antibody Treatment for Malignant Melanoma.

    Science.gov (United States)

    Szegezdi, Eva; Leverkus, Martin

    2016-02-01

    Discovery of oncogene and immune checkpoint targeting has transformed melanoma therapy in the last 5 years. However, treatment of primary or secondary drug-resistant melanoma remains a challenge. Agents designed to activate the cell death machinery directly, for example by activating the death receptors expressed by melanoma cells, could break drug resistance, and they may achieve long-lasting therapeutic success. He et al. report their studies of an MCSPxDR5 bispecific, tetravalent antibody that can simultaneously target death receptor 5 (DR5, TRAIL-R2) and melanoma-associated chondroitin sulfate proteoglycan (MCSP). This antibody can exert strong and selective DR5-dependent cytotoxic activity against MCSP-expressing melanoma cells. Crosslinking of the antibody with Fcγ-receptors increased the cytotoxic potential further, without compromising its selectivity. This approach offers a novel immunotherapeutic tool via coupling of three cooperating processes: delivering the death receptor agonist to the malignant cell population, potent activation of DR5-mediated cell death signaling, and recruitment of Fcγ-receptor-carrying immune cells that can mount an immune response against the tumor cells. PMID:26802233

  6. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells

    Directory of Open Access Journals (Sweden)

    Dettori Maria

    2007-01-01

    Full Text Available Abstract Background Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic activity on melanoma cells. We tested eugenol together with six natural and synthetic eugenol-related compounds for their capability to inhibit cell growth on primary melanoma cell lines established from patients' tissue samples. Results Eugenol and isoeugenol monomers and their respective O-methylated forms did not show to inhibit melanoma cells proliferation. Conversely, the dimeric forms (biphenyls showed some antiproliferative activity which was mild for dehydrodieugenol, higher for its O,O'-methylated form (O,O'-dimethyl-dehydrodieugenol, and markedly pronounced for the racemic mixture of the brominated biphenyl (6,6'-dibromo-dehydrodieugenol (S7, being its enantiomeric form (S the most effective compared to the other compounds. Such activity resulted to be selective against tumour cells, without affecting cultured normal human skin fibroblasts. Dose and time dependence curves have been obtained for the enantiomeric form S7-(S. Then IC50 and minimal effective doses and times have been established for the melanoma cell lines tested. TUNEL and phosphatidylserine exposure assays demonstrated the occurrence of apoptotic events associated with the antiproliferative activity of S7-(S. Cytotoxic activity and apoptosis induced by treating melanoma cells with eugenol-related biphenyls was partially dependent by caspase activation. Conclusion Our findings demonstrate that the eugenol related biphenyl (S-6,6'-dibromo-dehydrodieugenol elicits specific

  7. Regressing thin cutaneous malignant melanomas (< or = 1.0 mm) are associated with angiogenesis.

    OpenAIRE

    Barnhill, R. L.; Levy, M. A.

    1993-01-01

    In previous studies, we have shown that angiogenesis is often first noted in cutaneous malignant melanomas (CMMs) under 1.0 mm in thickness. Because angiogenesis may signal a more aggressive tumor phenotype, it is important to establish the circumstances associated with onset of angiogenesis. In the present study, we have quantified tumor vascularity in a series of CMMs under 1.0 mm in thickness and either associated with or lacking histologic regression. Microvessels were identified with the...

  8. Malignant melanomas of the nasal cavity after occupational exposure to formaldehyde.

    OpenAIRE

    Holmstrom, M.; Lund, V J

    1991-01-01

    Formaldehyde is a well known nasal carcinogen in rodents, but so far there has been no convincing evidence that workers occupationally exposed to formaldehyde have an increased risk of nasal cancer. In this study three cases of malignant melanoma of the nasal mucosa in persons occupationally exposed to formaldehyde for a long time are presented. The occurrence of such a rare tumour in patients with significant exposure to a known carcinogen warrants further investigation.

  9. A 60-Year-Old Man with Cerebral Metastasis of Malignant Melanoma of Left Sole

    OpenAIRE

    Abhisak Bhattacharjee; Nabir Hossain

    2016-01-01

    A 60-year-old man was diagnosed as a case of malignant melanoma on the left sole and received three cycles of neoadjuvant chemotherapy. Then local excision of the lesion was done. During preoperative diagnostic work-up, there were no features of metastases in lung, liver and bones. On the 3rd postoperative day he presented with right sided hemiparesis. After appearance of neurological features, computed tomography was done and it showed multiple cerebral metastases surrounded by brain edema i...

  10. Malignant melanoma of cervical and parotid lymph nodes with an unknown primary site

    OpenAIRE

    Nasri, S.; Namazie, A; Dulguerov, Pavel; Mickel, R

    1994-01-01

    Forty-six patients with malignant melanoma metastatic to cervical or parotid lymph nodes with an unknown primary site were treated at UCLA Medical Center from 1964 through 1991. Treatment consisted of parotidectomy and/or neck dissection with or without adjuvant therapy. The initial presentation was a cervical mass in 74% and a parotid mass in 26% of patients. Metastasis distal to the head and neck nodal basins developed in 22% of patients. Involvement of more than four cervical or parotid no...

  11. Pigmented Bowen’s Disease of the Genitalia Masquerading as Malignant Melanoma

    OpenAIRE

    Emel Öztürk Durmaz; Işın Doğan Ekici; Ferda Özkan; Sedef Şahin

    2015-01-01

    Abstract Pigmented Bowen’s disease is a rare subtype of in situ squamous cell carcinoma of the skin and mucosa, with a potential risk of invasion and metastasis. It is universally accepted that human papillomavirus (HPV) is the cause of genital Bowen’s disease. Herein we report an unusual case of pigmented Bowen’s disease of the genital area that clinically simulated malignant melanoma. Accurate diagnosis could only be established after histological examination. Polymerase chain reaction (PCR...

  12. 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......, therefore, essential to keep the morbidity and economic costs low, while keeping the quality of the procedure high....

  13. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells

    OpenAIRE

    Pisano, Marina; Pagnan, Gabriella; Loi, Monica; Mura, Maria Elena; Tilocca, Maria Giovanna; Palmieri, Giuseppe; Fabbri, Davide; Dettori, Maria Antonietta; Delogu, Giovanna; Ponzoni, Mirco; Rozzo, Carla Maria

    2007-01-01

    Background. Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic ac...

  14. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells

    OpenAIRE

    Pisano, Marina; Pagnan, Gabriella; Loi, Monica; Mura, Maria Elena; Tilocca, Maria Giovanna; Palmieri, Giuseppe; Fabbri, Davide; Dettori, Maria Antonietta; Delogu, Giovanna; Ponzoni, Mirco; Rozzo, Carla

    2007-01-01

    Background Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotoxic activi...

  15. Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells

    OpenAIRE

    Dettori Maria; Fabbri Davide; Palmieri Giuseppe; Tilocca Maria; Mura Maria; Loi Monica; Pagnan Gabriella; Pisano Marina; Delogu Giovanna; Ponzoni Mirco; Rozzo Carla

    2007-01-01

    Abstract Background Malignant melanoma is one of the most aggressive skin cancer and chemotherapeutic agents currently in use are still unsatisfactory. Prevention and early diagnosis are the only effective tools against this tumour whose incidence and mortality rates are highly increased during the last decades in fair skin populations. Therefore the search for novel therapeutic approaches is warranted. Aim of this work was to identify and test new compounds with antiproliferative and cytotox...

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

    International Nuclear Information System (INIS)

    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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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......-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......-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...

  18. Carborane compounds for neutron capture therapy of malignant melanoma

    International Nuclear Information System (INIS)

    The possibility of using thiouracil as a vehicle for stable nuclei such as 10B for neutron capture therapy (NCT) of melanoma was first discussed by Fairchild and co-workers in 1982. The author's research has been directed towards the design and synthesis of a number of o-carboranyl-thiouracils, the ten boron atoms of the carborane cage having a clear advantage for NCT. The first step was the preparation, previously reported, of thiouracils bearing an alkyl group continuing a triple bond for later elaboration to a carborane. The present paper describes the continuation of this work with the preparation of the carboranes of this series and its extension to the synthesis of a thiouracil in which a carboranylalkyl group is attached to the nitrogen in the 3-position

  19. Malignant melanoma in a grey horse: case presentation and review of equine melanoma treatment options

    OpenAIRE

    Metcalfe, Lucy VA; O’Brien, Peter J; Papakonstantinou, Stratos; Cahalan, Stephen D; McAllister, Hester; Duggan, Vivienne E

    2013-01-01

    A 15 year-old grey Thoroughbred gelding presented for investigation of chronic weight loss and recent onset of respiratory difficulty. Clinical examination confirmed tachypnoea with increased respiratory effort. Thoracic ultrasound examination detected pleural effusion. The dyspnoea was related to the large volume of pleural effusion and, following post-mortem examination, to the presence of a large mediastinal mass. Multiple pigmented masses, likely melanomas, were detected peri-anally. Thor...

  20. Primary Malignant Melanoma of the Ovary: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Nazlı DEMİR GÖK

    2011-05-01

    Full Text Available Ovarian malignant melanomas are extremely rare tumors. Most of them are secondary tumors and disseminated metastases are recognized at the time of diagnosis. Primary tumors are even more rare and usually associated with a teratoma. A 67-year-old female had a pelvic mass that was recognized on ultrasonography (USG and physical examination. Intraoperative pathological consultation was reported as “pigmented solid ovarian tumor, probably compatible with malignant melanoma”. Paraffin sections, and histochemical (Masson Fontana and Prussia blue and immunohistochemical examination (S-100 and HMB-45 were also consistent with “malignant melanoma”. This case was accepted as “Probably primary ovarian malignant melanoma” in lack of any other tumor focus on detailed clinical and radiological investigation, skin biopsies or pigmented lesions in medical history. It is reported for being an extremely rare tumor and its distinctive characteristics for differential diagnosis are emphasized.

  1. Prognostic factors and disease-specific survival among immigrants diagnosed with cutaneous malignant melanoma in Sweden.

    Science.gov (United States)

    Simberg-Danell, Caroline; Lyth, Johan; Månsson-Brahme, Eva; Frohm-Nilsson, Margareta; Carstensen, John; Hansson, Johan; Eriksson, Hanna

    2016-08-01

    Little is known about cutaneous malignant melanoma (CMM) among immigrants in Europe. We aimed to investigate clinical characteristics and disease-specific survival among first- and second-generation immigrants in Sweden. This nationwide population-based study included 27,235 patients from the Swedish Melanoma Register diagnosed with primary invasive CMM, 1990-2007. Data were linked to nationwide, population-based registers followed up through 2013. Logistic regression and Cox regression models were used to determine the association between immigrant status, stage and CMM prognosis, respectively. After adjustments for confounders, first generation immigrants from Southern Europe were associated with significantly more advanced stages of disease compared to Swedish-born patients [Stage II vs. I: Odds ratio (OR) = 2.37, 95% CI = 1.61-3.50. Stage III-IV vs I: OR = 2.40, 95% CI = 1.08-5.37]. The ORs of stage II-IV versus stage I disease were increased among men (OR = 1.9; 95% CI = 1.1-3.3; p = 0.020), and women (OR = 4.8; 95% CI = 2.6-9.1; p < 0.001) in a subgroup of immigrants from former Yugoslavia compared to Swedish-born patients. The CMM-specific survival was significantly decreased among women from former Yugoslavia versus Swedish-born women [hazard ratio (HR)=2.2; 95% CI = 1.1-4.2; p = 0.043]. After additional adjustments including stage, the survival difference was no longer significant. No survival difference between the second generation immigrant group and Swedish-born patients were observed. In conclusion, a worse CMM-specific survival in women from former Yugoslavia was associated with more advanced stages of CMM at diagnosis. Secondary prevention efforts focusing on specific groups may be needed to further improve the CMM prognosis. PMID:27004457

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

    Hirz, Manuela; Herden, Christiane

    2016-07-01

    The diagnosis of malignant melanoma can be difficult because these tumors can be amelanotic and may contain diverse variants and divergent differentiations, of which the signet-ring cell subtype is very rare and has only been described in humans, dogs, cats, and a hamster. We describe herein histopathologic and immunohistochemical approaches taken to diagnose a case of signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. A tumor within the abdominal skin of a 2-year-old cat was composed of signet-ring cells and irregularly interwoven streams of spindle cells. Both neoplastic cell types were periodic-acid-Schiff, Fontana, and Sudan black B negative. Signet-ring cells strongly expressed vimentin and S100 protein. Spindle cells strongly expressed vimentin and smooth muscle actin; some cells expressed S100, moderately neuron-specific enolase, and others variably actin and desmin. A few round cells expressed melan A, and a few plump spindle cells expressed melan A and PNL2, confirming the diagnosis of amelanotic signet-ring cell malignant melanoma with myofibroblastic differentiation in a cat. Differential diagnoses were excluded, including signet-ring cell forms of adenocarcinomas, lymphomas, liposarcomas, leiomyosarcomas, squamous cell carcinomas, basal cell carcinomas, and adnexal tumors. PMID:27154314

  4. 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

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

    International Nuclear Information System (INIS)

    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. 99mTc-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 99mTc-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 skiptype 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 confirmed

  6. Single sternal metastasis due to malignant melanoma with unexpected long-term survival: a case report

    Directory of Open Access Journals (Sweden)

    Gogakos AS

    2016-01-01

    Full Text Available Apostolos S Gogakos,1 Dimitrios Paliouras,1 Christos Asteriou,1 Thomas Rallis,1 Achilleas Lazopoulos,1 Fotios Chatzinikolaou,2 Athanassios Zissimopoulos,3 Drosos Tsavlis,4 Katerina Tsirgogianni,4 Konstantinos Zarogoulidis,4 Konstantinos Porpodis,4 Kosmas Tsakiridis,5 Georgia Pitsiou,4 Ioannis Kioumis,4 Ilias Karapantzos,6 Chrysanthi Karapantzou,6 Nikos Sachpekidis,5 Paul Zarogoulidis,4 Nikolaos Barbetakis1 1Thoracic Surgery Department, 2Department of Pathology, Theagenio Cancer Hospital, Thessaloniki, 3Nuclear Medicine Department, University General Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, 4Pulmonary Department – Oncology Unit, “G. Papanikolaou” General Hospital, Aristotle University of Thessaloniki, 5Cardiothoracic Surgery Department, 6Ear, Nose and Throat Department, “Saint Luke” Private Hospital, Panorama, Thessaloniki, Greece Abstract: Metastases from melanoma have a very poor prognosis for the patient. Single metastatic lesions in the sternum due to melanoma are extremely rare. A rare case of a presternal mass in a 56-year-old patient who had undergone excision for malignant melanoma is presented. Review of the patient’s history and surgical resection of a single metastatic soft tissue lesion offer the best chance of long-term survival. Keywords: melanoma, metastasis, chest wall, sternum

  7. 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.

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

    International Nuclear Information System (INIS)

    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 108 (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)

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

    International Nuclear Information System (INIS)

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

  10. Effect of ionizing radiation on receptor tyrosine kinases and p16 expression in human malignant melanoma cell lines

    International Nuclear Information System (INIS)

    Receptor tyrosine kinases (RTK) of subclass I are a group of cell surface receptors which upon binding of a ligand excert signal transduction processes. They are involved in the pathogenesis of different types of cancer, such as malignant melanoma or mammary carcinoma. p16, a cell cycle regulator has been shown to be a decisive tumor suppressor gene in human malignant melanoma. Since the effect of UV-radiation on melanoma cells has been demonstrated, a possible effect of ionizing radiation on the expression of RTK and p16 was studied in melanoma cell lines by Northern blot analysis and RT-PCR. The expression of the Epidermal Growth Factor Receptor, her2/neu and a human homologous exon of Xmrk, the causative oncogene in melanoma formation in the teleost fish Xiphophorus was studied in human malignant melanoma cell lines after exposure to 1 - 6 Gy of ionizing radiation (240 kV x-ray, FOD 40 cm, dose rate 1 Gy/min). It could be demonstrated that the expression levels of these RTK are upregulated after exposure to ionizing radiation, showing a maximum at 6 Gy for the Xmrk homologous exon and her2/neu whereas EGFR reached a maximum at 1 Gy. p16 expression is altered in a similar way by ionizing radiation. These data clearly indicate that oncogene and tumor suppressor gene expression are affected by ionizing radiation in melanoma cell lines, providing an explanation for the lack of radiosensitivity of many primary malignant melanomas and melanoma metastases. On the contrary, the upregulated RTK expression, e.g. the EGFR expression could be utilized for a targeted radiation-gene therapy

  11. [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

    2016-03-01

    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

  12. Radicality of initial surgery for primary malignant melanoma of the vagina.

    Science.gov (United States)

    Todo, Yukiharu; Okamoto, Kazuhira; Suzuki, Yoshihiro; Minobe, Shinichiro; Kato, Hidenori

    2016-04-01

    Radical surgery is considered not to improve the prognosis of primary malignant melanoma of the vagina (PMMV). This study was carried out to review the general consensus. A systematic review was performed on the basis of data from 10 patients in our cohort and 147 patients in the previous literature. The radicality of the initial surgery (RAINS) score was defined as the total number of points in terms of the resected organs. The target organs were the vagina, vulva, urethra, bladder, uterus, anus, rectum, pelvic lymph nodes, and inguinal lymph nodes. Overall survival (OS) according to the RAINS score was analyzed using the Kaplan-Meier method. Information on tumor stage, size, and depth of invasion was not obtained in 15, 47, and 43% of patients, respectively. The median follow-up period was 18 months. OS with a RAINS score of at least 7 was significantly longer than that with a RAINS score of up to 6 (median survival time, 41 vs. 19 months; log-rank test, P=0.037), despite the fact that the former group included significantly more patients with advanced-stage disease. A significant difference in OS was not found between patients with a RAINS score of at least 6 and up to 5. The therapeutic significance of radical surgery for PMMV has not been assessed appropriately in previous studies because of the lack of comparability among groups and differences in the definitions of surgical radicality. Patients with PMMV might benefit from initial surgery with appropriate surgical radicality, despite incomplete validation of the RAINS score. PMID:26825038

  13. An uncommon presentation and course of metastatic malignant melanoma: a case report

    Directory of Open Access Journals (Sweden)

    Dalhaug Astrid

    2007-11-01

    Full Text Available Abstract Most patients with brain metastases from malignant melanoma are diagnosed after treatment for known extracranial metastases and have a poor outcome despite various local and systemic therapeutic approaches. Here we discuss an unusual case where a 45-year old patient presented with a brain metastasis as the first symptom of disease and where the presumed primary lesion later was found in the gastro-intestinal tract. Treatment consisted of sequential surgical removal of a total of 4 tumor sites (2 extracranially, whole-brain radiotherapy and two radiosurgery procedures within 13 months. Following her last treatment, the patient has now been in remission for 20 months. This case illustrates that some patients with multi-organ melanoma manifestations may benefit from the repeated use of effective local therapeutic approaches and may experience a quite favourable prognosis.

  14. 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.

  15. N-isopropyl-p-I-123-Iodoamphetamine is a sensitive test for detecting malignant melanoma

    International Nuclear Information System (INIS)

    N-isopropyl-p-I-123-Iodoamphetamine (I-123-IMP) was originally developed for the measurement of the brain blood flow. I-123-IMP is known to be incorporated into melanin-producing cells suggesting that I-123-IMP is incorporated in malignant melnoma. We tested both I-123-IMP and Ga-67 citrate in 36 cases with malignant melanoma in order to compare their clinical utility in the same patients. Of the 22 primary lesions, 11 (50%) were detected by I-123-IMP scan, but only 6 (22.7%) were detected by Ga-67 citrate scan. Of the 28 metastatic lesions, 15 (53.6%) were detected by I-123-IMP scan, but only 13 (46.4%) were detected by Ga-67 citrate scan. Among the I-123-IMP scans, there were no false positive cases, but Ga-67 citrate detected post operative lesions. In conclusion, I-123 IMP has advantages in the detection of malignant melanoma in terms of sensitivity and specificity. (author)

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

    International Nuclear Information System (INIS)

    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

  17. 〈Case Reports〉Pigmented Bowen's disease of the palm mimicking malignant melanoma: report of a case

    OpenAIRE

    Yoshida, Masuki; Kawada, Akira

    2013-01-01

    [Abstract] A variety of cutaneous lesions may clinically simulate malignant melanoma, including Bowen's disease, which is a squamous cell carcinoma in situ that typically presents as a scaly pink to erythematous patch or plaque. On rare occasions, the lesion is pigmented and may resemble seborrheic keratosis, actinic keratosis, basal cell carcinoma, atypical nevus, or melanoma, and the correct diagnosis is suggested by dermatoscopy. We report an unusual case of pigmented Bowen's disease of th...

  18. Increased selective 10B-uptake by malignant melanoma using systemic administration of 10B1-BPA·fructose complex

    International Nuclear Information System (INIS)

    10B1-para-Boronophenylalanine (10B1-BPA) has selective affinity for malignant melanoma. In the authors' first human case, they succeeded in obtaining complete regression of a metastatic subcutaneous melanoma lesion by neutron capture therapy (NCT) using distant perilesional injections of 10B1-BPA hydrochloride. Furthermore, they have cured primary cutaneous melanoma lesions of various types in 5 additional patients by single or one repeated NCT using a combination of oral administration, subcutaneous and distant perilesional injections of 10B1-BPA·fructose complex at around pH 7.4. They have been pursuing NCT using increased systemic administration of 10B1-BPA, which can lead to cure of multiple (widely-distributed) melanoma lesions. In this study, they analyzed boron dynamics in melanoma, skin and blood in tumor-bearing hamsters and a human patient after intravenous (i.v.) or subcutaneous (s.c.) injection of 10B1-BPA·fructose complex

  19. [The cellular immunity indices of patients with malignant melanoma using the viral immunomodulator rigvir].

    Science.gov (United States)

    Glinkina, L S; Bruvere, R Zh; Venskus, D R; Garklava, R R; Muceniece, A J

    1992-01-01

    The effect of rigvir, an immunomodulator of the viral origin, on cell-mediated immunity was studied in patients with skin malignant melanoma. Rosette formation and monoclonal antibody techniques were used to measure blood immunocompetent cell levels in patients with the above pathology, cases of benign skin tumors and healthy subjects. Rigvir was shown to influence natural resistance by raising blood monocyte and large granule-containing lymphocyte levels. It potentiated recruitment of pre-T-lymphocytes and young active T-lymphocytes to the peripheral blood. PMID:1300752

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    presented a 10 cm rapidly growing mass in her right axilla. The mass in the axilla measured 12.5 ΄ 9 ΄ cm. It revealed a lymph node metastases with a tumor growth composed of two different contiguous morphological and immunohistochemical components, respectively, melanosomes and leiomyosarcoma. The...... 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...

  1. In-situ hybridization based quantification of hTR: a possible biomarker in malignant melanoma

    DEFF Research Database (Denmark)

    Vagner, Josephine; Steiniche, Torben; Stougaard, Magnus

    2015-01-01

    Aims Telomerase is reactivated in most cancers and there is accumulating evidence for it being a driver event in malignant melanoma (MM). Thus, our aim was to evaluate if in situ hybridisation (ISH)-based quantification of the telomerase RNA (hTR) could be used to distinguish MM from nevi and if...... the Breslow thickness suggesting that hTR might be a valuable biomarker in MM. Furthermore, as ISH-based detection requires presence of both hTR and the reverse transcriptase (hTERT) it might be an indicator of active telomerase and thus have future relevance as a predictive biomarker for anti-telomerase...

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

    International Nuclear Information System (INIS)

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

  3. BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs

    Directory of Open Access Journals (Sweden)

    Carbone Michele

    2012-08-01

    Full Text Available Abstract Background BRCA1–associated protein 1 (BAP1 is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W with germline BAP1 mutations and increased risk of malignant mesothelioma. Methods Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ2 test or two-tailed Fisher’s exact test. Results Melanocytic tumors: of the five members of the L family studied, four (80% carried a germline BAP1 mutation (p.Gln684* and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48 and four of them (57% presented one or more atypical melanocytic tumors, that we propose to call “melanocytic BAP1-mutated atypical intradermal tumors” (MBAITs. Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001. Conclusions Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a

  4. 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.

  5. 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.

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

    DEFF Research Database (Denmark)

    Nyholm, Anne Marie; Lerche, Catharina M; Manfé, Valentina; Biskup, Edyta; Johansen, Peter; Morling, Niels; Thomsen, Birthe Mørk; Glud, Martin; Gniadecki, Robert

    2014-01-01

    of lymph node metastasis in cutaneous malignant melanoma. Our goal was therefore to further examine this theory. METHODS: We used in-situ-hybridization to visualise miR-125b expression in primary tumours and in lymph node metastasis. Then using a miRVector plasmid containing a miR-125b-1 insert we...... 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...

  7. 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.

  8. The Non-Coding RNA Llme23 Drives the Malignant Property of Human Melanoma Cells

    Institute of Scientific and Technical Information of China (English)

    Chuan-Fang Wu; Guang-Hong Tan; Cheng-Chuan Ma; Ling Li

    2013-01-01

    Several lines of evidence support the notion that increased RNA-binding ability of polypyrimidine tract-binding (PTB) proteinassociated splicing factor (PSF) and aberrant expression of long non-coding RNAs (lncRNAs) are associated with mouse and human tumors.To identify the PSF-binding IncRNA involved in human oncogenesis,we screened a nuclear RNA repertoire of human melanoma cell line,YUSAC,through RNA-SELEX affinity chromatography.A previously unreported lncRNA,termed as Lime23,was found to bind immobilized PSF resin.The specific binding of Llme23 to both recombinant and native PSF protein was confirmed in vitro and in vivo.The expression of PSF-binding Llme23 is exclusively detected in human melanoma lines.Knocking down Lime23 remarkably suppressed the malignant property of YUSAC cells,accompanied by the repressed expression of proto-oncogene Rab23.These results may indicate that Llme23 can function as an oncogenic RNA and directly associate the PSF-binding IncRNA with human melanoma.

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

    OpenAIRE

    Shen, Weidong; Sakamoto, Naoko; Yang, Limin

    2016-01-01

    Background The objectives of this study were to evaluate and model the probability of melanoma-specific death and competing causes of death for patients with melanoma by competing risk analysis, and to build competing risk nomograms to provide individualized and accurate predictive tools. Methods Melanoma data were obtained from the Surveillance Epidemiology and End Results program. All patients diagnosed with primary non-metastatic melanoma during the years 2004–2007 were potentially eligibl...

  10. 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.

  11. Photodynamic therapy of advanced malignant tumors

    Science.gov (United States)

    Wang, Lian-xing; Dai, Lu-pin; Lu, Wen-qin

    1993-03-01

    Forty patients with advanced tumors were treated by photodynamic therapy (PDT) from May 1991 to August 1991 in our hospital with age ranges from 30 to 81 years old. The pathological diagnosis shows that 13 had tumors in the colon, 3 in the stomach, 2 in the oesophageal, 2 in the palatum, 1 in the cervix, and 19 others with malignant cancers of the skin. The histology was as follows: squamous cell in 20, adenocarcinoma in 19, melanocarcinoma in 1. By TNM classification there were no cases of T1, 5 cases of T2, and 35 cases of T2 - T3. All patients were stage IV. The overall effective rate was 85%, our experience is that the PDT is suitable for the patients with advanced tumor, especially those whose tumor recurrences are hard to treat after conventional treatment (surgery, radiotherapy, chemotherapy). The PDT appears to be a new and promising possibility to treat advanced tumors and to improve the patients' survival rates.

  12. [Human recombinant leukocyte interferon alpha-2-A in 22 cases of metastatic malignant melanoma].

    Science.gov (United States)

    Maral, J; Steinberg, M; Weil, M; Chleq, C; Khayat, D; Banzet, P; Jacquillat, C

    1987-06-01

    Twenty-two patients with metastatic malignant melanoma received either 36 X 10(6) U (15 patients) or 18 X 10(6) U (7 patients) of human recombinant interferon alpha-2-A daily for 3 months by the intramuscular route, with progressive increase of dosage. This was followed in responders by a maintenance treatment consisting of 3 intramuscular injections per week in the same doses as those received at the end of the induction treatment. Out of 18 patients assessable for effectiveness, 1 had complete remission (7 months +) and 3 had partial response (52,61 and 82 days respectively), an overall improvement rate of 22%. The main side-effects observed were: pseudoinfluenza syndrome (100%), fatigue (100%), somnolence (95%), anorexia (90%) and haematological disorders. Dosage reduction was necessary in 13 of the 15 patients receiving 36 MU. This study shows that human recombinant interferon alpha-2-A has antitumoral activity in metastatic malignant melanoma. Other studies, notably with therapeutic combinations, are needed to determine the optimal dosage regimen of the drug and to increase its effectiveness. PMID:2955323

  13. Prognostic Significance of CD169+ Lymph Node Sinus Macrophages in Patients with Malignant Melanoma.

    Science.gov (United States)

    Saito, Yoichi; Ohnishi, Koji; Miyashita, Azusa; Nakahara, Satoshi; Fujiwara, Yukio; Horlad, Hasita; Motoshima, Takanobu; Fukushima, Satoshi; Jinnin, Masatoshi; Ihn, Hironobu; Takeya, Motohiro; Komohara, Yoshihiro

    2015-12-01

    CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169(+) macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169(+) macrophages in patients with malignant melanoma, we evaluated tissue samples from 93 patients to investigate CD169 expression in regional lymph nodes (RLN) and determine the relationship of this expression with overall survival and various clinicopathologic factors. Higher densities of CD169(+) cells were significantly associated with longer overall survival (P = 0.001). A multivariate analysis showed that the density of CD169(+) cells was an independent prognostic factor, with higher densities correlating with higher density of CD8(+) cytotoxic T cells within tumor sites. High CD169 expression in macrophages could be stimulated by IFNα in vitro, and in RLNs, IFNα-producing macrophages and CD303(+) plasmacytoid dendritic cells were identified surrounding CD169(+) macrophages. These data suggest that IFNα-stimulated CD169(+) macrophages in RLNs are closely involved in T-cell-mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma. PMID:26297710

  14. Chemokine Receptor CXCR4 Is a Novel Marker for the Progression of Cutaneous Malignant Melanomas

    International Nuclear Information System (INIS)

    The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis

  15. Apoptotic effect and mechanisms of AHPN on human skin malignant melanoma cell A375

    Institute of Scientific and Technical Information of China (English)

    Min Pan; Zhenhui Peng; Shengxiang Xiao; Jianwen Ren; Yan Liu; Xiaoli Li; Zhengxiao Li

    2008-01-01

    Objective: To study apoptotic effects of synthetic retinoic acid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalene carboxylic acid(AHPN) on human skin malignant melanoma A375 cells in comparison with the natural iigand all-trans-retinoic acid(ATRA) in vitro and the mechanisms related to the actions of AHPN. Methods:MTT assay was used to determine the anti-proliferative effects of AHPN and ATRA on A375 cells. Flow cytometry was performed to investigate the influence of AHPN and ATRA on cell cycle and cell apoptosis. In addition, transfection and luciferase activity assays were employed to explore the mechanisms of how AHPN executes its proapoptotic function. Results:Firstly, AHPN promoted apoptosis and G1 arrest in A375 cells compared with ATRA. Secondly, the activity of NF-kB in A375 cells treated with AHPN increased 2-3 times compared with solvent DMSO treatment. Conelusion:AHPN,in comparison with ATRA, is a more effective alternative for therapy of malignant melanoma. The potentially proapoptotic function of AHPN requires activation of NF-kB.

  16. 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. PMID:27276060

  17. 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.

  18. Management of intestinal obstruction in advanced malignancy

    Directory of Open Access Journals (Sweden)

    Henry John Murray Ferguson

    2015-09-01

    Full Text Available Patients with incurable, advanced abdominal or pelvic malignancy often present to acute surgical departments with symptoms and signs of intestinal obstruction. It is rare for bowel strangulation to occur in these presentations, and spontaneous resolution often occurs, so the luxury of time should be afforded while decisions are made regarding surgery. Cross-sectional imaging is valuable in determining the underlying mechanism and pathology. The majority of these patients will not be suitable for an operation, and will be best managed in conjunction with a palliative medicine team. Surgeons require a good working knowledge of the mechanisms of action of anti-emetics, anti-secretories and analgesics to tailor early management to individual patients, while decisions regarding potential surgery are made. Deciding if and when to perform operative intervention in this group is complex, and fraught with both technical and emotional challenges. Surgery in this group is highly morbid, with no current evidence available concerning quality of life following surgery. The limited evidence concerning operative strategy suggests that resection and primary anastomosis results in improved survival, over bypass or stoma formation. Realistic prognostication and involvement of the patient, care-givers and the multidisciplinary team in treatment decisions is mandatory if optimum outcomes are to be achieved.

  19. Histological study of choroidal malignant melanoma treated by carbon ion radiotherapy

    International Nuclear Information System (INIS)

    The purpose of this study was to report, we believe for the first time, a histological study of choroidal malignant melanoma treated by carbon ion beam radiotherapy. A 75-year-old Japanese man was diagnosed as having a choroidal melanoma after undergoing magnetic resonance imaging (MRI). Positron emission tomography (PET) revealed a hot spot in the same location as the intraocular mass seen in MRI. Carbon ion radiotherapy was performed with a total dose of 77 Gy, and the hot spot seen by PET disappeared completely. At 15 months after carbon ion therapy, the eye had to be enucleated because of uncontrollable ocular hypertension. It was examined histologically in serial sections. A large tumor mass (15 x 12 mm) with high pigmentation was found in the vitreous space. Almost all tumor cells showed necrosis in every section. A small number of intact tumor cells were present at the periphery. The overlying retina did not show any necrosis, but showed mild to moderate gliosis. No intraretinal hemorrhage, lipid deposit, or protein exudate was apparent. Almost all tumor cells showed necrosis after radiotherapy with a carbon ion beam. However, the effect on the adjacent tissues was determined as minimal in histological analysis. (author)

  20. In vitro incorporation of boronophenylalanine by amelanotic and melanotic murine and human malignant melanoma cell lines

    International Nuclear Information System (INIS)

    Pelleted cells were irradiated as previously described, following a 20 h incubation in RPM1 1640 medium, in the presence or absence of 10μg/ml D,L-paraboronophenylalanine hydrochloride (10B1-BPA.HCl). Thermal neutrons were derived from Moata, a 100-kW Argonaut-type light water reactor. The neutron flux was 2.6 x 109 n/cm2/s, dose rate 3.7 Gy/h (n+γ) and the dose range 0.6 - 0.8 Gy. Cells were plated onto X-irradiated feeder layers in triplicate in 25cm2 Falcon flasks and colonies counted after 11-12 days. No differences in thermal neutron radiosensitivity were observed for two amelanotic cell lines. A small but significant difference was observed for the melanotic cell line (418) grown in the presence or absence of BPA. Subsequent experiments showed that the uptake of boron was low in the B16 murine malignant melanoma cell line cultured in the presence of BPA. It was therefore necessary to investigate the boron uptake and incorporation in melanoma cells by increasing the BPA concentration, increasing melanization using different variants of the B16 cell lines, and alternative methods of cell layer detachment

  1. HIGH DOSE FRACTION RADIOTHERAPY FOR MUCOSAL MALIGNANT MELANOMA OF THE HEAD AND NECK

    Institute of Scientific and Technical Information of China (English)

    Liu Xiuying; Li Huiling; Zheng Tianrong; Lin Xiangsong

    1998-01-01

    Objective:To evatuate the results of high dose fraction radiotherapy for mucosal malignant melanoma of the head and neck (HNMM). Methods: From 1984-1994, 35 patients with HNMM were enrolled in this study. Among them, 27 cases localized to the nasal cavity or para-nasal sinus, 8 to the oral cavity. All patients received high dose fraction radiotherapy (6--8 Gy/fraction)with the total dose ranged from 40 to 60 Gy. Results: The minimum follow-up was 2 years (ranged 2-7 years). The overall 3- and 5-year survival rate was 45.7% and 24%,respectively. Conclusion: High dose fraction radiotherapy is effective for local control of HNMM.

  2. 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...... findings 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....

  3. HER4 and its cytoplasmic isoforms are associated with progression-free survival of malignant melanoma

    DEFF Research Database (Denmark)

    Nielsen, Trine O; Poulsen, Steen Seier; Journe, Fabrice;

    2014-01-01

    RNA quantification was carried out of all four EGF receptors (EGFR, HER2, HER3, and HER4) and the HER4 cytoplasmic isoforms in lymph node metastases from patients with malignant melanoma. We related their expression to progression of the disease. HER4 expression was found to be an indicator of short progression......-free survival (P=0.0340). Interestingly, of the two cytoplasmic splice variants of HER4, the association of CYT1 (P=0.0176) with progression-free survival was more pronounced than that for CYT2 (P=0.0458). Also, HER3 was associated with progression-free survival (P=0.0169), whereas no association was found for...

  4. Phase II study of low-dose recombinant leukocyte A interferon in disseminated malignant melanoma.

    Science.gov (United States)

    Creagan, E T; Ahmann, D L; Green, S J; Long, H J; Frytak, S; O'Fallon, J R; Itri, L M

    1984-09-01

    Thirty patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 12 X 10(6) U/m2, three times weekly for a planned treatment duration of three months. This dose was selected in view of our prior phase II data indicating that 50 X 10(6) U/m2 three times weekly produced excessive toxicity. In this current trial we observed three objective partial regressions (20%) among the 15 better-risk patients (performance score 0, 1, and no prior chemotherapy) with times to disease progression of 1.9, 9.6, and 12.9+ months. There were also three regressions (one complete and two partial) among the 15 poor-risk patients (performance score 2, 3, or prior chemotherapy) with progression times of 3, 3.2, and 9.6+ months. For all patients, the median survival time was 4.2 months. One half of the patients were observed to have progressive disease within one month of commencing treatment. Responding metastatic lesions were limited to soft tissue, although one patient also had a partial response of a lung nodule. The most substantial toxicities were moderate-to-severe myalgias (27%), nausea (33%), anorexia (47%), and fatigue (50%). Among the 22 patients with weight loss, the median was 2.3 kg (range, 0.6 to 8.4 kg). Hematologic and hepatic toxicity was transient and of little clinical significance. Our study indicates that rIFN-alpha A in the dose and schedule that we used is clinically tolerable and has antitumor activity in malignant melanoma. The response rate was similar to results observed in our previous study of a higher dose regimen. PMID:6470751

  5. Radiosensitivity of human malignant melanomas evaluated by cytokinesis- block micronucleus assay

    International Nuclear Information System (INIS)

    Cytokinesis-block micronucleus assay (CB-MNA) was applied for comparison of radiation sensitivity of 25 human malignant melanomas in primary culture. Cells obtained from tumor specimens were irradiated (0-4 Gy) in dishes, incubated with cytochalasin B (2 μg . cm-3) to block cytokinesis, stained in situ and micronuclei (MN) scored in bi-nucleate cells (BNC). Proportions of BNC in nonirradiated controls after fixed time of incubation (96 h) ranged from (2.3 to 38% indicating great differences (C.V. = 74%) in proliferative activity among tumors evaluated. No correlation was observed between proliferative activity and susceptibility of cells to induction of MN by radiation. The great inter-tumor heterogeneity was observed in repeat in respect of radiation sensitivity expressed either as normalized (Net) frequency (Fq) of BNC with MN or as number of MN per BNC. Both endpoints differed widely at 2 Gy and 4 Gy as well (NetFqBNC with MN = 0.28-25.4% or 1.5-45% and MN/BNC = 0.004-0.309 or 0.013-0.593 respectively at 2 Gy and 4 Gy) with coefficients of ranging from 44 to 57%. Extreme difference in MN frequency was also observed between one primary tumor and its metastasis indicating intra-tumor heterogeneity. Our results suggest that CB-MNA may contribute some clinically useful information for discriminating tumors that will eventually respond to radiotherapy and those that will probably not. However, studies aimed at comparison of MN induction in vitro with clinical radio-responsiveness of malignant melanomas are urgently required. (author)

  6. 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.

  7. The DEAD/DEAH box helicase, DDX11, is essential for the survival of advanced melanomas

    Directory of Open Access Journals (Sweden)

    Bhattacharya Chitralekha

    2012-11-01

    Full Text Available Abstract Background Despite continuous efforts to identify genes that are pivotal regulators of advanced melanoma and closely related to it, to determine which of these genes have to be blocked in their function to keep this highly aggressive disease in check, it is far from clear which molecular pathway(s and specific genes therein, is the Achilles’ heel of primary and metastatic melanoma. In this report, we present data, which document that the DEAD-box helicase DDX11, which is required for sister chromatid cohesion, is a crucial gatekeeper for melanoma cell survival. Methods Performing immunohistochemistry and immunoblot analysis, we determined expression of DDX11 in melanoma tissues and cell lines. Following transfection of melanoma cells with a DDX11-specific siRNA, we conducted a qPCR analysis to determine downregulation of DDX11 in the transfected melanoma cells. In subsequent studies, which focused upon an analysis of fluorescently labeled as well as Giesma-stained chromosome spreads, a proliferation analysis and apoptosis assays, we determined the impact of suppressing DDX11 expression on melanoma cells representing advanced melanoma. Result The findings of the study presented herein document that DDX11 is upregulated with progression from noninvasive to invasive melanoma, and that it is expressed at high levels in advanced melanoma. Furthermore, and equally important, we demonstrate that blocking the expression of DDX11 leads not only to inhibition of melanoma cell proliferation and severe defects in chromosome segregation, but also drives melanoma cells rapidly into massive apoptosis. Conclusion To date, little is known as to whether helicases play a role in melanoma development and specifically, in the progression from early to advanced melanoma. In this report, we show that the helicase DDX11 is expressed at high levels in primary and metastatic melanoma, and that interfering with its expression leads to severe chromosome

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

    International Nuclear Information System (INIS)

    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, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both 18F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that 18F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging. (orig.)

  9. 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; Rabøl, A; Jensen, M; Holm, S; Sørensen, S S; Drzewiecki, K T; Højgaard, L; Friberg, L

    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 pa...... method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. 18F-FDG PET is useful as a supplement to clinical examination in melanoma staging.......-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......, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With 18F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100...

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

    Energy Technology Data Exchange (ETDEWEB)

    Eigtved, A. [Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital (Denmark); PET and Cyclotron Unit, Rigshospitalet, Copenhagen University Hospital, Copenhagen (Denmark); Andersson, A.P.; Dahlstroem, K.; Drzewiecki, K.T. [Dept. of Plastic and Reconstructive Surgery, Rigshospitalet, Copenhagen University Hospital (Denmark); Raboel, A.; Jensen, M.; Holm, S.; Soerensen, S.S.; Hoejgaard, L.; Friberg, L. [Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Rigshospitalet, Copenhagen University Hospital (Denmark)

    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 ({sup 18}F-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, ultrasound, radiography, and liver function tests and histology or clinical follow-up. With {sup 18}F-FDG PET we found for all foci a sensitivity of 97% and a specificity of 56%, compared with 62% and 22%, respectively, when using routine methods. For intra-abdominal foci, the sensitivity and specificity were 100% for both {sup 18}F-FDG PET and routine methods. Corresponding figures for pulmonary/intrathoracic foci were 100% and 33%, respectively. Of the patients included in this study, 34% would not have been staged correctly by conventional methods alone. We conclude from this study that {sup 18}F-FDG PET is a sensitive method superior to conventional methods for detecting widespread metastases from malignant melanoma. Mutilating surgery of no benefit can thereby be avoided. {sup 18}F-FDG PET is useful as a supplement to clinical examination in melanoma staging. (orig.)

  11. Radiofrequency hyperthermia for advanced malignant liver tumors

    International Nuclear Information System (INIS)

    Purpose: To evaluate thermometry and the clinical results of radiofrequency (RF) thermotherapy for advanced malignant liver tumors. Materials and Methods One-hundred and seventy-three patients with malignant liver tumors treated between 1983 and 1995 underwent hyperthermia. Surgery were contraindicated in all patients. The 173 tumors consisted of 114 hepatocellular carcinomas(HCCs), and 59 non-HCCs(45 metastatic liver tumors and 12 cholangiocarcinomas). Eight MHz RF capacitive heating equipment was used for hyperthermia. Two opposing 25-cm or 30-cm electrodes were generally used for heating liver tumors. Our standard protocol was to administer hyperthermia 40-50 minutes twice a week to a total of 8 sessions. Temperature of the liver tumor was measured by microthermocouples. In each patient, a single catheter was inserted into the liver tumor through the normal liver. Transcatheter arterial embolization, radiotherapy, immunotherapy, and chemotherapy were combined with hyperthermia depending on the patient's liver function and tumor location. The therapeutic efficacy was evaluated by the change in tumor size assessed by computed tomography (CT) three or four months after the completion of treatment. Results One-hundred and forty (81%) of 173 patients underwent hyperthermia more than 4 times. Thermometry could be performed in 77(55%) of these 140 patients. Neither systolic nor diastolic blood pressure changed significantly after hyperthermia. However, pulse rate significantly increased from 82.8 ± 1.1 to 96.5 ± 1.3 beats/min. Only 21 patients (11%) showed a decrease in pulse rate after hyperthermia. Body temperature increased from 36.3 ±0.1 to 37.4±0.2 after hyperthermia. Sequelae of hyperthermia included focal fat burning in 20 (12%), gastric ulceration in 4 (2%), and liver necrosis in 1(1%). Sequelae of thermometry were severe peritoneal pain in 7 (11%), intraperitoneal hematoma in 1(1%), and pneumothorax in one (1%) patient. The maximal tumor temperature

  12. 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.

  13. Radionuclide method of research of a condition of sentinel lymph nodes at malignant tumors of a mammary gland and melanoma

    International Nuclear Information System (INIS)

    Radionuclide method of research of a condition of sentinel lymph nodes at malignant tumors of a mam-mary gland and melanoma. The basic theoretical thesis's about the importance of researches of sentinel lymph nodes with use of intraoperative gamma detection are given in article. Techniques of a lymphoscintigraphy and radionuclide detection by means of a radiocolloid are described. Results of own researches, namely - carrying out lymphoscintigraphy and radio-nuclide detection at 196 patients with a melanoma and at 43 - with a cancer of a mammary gland are analyzed

  14. Cure of malignant melanoma by single thermal neutron capture treatment using melanoma-seeking compounds: 10B/melanogenesis interaction to in vitro/in vivo radiobiological analysis to preclinical studies

    International Nuclear Information System (INIS)

    This paper discusses the synthesis of new tumor-seeking 10B-compounds which possess selective affinity for the specific metabolic activity of the target cancer cells. Since not only malignant melanomas but also many kinds of human cancers, for example thyroid cancer and squamous cell carcinoma, synthesize their specific protein, the aim is to establish selective thermal neutron capture treatment of malignant melanoma as a prototype of such cancer cells

  15. There's no such thing as a healthy glow: cutaneous malignant melanoma--the case against suntanning.

    Science.gov (United States)

    McPhail, G

    1997-06-01

    One of the objectives of the 1992 United Kingdom Government White Paper 'Health of the Nation', is to reduce ill health and death caused by skin cancers by the year 2005. The Europe Against Cancer Programme shares those aims for the entire European population. Skin cancer was the first cancer demonstrated to have a chemical cause, with Percival Pott's 1775 description of squamous cell carcinoma of the scrotum induced by chimney soot, and skin cancers were also the first to be linked with ionising radiation. Currently there is a general consensus amongst researchers which acknowledges solar ultraviolet radiation as the major carcinogenic agent for the development of skin cancers. Changing attitudes and lifestyles affecting sun exposure is deemed responsible for the upward trends in incidence and mortality from skin cancers. The recognition of skin cancer as a preventable malignancy has implications for the health promotion role of nurses and of their multidisciplinary colleagues throughout Europe. This paper reviews the literature relating to sunlight as a risk factor for cutaneous malignant melanoma, and considers the behavioural issues which need to be addressed by healthcare professionals generally, and by nurses specifically, when establishing or participating in health promotion initiatives. PMID:9233166

  16. MGMT gene promoter methylation in malignant melanoma patients%恶性黑色素瘤患者MGMT基因启动子甲基化研究

    Institute of Scientific and Technical Information of China (English)

    于玮玮; 俎明; 李强; 郭军; 孔燕; 代杰; 迟志宏; 斯璐; 崔传亮; 盛锡楠; 李思明; 毛丽丽

    2011-01-01

    Objective This study was designed to investigate the association of MGMT promoter methylation and MGMT protein expression in Chinese malignant melanoma patients.Methods We analyzed the MGMT promoter methylation by methylation-specific polymerase chain reaction (MS-PCR) and protein expression by immunohistochemistry (IHC) in 44 malignant melanoma cases.Results We found that MGMT promoter hypermethylation occurred in 18 of 44 (40.9% ) cases, MGMT protein expression rate of MGMT promoter methylation patients was 27.8% (5/18) and MGMT protein expression rate of MGMT promoter unmethylation patients was 65.4% (17/26).The presence of hypermethylation was associated with loss of MGMT protein (P = 0.014).Conclusion In the advanced malignant melanoma MGMT promoter methylation may reduce MGMT protein expression;the examination of MGMT promoter methylation status in melanoma may be useful for stratefying patients with melanoma into suitable chemotherapy such as alkylating agents, and offer theoretical and practical basis to personalized treatments.%目的 分析中国恶性黑色素瘤患者MGMT启动子甲基化水平和蛋白表达的关系.方法 通过MS-PCR方法检测44例恶性黑色素瘤患者MGMT启动子甲基化水平,免疫组化法检测MGMT蛋白的表达.结果 44例恶性黑色素瘤患者的MGMT启动子甲基化率为40.9%(18/44),MGMT启动子甲基化患者的MGMT蛋白表达率为27.8%(5/18),非甲基化患者的MGMT蛋白表达率为65.4%(17/26),MGMT启动子甲基化与MGMT蛋白的低表达有相关性(P=0.014).结论 在晚期恶性黑色素瘤中MGMT启动子甲基化可能降低MGMT蛋白的表达,提示可以通过分析晚期黑色素瘤患者MGMT基因启动子甲基化状态,预测患者对烷化剂类药物的敏感性,为实现个体化治疗提供理论和实践依据.

  17. Characterization of melanoma associated spongiform scleropathy

    DEFF Research Database (Denmark)

    Alyahya, Ghassan Ayish Jabur; Heegaard, Steffen; Prause, J.U.

    ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology......ophthalmology, melanoma associated spongiform scleropathy (MASS), MASS, malignant uveal melanoma, sclera, ciliary body, choroid, histopathology...

  18. Melanoma

    Science.gov (United States)

    ... may be melanoma is the ABCDE checklist: A – Asymmetry: One half of the mole does not look ... 276. PMID: 16050450. Last Updated: 12 Feb 2009 Information for other ages: Table of Contents: Overview Who's ...

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

    International Nuclear Information System (INIS)

    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

  20. Increased frequency of minimal homozygous deletions is associated with poor prognosis in primary malignant melanoma patients.

    Science.gov (United States)

    Boi, Sebastiana; Tebaldi, Toma; Re, Angela; Cantaloni, Chiara; Adami, Valentina; Barbareschi, Mattia; Cristofolini, Mario; Pasini, Luigi; Quattrone, Alessandro

    2014-06-01

    Identification of prognostic melanoma-associated copy number alterations (CNAs) is still an area of active research. Here, we investigated by high-resolution array comparative genomic hybridization (aCGH) a cohort of 31 paraffin-preserved primary malignant melanomas (MMs), whose prognosis was not predictable on the basis of conventional histopathological parameters. Although we identified a variety of highly recurrent sites of genomic lesions, the total number of CNAs per patient was not a discriminator of MM outcome. Furthermore, validation of aCGH by quantitative PCR on an extended population of 65 MM samples confirmed the absence of predictive value for the most recurrent CNA loci. Instead, our analysis revealed specific prognostic potential of the frequency of homozygous deletions (representing less than 3% of the total CNAs on average per sample), which was strongly associated with sentinel lymph node (SLN) invasion (P = 0.003), and distant metastasis (P = 0.003). Increased number of homozygous deletions was also indicative of poor patient survival (P = 0.01), both in our samples and in an independent validation of public dataset of primary and metastatic MMs. Moreover, we identified 77 hotspots of minimal common homozygous deletions, enriched in genes involved in cell adhesion processes and cell-communication functions, which preferentially accumulated in primary MMs showing the most severe outcome. Therefore, specific loss of gene loci in regions of minimal homozygous deletion may represent a pivotal type of genomic alteration accumulating during MM progression with potential prognostic implication. PMID:24615732

  1. Effective local control of malignant melanoma by intratumoural injection of a beta-emitting radionuclide

    International Nuclear Information System (INIS)

    tumours demonstrated central necrosis and peripheral residual cells with progressive cytoplasmic and nuclear swelling without apoptotic features. Expression of proteins and mRNAs of p53 and bax increased until 3 days, as compared with 48 h for p21; thereafter, the expression gradually decreased. TUNEL-positive nuclei could be seen from 2 days until 2 weeks after treatment. Flow cytometry did not demonstrate an increase in apoptotic features as compared with the control animals. In conclusion, intratumoural injection of the unsealed beta-emitting radionuclide 166Ho appears to be a promising alternative radiotherapeutic modality for the local control of malignant melanoma. The main cell death mechanisms with this technique seem to be radiation-induced central necrosis and peripheral growth arrest or secondary necrosis of tumour cells, rather than apoptosis. (orig/MG) (orig.)

  2. 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)

    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

  3. 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)

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

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

  6. Trends in cutaneous malignant melanoma in Sweden 1997-2011: Thinner tumours and improved survival among men

    OpenAIRE

    Lyth, Johan; Eriksson, H; J. Hansson(Lulea University, Lulea, Sweden); Ingvar, C; Jansson, M.; Lapins, J.; Månsson-Brahme, E.; Naredi, P; Stierner, U; Ullenhag, G.; Carstensen, John; Lindholm, C.

    2015-01-01

    Background: Both patient survival and the proportion of patients diagnosed with thin cutaneous malignant melanoma (CMM) have been steadily rising in Sweden as in most western countries, though the rate of improvement in survival appears to have declined in Sweden at the end of last millennium. Objectives: To analyse the most recent trends in the distribution of tumour thickness (T-category) as well as CMM-specific survival in Swedish patients diagnosed 1997-2011. Methods: This nationwide popu...

  7. TrkA is amplified in malignant melanoma patients and induces an anti-proliferative response in cell lines

    OpenAIRE

    Pasini, Luigi; Re, Angela; Tebaldi, Toma; Ricci, Gianluca; Boi, Sebastiana; Adami, Valentina; Barbareschi, Mattia; Quattrone, Alessandro

    2015-01-01

    Background The nerve growth factor (NGF) receptor tyrosine-kinase TrkA is a well-known determinant of the melanocytic lineage, through modulation of the MAPK and AKT cascades. While TrkA gene is frequently rearranged in cancers, its involvement in malignant melanoma (MM) development is still unclear. Methods We analyzed a dataset of primary cutaneous MM (n = 31) by array comparative genomic hybridization (aCGH), to identify genomic amplifications associated with tumor progression. The analysi...

  8. Increased tartrate-resistant acid phosphatase (TRAP) expression in malignant breast, ovarian and melanoma tissue: an investigational study

    International Nuclear Information System (INIS)

    Tartrate-resistant acid phosphatase (TRAP) is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies

  9. 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. PMID:27484276

  10. 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

  11. A new look at drugs targeting malignant melanoma--an application for mass spectrometry imaging.

    Science.gov (United States)

    Sugihara, Yutaka; Végvári, Akos; Welinder, Charlotte; Jönsson, Göran; Ingvar, Christian; Lundgren, Lotta; Olsson, Håkan; Breslin, Thomas; Wieslander, Elisabet; Laurell, Thomas; Rezeli, Melinda; Jansson, Bo; Nishimura, Toshihide; Fehniger, Thomas E; Baldetorp, Bo; Marko-Varga, György

    2014-09-01

    Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor targeting BRAF-mutated protein, has shown significant efficacy in slowing disease progression. In this paper, we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using MS fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment. PMID:25044963

  12. Combined BCG and irradiation treatment of skin metastases originating from malignant melanoma

    International Nuclear Information System (INIS)

    Treatment with BCG (Bacillus Calmette-Guerin) followed by irradiation was attempted to improve response to therapy by cutaneous metastases from malignant skin melanomas. Both agents were applied in low doses, known to cause minimal side effects. Nineteen patients, divided into three groups, entered the clinical trial. The first group consisted of five patients with numerous, small skin metastases. The nine patients of the second group presented a small number of relatively large metastases that usually appeared as a residual disease in the surgically treated area. Five patients with numerous, large metastases were included in the third group. The treatment sequence consisted of applying BCG intralesionally in doses from 4 x 105 to 1.17 x 107 viable units. After a free interval, the affected area was irradiated with doses from 1500-2500 ret. Patients with numerous small metastases and those with a small number of larger metastases, i.e., patients of the first and second group, showed a complete response and in these cases regression affected all the noninjected nodules and was also effective when regression could not have been achieved by BCG alone

  13. Association between tumor size and Breslow's thickness in malignant melanoma: a cross-sectional, multicenter study.

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    Moreno-Ramírez, David; Ojeda-Vila, Teresa; Ríos-Martín, Juan J; Nieto-García, Adoración; Ferrándiz, Lara

    2015-10-01

    The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, Pstrength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness. PMID:26237766

  14. Genetics and epigenetics of cutaneous malignant melanoma: a concert out of tune.

    Science.gov (United States)

    van den Hurk, Karin; Niessen, Hanneke E C; Veeck, Jürgen; van den Oord, Joost J; van Steensel, Maurice A M; Zur Hausen, Axel; van Engeland, Manon; Winnepenninckx, Véronique J L

    2012-08-01

    Cutaneous malignant melanoma (CMM) is the most life-threatening neoplasm of the skin and is considered a major health problem as both incidence and mortality rates continue to rise. Once CMM has metastasized it becomes therapy-resistant and is an inevitably deadly disease. Understanding the molecular mechanisms that are involved in the initiation and progression of CMM is crucial for overcoming the commonly observed drug resistance as well as developing novel targeted treatment strategies. This molecular knowledge may further lead to the identification of clinically relevant biomarkers for early CMM detection, risk stratification, or prediction of response to therapy, altogether improving the clinical management of this disease. In this review we summarize the currently identified genetic and epigenetic alterations in CMM development. Although the genetic components underlying CMM are clearly emerging, a complete picture of the epigenetic alterations on DNA (DNA methylation), RNA (non-coding RNAs), and protein level (histone modifications, Polycomb group proteins, and chromatin remodeling) and the combinatorial interactions between these events is lacking. More detailed knowledge, however, is accumulating for genetic and epigenetic interactions in the aberrant regulation of the INK4b-ARF-INK4a and microphthalmia-associated transcription factor (MITF) loci. Importantly, we point out that it is this interplay of genetics and epigenetics that effectively leads to distorted gene expression patterns in CMM. PMID:22503822

  15. 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

  16. Amelanotic malignant melanoma of the esophagus: Report of two cases with immunohistochemical and molecular genetic study of KIT and PDGFRA

    Institute of Scientific and Technical Information of China (English)

    Tadashi Terada

    2009-01-01

    The author reports herein two cases of amelanotic malignant melanoma of the esophagus. Case 1 is an 87-year-old woman who was admitted to our hospital because of nausea and vomiting. Endoscopic examination revealed an ulcerated tumor of the distal esophagus,and a biopsy was taken. The biopsy showed malignant polygonal and spindle cells. No melanin pigment was recognized. Immunohistochemically, the tumor cells were positive for melanosome (HMB45), S100 protein,KIT and Platelet derived growth factor receptor-α (PDGFRA).The patient was treated by chemotherapy and radiation, but died of systemic metastasis 12 mo after the presentation. Case 2 is a 56-year-old man presenting with dysphagia. Endoscopic examination revealed a polypoid tumor in the middle esophagus, and a biopsy was obtained. The biopsy showed malignant spindle cells without melanin pigment. Immunohistochemically,the tumor cells were positively labeled for melanosome,S100 protein, KIT and PDGFRA. The patient refused operation,and was treated by palliative chemotherapy and radiation. He died of metastasis 7 mo after the admission. In both cases, molecular genetic analyses of KIT gene (exons 9, 11, 13 and 17) and PDGFRA gene (exons 12 and 18) were performed by the PCR direct sequencing method, which showed no mutations of KIT and PDGFRA genes. This is the first report of esophageal malignant melanoma with an examination of the expression of KIT and PDGFRA and the mutational status of KIT and PDGFRA genes.

  17. Epidemiology of malignant melanoma in the province of Palermo (2003-2005

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    Maria Antonietta Cascio

    2011-12-01

    Full Text Available

    Background: The incidence of melanoma has steadily increased worldwide and shows geographical variability according to latitude. The aim of this study was to describe the incidence of cutaneous malignant melanoma (CMM cases in the Province of Palermo during the period 2003-2005.

    Methods: 231 incident cases of CMM, registered by the Cancer Registry of Palermo, were analysed. Anatomic localization, histological type, thickness, ulceration, margins, any lymph node involvement and metastases were evaluated. A statistical analysis of survival rates was performed.

    Results: Distribution by sex and stage of diagnosis showed a slight, but not significant, difference between females and males diagnosed both in early and late stage CMM. Age incidence rates were higher in women before the age of 40 and in men over the age of 50. No statistically significant difference in stage was observed between residents in Palermo and of its Province.
    148 cases (64% were found in people living in Palermo, with an incidence rate (EU of 7.2 over 100,000 in males and 6.1 in females, while in the province the incidence rate was lower (4.7 vs 3.9 . Univariate analysis by gender showed better survival in females than in males and a better survival for age <49 and for stage I-II at diagnosis (p<0.05. Multivariate analysis including gender, age and cancer stage showed that survival is significantly positively related to earlier stage (p<0.05 and younger age (p=0.01 but not to sex (p=0.19.

    Conclusions: Diagnosis of CMM is mainly performed in the early stages, in both sexes and regardless of residence, suggesting no difference in early diagnosis and access to care between city and province. The incidence of CMM appears to be higher in the city compared to the province. Survival following diagnosis was strongly, and independently, related to age and stage of CMM, while gender did not

  18. Effects of different doses of 2-methoxy-estradiol on the proliferation, apoptosis and angiogenesis genes in malignant melanoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-Bo Tong

    2016-01-01

    Objective:To study the inhibitory effect of different doses of 2-methoxy-estradiol on the growth of malignant melanoma cells in vitro.Methods:First, melanoma B16 cells were cultured, and then 0μmol / L, 10 μmol / L, 20 μmol / L, 30umol / L and 40 umol / L of 2-ME were added. Last, cell viability was detected MTS kit, and the contents of proliferation gene, apoptosis gene and angiogenesis gene in both cells and culture medium were determined by Elisa.Results:2-ME reduced cell viability in a dose-dependent and time-dependent way. After 40 umol/L of 2-ME treatment, Mcl-1 and CYR61 contents in cells decreased significantly, while Fas and Caspase14 contents increased significantly. HIF-1α, VEGF, SDF-1 and CXCR4 decreased significantly in both cells and culture medium.Conclusions:Different doses of 2-ME can inhibit the growth of malignant melanoma cells in vitro by reducing the cell viability and inhibiting cell proliferation and angiogenesis.

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

    Science.gov (United States)

    Xiong, Wei; Peng, Lixia; Chen, Hongbo; Li, Qin

    2015-01-01

    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. PMID:25945046

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

    Directory of Open Access Journals (Sweden)

    Kim Jung Han

    2010-04-01

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

  1. Primary glandular melanoma of male breast with nodal metastasis

    OpenAIRE

    Jayabal Pandiaraja

    2016-01-01

    Malignant melanoma is a malignancy that develops from melanocytes. Breast is an uncommon site for malignant melanoma. Melanoma of the breast occurs in various situations such as primary melanoma of breast skin, metastatic melanoma of breast, in-transit metastasis to the breast, and primary glandular breast melanoma. Most of the melanoma breast either cutaneous melanoma or metastatic melanoma. Primary glandular melanoma of male breast with nodal involvement is rarely reported compared to prima...

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

    Science.gov (United States)

    Larsen, Ann-Cathrine

    2016-05-01

    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 uveal, cutaneous and mucosal melanoma. The aim was to determine the incidence rate of conjunctival melanoma, and to relate clinicopathological features and treatment to prognosis. A further aim was to determine the prevalence of BRAF mutations in conjunctival melanoma, to determine whether BRAF mutations are early events in pathogenesis, and relate clinicopathological features and prognosis to BRAF-mutation status. Finally, we wanted to identify tumour-specific and prognostic microRNAs in conjunctival melanoma, and to compare these with the microRNA expression of other melanoma subtypes. In order to investigate these rare tumours, we studied all the conjunctival melanomas that had been surgically removed in Denmark over a period of 52 years (1960-2012). Tissue samples, clinical files, pathology reports and follow-up data were collected and re-evaluated. Using droplet digital polymerase chain reaction and immunohistochemistry, we investigated BRAF mutations; and using microRNA expression profiling, we investigated differentially expressed microRNAs. The overall incidence of conjunctival melanoma was 0.5/1 000 000/year, and it increased in Denmark over 52 years. The increase was mainly caused by an increase in older patients (>65 years) and bulbar lesions. Clinicopathological features significantly associated with a poor prognosis were extrabulbar location, involvement of adjacent tissue structures, tumour thickness exceeding 2 mm and local tumour recurrence. Patients undergoing incisional biopsy and/or treatment involving excision without adjuvant therapy fared worse than patients treated with excision and any type of adjuvant treatment. We found that 35% (39/110) of

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

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    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

  4. Ipilimumab for Previously Untreated Unresectable Malignant Melanoma: A Critique of the Evidence.

    Science.gov (United States)

    Giannopoulou, Christina; Sideris, Eleftherios; Wade, Ros; Moe-Byrne, Thirimon; Eastwood, Alison; McKenna, Claire

    2015-12-01

    The National Institute for Health and Care Excellence (NICE) invited the manufacturer of ipilimumab (Bristol-Myers Squibb Pharmaceuticals Limited) to submit clinical and cost-effectiveness evidence for previously untreated advanced (unresectable or metastatic) melanoma as part of the Institute's Single Technology Appraisal process. The Centre for Reviews and Dissemination and Centre for Health Economics at the University of York were commissioned to act as the independent Evidence Review Group (ERG). This article presents a summary of the manufacturer's submission of ipilimumab, the ERG review and the resulting NICE guidance TA319, issued in July 2014. Ipilimumab at a recommended dose of 3 mg/kg monotherapy was previously granted marketing authorisation by the European Medicines Agency in adult patients who had received prior therapy and was recommended by NICE in guidance TA268. In October 2013, the EMA approved the extension of this indication to previously untreated advanced melanoma patients. NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the NICE Appraisal Committee was whether ipilimumab at a recommended dose of 3 mg/kg monotherapy was effective and cost effective compared with first-line standard of care involving dacarbazine (DTIC) and vemurafenib (for BRAF V600 mutation-positive patients). The CA184-024 trial was the primary source of clinical evidence for ipilimumab. However, this was based on a dose of 10 mg/kg with concomitant DTIC. The results over a 5-year period indicated that ipilimumab 10 mg/kg plus DTIC demonstrated a significant increase in median overall survival (OS) of 2.1 months compared with DTIC plus placebo (11.2 vs. 9.1 months). The BRIM-3 trial, which was an open-label randomised controlled trial (RCT) in BRAF V600 mutation-positive patients, was the primary source of evidence for an indirect comparison with vemurafenib. The results showed that vemurafenib increased median OS by 3

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

    International Nuclear Information System (INIS)

    To retrospectively access outcome and toxicity of whole brain radiotherapy (WBRT) in patients with multiple brain metastases (BM) from malignant melanoma (MM). 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. 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 < 0.001) as well as RPA class (p < 0.001) influenced significantly on OS and patients had a significantly longer OS after surgical resection (p = 0.001, median 3.0 vs. 5.8 months, multivariate p = 0.007). Having extra-cerebral metastases didn't significantly impact on OS (p = 0.21). 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

  6. 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.

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

    Science.gov (United States)

    Liu, Jibin; Shen, Biao; Shi, Minxin; Cai, Jing

    2016-01-01

    Background 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. Methods Studies were identified through searching the PubMed and MEDLINE databases (to November, 2015). Study-specific risk estimates were pooled under the random-effects model. Results 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). Conclusions 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. PMID:26816289

  8. Spotlight on pembrolizumab in the treatment of advanced melanoma

    Directory of Open Access Journals (Sweden)

    Rajakulendran T

    2015-06-01

    Full Text Available Thanashan Rajakulendran,1 David N Adam2 1Department of Medicine, Division of Dermatology, Postgraduate Medical Education, 2Department of Medicine, Division of Dermatology, St Michael’s Hospital, University of Toronto, Toronto, ON, Canada Abstract: Metastatic melanoma is an aggressive cancer with a poor prognosis. Many approved therapies often do not achieve durable responses in patients. This underscores the need for novel therapeutic strategies. Recruiting a robust immune response is an important antineoplastic treatment strategy. Immune checkpoints offer a molecular target for modulating the immune response and a promising therapeutic target in metastatic melanoma. Here we discuss the recent approval of pembrolizumab by the US Food and Drug Administration for the treatment of metastatic melanoma and its impact on future management of the disease. Keywords: pembrolizumab, melanoma, immune checkpoint, PD-1, PD-L1

  9. Seven Novel and Stable Translocations Associated with Oncogenic Gene Expression in Malignant Melanoma

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    Ichiro Okamoto

    2005-04-01

    Full Text Available Cytogenetics has not only precipitated the discovery of several oncogenes, but has also led to the molecular classification of numerous malignancies. The correct identification of aberrations in many tumors has, however, been hindered by extensive tumor complexity and the limitations of molecular cytogenetic techniques. In this study, we have investigated five malignant melanoma (MM cell lines from at least three different passages using high-resolution R-banding and the recently developed methods of comparative genomic hybridization and multicolor or multiplex fluorescence in situ hybridization. We subsequently detected nine consistent translocations, seven of which were novel: dic(1;11(p10;q14, der(9t(3;9(p12;p11, der(4t(9;4;7(q33::p15-q23::q21, der(14t(5;14 (q12;q32, der(9t(9;22(p21;q11, der(19t(19;20(p13.3;p11, der(10t(2;12;7;10(q31::p12→pter::q11.2→q31::q21,der(19t(10;19(q23;q13, and der(20t(Y;20(q11.23;q13.3. Furthermore, using the human HG-U133A Gene-Chip, positive expression levels of oncogenes or tumor-related genes located at the regions of chromosomal breakpoints were identified, including AKT1, BMI1, CDK6, CTNNB1, E2F1, GPNMB, GPRK7, KBRAS2, LDB2, LIMK1, MAPK1, MEL, MP1, MUC18, NRCAM, PBX3, RAB22A, RAB38, SNK, and STK4, indicating an association between chromosomal breakpoints and altered gene expression. Moreover, we also show that growth of all five cell lines can be significantly reduced by downregulating CDK6 gene expression with small interfering RNA (siRNA. Because the majority of these breakpoints have been reported previously in MM, our results support the idea of commonmechanisms in this disease.

  10. Construction of Ang2-siRNA chitosan magnetic nanoparticles and the effect on Ang2 gene expression in human malignant melanoma cells

    Science.gov (United States)

    LIU, ZHAO-LIANG; YOU, CAI-LIAN; WANG, BIAO; LIN, JIAN-HONG; HU, XUE-FENG; SHAN, XIU-YING; WANG, MEI-SHUI; ZHENG, HOU-BING; ZHANG, YAN-DING

    2016-01-01

    The aim of the present study was to construct angiopoietin-2 (Ang2)-small interfering (si)RNA chitosan magnetic nanoparticles and to observe the interference effects of the nanoparticles on the expression of the Ang2 gene in human malignant melanoma cells. Ang2-siRNA chitosan magnetic nanoparticles were constructed and transfected into human malignant melanoma cells in vitro. Red fluorescent protein expression was observed, and the transfection efficiency was analyzed. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to assess the inhibition efficiency of Ang2 gene expression. Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed, and at a mass ratio of plasmid to magnetic chitosan nanoparticles of 1:100, the transfection efficiency into human malignant melanoma cells was the highest of the ratios assessed, reaching 61.17%. RT-qPCR analysis showed that the magnetic chitosan nanoparticles effectively inhibited Ang2 gene expression in cells, and the inhibition efficiency reached 59.56% (P<0.05). Ang2-siRNA chitosan magnetic nanoparticles were successfully constructed. The in vitro studies showed that the nanoparticles inhibited Ang2 gene expression in human malignant melanoma tumor cells, which laid the foundation and provided experimental evidence for additional future in vivo studies of intervention targeting malignant melanoma tumor growth in nude mice. PMID:27313729

  11. Sorafenib in advanced melanoma: a critical role for pharmacokinetics?

    OpenAIRE

    Pécuchet, N; Lebbe, C; Mir, O; Billemont, B; Blanchet, B; Franck, N; Viguier, M; Coriat, R.; Tod, M; Avril, M-F; Goldwasser, F

    2012-01-01

    Background: Inter-patient pharmacokinetic variability can lead to suboptimal drug exposure, and therefore might impact the efficacy of sorafenib. This study reports long-term pharmacokinetic monitoring of patients treated with sorafenib and a retrospective pharmacodynamic/pharmacokinetic analysis in melanoma patients. Patients and methods: Heavily pretreated patients with stage IV melanoma were started on sorafenib 400 mg twice daily (bid). In the absence of limiting toxicity, dose escalation...

  12. Antiproliferative Activity of Double Point Modified Analogs of 1,25-Dihydroxyvitamin D2 Against Human Malignant Melanoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Anna Piotrowska

    2016-01-01

    Full Text Available Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM analogs of 1,25-dihydroxyvitamin D2 (1,25(OH2D2 induced differentiation of the vitamin D receptor (VDR positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl and in the A-ring (5,6-trans modification, the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM. Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

  13. Cancer Malignancy Is Enhanced by Glyceraldehyde-Derived Advanced Glycation End-Products

    Directory of Open Access Journals (Sweden)

    Jun-Ichi Takino

    2010-01-01

    Full Text Available The receptor for advanced glycation end-products (RAGEs is associated with the malignancy of cancer. A recent study has suggested that glyceraldehyde-derived AGEs (Glycer-AGEs enhanced the malignancy of melanoma cells, but glucose-derived AGEs did not. However, the effects of Glycer-AGEs on other cancer cells remain poorly understood, and the molecular mechanisms behind the above-mentioned effect have not been clarified. The present paper aimed to examine the effect of Glycer-AGEs on cultured lung cancer A549 cells. RAGE was expressed in A549 cells. Glycer-AGEs significantly attenuated cell proliferation. Furthermore, Glycer-AGEs enhanced the migration capacity of the cells by activating Rac1 via ROS and also increased their invasion capacity. We demonstrated that Glycer-AGEs enhanced the migration and invasion of A549 cells rather than their proliferation. These results suggest that Glycer-AGEs play a critical role in the malignancy of cancer rather than its proliferation and are potential targets for therapeutic intervention.

  14. Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle

    OpenAIRE

    GUTMAN, HAIM; BEN-AMI, EYTAN; SHAPIRA-FROMMER, RONI; Schachter, Jacob

    2012-01-01

    Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3–307) mon...

  15. The Evolving Role of Radiation Therapy in the Management of Malignant Melanoma

    International Nuclear Information System (INIS)

    The incidence of melanoma is rising in the United States, leading to an estimated 68,720 new diagnoses and 8,650 deaths annually. The natural history involves metastases to lymph nodes, lung, liver, brain, and often to other sites. Primary treatment for melanoma is surgical excision of the primary tumor and affected lymph nodes. The role of adjuvant or definitive radiation therapy in the treatment of melanoma remains controversial, because melanoma has traditionally been viewed as a prototypical radioresistant cancer. However, recent studies suggest that under certain clinical circumstances, there may be a significant role for radiation therapy in melanoma treatment. Stereotactic radiosurgery for brain metastases has shown effective local control. High dose per fraction radiation therapy has been associated with a lower rate of locoregional recurrence of sinonasal melanoma. Plaque brachytherapy has evolved into a promising alternative to enucleation at the expense of moderate reduction in visual acuity. Adjuvant radiation therapy following lymphadenectomy in node-positive melanoma prevents local and regional recurrence. The newer clinical data along with emerging radiobiological data indicate that radiotherapy is likely to play a greater role in melanoma management and should be considered as a treatment option.

  16. Pesquisa de células malignas circulantes em pacientes com melanoma maligno de coróide Detection of circulating malignant cells in patients with uveal melanoma

    Directory of Open Access Journals (Sweden)

    Bruno F. Fernandes

    2007-08-01

    Full Text Available OBJETIVO: Avaliar a possibilidade de identificação de células malignas circulantes nas amostras de sangue periférico de pacientes brasileiros com melanoma maligno de coróide enviadas para análise no exterior. MÉTODOS: Os marcadores melan-A e tirosinase foram usados para detectar a presença de células malignas circulantes, pela transcrição reversa seguida de reação em cadeia da polimerase e análise seqüencial de DNA (RT-nested-PCR, em seis pacientes com melanoma maligno de coróide, diagnosticados no Brasil. RESULTADOS: Cinco pacientes deste grupo (83,33% foram considerados positivos. A reação de RT-nested-PCR foi positiva para melan-A em quatro (66,7% e positiva para tirosinase em quatro (66,7% dos seis pacientes testados. Três (50% pacientes foram positivos para os dois marcadores. Um (16,7% paciente foi negativo para ambos marcadores. CONCLUSÃO: A pesquisa de células malignas circulantes usando RT-nested-PCR, foi positiva na maioria dos pacientes estudados. A qualidade das amostras de sangue periférico dos pacientes brasileiros foi mantida no material preservado mesmo após ter sido enviado ao exterior.PURPOSE: The purpose of our study was to detect circulating malignant cells (CMCs in oversea-shipped blood samples of patients with uveal melanoma diagnosed in Brazil. METHODOS: Melan-A and tyrosinase were the two markers used for the detection of CMCs, using reverse transcriptase nested polymerase chain reaction (RT-nested-PCR in 6 patients with uveal melanoma. The expression of beta-actin and GAPDH were used to assess the quality of the material. RESULTS: Five patients (83.33% tested positive for the presence of CMCs. The RT-nested-PCR was positive for melan-A in 4 patients (66.7% and positive for tyrosinase in 4 (66.7% of the 6 patients. Three (50% patients were positive for both markers. One (16.7% patient was negative for both markers. All negative controls were negative. CONCLUSION: The quality of the blood samples

  17. 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.

  18. Increased tartrate-resistant acid phosphatase (TRAP expression in malignant breast, ovarian and melanoma tissue: an investigational study

    Directory of Open Access Journals (Sweden)

    Eck M

    2006-07-01

    Full Text Available Abstract Background Tartrate-resistant acid phosphatase (TRAP is a metalloprotein enzyme that belongs to the acid phosphatases and is known to be expressed by osteoclasts. It has already been investigated as a marker of bone metastases in cancer patients. In this study, which examined the value of serum TRAP concentrations as a marker of bone disease in breast cancer patients, we observed high concentrations of TRAP even in patients without bone metastases. To elucidate this phenomenon, we examined the expression of TRAP in breast cancer cells and the cells of several other malignancies. Methods TRAP concentrations in the serum of tumor patients were determined by ELISA. The expression of TRAP in breast, ovarian, and cervical cancer and malignant melanoma was analyzed by immunohistochemistry. RT-PCR and immunocytology were used to evaluate TRAP expression in cultured tumor cells. Results A marked increase in serum TRAP concentrations was observed in patients with breast and ovarian cancer, regardless of the presence or absence of bone disease. TRAP expression was found in breast and ovarian cancers and malignant melanoma, while cervical cancer showed only minimal expression of TRAP. Expression of TRAP was absent in benign tissue or was much less marked than in the corresponding malignant tissue. TRAP expression was also demonstrated in cultured primary cancer cells and in commercially available cell lines. Conclusion Overexpression of TRAP was detected in the cells of various different tumors. TRAP might be useful as a marker of progression of malignant disease. It could also be a potential target for future cancer therapies.

  19. Three-Dimensional Image Fusion of SPECT and CT Scans for Locating Sentinel Lymph Nodes in Malignant Melanomas

    Directory of Open Access Journals (Sweden)

    Michiko Akiyama

    2011-03-01

    Full Text Available Image fusion software can derive a fusion image from single photon emission computed tomography and computed tomography scans. We applied a three-dimensional fusion image to detect sentinel lymph nodes (SLNs in 3 patients with malignant melanomas of the lumbar, vulvar and head region, respectively. During each operation, we detected SLNs at the expected site, as indicated by the fusion images. The three-dimensional image fusion could thus be confirmed as a simple and helpful method for precisely localizing SLNs in these patients.

  20. Characterization of human γδ T lymphocytes infiltrating primary malignant melanomas.

    Directory of Open Access Journals (Sweden)

    Adriana Cordova

    Full Text Available T lymphocytes are often induced naturally in melanoma patients and infiltrate tumors. Given that γδ T cells mediate antigen-specific killing of tumor cells, we studied the representation and the in vitro cytokine production and cytotoxic activity of tumor infiltrating γδ T cells from 74 patients with primary melanoma. We found that γδ T cells represent the major lymphocyte population infiltrating melanoma, and both Vδ1(+ and Vδ2(+ cells are involved. The majority of melanoma-infiltrating γδ cells showed effector memory and terminally-differentiated phenotypes and, accordingly, polyclonal γδ T cell lines obtained from tumor-infiltrating immune cells produced IFN-γ and TNF-α and were capable of killing melanoma cell lines in vitro. The cytotoxic capability of Vδ2 cell lines was further improved by pre-treatment of tumor target cells with zoledronate. Moreover, higher rate of γδ T cells isolation and percentages of Vδ2 cells correlate with early stage of development of melanoma and absence of metastasis. Altogether, our results suggest that a natural immune response mediated by γδ T lymphocytes may contribute to the immunosurveillance of melanoma.

  1. Review of clinical studies on dendritic cell-based vaccination of patients with malignant melanoma: assessment of correlation between clinical response and vaccine parameters

    DEFF Research Database (Denmark)

    Engell-Noerregaard, Lotte; Hansen, Troels Holz; Andersen, Mads Hald;

    2009-01-01

    During the past years numerous clinical trials have been carried out to assess the ability of dendritic cell (DC) based immunotherapy to induce clinically relevant immune responses in patients with malignant diseases. A broad range of cancer types have been targeted including malignant melanoma...... which in the disseminated stage have a very poor prognosis and only limited treatment options with moderate effectiveness. Herein we describe the results of a focused search of recently published clinical studies on dendritic cell vaccination in melanoma and review different vaccine parameters which are...... included for analysis covering a total of 626 patients with malignant melanoma treated with DC based therapy. Clinical response (CR, PR and SD) were found to be significantly correlated with the use of peptide antigens (p = 0.03), the use of any helper antigen/adjuvant (p = 0.002), and induction of antigen...

  2. MicroRNA let-7b targets important cell cycle molecules in malignant melanoma cells and interferes with anchorage-independent growth

    Institute of Scientific and Technical Information of China (English)

    Julia Schultz; Peter Lorenz; Gerd Gross; Saleh Ibrahim; Manfred Kunz

    2008-01-01

    A microRNA expression screen was performed analyzing 157 different microRNAs in laser-microdissected tissues from benign melanocytic nevi (n=10) and primary malignant melanomas (n=10),using quantitative real-time PCR.Differential expression was found for 72 microRNAs.Members of the let-7 family of microRNAs were significantly downregulated in primary melanomas as compared with benign nevi,suggestive for a possible role of these molecules as tumor suppressors in malignant melanoma.Interestingly,similar findings had been described for lung and colon cancer.Overexpression of let-7b in melanoma cells in vitro downregulated the expression of cyclins D1,D3,and A,and cyclin-dependent kinase (Cdk) 4,all of which had been described to play a role in melanoma development.The effect oflet-7b on protein expression was due to targeting of 3'-untranslated regions (3'UTRs) of individual mRNAs,as exemplified by reporter gene analyses for cyclin DI.In line with its downmodulating effects on cell cycle regulators,let-7b inhibited cell cycle progression and anchorage-independent growth of melanoma cells.Taken together,these findings not only point to new regulatory mechanisms of early melanoma development,but also may open avenues for future targeted therapies of this tumor.

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

    International Nuclear Information System (INIS)

    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. 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. A significantly higher percentage of nevi (87%), compared to primary melanomas (20%) and metastases (48%), expressed BRMS1 in the nucelus (p < 0.0001). Strong nuclear staining intensity was observed in 67% of nevi, and in 9% and 24% of the primary and metastatic melanomas, respectively (p < 0.0001). Comparable cytoplasmic expression was observed (nevi; 87%, primaries; 86%, metastases; 72%). However, a decline in cytoplasmic staining intensity was observed in metastases compared to nevi and primary tumors (26%, 47%, and 58%, respectively, p < 0.0001). Score index (percentage immunopositive celles multiplied with staining intensity) revealed that high cytoplasmic score index (≥ 4) was associated with thinner tumors (p = 0.04), lack of ulceration (p = 0.02) and increased disease-free survival (p = 0.036). When intensity and percentage BRMS1 positive cells were analyzed separately, intensity remained associated with tumor thickness (p = 0.024) and ulceration (p = 0.004) but was inversely associated with expression of proliferation markers (cyclin D3 (p = 0.008), cyclin A (p = 0.007), and p21Waf1/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

  4. Advances in diagnosis and treatment of malignant pleural mesothelioma

    Directory of Open Access Journals (Sweden)

    Giorgio Vittorio Scagliotti

    2011-12-01

    Full Text Available Malignant pleural mesothelioma (MPM is an aggressive but relatively rare malignancy with median survival ranging from 8 to 14 months depending on stage and presentation of disease. New diagnostic procedures are urgently needed, selecting patients in earlier stages to evaluate therapeutic approaches which combine chemotherapy, surgery and radiotherapy. Combination chemotherapy represents the only resource available for advanced disease.The combination of cisplatin and pemetrexed is the treatment of choice. This review summarizes the latest developments in diagnostic techniques and the available therapeutic options for the management of MPM. Particular attention is given to the molecular basis of biologically targeted therapies to be used in the future.

  5. 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

  6. Objective histopathologic grading of cutaneous malignant melanomas by stereologic estimation of nuclear volume. Prediction of survival and disease-free period

    DEFF Research Database (Denmark)

    Sørensen, Flemming Brandt

    1989-01-01

    independent prognostic significance, which may be due to attributes of the small data base. It is concluded that Vv may be a powerful prognostic indicator in cutaneous melanomas, suitable for objective malignancy grading. The clinical and prognostic value of nuclear Vv needs further investigation in a larger......Modern stereologic techniques enable unbiased and shape-independent estimation of the three-dimensional nuclear volume (Vv). This study investigates the prognostic impact of Vv in 47 patients with malignant melanomas (10 years of follow-up) and compares Vv to traditional prognostic parameters and...

  7. Tumor Vascularity Is Not a Prognostic Factor for Malignant Melanoma of the Skin

    OpenAIRE

    Busam, Klaus J.; Berwick, Marianne; Blessing, Karen; Fandrey, Katrin; Kang, Sewon; Karaoli, Themis; Fine, Judy; Cochran, Alistair J.; White, Wain L.; Rivers, Jason; Elder, David E; Po Wen, Duan-Ren; Heyman, Bradley H.; Barnhill, Raymond L.

    1995-01-01

    Tumor vascularity has been proposed as a prognostic indicator for a number of solid tumors. Although a correlation between microvessel number and metastatic behavior has also been suggested for cutaneous melanoma, the small number of cases studied to date allows one to draw only preliminary conclusions. In this study, we have assessed tumor vascularity in cutaneous melanoma by comparing 60 cases of metastasizing and non-metastasizing tumors matched for tumor thickness, age, sex, and anatomic ...

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

    International Nuclear Information System (INIS)

    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. Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma.

    Science.gov (United States)

    Damodaran, Senthil; Mrozek, Ewa; Liebner, David; Kendra, Kari

    2014-12-01

    High-dose interleukin-2 (IL-2) is an available treatment option for patients with metastatic melanoma or renal cell carcinoma, and is associated with sustained complete and partial responses in a subset of patients. IL-2, however, is not devoid of toxicities, most of which involve the cardiovascular system and manifest as hypotension, arrhythmias, and cardiomyopathy. This report describes an unusual presentation of takotsubo cardiomyopathy in a postmenopausal woman receiving high-dose IL-2 for metastatic melanoma. PMID:25505207

  10. Microincisional vitrectomy for retinal detachment in I-125 brachytherapy-treated patients with posterior uveal malignant melanoma

    Directory of Open Access Journals (Sweden)

    Lonngi M

    2013-02-01

    Full Text Available Marcela Lonngi,1 Samuel K Houston,1 Timothy G Murray,1–3 Robert A Sisk,4 Christina L Decatur,1 Milena Cavalcante,1 Arnold M Markoe31Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USA; 2Murray Ocular Oncology and Retina, Miami, FL, USA; 3Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA; 4Department of Ophthalmology, Cincinnati Eye Institute, Cincinnati, OH, USAPurpose: To analyze functional and anatomical outcomes following 23/25+ gauge microincisional pars plana vitrectomy surgery (MIVS in patients with radiation-related retinal detachment after successful 125-iodine (I-125 brachytherapy treatment for malignant uveal melanoma.Patients and methods: Retrospective case series of 102 consecutive eyes of 102 patients with history of uveal melanoma treated with I-125 brachytherapy that underwent MIVS at the Bascom Palmer Eye Institute. All cases were evaluated for surgical complications and local tumor control. Extended follow-up included Snellen’s best-corrected visual acuity, intraocular pressure evaluation, quantitative echography, indirect ophthalmoscopy, and fundus imaging with optical coherence tomography/wide-field photography.Results: All patients had radiation-related complications, including retinal detachment (102 eyes, vasculopathy (91 eyes, optic neuropathy (32 eyes, and/or vitreous hemorrhage (8 eyes. Sixty-seven patients had vitreoretinal traction. Average follow-up after MIVS was 19.5 months, and from plaque removal was 57.7 months. Interval from plaque to MIVS was 38.1 months. Initial visual acuity was 20/258, which improved to 20/101 at 1 month, 20/110 at 3 months, 20/116 at 6 months, and 20/113 at 12 months (P < 0.05. No eyes required enucleation. Melanoma-related mortality was 0.9% (1/102. There was no intra- or extraocular tumor dissemination, and no tumor recurrence.Conclusion: MIVS was effective in improving

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

    International Nuclear Information System (INIS)

    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. Recovery of human malignant melanoma cells from potentially lethal radiation damage after gamma-irradiation and cell kinetic analysis

    International Nuclear Information System (INIS)

    In order to elucidate radioresistance mechanism of malignant melanoma cells, a human malignant melanoma cell line, HMV-1, was examined in vitro. A larger shoulder on the HMV-1 cell survival curve (the Dsub(q) number, 292 rad) suggested a greater ability of these cells to recover from sublethal radiation damage. HMV-1 cells in plateau-phase cultures possessed a much greater ability to recover from potentially lethal radiation damage (PLD) (the Do ratio, 1.7) than Hela S3 cells (the Do ratio, 1.1). The progression of HMV-1 cells was remarkably inhibited (from G1 phase to S phase) by gamma-irradiation of 1,000 rad; that is, G1 block was induced by it. The fact that HMV-1 cells possess a great ability to recover from PLD at cell levels suggested the involvement of DNA repair at molecular levels. G1 block is considered to reflect the ability of DNA repair. DNA damaged by radiation will be repaired prior to the initiation of DNA replication. (Namekawa, K.)

  13. A case of obstructive sleep apnea syndrome caused by malignant melanoma in the nasal cavity and paranasal sinus

    Directory of Open Access Journals (Sweden)

    Nobuhiro Asai

    2013-01-01

    Full Text Available A 71 year-old obese woman complained of obstructive sleep apnea syndrome (OSAS related symptoms. The apnea-hypopnea index (AHI was 73.5/hour. She presented with nasal bleeding to an ENT doctor. A mass on the nasal septum was seen and biopsy was performed. Histological confirmation showed malignant melanoma. The tumor stage proved to be cT4aN2M1 (stage IV due to multiple metastatic lesions. After palliative irradiation, the nasal tumor was reduced in size and her symptoms of OSAS were improved. The second AHI revealed 13.5/hour. This case was considered to be OSAS caused by a tumor obstructing the nasal cavity. This might suggest the necessity of routine work-up of the upper airway in cases of patients with sleep disorder. Otherwise, OSAS caused by such obstruction might be missed. We report a very rare case with secondary OSAS caused by malignant melanoma in the nasal cavity and paranasal sinus.

  14. VON RECKLINGHAUSEN’S DISEASE ASSOCIATED WITH PAPILARY THYROID CARCINOMA AND MALIGNANT MELANOMA WITH MULTIPLE METASTASIS – CASE REPORT

    Directory of Open Access Journals (Sweden)

    D. Niculescu

    2006-04-01

    Full Text Available We present the case of a 56 years old, women, known with Recklinghausen’s Disease (RD since 15 years old. She was in the evidence of Iasi Endocrynology Clinic with nodulary goitre since ’97, being treated with Euthyrox until 2005. Due to symptomatology worsening (asphyxia feeling, agitation, palpitations, insomnia, irritability, dizziness and to thyroid increase the surgical procedure was recommended. A right lobeisthmectomy was performed in 2005, but the Histopathology Exam revealed an occult Papillary Thyroid Carcinoma (PTC pT1NxMxG1 (sclerous infiltrative 3 mm node on joint nodular goitre with metaplasia, hemorrhage, sclero hyalinisation and lymphomatous thyroiditis aspects. She was treated with L Thyroxin, chemotherapy (Cisplatinum, Dacarbazin and radioactive iodine therapy. After oncological evaluation she was addressed to the First Surgery Clinic for thyroidectomy totalisation and the treatment of an umbilical tumour occurred after the fourth cure (June-July 2005. The patient was evaluated by physical exam, ultrasonography and computed tomography (cervical and abdominal which revealed tumours in the cervical region and in the liver. Thyroidectomy totalisation with limphadenectomy and an abdominal laparoscopy and biopsy were performed. The pathologic exam diagnosed multiple metastasis of malignant melanoma (MM localized in the cervical region, in the liver, great omentum and cervical limphatic nodes. The postoperative follow-up revealed multiple bone mestastasis from the malignanat melanoma. The case particularities were: association of RD with 2 primitive malignant tumours (occult PTC and MM, both diagnosed histopathologically and the multiple bone metastasis developed in a short time.

  15. Diagnostic accuracy of contrast-enhanced FDG-PET/CT in primary staging of cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    To evaluate the diagnostic accuracy of contrast-enhanced FDG-PET/CT (ce-PET/CT), PET-only, and CT-only in patients with newly diagnosed and resected cutaneous malignant melanoma. A final group of 56 patients (mean age 62 years, range 23-86 years; 29 women, 27 men) were staged with ce-PET/CT after resection of the primary tumour. Histopathology as well as clinical follow-up (mean 780 days, range 102-1,390 days) served as the standards of reference. Differences between the staging modalities were tested for statistical significance with McNemar's test. All imaging procedures provided low sensitivities in the detection of lymph nodes (sensitivity N-stage: PET/CT and PET-only 38.5%; CT-only 23.1%) and distant metastases (sensitivity M-stage: PET/CT 41.7%, PET-only 33.3%, CT-only 25.0%) in initial staging after resection of the primary tumour. No statistically significant differences were detected between the imaging procedures (p > 0.05). PET/CT resulted in an alteration in further treatment in two patients compared to PET-only and in four patients compared to CT-only. All imaging modalities had a low sensitivity on initial staging of patients with malignant melanoma. Thus, close patient follow-up must be considered mandatory. (orig.)

  16. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography

    International Nuclear Information System (INIS)

    Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma. Material and methods: Thirty-five patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up >6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined. Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content. Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET

  17. Detectability of liver metastases in malignant melanoma: prospective comparison of magnetic resonance imaging and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Nadir [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)]. E-mail: gha@mrs1.ukl.uni-freiburg.de; Altehoefer, Carsten [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Hoegerle, Stefan [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Nitzsche, Egbert [Departments of Nuclear Medicine, University Hospital Freiburg, Freiburg (Germany); Lohrmann, Christian [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Schaefer, Oliver [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Kotter, Elmar [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany); Langer, Mathias [Departments of Diagnostic Radiology, University Hospital Freiburg, Freiburg 79106 (Germany)

    2005-05-01

    Purpose: We evaluated the diagnostic accuracy of magnetic resonance imaging (MRI) and positron emission tomography (PET) for detection of liver metastases in malignant melanoma. Material and methods: Thirty-five patients with 39 combined unenhanced MRI and fluorine-18 deoxyglucose (F-18 FDG) PET scans were prospectively studied. In discordant imaging findings final diagnosis was proven by clinical follow-up >6 months and demonstration of progressive liver metastases by at least one imaging method. Sensitivities and specificities were compared and the influence of lesion size and melanin content on diagnostic accuracy was determined. Results: MRI and PET were concordantly negative for presence and number of liver metastases in 28 patients and positive in four patients. PET and MRI were false positive in one patient each. In one patient MRI showed a single metastases not seen by PET and in one patient MRI demonstrated more metastases at the first examination. In follow-up investigations MRI revealed more metastases than PET in both patients. The sensitivities for lesion detection were 47% (16/34) for PET and 100% for MRI. Lesion detectability by PET was related to lesion size (P < 0.0001) but not to melanin content. Conclusion: MRI is more sensitive in the detection of liver metastases in patients with malignant melanoma. Small lesions are easily missed by PET, while melanin content does not influence detectability by PET.

  18. Oral Melanoma

    Directory of Open Access Journals (Sweden)

    A Forouzandeh

    2002-02-01

    Full Text Available Melanoma is a malignant tumor that originates from melanocyte cells. Its oral type is rare. The goal of this investigation was to determine the prevalence of oral malignant melanoma in Iran, as determined by age, sex and location. This research reviewed 623 cases of oral and non-oral malignant melanoma in Immam-Khomeini hospital, Mearaj cancer institute and department of oral pathology of dental faculty, Tehran University of Medical Sciences in a period of 19 years from 1981-1999. The results showed that 54 cases of biopsy lesions were melanoma of oral cavity that included 7.8% of these lesions. The mean age incidence of oral melanoma was 55.5(between 26-86 years. The most prevalent sites were palate (37.1% and alveolar mucosa (20.4% and less common sites included floor of mouth. buccal mucosa and tongue.

  19. Advances in personalized targeted treatment of metastatic melanoma and non-invasive tumor monitoring

    Directory of Open Access Journals (Sweden)

    MelZiman

    2013-03-01

    Full Text Available Despite extensive scientific progress in the melanoma field, treatment of advanced stage melanoma with chemotherapeutics and biotherapeutics has rarely provided response rates higher than 20%. In the past decade, targeted inhibitors have been developed for metastatic melanoma, leading to the advent of more personalized therapies of genetically characterized tumors. Here we review current melanoma treatments and emerging targeted molecular therapies. In particular we discuss the mutant BRAF inhibitors Vemurafenib and Dabrafenib, which markedly inhibit tumor growth and advance patients’ overall survival. However this response is almost inevitably followed by complete tumor relapse due to drug resistance hampering the encouraging initial responses. Several mechanisms of resistance within and outside the MAPK pathway have now been uncovered and have paved the way for clinical trials of combination therapies to try and overcome tumor relapse. It is apparent that personalized treatment management will be required in this new era of targeted treatment. Circulating tumor cells (CTCs provide an easily accessible means of monitoring patient relapse and several new approaches are available for the molecular characterization of CTCs. Thus CTCs provide a monitoring tool to evaluate treatment efficacy and early detection of drug resistance in real time. We detail here how advances in the molecular analysis of CTCs may provide insight into new avenues of approaching therapeutic options that would benefit personalized melanoma management.

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

    International Nuclear Information System (INIS)

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

    International Nuclear Information System (INIS)

    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 32P 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)

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

    International Nuclear Information System (INIS)

    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 (p1.5 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.)

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

    DEFF Research Database (Denmark)

    Glud, Martin; Rossing, Maria; Hother, Christoffer;

    2010-01-01

    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...

  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)

    In order to clarify the specific affinity of 10B1-p-boronophenylalanine.HCl (10B1-BPA) to melanoma cells, the killing effects of 10B1-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 10B1-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 10B1-BPA had more enhanced killing sensitivity to thermal neutron irradiation than amelanotic melanoma cells pre-incubated similarly with 10B1-BPA. 10B1-BPA pre-incubation had no enhanced killing effects on Alexander cells, but had slightly enhanced killing effects on HeLa cells. These results indicate that 10B1-BPA could be incorporated by a specific uptake mechanism of melanoma cells and accumulated within melanotic melanoma cells and that 10B1-BPA at present could be the best chemical for the thermal neutron capture therapy of human malignant melanoma. (Namekawa, K.)

  5. 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 and...

  6. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    Science.gov (United States)

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  7. Tattoo pigment in an axillary lymph node simulating metastatic malignant melanoma

    OpenAIRE

    Jack, CM; Adwani, A; Krishnan, H

    2005-01-01

    We report a case of axillary lymphadenopathy thirty years after a decorative tattoo clinically mimicking metastatic melanoma. The importance of relying on histological confirmation of metastatic disease before altering extent of surgery is discussed. The importance of recording presence of decorative tattoos is stressed.

  8. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    Directory of Open Access Journals (Sweden)

    Coventry BJ

    2015-04-01

    Full Text Available Brendon J Coventry, Dominique Baume, Carrie Lilly Discipline of Surgery, Royal Adelaide Hospital, University of Adelaide, Adelaide, SA, Australia Background: Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Methods: Cases of long-term survival of ≥3 years' duration (from diagnosis of metastatic disease were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Results: Eighteen cases were identified that identified survival of ≥3 years' duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94% had survived ≥5 years, and eleven patients (61% had survived ≥10 years (range: 3–15 years. The median survival duration with metastatic disease was 11 years; 15 remained alive and three

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

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    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

  10. MEK inhibitors and their potential in the treatment of advanced melanoma: the advantages of combination therapy

    Science.gov (United States)

    Tran, Khiem A; Cheng, Michelle Y; Mitra, Anupam; Ogawa, Hiromi; Shi, Vivian Y; Olney, Laura P; Kloxin, April M; Maverakis, Emanual

    2016-01-01

    The treatment of melanoma has improved markedly over the last several years with the advent of more targeted therapies. Unfortunately, complex compensation mechanisms, such as those of the mitogen-activated protein kinase (MAPK) pathway, have limited the clinical benefit of these treatments. Recently, a better understanding of melanoma resistance mechanisms has given way to intelligently designed multidrug regimes. Herein, we review the extensive pathways of BRAF inhibitor (vemurafenib and dabrafenib) resistance. We also review the advantages of dual therapy, including the addition of an MEK inhibitor (cobimetinib or trametinib), which has proven to increase progression-free survival when compared to BRAF inhibitor monotherapy. Finally, this review touches on future treatment strategies that are being developed for advanced melanoma, including the possibility of triple therapy with immune checkpoint inhibitors and the work on optimizing sequential therapy. PMID:26730180

  11. The effect of heavy-ion beams to mouse malignant melanoma cell line having highly metastatic potential

    International Nuclear Information System (INIS)

    The aim of this study is to clarify the effect of carbon-ion beams (C-ions) on metastatic potential of melanoma. B16/BL6 cells, a highly metastatic mouse malignant melanoma cell line, were exposed to C-ions or X-rays in vitro. Survival curves showed higher cytotoxic effects of C-ions than X-rays. Additionally, the potentials of migration and invasion were suppressed by C-ions, however those enhanced by X-rays at low dose points compared with controls. Interestingly, the relative biological effectiveness (RBE) of migration and invasion ability was higher than that of cell killing. On the other hand, the cells were implanted in C57BL/6J mice, and tumors were irradiated at the center of 6 cm-SOBP C-ions or γ-rays. C-ions significantly suppressed the tumor growth. The numbers of lung metastatic nodules from local tumors irradiated or non-irradiated decreased with the dose, and C-ions were more effective compared with γ-rays. The metastatic potentials of survived cells in a tumor after irradiation was analyzed, and C-ions showed smaller number of metastasis than γ-rays when the tumor cell survivals were 10%. It might suggest that C-ions inhibit metastasis at radiotherapy compared with the therapy using photons. (author)

  12. 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; Klima, Martin; Sanderhoff, May; Dahl, Christina; Abildgaard, Cecilie; Thorup, Katrine; Moghimi, Seyed Moein; Jensen, Per Bo; Bartek, Jiri; Guldberg, Per; Christensen, Claus

    2013-01-01

    Oncogene addiction describes how cancer cells exhibit dependence on single oncogenes to escape apoptosis and senescence. While oncogene addiction constitutes the basis for new cancer treatment strategies targeting individual kinases and pathways activated by oncogenic mutations, the biochemical...... 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 an...

  13. Malignant melanoma of the choroid: treatment with episcleral /sup 198/Au plaque and xenon-arc photocoagulation

    Energy Technology Data Exchange (ETDEWEB)

    Moura, R.A.; McPherson, A.R.; Easley, J.

    1985-02-01

    A method of treatment for posteriorly located malignant melanomas of the choroid is reviewed. Twenty-six patients have been treated either by radioactive gold (/sup 198/Au) seed radiation plaque, alone or in combination with postradiation xenon-arc photocoagulation. Success, defined as the preservation of the globe with tumor ablated or regressed, was achieved in 92.3% of the treated eyes. These patients have been followed from 1 to 8.5 years, with an average follow-up of 44.84 months. Fifteen out of 26 patients (57.69%) had a final visual acuity of 20/50 or better. The main complications were radiation retinopathy (19.2%) and cystoid macular edema (19.2%). There were two enucleations, one after 29 months and one after 24 months following treatment.

  14. Phase II study of recombinant leukocyte A interferon (rIFN-alpha A) in disseminated malignant melanoma.

    Science.gov (United States)

    Creagan, E T; Ahmann, D L; Green, S J; Long, H J; Rubin, J; Schutt, A J; Dziewanowski, Z E

    1984-12-15

    Thirty-one patients with disseminated malignant melanoma received intramuscular recombinant leukocyte A interferon (rIFN-alpha A), 50 X 10(6) units/m2 three times weekly for a planned treatment duration of 3 months. Seven objective regressions (23%), which ranged in duration from 3 to 11.2+ months, were observed. Forty-two percent of 12 patients who were fully active (Eastern Cooperative Oncology Group [ECOG] performance score, 0) responded compared to 11% of 19 patients with impairment of performance status (ECOG, 1-3). Prior chemotherapy did not influence response rate. For all patients the median time to progression and of survival was 2 months and 6 months, respectively. Four patients had partial regressions in soft tissue (3, 4.6 months), pulmonary (7 months), and prostatic lesions (3 months). The latter was biopsy-proven and assessed by serial computerized tomography (CT) scans. Three had complete regressions of soft tissue disease (2 patients, 6.4 and 10+ months each), and liver involvement (11.2+ months). The major toxicities were moderate to severe fatigue (87%), anorexia (58%), and confusion (23%). Performance score deteriorated in 84% of patients during the time they were receiving rIFN-alpha A. Among the 13 patients whose tumors did not progress for at least 12 weeks, 7 required dose reductions or termination of treatment due to toxicities. Hematologic and hepatic toxicity was transient and of little clinical significance. The study indicates that rIFN-alpha A has some antitumor activity accompanied by difficult side effects in patients with disseminated malignant melanoma. PMID:6498762

  15. Having children with multiple partners is associated with reduced risk of malignant melanoma: an observation seeking a plausible explanation

    Directory of Open Access Journals (Sweden)

    Anne V Olesen

    2010-10-01

    Full Text Available Anne V Olesen1,2,3, Erik T Parner4, Preben B Mortensen5, Cecilia H Ramlau-Hansen6, Jørn Olsen71Institute of Public Health, Department of Epidemiology, University of Aarhus; 2Unit for Psychiatric Research, Aalborg Psychiatric Hospital; 3Department of Clinical Epidemiology, Aarhus University Hospital; 4Institute of Public Health, Department of Biostatistics; 5National Centre for Register-based Research; 6Department of Occupational Medicine, Aarhus University Hospital, Denmark; 7Department of Epidemiology, School of Public Health, University of California, Los Angeles, USAObjective: We examined the association between the number of partners that mothers and fathers have children with and occurrence of cutaneous malignant melanoma (CMM.Methods: We conducted a complete registry-based follow-up of all Danish mothers born after 1935 from the birth of their second child until CMM, death, emigration, or end of study in 2002. We conducted a similar follow-up of the corresponding fathers. Incidence rate ratios (IRR and confidence intervals (CI were estimated by Poisson regression.Results: This study corroborates that women having children with three or more men are half as likely to have CMM as women who have children with one man: incidence rate ratio (IRR = 0.51, 95% CI: 0.29, 0.91; having children by two fathers reduces risk among women by 20%: IRR = 0.80, 95% CI: 0.70, 0.91. Fathers with multiple partners tend to face a similar risk reduction.Conclusion: The similar patterns of mothers and fathers challenge us to consider and propose likely mechanisms common to both sexes. The patterns of reduced risk have now been reported in two large independent complete population-based studies in Sweden and Denmark.Keywords: malignant melanoma, epidemiology, children with multiple partners

  16. Oncolytic virotherapy for human malignant mesothelioma: recent advances

    Directory of Open Access Journals (Sweden)

    Boisgerault N

    2015-09-01

    Full Text Available Nicolas Boisgerault,1–3 Carole Achard,1–3 Tiphaine Delaunay,1–3 Laurent Cellerin,4 Frédéric Tangy,5 Marc Grégoire,1–3 Jean-François Fonteneau1–31INSERM, UMR892, 2CNRS, UMR6299, Health Research Institute of the University of Nantes, 3University of Nantes, 4Nantes CHU Hospital, Department of Thoracic and Digestive Oncology, 5Viral Genomics and Vaccination Unit, Institut Pasteur, Paris, CNRS UMR-3569, FranceAbstract: Cancer virotherapy is an attractive alternative to conventional treatments because it offers a wide range of antitumor effects due to 1 the diversity of the oncolytic viruses that are now available and 2 their multifaceted activities against both tumor cells and tumor vessels, in addition to their ability to induce antitumor immune responses. In this review, we summarize preclinical and clinical data regarding the targeting of malignant mesothelioma (MM by oncolytic viruses. We also discuss the potential of other oncolytic viruses that have already shown antitumor effects against several malignancies in advanced clinical trials but are yet to be tested against MM cells. Finally, we review how the activation of the immune system and combinations with other types of anticancer treatments could support the development of oncolytic virotherapy for the treatment of MM.Keywords: oncolytic viruses, cancer virotherapy, malignant mesothelioma, antitumor immune responses, immunotherapy

  17. Tissue distribution and differential expression of melanocortin 1 receptor, a malignant melanoma marker

    OpenAIRE

    Salazar-Onfray, F; López, M.; Lundqvist, A.; Aguirre, A.; Escobar, A; Serrano, A; Korenblit, C; PETERSSON,M; Chhajlani, V.; Larsson, O; Kiessling, R.

    2002-01-01

    The melanocortin 1 receptor is a G-protein-coupled receptor, described to be expressed on melanomas and melanocytes. Subsequent RT–PCR studies demonstrated the presence of melanocortin 1 receptor mRNA in other tissues such as pituitary gland and testis. Previously, we have demonstrated that three HLA-A2 binding nonamer peptides derived from melanocortin 1 receptor can elicit peptide-specific CTL which can recognize target cells transfected with the melanocortin 1 receptor gene and MHC class I...

  18. 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.

  19. Melanoma immunotherapy dominates the field.

    Science.gov (United States)

    Diamantopoulos, Panagiotis; Gogas, Helen

    2016-07-01

    The incidence of melanoma is increasing worldwide and despite early detection and intervention, the number of patients dying from metastatic disease continues to rise. The prognosis of advanced melanoma remains poor, with median survival between 6 and 9 months. Over the past 30 years and despite extensive clinical research, the treatment options for metastatic disease were limited and melanoma is still considered as one of the most therapy-resistant malignancies. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimens failed to show a significant improvement in overall survival (OS). Recent advances and in-depth understanding of the biology of melanoma, have contributed to the development of new agents. Based on the molecular and immunological background of the disease, these new drugs have shown benefit in overall and progression-free survival (PFS). As the picture of the disease begins to change, oncologists need to alter their approach to melanoma treatment and consider disease biology together with targeted individualized treatment. In this review the authors attempt to offer an insight in the present and past melanoma treatment options, with a focus on the recently approved immunotherapeutic agents and the clinical perspectives of these new weapons against metastatic melanoma. PMID:27563656

  20. Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations12

    Science.gov (United States)

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

    2009-01-01

    The Raf/MEK/ERK pathway is an important mediator of tumor cell proliferation and angiogenesis. Here, we investigated the growth-inhibitory and antiangiogenic properties of PD0325901, a novel MEK inhibitor, in human melanoma cells. PD0325901 effects were determined in a panel of melanoma cell lines with different genetic aberrations. PD0325901 markedly inhibited ERK phosphorylation and growth of both BRAF mutant and wild-type melanoma cell lines, with IC50 in the nanomolar range even in the least responsive models. Growth inhibition was observed both in vitro and in vivo in xenograft models, regardless of BRAF mutation status, and was due to G1-phase cell cycle arrest and subsequent induction of apoptosis. Cell cycle (cyclin D1, c-Myc, and p27KIP1) and apoptosis (Bcl-2 and survivin) regulators were modulated by PD0325901 at the protein level. Gene expression profiling revealed profound modulation of several genes involved in the negative control of MAPK signaling and melanoma cell differentiation, suggesting alternative, potentially relevant mechanisms of action. Finally, PD0325901 inhibited the production of the proangiogenic factors vascular endothelial growth factor and interleukin 8 at a transcriptional level. In conclusion, PD0325901 exerts potent growth-inhibitory, proapoptotic, and antiangiogenic activity in melanoma lines, regardless of their BRAF mutation status. Deeper understanding of the molecular mechanisms of action of MEK inhibitors will likely translate into more effective treatment strategies for patients experiencing malignant melanoma. PMID:19649202

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

    International Nuclear Information System (INIS)

    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

  2. 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

  3. 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

  4. Long-term survival in advanced melanoma patients using repeated therapies: successive immunomodulation improving the odds?

    International Nuclear Information System (INIS)

    Patients with advanced metastatic melanoma are often confronted with little prospect of medium- to longer-term survival by any currently available therapeutic means. However, most clinicians are aware of exceptional cases where survival defies the notion of futility. Prolonged survival from immunotherapies, including interleukin-2, vaccines and antibodies to cytotoxic lymphocyte antigen-4, and programmed death-1 receptor inhibitory monoclonal antibody, implies a role for immune system modulation. We aimed to identify cases where exceptional survival from advanced melanoma occurred prior to recent novel therapies to facilitate better understanding of this phenomenon. Cases of long-term survival of ≥3 years’ duration (from diagnosis of metastatic disease) were identified from the database of one clinician; these cases were treated before the availability of newer immunotherapies, and they were documented and examined. A literature search for reported outcome measures from published studies using older and recent therapies for advanced melanoma was conducted to enable the comparison of data. Eighteen cases were identified that identified survival of ≥3 years’ duration from metastatic disease (12 American Joint Committee on Cancer [AJCC] Stage IV cases; six AJCC III cases) diagnosis. These were assessed and reported to detail the clinical course. Standard clinical prognostication methods predicted high risk of early mortality in those patients. No identifiable differences could be detected between these and other patients with similar patterns of disease. At evaluation, 17 patients (94%) had survived ≥5 years, and eleven patients (61%) had survived ≥10 years (range: 3–15 years). The median survival duration with metastatic disease was 11 years; 15 remained alive and three had died. Published studies of melanoma therapies were tabled for comparison. The fact that 18 cases of exceptional survival in advanced melanoma were identified is remarkable in itself

  5. Malignant melanoma of the nasal septum, a rare tumor, occurring in a 54-year-old patient after hereditary retinoblastoma treatment.

    Science.gov (United States)

    Djiguimdé, Windinmanégdé Pierre; Diomandé, Ibrahim Abib; Bonnin, Nicolas; Saroul, Nicolas; Touré, Abdoulaye; Sanou, Jérôme; Sankara, Paté; Russier, Marc; Gilain, Laurent; Ahnoux-Zabsonré, Ahgbatouhabéba; Meda, Nonfounikoun; Bacin, Franck

    2016-01-01

    The authors report a case of a malignant melanoma of the nasal cavity that is a rare tumor and very aggressive, constituting 1% of all melanomas. It appeared in a patient 54 years after he was treated for a hereditary retinoblastoma. Its symptoms are nonspecific, and often marked by epistaxis. Its diagnosis is histological, supported by immunohistochemistry. Its prognosis is often unfavorable, and characterized by the occurrence of metastases and recurrences. Because of the risk of secondary cancer that exists in any survivor of hereditary retinoblastoma, we must think of possible mucosal melanoma of the nasal sinus in these patients in cases of chronic epistaxis. The prognosis of this tumor depends on its early diagnosis and surgical treatment. PMID:26929670

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

    International Nuclear Information System (INIS)

    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)

  7. New developments in the management of advanced melanoma – role of pembrolizumab

    Directory of Open Access Journals (Sweden)

    Improta G

    2015-09-01

    Full Text Available Giuseppina Improta,1 Isabella Leone,1 Marco Donia,2 Stefania Gieri,3 Giuseppe Pelosi,4,5 Filippo Fraggetta6 1Laboratory of Clinical Research and Advanced Diagnostics, IRCCS-CROB, Rionero in Vulture, Potenza, Italy; 2Center for Cancer Immune Therapy, Department of Hematology, Copenhagen University Hospital, Herlev, Denmark; 3Laboratory of Oncologic Technologies, IBFM-CNR, Cefalù, Potenza, 4Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale Tumori, Milan, 5Department of Biomedical and Clinical Sciences “Luigi Sacco”, Università degli Studi di Milano, Milan, 6Department of Pathology, Cannizzaro Hospital, Catania, Italy Abstract: Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma. Keywords: advanced melanoma, immunotherapy, PD-1 inhibitor, pembrolizumab

  8. 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

  9. 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

    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...... colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous......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...

  10. 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...... 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...

  11. Systemic chemotherapy of advanced head and neck malignancies.

    Science.gov (United States)

    Dowell, K E; Armstrong, D M; Aust, J B; Cruz, A B

    1975-04-01

    Several Phase II chemotherapy protocols were evaluated in patients with advanced malignancies; 158 were evaluable head and neck cases. The protocols were as follows: five-drug combination (COMFP), four-drug (COMF), (CCNU, Adriamycin, DTIC, and cytosine arabinoside. Insufficient numbers and data were received to adequately evaluate Yoshi 864, 5 Azacytidine, porfiromycin, BCNU, and Azaserine. Significant responses to therapy were noted in the four and five-drug combinations in which 30-44% of the patients had 50% or greater regression, with an average duration of 2.2 months. Adriamycin and CCNU demonstrated lesser antitumor effects, while DTIC and cytosine arabinoside did not demonstrate significant antitumor activity in the head and neck areas. Usual toxicity consisted largely of nausea and vomiting, leukopenia, and thrombocytopenia. Alopecia was not pronouced in Adriamycin-treated patients. It appears that combination chemotherapy had a higher response rate compared to single agents used in the different cooperative protocols. PMID:1116105

  12. 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; Holmén, Anders; Persson, Bertil; Sandberg, Carin; Nilbert, Mef

    outcome. Material and methods All patients with primary invasive CMM diagnosed in 2004-2013 in the southern and the western Swedish health care regions with a population of 2.9 million adults were eligible for the study. Population-based data were obtained from the national Cancer Register 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...... geographic disparities in CMM stage influenced relative survival with an excess five-year mortality ratio in the southern region versus the western region of 1.49 (95% confidence interval 1.22-1.82). The excess mortality ratio for patients with low versus high educational level was 1.81 (1...

  13. Luteolin reduces the invasive potential of malignant melanoma cells by targeting β3 integrin and the epithelial-mesenchymal transition

    Institute of Scientific and Technical Information of China (English)

    Jun-shan RUAN; Yin LU; Yu-ping LIU; Lei ZHANG; Ling-geng YAN; Fang-tian FAN; Cun-si SHEN; Ai-yun WANG; Shi-zhong ZHENG; Shao-ming WANG

    2012-01-01

    Aim:To investigate whether luteolin,a highly prevalent flavonoid,reverses the effects of epithelial-mesenchymal transition (EMT) in vitro and in vivo and to determine the mechanisms underlying this reversal.Methods:Murine malignant melanoma B16F10 cells were exposed to 1% O2 for 24 h.Cellular mobility and adhesion were assessed using Boyden chamber transwell assay and cell adhesion assay,respectively.EMT-related proteins,such as E-cadherin and N-cad-herin,were examined using Western blotting.Female C57BL/6 mice (6 to 8 weeks old) were injected with B16F10 cells (1×106 cells in 0.2 mL per mouse) via the lateral tail vein.The mice were treated with luteolin (10 or 20 mg/kg,ip) daily for 23 d.On the 23rd day after tumor injection,the mice were sacrificed,and the lungs were collected,and metastatic foci in the lung surfaces were photographed.Tissue sections were analyzed with immunohistochemistry and HE staining.Results:Hypoxia changed the morphology of B16F10 cells in vitro from the cobblestone-like to mesenchymal-like strips,which was accompanied by increased cellular adhesion and invasion.Luteolin (5-50 μmol/L) suppressed the hypoxia-induced changes in the cells in a dose-dependent manner.Hypoxia significantly decreased the expression of E-cadherin while increased the expression of N-cadherin in the cells (indicating the occurrence of EMT-like transformation),which was reversed by luteolin (5 μmol/L).In B16F10 cells,luteolin up-regulated E-cadherin at least partly via inhibiting the β3 integrin/FAK signal pathway.In experimental metastasis model mice,treatment with luteolin (10 or 20 mg/kg) reduced metastatic colonization in the lungs by 50%.Furthermore,the treatment increased the expression of E-cadherin while reduced the expression of vimentin and β3 integrin in the tumor tissues.Conclusion:Luteolin inhibits the hypoxia-induced EMT in malignant melanoma cells both in vitro and in vivo via the regulation of β3integrin,suggesting that luteolin may be

  14. The role of radiotherapy for interdisciplinary treatment of the malignant melanoma

    International Nuclear Information System (INIS)

    As compared to new foreign studies, the recent German literature highlights the hyperthermal infusion therapy but gives only poor information about the progress of local radiotherapy for stage I and II. Above all, the endolymphatic radionuclide therapy is only seldom mentioned. With our own patients (n = 106), we could achieve a five-year cure rate of more than 73% for stage I. Almost 90% of the patients had a Clark level of III to V, 65% had a level of IV. With respect to the relatively simple method and the low rate of complications, one can no longer ignore the identical results of the Deutsche Arbeitsgemeinschaft with 338 cases hitherto. For stage II, fast electrons and, eventually, neutrons can be applied according to the situation; a combination with local hyperthermia and chemical radiosensitizers is being tested. Pilot experiments made in London (Catterall) with neutrons have shown encouraging results, and the observations made by us at the cyclotron of Essen induces us to reexaminate patients with recurrent tumors and/or lymph node metastases. With regard to the fully sufficient radiosensibility of many melanomas proved by recent radiobiologic research, fractionation schemes other than the usual daily irradiation have become particularly important. The exclusive superficial irradiation in case of melanoma is a historical method which is only applicable for small local recurrences and in-transit metastases. The more recent radiotherapeutic possibilities mentioned in this report, however, are worth further consideration in the future clinical and therapeutical research. A table is presented containing some proposals in this connection. (orig.)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaliff, V.; Hicks, R.J.; Binns, D.S.; Henderson, M.A.; Ainslie, J.; Jenner, D.A. [Peter McCallum Cancer Institute, Melbourne, VIC (Australia)

    1998-06-01

    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.

  16. Transcatheter arterial infusing chemotherapy for advanced malignant pancreatic islet cell tumors: four cases report

    International Nuclear Information System (INIS)

    Objective: To explore the clinical efficacy of transcatheter arterial infusion (TAI) chemotherapy for advanced malignant pancreatic islet cell tumors. Methods: Four patients (3 malignant insulin tumors, 1 non-functional malignant pancreatic islet cell tumor) with unresectable advanced malignant tumors were carried out TAI via celiac artery. The three malignant insulin tumors with multiple hepatic metastases were further performed with transcatheter arterial chemoembolization (TACE). The therapeutic cycles were repeated with intervals of 1-2 months. Results: Eleven therapeutic cycles (mean 2.8)were accomplished in 4 cases. Follow-up for 2-8 months, the clinical PR were achieved in three cases, furthermore with SD in one case. The clinical uprising blood glucose became normal in all three cases, and the abdominal distention and bellyache were relieved in the patient with non-functional malignant pancreatic islet cell tumor. No serious adverse effects occurred. Conclusions: TAI for unresectable advanced malignant pancreatic islet cell tumors is safe and effective. (authors)

  17. Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients

    International Nuclear Information System (INIS)

    Purpose. Circulating melanoma cells (CMCs) constitute a potentially important representation of time-resolved tumor biology in patients. To date, genomic characterization of CMCs has been limited due to the lack of a robust methodology capable of identifying them in a format suitable for downstream characterization. Here, we have developed a methodology to detect intact CMCs that enables phenotypic, morphometric and genomic analysis at the single cell level. Experimental design. Blood samples from 40 metastatic melanoma patients and 10 normal blood donors were prospectively collected. A panel of 7 chondroitin sulfate proteoglycan 4 (CSPG4)-specific monoclonal antibodies (mAbs) was used to immunocytochemically label CMCs. Detection was performed by automated digital fluorescence microscopy and multi-parametric computational analysis. Individual CMCs were captured by micromanipulation for whole genome amplification and copy number variation (CNV) analysis. Results. Based on CSPG4 expression and nuclear size, 1–250 CMCs were detected in 22 (55%) of 40 metastatic melanoma patients (0.5–371.5 CMCs ml−1). Morphometric analysis revealed that CMCs have a broad spectrum of morphologies and sizes but exhibit a relatively homogeneous nuclear size that was on average 1.5-fold larger than that of surrounding PBMCs. CNV analysis of single CMCs identified deletions of CDKN2A and PTEN, and amplification(s) of TERT, BRAF, KRAS and MDM2. Furthermore, novel chromosomal amplifications in chr12, 17 and 19 were also found. Conclusions. Our findings show that CSPG4 expressing CMCs can be found in the majority of advanced melanoma patients. High content analysis of this cell population may contribute to the design of effective personalized therapies in patients with melanoma. (paper)

  18. 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.

  19. New developments in the management of advanced melanoma – role of pembrolizumab

    Science.gov (United States)

    Improta, Giuseppina; Leone, Isabella; Donia, Marco; Gieri, Stefania; Pelosi, Giuseppe; Fraggetta, Filippo

    2015-01-01

    Cancer immunotherapy is now recognized to be fundamental in modern oncology, because immune system recruitment may represent a powerful and innovative strategy in cancer therapy. Pembrolizumab, a highly selective humanized monoclonal antibody directly blocking the interaction between programmed cell death-1 expressed by tumor-associated T-cells and its ligand programmed cell death-L1 present on tumor and stromal cells, was recently approved by US Food and Drug Administration for the treatment of patients with unresectable or metastatic melanoma and disease progression upon ipilimumab and BRAF inhibitor. This review will focus on the clinical development and use of pembrolizumab in the clinical practice and in the management of advanced melanoma. PMID:26396529

  20. Vaccination with melanoma lysate-pulsed dendritic cells, of patients with advanced colorectal carcinoma: report from a phase I study

    DEFF Research Database (Denmark)

    Burgdorf, S K; Fischer, A; Claesson, M H; Kirkin, A F; Dzhandzhugazyan, K N; Rosenberg, J

    2006-01-01

    Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma...... selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine...

  1. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case

    OpenAIRE

    D’Andrea, Mark A; Reddy, G. Kesava

    2015-01-01

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metast...

  2. von Willebrand factor fibers promote cancer-associated platelet aggregation in malignant melanoma of mice and humans.

    Science.gov (United States)

    Bauer, Alexander T; Suckau, Jan; Frank, Kathrin; Desch, Anna; Goertz, Lukas; Wagner, Andreas H; Hecker, Markus; Goerge, Tobias; Umansky, Ludmila; Beckhove, Philipp; Utikal, Jochen; Gorzelanny, Christian; Diaz-Valdes, Nancy; Umansky, Viktor; Schneider, Stefan W

    2015-05-14

    Tumor-mediated procoagulatory activity leads to venous thromboembolism and supports metastasis in cancer patients. A prerequisite for metastasis formation is the interaction of cancer cells with endothelial cells (ECs) followed by their extravasation. Although it is known that activation of ECs and the release of the procoagulatory protein von Willebrand factor (VWF) is essential for malignancy, the underlying mechanisms remain poorly understood. We hypothesized that VWF fibers in tumor vessels promote tumor-associated thromboembolism and metastasis. Using in vitro settings, mouse models, and human tumor samples, we showed that melanoma cells activate ECs followed by the luminal release of VWF fibers and platelet aggregation in tumor microvessels. Analysis of human blood samples and tumor tissue revealed that a promoted VWF release combined with a local inhibition of proteolytic activity and protein expression of ADAMTS13 (a disintegrin-like and metalloproteinase with thrombospondin type I repeats 13) accounts for this procoagulatory milieu. Blocking endothelial cell activation by the low-molecular-weight heparin tinzaparin was accompanied by a lack of VWF networks and inhibited tumor progression in a transgenic mouse model. Our findings implicate a mechanism wherein tumor-derived vascular endothelial growth factor-A (VEGF-A) promotes tumor progression and angiogenesis. Thus, targeting EC activation envisions new therapeutic strategies attenuating tumor-related angiogenesis and coagulation. PMID:25977583

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

    International Nuclear Information System (INIS)

    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

  4. 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

  5. Pharmacodynamic Characterization of the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma

    OpenAIRE

    Tap, William D.; Ke-Wei Gong; Judy Daring; Yiou Tseng; Charles Ginther; Giovanni Pauletti; Glaspy, John A; Richard Essner; Gideon Bollag; Peter Hirth; Chao Zhang; Slamon, Dennis J

    2010-01-01

    PURPOSE: About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that causes the steady-state activation of extracellular signal-regulated kinase (ERK). We sought to investigate the efficacy of PLX4032 (BRAF inhibitor) to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma. EXPERIMENTAL DESIGN: Well-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PL...

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

    OpenAIRE

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

    2009-01-01

    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 leas...

  7. Cutaneous melanoma

    International Nuclear Information System (INIS)

    The study of boron neutron capture therapy (BNCT) for malignant melanoma was initiated by Y. Mishima and his associates. Following basic research of 13 years, this team started the first clinical trial of cutaneous melanoma BNCT using 10B-para-boronophenylalanine (BPA) in 1985. Since then, 32 patients have been treated. We developed the following regimen for BNCT of malignant melanoma: 1) 170 - 250 mg/kg of BPA-fructose complex is administered by drip infusion over 3-hours. 2) The minimum dose for melanoma control by single irradiation is assumed to be 25 Gy-eq. 3) The maximum tolerable dose to the skin by single irradiation is assumed to be 18 Gy-eq. 4) As the therapeutic dose, the maximum tolerable dose to the skin itself is chosen. We report the clinical results of two patients with cutaneous melanoma treated by BNCT. We believe that cutaneous melanoma are suitable for BNCT and that the excellent results will have a great impact on patients in QOL. (author)

  8. The research advances in molecular mechanism of curcumin against melanoma%姜黄素抗黑色素瘤分子机制研究进展

    Institute of Scientific and Technical Information of China (English)

    谢婉莹; 欧阳鑫; 江冠民; 张秋桂

    2015-01-01

    Melanoma is a kind of malignant tumor that derived from the melanocytes which often located in skin,mu-cous membrane,eye and pigmentation area of the central nervous system. Although the incidence of malignant melano-ma is not high,it is characterized by high malignant degree because of its early invasion and metastasis which lead to patients have poor prognosis. At present,the comprehensive treatment strategy for malignant melanoma including sur-gery,radiotherapy,chemotherapy and Chinese traditional medicine,however,surgical treatment still remains the first choice for early stage patient,however,studies related to Chinese medicine treatment of melanoma is still in its infan-cy. In recent research,they demonstrate that curcumin which is the active ingredient of zingiberaceae plants,turmeric, rhizoma zedoariae,etc,has extensive pharmacological properties of anti - cancer,anti - inflammatory and antioxidant, especially the potential utility in tumor prevention and treatment. Curcumin can inhibit the proliferation and promote the apoptosis of melanoma cells. In this paper,we will review the research advances in molecular mechanism of curcu-min against melanoma.%黑色素瘤是源于皮肤,粘膜,眼和中枢神经系统色素沉着区域的黑色素细胞的恶性肿瘤,虽然其发病率不高,但恶性程度极高,并且瘤细胞很早就能发生侵袭与转移,从而使患者预后很差。目前黑色素瘤的治疗方式仍以外科手术治疗为主,联合放疗、化疗、中药的综合治疗方案,然而有关黑色素瘤的中医中药治疗方面的研究尚处于起步阶段。最新研究表明,姜科植物属姜黄、郁金、莪术等的活性成分之一姜黄素具有广泛的抗癌、抗炎、抗氧化等药理特性,特别是姜黄素在黑色瘤的预防和治疗中起到不容忽视的作用,姜黄素主要通过抑制黑色素瘤细胞的增殖,促进其凋亡等途径参与黑色素瘤细胞的消亡。本文主要针

  9. The occurrence of non-melanoma malignant skin lesions and non-cutaneous squamous-cell carcinoma among metastatic melanoma patients

    DEFF Research Database (Denmark)

    Li, Haojie; Pedersen, Lars; Nørgaard, Mette;

    2016-01-01

    ), 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. Conclusion CuSCC and non-cuSCC were rare events among metastatic melanoma patients....

  10. BRAF inhibition for advanced locoregional BRAF V600E mutant melanoma: a potential neoadjuvant strategy.

    Science.gov (United States)

    Sloot, Sarah; Zager, Jonathan S; Kudchadkar, Ragini R; Messina, Jane L; Benedict, Jacob J; Gonzalez, Ricardo J; DeConti, Ronald; Turner, Leslie M; McCardle, Timothy; Smalley, Keiran S M; Weber, Jeffrey S; Sondak, Vernon K; Gibney, Geoffrey T

    2016-02-01

    Selective BRAF inhibitors (BRAFi) yield objective responses in 50% of patients with metastatic BRAF V600E mutant melanoma. Adding an MEK inhibitor increases this response rate to 70%. Limited data are available on the outcomes of unresectable stage III patients, and it remains unclear whether BRAF-targeted therapy can be utilized as a neoadjuvant strategy. Data on patients with advanced locoregional BRAF V600E mutant melanoma treated with BRAF-targeted therapy at Moffitt Cancer Center were analyzed to determine response rates, subsequent resection rates after tumor downsizing, pathologic responses, and patient survival. Fifteen patients with locoregional disease treated with BRAF-targeted therapy, either BRAFi alone (vemurafenib; 11 patients) or a combination of BRAFi and an MEK inhibitor (dabrafenib plus trametinib or placebo; four patients), were identified. The median age was 50 years; the median follow-up was 25.4 months. The median BRAF-targeted therapy treatment duration was 6.0 months (range 1.2-29.4 months). Response Evaluation Criteria In Solid Tumors-based evaluation demonstrated objective response in 11 patients (73.3%). Six patients underwent resection of the remaining disease after therapy. Pathological analysis showed complete pathologic response (n=2), partial pathologic response (n=2), or no pathologic response (n=2). Four of six patients undergoing surgery have been alive for more than 2 years, including three patients currently free from active disease. No complications attributable to BRAF-targeted therapy were observed in the perioperative period. Dose reduction or discontinuation because of toxicities occurred in 10/15 patients. Neoadjuvant BRAF-targeted therapy may be effective in advanced locoregional BRAF V600E mutant melanoma patients in increasing resectability, yielding pathological responses, and achieving prolonged survival. PMID:26731560

  11. Preparation and characterization of a novel Al(18)F-NOTA-BZA conjugate for melanin-targeted imaging of malignant melanoma.

    Science.gov (United States)

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

    2016-08-15

    Melanin is an attractive target for the diagnosis and treatment of malignant melanoma. Previous studies have demonstrated the specific binding ability of benzamide moiety to melanin. In this study, we developed a novel (18)F-labeled NOTA-benzamide conjugate, Al(18)F-NOTA-BZA, which can be synthesized in 30min with a radiochemical yield of 20-35% and a radiochemical purity of >95%. Al(18)F-NOTA-BZA is highly hydrophilic (logP=-1.96) and shows good in vitro stability. Intravenous administration of Al(18)F-NOTA-BZA in two melanoma-bearing mouse models revealed highly specific uptake in B16F0 melanotic melanoma (6.67±0.91 and 1.50±0.26%ID/g at 15 and 120min p.i., respectively), but not in A375 amelanotic melanoma (0.87±0.21 and 0.24±0.09%ID/g at 15 and 120min p.i., respectively). The clearance from most normal tissues was fast. A microPET scan of Al(18)F-NOTA-BZA-injected mice also displayed high-contrast tumor images as compared with normal organs. Owing to the favorable in vivo distribution of Al(18)F-NOTA-BZA after intravenous administration, the estimated absorption dose was low in all normal organs and tissues. The melanin-specific binding ability, sustained tumor retention, fast normal tissues clearance and thelow projected human dosimetry supported that Al(18)F-NOTA-BZA is a very promising melanin-specific PET probe for melanin-positive melanoma. PMID:27445169

  12. Hereditary melanoma: Update on syndromes and management: Emerging melanoma cancer complexes and genetic counseling.

    Science.gov (United States)

    Soura, Efthymia; Eliades, Philip J; Shannon, Kristen; Stratigos, Alexander J; Tsao, Hensin

    2016-03-01

    Recent advances in cancer genomics have enabled the discovery of many cancer-predisposing genes that are being used to classify new familial melanoma/cancer syndromes. In addition to CDKN2A and CDK4, germline variants in TERT, MITF, and BAP1 have been added to the list of genes harboring melanoma-predisposing mutations. These newer entities may have escaped earlier description in part because of more advanced technologies now being used and in part because of their mixed cancer phenotype as opposed to a melanoma-focused syndrome. Dermatologists should be aware of (and be able to recognize) the clinical signs in high-risk patients in different contexts. Personal and family histories of cancer should always be sought in patients with multiple nevi or a positive history for melanoma, and should be updated annually. Various features that are unique to specific disorders, such as the appearance of melanocytic BAP1-mutated atypical intradermal tumors in cases of BAP1 melanoma syndrome, should also be recognized early. These patients should be offered regular screenings with the use of dermoscopy and total body photography, as needed. More importantly, referral to other specialists may be needed if a risk for internal malignancy is suspected. It is important to have in mind that these patients tend to develop multiple melanomas, along with various internal organ malignancies, often at younger ages; a multidisciplinary approach to their cancer screening and treatment is ideal. PMID:26892651

  13. Oral amelanotic melanoma of the maxilla.

    Directory of Open Access Journals (Sweden)

    Nasrollah Saghravanian

    2014-12-01

    Full Text Available Amelanotic melanoma is a variant of malignant melanoma comprising 2% to 8% of all malignant melanomas. The amelanotic presentation of melanoma in the oral cavity is extremely rare and has been reported only occasionally in the literature. Moreover, the lack of melanin makes these tumors difficult to diagnose than that of pigmented lesions and the prognosis tends to be poorer. Herein, we report an amelanotic melanoma involving the oral mucosa of the maxilla in a 27 year-old male.

  14. 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

  15. Cost-effectiveness of preoperative SPECT/CT combined with lymphoscintigraphy vs. lymphoscintigraphy for sentinel lymph node excision in patients with cutaneous malignant melanoma

    International Nuclear Information System (INIS)

    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

  16. Phase II study of recombinant leukocyte A interferon (IFN-rA) plus cimetidine in disseminated malignant melanoma.

    Science.gov (United States)

    Creagan, E T; Ahmann, D L; Green, S J; Long, H J; Frytak, S; Itri, L M

    1985-07-01

    Thirty-five eligible patients with disseminated malignant melanoma received intramuscular recombinant leukocyte interferon (IFN-rA), 50 X 10(6) U/m2 three times weekly (TIW) for an intended duration of 12 weeks concomitant with daily oral cimetidine, 1,200 mg/d in four divided doses. For all study participants, the median survival time was six months. Among 21 "good risk" patients (performance score [PS] 0, 1 and no prior chemotherapy), we observed seven partial regressions (33%). Six patients had stability of disease (29%), seven had immediate disease progression, and one discontinued treatment after two doses without tumor evaluation due to side effects. Times to disease progression of five patients with regressions of soft-tissue disease were 2.1, 3.3, 3.5, 3.7, and 4.3 months. Two patients had partial regressions of lung nodules for 2.0 and 3.8 months. We observed one regression among 14 "poor risk" patients (PS 2, 3, or prior chemotherapy). A 46-year-old woman with prior treatment had a partial regression of soft-tissue disease for 4.1 months. Four "poor risk" patients achieved disease stability, and nine progressed immediately. Leukopenia (WBC count less than 4,100/microL) affected 21 (66%) of 32 patients with WBC count data. The median count was 3,100/microL; range, 1,300 to 8,400/microL. We detected two cases of mild thrombocytopenia (100,000 and 120,000/microL). Other noteworthy toxicities included moderate-to-severe nausea (34%), anorexia (63%), and fatigue (80%). All patients experienced myalgias. Twenty patients had dosage decreases during the first cycle, and 14 of the 16 patients remaining on study after the first cycle required dosage reductions. The overall response rate is similar to our prior studies with IFN-rA as a single agent using TIW doses of 50 X 10(6) U/m2 and 12 X 10(6) U/m2 among 31 and 30 patients, respectively. PMID:4020408

  17. Novel ZnO:Ag nanocomposites induce significant oxidative stress in human fibroblast malignant melanoma (Ht144 cells

    Directory of Open Access Journals (Sweden)

    Syeda Arooj

    2015-02-01

    Full Text Available The use of photoactive nanoparticles (NPs such as zinc oxide (ZnO and its nanocomposites has become a promising anticancer strategy. However, ZnO has a low photocatalytic decomposition rate and the incorporation of metal ions such as silver (Ag improves their activity. Here different formulations of ZnO:Ag (1, 3, 5, 10, 20 and 30% Ag were synthesized by a simple co-precipitation method and characterized by powder X-ray diffraction, scanning electron microscopy, Rutherford back scattering and diffuse reflectance spectroscopy for their structure, morphology, composition and optical band gap. The NPs were investigated with regard to their different photocatalytic cytotoxic effects in human malignant melanoma (HT144 and normal (HCEC cells. The ZnO:Ag nanocomposites killed cancer cells more efficiently than normal cells under daylight exposure. Nanocomposites having higher Ag content (10, 20 and 30% were more toxic compared to low Ag content (1, 3 and 5%. For HT144, under daylight exposure, the IC50 values were ZnO:Ag (10%: 23.37 μg/mL, ZnO:Ag (20%: 19.95 μg/mL, and ZnO:Ag (30%: 15.78 μg/mL. ZnO:Ag (30% was toxic to HT144 (IC50: 23.34 μg/mL in dark as well. The three nanocomposites were further analyzed with regard to their ability to generate reactive oxygen species (ROS and induce lipid peroxidation. The particles led to an increase in levels of ROS at cytotoxic concentrations, but only HT144 showed strongly induced MDA level. Finally, NPs were investigated for the ROS species they generated in vitro. A highly significant increase of 1O2 in the samples exposed to daylight was observed. Hydroxyl radical species, HO•, were also generated to a lesser extent. Thus, the incorporation of Ag into ZnO NPs significantly improves their photo-oxidation capabilities. ZnO:Ag nanocomposites could provide a new therapeutic option to selectively target cancer cells.

  18. Biochemotherapy with Carmustine, Cisplatin, Dacarbazine, Tamoxifen and Low-dose Interleukin-2 for Patients with Metastatic Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    Po-Jung Su

    2011-10-01

    Full Text Available Background: The toxicity and efficacy of biochemotherapy with low-dose interleukin-2for patients with metastatic malignant melanoma (MM were studied.Method: Metastatic chemo-naïve MM patients were given biochemotherapy (BCDTregimen with carmustine (BCNU, cisplatin (CDDP, dacarbazine (DTIC,and tamoxifen and interleukin-2 (IL-2 18 Million International Units individed doses by subcutaneous injection three times a week for four weeks.BCDT consisted of BCNU (150 mg/m2, day l every 8 weeks, CDDP (25mg/m2, days l-3 every 4 weeks, DTIC (220 mg/m2, days 1-3 every 4 weeksand tamoxifen 10 mg twice a day. Treatment was repeated for a total of 6cycles, or until disease progression or unbearable toxicity.Results: From Nov 2001 to July 2005, 40 pa t i ent s (20 men; 20 women we r eenrolled. Their median age was 54 years (range 22-79 years. Subtypes ofmelanoma included 23 (57.5% acral lentiginous, 11 (27.5% nodular, 1(2.5% mucosal, and 5 (12.5% others. Grade 3-4 toxicities included neut r o p e n i a ( 2 7 . 5 % , a n e m i a ( 4 5 % , a n d t h r o m b o c y t o p e n i a ( 4 0 % .Constitutional IL-2 toxicities included indurate injection site (57.5%, fever(60%, chills (55%, itchy skin (42.5%, bone pain (32.5% and myalgia(45%. Grade 1-2 hypotension was noted in 12.5% of patients. Eosinophilia(range 5% to 71% was evident in 72.5% of patients. The response rate was32.5% inc luding 5% wi th a compl e t e r e spons e , 27.5% wi th a pa r t i a lresponse, and 17.5% with stable disease. The median progression-free survival was 6.2 months (95% CI: 2.9~9.6 months. The median overall survival was 11.3 months (95% CI: 7.0~15.6 months. Five patients (12.5%who presented with oligo-metastasis achieved five-year survivals.Conclusions: Our data demonstrated that low-dose IL-2 plus BCDT is tolerable. A durableresponse and long-term survival can be achieved in a small subgroup ofpatients.

  19. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  20. 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 BACKGROUND: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.

  1. Multi-center evaluation of the novel fully-automated PCR-based Idylla™ BRAF Mutation Test on formalin-fixed paraffin-embedded tissue of malignant melanoma.

    Science.gov (United States)

    Melchior, Linea; Grauslund, Morten; Bellosillo, Beatriz; Montagut, Clara; Torres, Erica; Moragón, Ester; Micalessi, Isabel; Frans, Johan; Noten, Veerle; Bourgain, Claire; Vriesema, Renske; van der Geize, Robert; Cokelaere, Kristof; Vercooren, Nancy; Crul, Katrien; Rüdiger, Thomas; Buchmüller, Diana; Reijans, Martin; Jans, Caroline

    2015-12-01

    The advent of BRAF-targeted therapies led to increased survival in patients with metastatic melanomas harboring a BRAF V600 mutation (implicated in 46-48% of malignant melanomas). The Idylla(™) System (Idylla(™)), i.e., the real-time-PCR-based Idylla(™) BRAF Mutation Test performed on the fully-automated Idylla(™) platform, enables detection of the most frequent BRAF V600 mutations (V600E/E2/D, V600K/R/M) in tumor material within approximately 90 min and with 1% detection limit. Idylla(™) performance was determined in a multi-center study by analyzing BRAF mutational status of 148 archival formalin-fixed paraffin-embedded (FFPE) tumor samples from malignant melanoma patients, and comparing Idylla(™) results with assessments made by commercial or in-house routine diagnostic methods. Of the 148 samples analyzed, Idylla(™) initially recorded 7 insufficient DNA input calls and 15 results discordant with routine method results. Further analysis learned that the quality of 8 samples was insufficient for Idylla(™) testing, 1 sample had an invalid routine test result, and Idylla(™) results were confirmed in 10 samples. Hence, Idylla(™) identified all mutations present, including 7 not identified by routine methods. Idylla(™) enables fully automated BRAF V600 testing directly on FFPE tumor tissue with increased sensitivity, ease-of-use, and much shorter turnaround time compared to existing diagnostic tests, making it a tool for rapid, simple and highly reliable analysis of therapeutically relevant BRAF mutations, in particular for diagnostic units without molecular expertise and infrastructure. PMID:26407762

  2. Melanoma screening: A plan for improving early detection.

    Science.gov (United States)

    Shellenberger, Richard; Nabhan, Mohammed; Kakaraparthi, Sweta

    2016-05-01

    Malignant melanoma ranks fifth in the number of new cases annually in the United States (US). Despite increasing incidence and lack of recent improvement in mortality, national melanoma screening guidelines are currently not in existence. Our purpose was to review the evidence regarding screening whole-body skin examinations for early detection and a possible mortality benefit for malignant melanoma. Data sources for our review were MEDLINE Complete, PubMed, Cochrane Library, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. Study selection included: epidemiologic data from the US and European cancer surveillance registries, population-based case-control screening trials, computer-simulated Markov model trials, and survey trials. Studies were limited to those published in the English language. Data was extracted using a dual extraction method. Data from studies have shown that the mortality of malignant melanoma is highly predicated on the tumor thickness at the time of diagnosis. Our data review is in support of the implementation of whole-body skin examinations, performed by primary care physicians, for the purpose of early detection of melanoma. A large national population-based, case-control, skin cancer screening trial in Germany has shown a reduction in melanoma-specific mortality. In conclusion, our review of the evidence supports physicians performed whole-body skin examination can lead to the detection of earlier stage melanomas as well as to a reduction in disease-specific mortality. We found a paucity of randomized trials to be a limitation of screening studies for many cancers, including melanoma. To improve screening rates and early detection of malignant melanoma, we propose making skin cancer education part of the curriculum in US primary care residency programs to become the genesis for widespread melanoma screening. Our study had no funding. Key messages Malignant melanoma is the fifth leading cancer in the United States (US). In the

  3. Melanoma inhibitor of apoptosis protein is expressed differentially in melanoma and melanocytic naevus, but similarly in primary and metastatic melanomas

    OpenAIRE

    Gong, J; Chen, N; Zhou, Q; Yang, B.; Wang, Y; Wang, X.

    2005-01-01

    Background: Malignant melanoma is highly resistant to current treatments. The inhibitor of apoptosis protein (IAP) family member, melanoma IAP (ML-IAP), is overexpressed in some melanoma cell lines, rendering them resistant to apoptotic signals. Targeting ML-IAP is a promising approach to treating melanoma. However, the status of ML-IAP expression in human melanoma tissues and the difference in expression between melanoma and melanocytic naevus are not known.

  4. Real-world treatment practice in patients with advanced melanoma in the era before ipilimumab: results from the IMAGE study.

    Science.gov (United States)

    Middleton, Mark R; Dalle, Stéphane; Claveau, Joel; Mut, Pilar; Hallmeyer, Sigrun; Plantin, Patrice; Highley, Martin; Kotapati, Srividya; Le, Trong Kim; Brokaw, Jane; Abernethy, Amy P

    2016-07-01

    The therapeutic landscape for advanced melanoma has recently been transformed by several novel agents (immune checkpoint inhibitors and molecular-targeted agents). The prospective, multi-site, observational study IMAGE (ipilimumab: management of advanced melanoma in real practice) included a retrospective cohort to describe real-world treatment prior to approval of the immune checkpoint inhibitor ipilimumab. This retrospective cohort of patients, who started second-line/subsequent treatment (index therapy) for advanced melanoma within 3 years before ipilimumab approval, was selected randomly by chart review. Collected data included treatment history, patient outcomes, and healthcare resource utilization. All patients had ≥1 year of follow-up data. This analysis included 177 patients from Europe (69%) and North America (31%). The most common index therapies (used alone or in combination) were fotemustine (23%), dacarbazine (21%), temozolomide (14%), and platinum-based chemotherapy (14%). Most patients (89%) discontinued index treatment during the study period; the most common reason was disease progression (59%). Among patients with tumor assessment (153/177; 86%), 2% had complete response, 5% had partial response, and 12% had stable disease on last tumor assessment. At 1-year study follow-up, median progression-free survival was 2.6 months (95% confidence interval [CI], 2.1-2.9) and median overall survival was 8.8 months (95% CI, 6.5-9.7). During follow-up, 95% of the patients had healthcare visits for advanced melanoma, 74% of whom were hospitalized or admitted to a hospice facility. These results provide insights into patient care with advanced melanoma in the era before ipilimumab and may serve as a benchmark for new agents in future real-world studies. PMID:27118102

  5. Are all melanomas dangerous?

    DEFF Research Database (Denmark)

    Nørgaard, Carsten; Glud, Martin; Gniadecki, Robert

    2011-01-01

    The increased incidence of cutaneous malignant melanoma, together with only minor changes in mortality, has brought into question the existence of a melanoma epidemic. The discrepancy between incidence and mortality suggests that most newly diagnosed melanomas have indolent behaviour. This review...... summarizes the most recent epidemiological findings regarding the incidence of cutaneous malignant melanoma, mortality, Breslow thickness and clinical stage. Studies published between 2005 and 2010 with more than 2,000 test subjects were included in this review. These studies all report an increase in...... incidence of melanoma during the last few decades, with by far the highest increase in tumours at a very early stage (T1 or IA). Little or no change was seen in mortality. However, increases in both mortality and incidence of thick melanomas were found in the oldest subgroups, especially in men. These...

  6. Electric pulses used in electrochemotherapy and electrogene therapy do not significantly change the expression profile of genes involved in the development of cancer in malignant melanoma cells

    Directory of Open Access Journals (Sweden)

    Glavac Damjan

    2009-08-01

    Full Text Available Abstract Background Electroporation is a versatile method for in vitro or in vivo delivery of different molecules into cells. However, no study so far has analysed the effects of electric pulses used in electrochemotherapy (ECT pulses or electric pulses used in electrogene therapy (EGT pulses on malignant cells. We studied the effect of ECT and EGT pulses on human malignant melanoma cells in vitro in order to understand and predict the possible effect of electric pulses on gene expression and their possible effect on cell behaviour. Methods We used microarrays with 2698 different oligonucleotides to obtain the expression profile of genes involved in apoptosis and cancer development in a malignant melanoma cell line (SK-MEL28 exposed to ECT pulses and EGT pulses. Results Cells exposed to ECT pulses showed a 68.8% average survival rate, while cells exposed to EGT pulses showed a 31.4% average survival rate. Only seven common genes were found differentially expressed in cells 16 h after exposure to ECT and EGT pulses. We found that ECT and EGT pulses induce an HSP70 stress response mechanism, repress histone protein H4, a major protein involved in chromatin assembly, and down-regulate components involved in protein synthesis. Conclusion Our results show that electroporation does not significantly change the expression profile of major tumour suppressor genes or oncogenes of the cell cycle. Moreover, electroporation also does not changes the expression of genes involved in the stability of DNA, supporting current evidence that electroporation is a safe method that does not promote tumorigenesis. However, in spite of being considered an isothermal method, it does to some extent induce stress, which resulted in the expression of the environmental stress response mechanism, HSP70.

  7. Electric pulses used in electrochemotherapy and electrogene therapy do not significantly change the expression profile of genes involved in the development of cancer in malignant melanoma cells

    International Nuclear Information System (INIS)

    Electroporation is a versatile method for in vitro or in vivo delivery of different molecules into cells. However, no study so far has analysed the effects of electric pulses used in electrochemotherapy (ECT pulses) or electric pulses used in electrogene therapy (EGT pulses) on malignant cells. We studied the effect of ECT and EGT pulses on human malignant melanoma cells in vitro in order to understand and predict the possible effect of electric pulses on gene expression and their possible effect on cell behaviour. We used microarrays with 2698 different oligonucleotides to obtain the expression profile of genes involved in apoptosis and cancer development in a malignant melanoma cell line (SK-MEL28) exposed to ECT pulses and EGT pulses. Cells exposed to ECT pulses showed a 68.8% average survival rate, while cells exposed to EGT pulses showed a 31.4% average survival rate. Only seven common genes were found differentially expressed in cells 16 h after exposure to ECT and EGT pulses. We found that ECT and EGT pulses induce an HSP70 stress response mechanism, repress histone protein H4, a major protein involved in chromatin assembly, and down-regulate components involved in protein synthesis. Our results show that electroporation does not significantly change the expression profile of major tumour suppressor genes or oncogenes of the cell cycle. Moreover, electroporation also does not changes the expression of genes involved in the stability of DNA, supporting current evidence that electroporation is a safe method that does not promote tumorigenesis. However, in spite of being considered an isothermal method, it does to some extent induce stress, which resulted in the expression of the environmental stress response mechanism, HSP70

  8. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaosong [Department of Oncology, the First Affiliated Hospital of Chinese PLA General Hospital, Beijing (China); Hode, Tomas; Guerra, Maria C [Immunophotonics Inc., 1601 South Providence Road, Columbia, Missouri 65211 (United States); Ferrel, Gabriela L [Hospital Nacional Edgardo Rebagliati Martins, Av. Edgardo Rebagliati 490 - Jesus Maria, Lima (Peru); Nordquist, Robert E [Wound Healing of Oklahoma, Inc., Oklahoma City, Oklahoma (United States); Chen, Wei R, E-mail: wchen@uco.edu [Department of Engineering and Physics, University of Central Oklahoma, Edmond, Oklahoma (United States)

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  9. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    International Nuclear Information System (INIS)

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  10. Radiobiology of malignant melanoma. Melanin behavior in gamma radiation induced oxidadative strees and genotoxicity: implications for radiotherapy

    OpenAIRE

    Fonseca, Sérgio Manuel Lopes da

    2009-01-01

    Os objectivos do presente trabalho são: avaliar o efeito sensibilizante ou protector da molécula de melanina na citotoxicidade e genotoxicidade da radiação ionizante, investigar a modulação do stress oxidativo radioinduzido em células de melanoma maligno na presença e ausência de melanina e interpretar os resultados na perspectiva da radioterapia do melanoma ou outras neoplasias malignas. É ainda apresentada uma revisão bibliográfica acerca dos cancros cutâneos com especial atenção para o ...

  11. In vivo assessment of optical properties of melanocytic skin lesions and differentiation of melanoma from non-malignant lesions by high-definition optical coherence tomography.

    Science.gov (United States)

    Boone, M A L M; Suppa, M; Dhaenens, F; Miyamoto, M; Marneffe, A; Jemec, G B E; Del Marmol, V; Nebosis, R

    2016-01-01

    One of the most challenging problems in clinical dermatology is the early detection of melanoma. Reflectance confocal microscopy (RCM) is an added tool to dermoscopy improving considerably diagnostic accuracy. However, diagnosis strongly depends on the experience of physicians. High-definition optical coherence tomography (HD-OCT) appears to offer additional structural and cellular information on melanocytic lesions complementary to that of RCM. However, the diagnostic potential of HD-OCT seems to be not high enough for ruling out the diagnosis of melanoma if based on morphology analysis. The aim of this paper is first to quantify in vivo optical properties such as light attenuation in melanocytic lesions by HD-OCT. The second objective is to determine the best critical value of these optical properties for melanoma diagnosis. The technique of semi-log plot whereby an exponential function becomes a straight line has been implemented on HD-OCT signals coming from four successive skin layers (epidermis, upper papillary dermis, deeper papillary dermis and superficial reticular dermis). This permitted the HD-OCT in vivo measurement of skin entrance signal (SES), relative attenuation factor normalized for the skin entrance signal (µ raf1) and half value layer (z 1/2). The diagnostic accuracy of HD-OCT for melanoma detection based on the optical properties, µ raf1 , SES and z 1/2 was high (95.6, 82.2 and 88.9 %, respectively). High negative predictive values could be found for these optical properties (96.7, 89.3 and 96.3 %, respectively) compared to morphologic assessment alone (89.9 %), reducing the risk of mistreating a malignant lesion to a more acceptable level (3.3 % instead of 11.1 %). HD-OCT seems to enable the combination of in vivo morphological analysis of cellular and 3-D micro-architectural structures with in vivo analysis of optical properties of tissue scatterers in melanocytic lesions. In vivo HD-OCT analysis of optical properties permits melanoma

  12. Melanoma Diagnosis

    Science.gov (United States)

    Horsch, Alexander

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

  13. Immune checkpoint blockade with concurrent electrochemotherapy in advanced melanoma: a retrospective multicenter analysis.

    Science.gov (United States)

    Heppt, Markus V; Eigentler, Thomas K; Kähler, Katharina C; Herbst, Rudolf A; Göppner, Daniela; Gambichler, Thilo; Ulrich, Jens; Dippel, Edgar; Loquai, Carmen; Schell, Beatrice; Schilling, Bastian; Schäd, Susanne G; Schultz, Erwin S; Matheis, Fanny; Tietze, Julia K; Berking, Carola

    2016-08-01

    Growing evidence suggests that concurrent loco-regional and systemic treatment modalities may lead to synergistic anti-tumor effects in advanced melanoma. In this retrospective multicenter study, we evaluate the use of electrochemotherapy (ECT) combined with ipilimumab or PD-1 inhibition. We investigated patients with unresectable or metastatic melanoma who received the combination of ECT and immune checkpoint blockade for distant or cutaneous metastases within 4 weeks. Clinical and laboratory data were collected and analyzed with respect to safety and efficacy. A total of 33 patients from 13 centers were identified with a median follow-up time of 9 months. Twenty-eight patients received ipilimumab, while five patients were treated with a PD-1 inhibitor (pembrolizumab n = 3, nivolumab n = 2). The local overall response rate (ORR) was 66.7 %. The systemic ORR was 19.2 and 40.0 % in the ipilimumab and PD-1 cohort, respectively. The median duration of response was not reached in either group. The median time to disease progression was 2.5 months for the entire population with 2 months for ipilimumab and 5 months for PD-1 blockade. The median overall survival was not reached in patients with ipilimumab and 15 months in the PD-1 group. Severe systemic adverse events were detected in 25.0 % in the ipilimumab group. No treatment-related deaths were observed. This is the first reported evaluation of ECT and simultaneous PD-1 inhibition and the largest published dataset on ECT with concurrent ipilimumab. The local response was lower than reported for ECT only. Ipilimumab combined with ECT was feasible, tolerable and showed a high systemic response rate. PMID:27294607

  14. Pharmacodynamic Characterization of the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma

    Directory of Open Access Journals (Sweden)

    William D. Tap

    2010-08-01

    Full Text Available PURPOSE: About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF that causes the steady-state activation of extracellular signal-regulated kinase (ERK. We sought to investigate the efficacy of PLX4032 (BRAF inhibitor to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma. EXPERIMENTAL DESIGN: Well-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling, cell cycle, apoptosis, and gene expression analyses were performed before and after exposure to drug. RESULTS: Using a growth-adjusted inhibitory concentration of 50% cutoff of 1 µM, 13 of 35 cell lines were sensitive to PLX4032, 16 resistant, and 6 intermediate (37%, 46%, and 17% respectively. PLX4032 caused growth inhibition, G0/G1 arrest, and restored apoptosis in the sensitive cell lines. A BRAF mutation predicted for but did not guarantee a response, whereas a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ line variants and/or a more differentiated melanocyte genotype had a preferential response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a nonmelanocytic genotype, and is associated with an increase in the gene expression of certain metallothioneins and mediators of angiogenesis. CONCLUSIONS: PLX4032 has robust activity in BRAF mutated melanoma. The preclinical use of this molecule identifies criteria for its proper clinical application, describes patterns of and reasons for response/resistance, and affords insight into the role of a BRAF mutation in melanoma.

  15. Pharmacodynamic Characterization of the Efficacy Signals Due to Selective BRAF Inhibition with PLX4032 in Malignant Melanoma12

    Science.gov (United States)

    Tap, William D; Gong, Ke-Wei; Dering, Judy; Tseng, Yiou; Ginther, Charles; Pauletti, Giovanni; Glaspy, John A; Essner, Richard; Bollag, Gideon; Hirth, Peter; Zhang, Chao; Slamon, Dennis J

    2010-01-01

    Purpose About 65% to 70% of melanomas harbor a mutation in v-raf murine sarcoma viral oncogene homolog B1 (BRAF) that causes the steady-state activation of extracellular signal-regulated kinase (ERK). We sought to investigate the efficacy of PLX4032 (BRAF inhibitor) to identify patterns/predictors of response/resistance and to study the effects of BRAF in melanoma. Experimental Design Well-characterized melanoma cell lines, including several with acquired drug resistance, were exposed to PLX4032. Growth inhibition, phosphosignaling, cell cycle, apoptosis, and gene expression analyses were performed before and after exposure to drug. Results Using a growth-adjusted inhibitory concentration of 50% cutoff of 1 µM, 13 of 35 cell lines were sensitive to PLX4032, 16 resistant, and 6 intermediate (37%, 46%, and 17% respectively). PLX4032 caused growth inhibition, G0/G1 arrest, and restored apoptosis in the sensitive cell lines. A BRAF mutation predicted for but did not guarantee a response, whereas a neuroblastoma RAS viral oncogene homolog mutation or wild-type BRAF conferred resistance. Cells with concurrent BRAF mutations and melanocortin 1 receptor germ line variants and/or a more differentiated melanocyte genotype had a preferential response. Acquired PLX4032 resistance reestablishes ERK signaling, promotes a nonmelanocytic genotype, and is associated with an increase in the gene expression of certain metallothioneins and mediators of angiogenesis. Conclusions PLX4032 has robust activity in BRAF mutated melanoma. The preclinical use of this molecule identifies criteria for its proper clinical application, describes patterns of and reasons for response/resistance, and affords insight into the role of a BRAF mutation in melanoma. PMID:20689758

  16. Long-term outcomes among older patients following nonmyeloablative conditioning and allogeneic hematopoietic cell transplantation for advanced hematologic malignancies

    DEFF Research Database (Denmark)

    Sorror, Mohamed L; Sandmaier, Brenda M; Storer, Barry E;

    2011-01-01

    A minimally toxic nonmyeloablative regimen was developed for allogeneic hematopoietic cell transplantation (HCT) to treat patients with advanced hematologic malignancies who are older or have comorbid conditions....

  17. Autophagy- An emerging target for melanoma therapy.

    Science.gov (United States)

    Ndoye, Abibatou; Weeraratna, Ashani T

    2016-01-01

    Melanoma accounts for only 5% of all cancers but is the leading cause of skin cancer death due to its high metastatic potential. Patients with metastatic melanoma have a 10-year survival rate of less than 10%. While the clinical landscape for melanoma is evolving rapidly, lack of response to therapies, as well as resistance to therapy remain critical obstacles for treatment of this disease. In recent years, a myriad of therapy resistance mechanisms have been unravelled, one of which is autophagy, the focus of this review. In advanced stages of malignancy, melanoma cells hijack the autophagy machinery in order to alleviate drug-induced and metabolic stress in the tumor microenvironment, thereby promoting resistance to multiple therapies, tumor cell survival, and progression.  Autophagy is an essential cellular process that maintains cellular homeostasis through the recycling of intracellular constituents. Early studies on the role of autophagy in cancer generated controversy as to whether autophagy was pro- or anti-tumorigenic. Currently, there is a consensus that autophagy is tumor-suppressive in the early stages of cancer and tumor-promoting in established tumors.  This review aims to highlight current understandings on the role of autophagy in melanoma malignancy, and specifically therapy resistance; as well as to evaluate recent strategies for therapeutic autophagy modulation. PMID:27583134

  18. 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)

    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

  19. 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

    Oncogene addiction describes how cancer cells exhibit dependence on single oncogenes to escape apoptosis and senescence. While oncogene addiction constitutes the basis for new cancer treatment strategies targeting individual kinases and pathways activated by oncogenic mutations, the biochemical...... 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...

  20. 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)

    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 3H]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

  1. CD45/CD8 myeloid histioid antigen and plasma cell antibody immune response in a case of malignant melanoma

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu-Velez

    2012-01-01

    Full Text Available The immune response in metastatic melanoma is not well established and therefore is of particular interest to test for recruitment of immune cells to the tumor. A 46-year-old Caucasian female was evaluated for an asymptomatic right forearm mass. The lesion had been present for at least 4 years and had become painful 4 months ago. Biopsies for hematoxylin and eosin (H and E staining, as well as immunohistochemical analysis were performed on the primary tumor and on sentinel lymph nodes. The H and E staining was consistent with metastatic melanoma. Positive staining was noted on the tumor cells with S-100, Mart-1/Melan A/CD63, PNL2, HMB45, and tyrosinase. Peritumoral and intratumoral inflammatory cells stained positive for CD8, CD45, PCNA, myeloid histoid antigen, antihuman plasma cell antibody, and focal BRCA1. The staining patterns of CD8/CD45, myeloid histoid antigen and plasma cell antibody on inflammatory cells around the melanoma cells suggest an unusual type of immune response.

  2. Patient derived cell culture and isolation of CD133⁺ putative cancer stem cells from melanoma.

    Science.gov (United States)

    Welte, Yvonne; Davies, Cathrin; Schäfer, Reinhold; Regenbrecht, Christian R A

    2013-01-01

    Despite improved treatments options for melanoma available today, patients with advanced malignant melanoma still have a poor prognosis for progression-free and overall survival. Therefore, translational research needs to provide further molecular evidence to improve targeted therapies for malignant melanomas. In the past, oncogenic mechanisms related to melanoma were extensively studied in established cell lines. On the way to more personalized treatment regimens based on individual genetic profiles, we propose to use patient-derived cell lines instead of generic cell lines. Together with high quality clinical data, especially on patient follow-up, these cells will be instrumental to better understand the molecular mechanisms behind melanoma progression. Here, we report the establishment of primary melanoma cultures from dissected fresh tumor tissue. This procedure includes mincing and dissociation of the tissue into single cells, removal of contaminations with erythrocytes and fibroblasts as well as primary culture and reliable verification of the cells' melanoma origin. Recent reports revealed that melanomas, like the majority of tumors, harbor a small subpopulation of cancer stem cells (CSCs), which seem to exclusively fuel tumor initiation and progression towards the metastatic state. One of the key markers for CSC identification and isolation in melanoma is CD133. To isolate CD133(+) CSCs from primary melanoma cultures, we have modified and optimized the Magnetic-Activated Cell Sorting (MACS) procedure from Miltenyi resulting in high sorting purity and viability of CD133(+) CSCs and CD133(-) bulk, which can be cultivated and functionally analyzed thereafter. PMID:23525090

  3. Clinical applications of recent molecular advances in urologic malignancies: no longer chasing a "mirage"?

    Science.gov (United States)

    Netto, George J

    2013-05-01

    As our understanding of the molecular events leading to the development and progression of genitourologic malignancies, new markers of detection, prognostication, and therapy prediction can be exploited in the management of these prevalent tumors. The current review discusses the recent advances in prostate, bladder, renal, and testicular neoplasms that are pertinent to the anatomic pathologist. PMID:23574774

  4. 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...

  5. A review of advanced genetic testing for clinical prognostication in uveal melanoma.

    Science.gov (United States)

    Werdich, Xiang Q; Jakobiec, Frederick A; Singh, Arun D; Kim, Ivana K

    2013-01-01

    Uveal melanoma (UM) has a strong propensity to metastasize and the prognosis for metastatic disease is very poor. It has been suggested that occult micrometastases are already present, but undetectable, in many patients at the time when the primary ocular tumor is diagnosed and treated. To identify high-risk patients for close monitoring and early intervention with prophylactic adjuvant systemic therapy, an accurate predictive system is necessary for stratifying those patients at risk of developing metastatic disease. To date, many clinical and histopathological features, molecular pathway characteristics, and genetic fingerprints of UM have been suggested for disease prognostication. Among the newest of them, tumor genetics has received the most attention in demonstrating promise as a prognostic tool. Because of the plethora of recent developments, we summarize and compare in this review the important standard and more advanced cytogenetic prognostic markers. We further describe the variety of genetic tests available for prognostication of UM, and provide a critical assessment of the respective advantages and disadvantages of these tools. PMID:24010756

  6. Decoding Melanoma Metastasis

    International Nuclear Information System (INIS)

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis

  7. Decoding Melanoma Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Damsky, William E. Jr. [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States); Department of Pathology, University of Vermont College of Medicine, Burlington, Vermont (United States); Rosenbaum, Lara E.; Bosenberg, Marcus, E-mail: Marcus.Bosenberg@yale.edu [Department of Dermatology, Yale School of Medicine, New Haven, Connecticut (United States)

    2010-12-30

    Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

  8. 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)

    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)

  9. 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)

    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.)

  10. Molecular and therapeutic advances in the diagnosis and management of malignant pheochromocytomas and paragangliomas.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2013-01-01

    Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare catecholamine-secreting tumors derived from chromaffin cells originating in the neural crest. These tumors represent a significant diagnostic and therapeutic challenge because the diagnosis of malignancy is frequently made in retrospect by the development of metastatic or recurrent disease. Complete surgical resection offers the only potential for cure; however, recurrence can occur even after apparently successful resection of the primary tumor. The prognosis for malignant disease is poor because traditional treatment modalities have been limited. The last decade has witnessed exciting discoveries in the study of PCCs and PGLs; advances in molecular genetics have uncovered hereditary and germline mutations of at least 10 genes that contribute to the development of these tumors, and increasing knowledge of genotype-phenotype interactions has facilitated more accurate determination of malignant potential. Elucidating the molecular mechanisms responsible for malignant transformation in these tumors has opened avenues of investigation into targeted therapeutics that show promising results. There have also been significant advances in functional and radiological imaging and in the surgical approach to adrenalectomy, which remains the mainstay of treatment for PCC. In this review, we discuss the currently available diagnostic and therapeutic options for patients with malignant PCCs and PGLs and detail the molecular rationale and clinical evidence for novel and emerging diagnostic and therapeutic strategies.

  11. Radiopharmacological characterization of ⁶⁴Cu-labeled α-MSH analogs for potential use in imaging of malignant melanoma.

    Science.gov (United States)

    Gao, Feng; Sihver, Wiebke; Jurischka, Christoph; Bergmann, Ralf; Haase-Kohn, Cathleen; Mosch, Birgit; Steinbach, Jörg; Carta, Davide; Bolzati, Cristina; Calderan, Andrea; Pietzsch, Jens; Pietzsch, Hans-Jürgen

    2016-03-01

    The melanocortin-1 receptor (MC1R) plays an important role in melanoma growth, angiogenesis and metastasis, and is overexpressed in melanoma cells. α-Melanocyte stimulating hormone (α-MSH) and derivatives are known to bind with high affinity at this receptor that provides the potential for selective targeting of melanoma. In this study, one linear α-MSH-derived peptide Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) without linker and with εAhx-β-Ala linker, and a cyclic α-MSH derivative, [Lys-Glu-His-D-Phe-Arg-Trp-Glu]-Arg-Pro-Val-NH2 (NAP-NS2) with εAhx-β-Ala linker were conjugated with p-SCN-Bn-NOTA and labeled with (64)Cu. Radiochemical and radiopharmacological investigations were performed with regard to transchelation, stability, lipophilicity and in vitro binding assays as well as biodistribution in healthy rats. No transchelation reactions, but high metabolic stability and water solubility were demonstrated. The linear derivatives showed higher affinity than the cyclic one. [(64)Cu]Cu-NOTA-εAhx-β-Ala-NAP-NS1 ([(64)Cu]Cu-2) displayed rapid cellular association and dissociation in murine B16F10 cell homogenate. All [(64)Cu]Cu-labeled conjugates exhibited affinities in the low nanomolar range in B16F10. [(64)Cu]Cu-2 showed also high affinity in human MeWo and TXM13 cell homogenate. In vivo studies suggested that [(64)Cu]Cu-2 was stable, with about 85 % of intact peptide in rat plasma at 2 h p.i. Biodistribution confirmed the renal pathway as the major elimination route. The uptake of [(64)Cu]Cu-2 in the kidney was 5.9 % ID/g at 5 min p.i. and decreased to 2.0 % ID/g at 60 min p.i. Due to the prospective radiochemical and radiopharmacological properties of the linear α-MSH derivative [(64)Cu]Cu-2, this conjugate is a promising candidate for tracer development in human melanoma imaging. PMID:26643502

  12. Primary rectal melanoma - a case report

    Directory of Open Access Journals (Sweden)

    Somak Das

    2015-01-01

    Full Text Available The most common site for malignant melanoma is skin, then eye and third is anorectal region. Primary anorectal malignant melanoma is still very uncommon. It is usually very aggressive and presents with altered bowel habit and rectal bleeding. Proctoscopy shows non-pigmented or lightly pigmented polypoid lesion. Histopathology is confirmatory. Early radical excision is mandatory. A 56 year-old female was presented with malignant melanoma of the lower third of rectum. We report this case for its rarity.

  13. Fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in malignant melanoma: Diagnostic comparison with conventional imaging methods

    International Nuclear Information System (INIS)

    Purpose: To assess the diagnostic value of fluor-18-fluorodeoxyglucose positron emission tomography (FDG-PET) in screening for melanoma metastases. Material and Methods: The case records of 94 melanoma patients who had been examined by whole-body FDG-PET between 1995 and 1999 were evaluated retrospectively. Forty patients showed evidence of lymphogenous and 42 of hematogenous metastasis. The maximal interval between PET and the diagnostic procedure under comparison was 2 weeks. Confirmation of the findings was based on histology or the clinical or radiological course. Results: In 24 patients, all diagnostic examinations including CT had been performed within 2 weeks from PET. In no case did PET change the staging. In 13 patients, PET agreed with morphological diagnosis in the number of metastatically invaded organs. This included 3 patients without metastases. The estimated number of organs invaded by metastases was higher with PET in 5 patients and higher with morphological imaging techniques in 6 patients. Among the PET findings with higher or equivocal counts of organs with metastases there were 2 confirmed false-positive findings. Conclusion: In a selected patient population, FDG-PET was found to be inferior to CT for diagnosing lung and liver metastases. The supplementary use of FDG-PET is not generally of value once metastasis has been established

  14. Radioimmunoimaging in malignant melanoma patients with the use of indium-111-labeled antimelanoma monoclonal antibody (ZME-018) to high-molecular-weight antigen

    International Nuclear Information System (INIS)

    Radioimmunolocalization of an 111In-labeled, mouse antimelanoma monoclonal antibody (MAb), ZME-018, was examined in 30 patients with metastatic malignant melanoma. Each patient received a single iv infusion of MAb at concentrations ranging from 0.6 to 40 mg, coupled to 5 mCi 111In by the chelating agent pentetic acid. No toxicity was observed in any patient. Total-body and region of interest scans performed at 4, 24, and 72 hours following MAb administration revealed uptake in 110 of 171 previously diagnosed metastases for a sensitivity of 64%. Nonspecific uptake of radioactivity was consistently observed in the liver and spleen, and less frequently in the bowel, testes, axillae, and bone. Sensitivity of detection increased significantly at doses of MAb above 2.5 mg, with 74% of the lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (P less than .005). Sensitivity actually decreased slightly at the 40-mg dose. There was a significant correlation between tumor uptake of MAb-111In-conjugate and increasing tumor size. Soft tissue lesions, such as skin and lymph node metastases, were imaged to a greater extent (77%) than were visceral metastases (40%). Mean plasma clearance of ZME-018 was prolonged with a half-life of 33.6 hours in patients receiving 40 mg, compared with 17.8 hours in patients given 2.5 mg (P less than .01). Urinary excretion of the isotope averaged 11.4% of the injected dose over 48 hours. Hence radioimmunolocalization of melanoma with 111In-ZME-018 appeared feasible. The sensitivity of the technique varies with MAb dose, specific activity of 111In-MAb conjugate, tumor size, and disease site

  15. The prognostic significance of indoleamine-2,3-dioxygenase and the receptors for transforming growth factor β and interferon γ in metastatic lymph nodes in malignant melanoma.

    Science.gov (United States)

    Pelak, Maciej J; Śnietura, Mirosław; Lange, Dariusz; Nikiel, Barbara; Pecka, Katarzyna M

    2015-12-01

    We analyzed the prognostic significance of indoleamine-2,3-dioxygenase (IDO) and type 1 receptors for transforming growth factor beta (TGF-βR1) and interferon gamma (IFN-γR1) in resected nodal metastases of 48 malignant melanoma patients. In 32 cases the corresponding skin tumors were available. We used immunohistochemical (IHC) staining which was assessed by pathologists and by a computer-aided algorithm that yielded quantitative results, both absolute and relative. We correlated the results with the patient outcome. We identified absolute computer-assessed IDO levels as positively correlated with increased risk of death in a multivariate model (HR = 1.02; 95% CI: 1.002-1.04; p = 0.03). In univariate analysis, patients with IDO levels below the median had a better overall survival time (30.3 vs. 17.5 months; p = 0.03). TGF-βR1 and IFN-γR1 expression was modestly correlated (R = 0.34; p lt; 0.05) and TGF-βR1 expression was lower in lymph nodes than in matched primary skin tumors (Z = 2.87; p = 0.004). The pathologists' and computer-aided IHC assessment demonstrated high correlation levels (R = 0.61, R = 0.74 and R = 0.88 for IDO, TGF-βR1 and IFN-γR1, respectively). Indoleamine-2,3-dioxygenase is prognostic for the patient outcome in melanoma with nodal involvement and should be investigated prospectively for its predictive significance. IHC assessment by computer-aided methods is recommended as its gives IHC more objectivity and reproducibility. ecting mismatch repair deficiency. Association of CDX2 and PMS2 in the present study is necessary to conduct further genetic and pathological studies focusing on these two markers together. PMID:27003769

  16. 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)

    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 singlet oxygen, a very active form of oxygen that damages important biomolecules and results eventually in cell death. The photosensitive dye Indocyanine greenand a Ti - Sapphire laser (780 nm wave length ) and power density of 55 m Watt/ cm2 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

  17. The proportion cured of patients diagnosed with Stage III-IV cutaneous malignant melanoma in Sweden 1990-2007: A population-based study.

    Science.gov (United States)

    Eriksson, Hanna; Lyth, Johan; Andersson, Therese M-L

    2016-06-15

    The survival in cutaneous malignant melanoma (CMM) is highly dependent on the stage of the disease. Stage III-IV CMM patients are at high risk of relapse with a heterogeneous outcome, but not all experience excess mortality due to their disease. This group is referred to as the cure proportion representing the proportion of patients who experience the same mortality rate as the general population. The aim of this study was to estimate the cure proportion of patients diagnosed with Stage III-IV CMM in Sweden. From the population-based Swedish Melanoma Register, we included 856 patients diagnosed with primary Stage III-IV CMM, 1990-2007, followed-up through 2013. We used flexible parametric cure models to estimate cure proportions and median survival times (MSTs) of uncured by sex, age, tumor site, ulceration status (in Stage III patients) and disease stage. The standardized (over sex, age and site) cure proportion was lower in Stage IV CMMs (0.15, 95% CI 0.09-0.22) than non-ulcerated Stage III CMMs (0.48, 95% CI 0.41-0.55) with a statistically significant difference of 0.33 (95% CI = 0.24-0.41). Ulcerated Stage III CMMs had a cure proportion of 0.27 (95% CI 0.21-0.32) with a statistically significant difference compared to non-ulcerated Stage III CMMs (difference 0.21; 95% CI = 0.13-0.30). The standardized MST of uncured was approximately 9-10 months longer for non-ulcerated versus ulcerated Stage III CMMs. We could demonstrate a significantly better outcome in patients diagnosed with non-ulcerated Stage III CMMs compared to ulcerated Stage III CMMs and Stage IV disease after adjusting for age, sex and tumor site. PMID:26815934

  18. CT imaging of bone and bone marrow infiltration in malignant melanoma--Challenges and limitations for clinical staging in comparison to 18FDG-PET/CT.

    Science.gov (United States)

    Bier, Georg; Hoffmann, Vera; Kloth, Christopher; Othman, Ahmed E; Eigentler, Thomas; Garbe, Claus; La Fougère, Christian; Pfannenberg, Christina; Nikolaou, Konstantin; Klumpp, Bernhard

    2016-04-01

    Rationale of this study was the evaluation of the diagnostic value of computed tomography (CT) in the detection of bone marrow infiltration in comparison to PET/CT. Fifty patients (age 61 ± 15.12 years) with metastatic malignant melanoma underwent 18F-FDG-PET/CT, including contrast-enhanced CT. 2 readers evaluated the CT images in consensus for bone and bone marrow lesions focusing on lesion location, type and size. PET/CT was used as reference standard to estimate sensitivity, specificity, negative and positive predictive value. Moreover, the bone marrow density was estimated in the long bones and the sacral bone. Serum hamoglobin, thrombocyte level and S100 protein were correlated with the presence or absence of bone and bone marrow lesions. According to PET/CT as standard of reference, of 594 bone and medullary lesions 495 were considered malignant. Of these 77.8% were medullary, 20.4% lytic, 1% sclerotic and 0.8% mixed lytic/sclerotic. Contrast-enhanced CT yielded a lesion-based sensitivity of 36.8% and a specificity of 87.9% (PPV 93.8%; NPV 21.8%). Patient-based sensitivity and specificity were 78.8% and 82.4%, respectively. Of the missed lesions, most were medullary (95.8%). A disseminated bone marrow involvement (defined as >10 bone marrow lesions or diffuse infiltration of a whole body segment) was described in 11 cases, in 6 cases the disseminated involvement was underestimated or missed on CT. In cases with disseminated bone marrow involvement the bone marrow density was significantly higher in the humerus (p=0.04), but not in the femur or sacral bone (p=0.06). Multivariate analysis revealed no isolated effect of bone metastases on S100 serum and hemoglobin level, but both were significantly altered in patients with disseminated bone marrow involvement (p<0.05). In conclusion, the diagnostic value of computed tomography for the detection of bone marrow metastases in patients with melanoma, is limited. Especially in cases with disseminated bone marrow

  19. 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

  20. The impact of surgery and mild hyperthermia on tumor response and angioneogenesis of malignant melanoma in a rat perfusion model

    International Nuclear Information System (INIS)

    The aim of this experimental study was to determine the effect of mild hyperthermia on tumor response and angioneogenesis in an isolated limb perfusion model with a human melanoma xenograft. A human melanoma xenograft was implanted into the hindlimbs of 30 athymic nude rats. The animals were randomized into five groups: group I: control, group II: sham group, group III: external hyperthermia with a tissue temperature of 41.5°C for 30 minutes without ILP, group IV: normothermic ILP (tissue temperature 37°C for 30 minutes, group V: hyperthermic ILP (tissue temperature 41.5°C for 30 minutes). Tumor response was evaluated by tumor size determination and immunohistochemical analysis 6 weeks postoperatively. Tissue sections were investigated for expression of CD34 and basic fibroblast growth factor (bFGF). Average tumor volumes of the controls (I) increased from 105 mm3 to 1388 mm3. In the sham operated group (II) tumor volumes were significantly larger than in group I. Tumor volumes in group IV were significantly smaller than in group I and lowest in group V. There were no significant differences in size between group I and group III after six weeks. In group III and IV each, 5 animals showed tumor progression and one had a partial tumor response. In group V only 2 animals showed tumor progression. Immunhistochemical analysis of the tissue sections demonstrated that angioneogenesis was more pronounced in group II than in group I and less pronounced in group IV and V compared with group I. Our results suggest that even a surgical manipulation such as a skin incision promotes tumor growth, probably by induction of growth factors like bFGF. External hyperthermia of 41.5°C tissue temperature for 30 minutes only has no impact on tumor growth and angioneogenesis in vivo

  1. Advances in haplo-identical stem cell transplantation in adults with high-risk hematological malignancies

    OpenAIRE

    Ricci, Michael J; Medin, Jeffrey A; Foley, Ronan S

    2014-01-01

    Allogeneic bone marrow transplant is a life-saving procedure for adults and children that have high-risk or relapsed hematological malignancies. Incremental advances in the procedure, as well as expanded sources of donor hematopoietic cell grafts have significantly improved overall rates of success. Yet, the outcomes for patients for whom suitable donors cannot be found remain a significant limitation. These patients may benefit from a hematopoietic cell transplant wherein a relative donor is...

  2. Influence of 18F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

    International Nuclear Information System (INIS)

    To evaluate the influence of 18F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data. Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent 18F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as ''major'' (e.g. change from metastasectomy to systemic therapy) or ''minor'' (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated. In the 52 patients in the primary staging group, the results of 18F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. 18F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of 18F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom 18F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %). Primary staging of patients with stage III/IV melanoma should be performed with 18F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients with advanced disease. (orig.)

  3. Influence of {sup 18}F-FDG PET/CT on therapy management in patients with stage III/IV malignant melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Schuele, Susann-Cathrin; Nikolaou, Konstantin; Pfannenberg, Christina [Eberhard-Karls-University Tuebingen, Department of Diagnostic and Interventional Radiology, Tuebingen (Germany); Eigentler, Thomas Kurt; Garbe, Claus [Eberhard-Karls-University Tuebingen, Skin Cancer Programme, Department of Dermatology, Tuebingen (Germany); Fougere, Christian la [Eberhard-Karls-University Tuebingen, Department of Nuclear Medicine, Tuebingen (Germany)

    2016-03-15

    To evaluate the influence of {sup 18}F-FDG PET/CT in comparison to CT alone on treatment decisions in patients with advanced melanoma and to analyse the 5-year survival data in comparison to literature data. Therapy management in 64 consecutive patients (primary staging n = 52; surveillance n = 12) with stage III/IV melanoma who underwent {sup 18}F-FDG PET/CT between 2004 and 2005 in our department was retrospectively analysed. Treatment decisions were made by two dermatooncologists for each patient twice, first based on the CT results and then based on the PET/CT results. Therapy changes based on the PET/CT results were classified as ''major'' (e.g. change from metastasectomy to systemic therapy) or ''minor'' (e.g. change from first to second line chemotherapy). The 5-year survival data of different patient cohorts were calculated. In the 52 patients in the primary staging group, the results of {sup 18}F-FDG PET/CT led to therapy change in 59 % and a major therapy change in 52 %. {sup 18}F-FDG PET/CT led to the avoidance of futile operations in 13 patients with suspicious lesions on CT that were deemed nontumorous on PET/CT. In the 12 patients in the surveillance group, the results of {sup 18}F-FDG PET/CT led to therapy change in 33 % and a major change in 17 %. The 5-year survival rates were 30 % in the entire cohort, 34 % in the primary staging group, and 17 % in the surveillance group. A significant overall survival benefit was observed in patients in whom {sup 18}F-FDG PET/CT excluded metastases or in whom metastases could be completely removed compared with patients who were not eligible for surgery (41 % vs. 10 %). Primary staging of patients with stage III/IV melanoma should be performed with {sup 18}F-FDG PET/CT, leading to higher diagnostic accuracy and enabling individualized therapeutic management, especially optimal patient selection for metastasectomy. This strategy may extend long-term survival even in patients

  4. Interleukin-6 and melanoma

    DEFF Research Database (Denmark)

    Hoejberg, Lise; Bastholt, Lars; Schmidt, Henrik

    2012-01-01

    Interleukin-6 (IL-6) is a pleiotropic immunomodulatory cytokine produced by various types of cells, including melanoma cells. IL-6 plays a major role in the pathogenesis and development of malignancies. It promotes tumour growth by inhibition of apoptosis and induces tumour angiogenesis. IL-6 is...... deregulated in many types of cancers, and increased serum concentration of IL-6 has been correlated with a worse prognosis in patients with different cancers, including melanoma. Several serum cytokines including IL-6 play an important role in the development and progression of melanoma; however, the specific...... biological functions of IL-6 in progression of melanoma are unknown. In this review, we present studies on cell cultures and mouse models and summarize published clinical studies on IL-6 and melanoma....

  5. 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)

    injection. It was higher than those of 125I-L-PC; 6.5 ± 0.8 and 67Ga-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

  6. Serum anti-BPAG1 auto-antibody is a novel marker for human melanoma.

    Directory of Open Access Journals (Sweden)

    Takashi Shimbo

    Full Text Available Malignant melanoma is one of the most aggressive types of tumor. Because malignant melanoma is difficult to treat once it has metastasized, early detection and treatment are essential. The search for reliable biomarkers of early-stage melanoma, therefore, has received much attention. By using a novel method of screening tumor antigens and their auto-antibodies, we identified bullous pemphigoid antigen 1 (BPAG1 as a melanoma antigen recognized by its auto-antibody. BPAG1 is an auto-antigen in the skin disease bullous pemphigoid (BP and anti-BPAG1 auto-antibodies are detectable in sera from BP patients and are used for BP diagnosis. However, BPAG1 has been viewed as predominantly a keratinocyte-associated protein and a relationship between BPAG1 expression and melanoma has not been previously reported. In the present study, we show that bpag1 is expressed in the mouse F10 melanoma cell line in vitro and F10 melanoma tumors in vivo and that BPAG1 is expressed in human melanoma cell lines (A375 and G361 and normal human melanocytes. Moreover, the levels of anti-BPAG1 auto-antibodies in the sera of melanoma patients were significantly higher than in the sera of healthy volunteers (p<0.01. Furthermore, anti-BPAG1 auto-antibodies were detected in melanoma patients at both early and advanced stages of disease. Here, we report anti-BPAG1 auto-antibodies as a promising marker for the diagnosis of melanoma, and we discuss the significance of the detection of such auto-antibodies in cancer biology and patients.

  7. Functional graphene oxide as a plasmid-based Stat3 siRNA carrier inhibits mouse malignant melanoma growth in vivo

    International Nuclear Information System (INIS)

    Graphene oxide (GO) has attracted intensive interest in the biomedical field in recent years. We investigate whether the use of functional graphene oxide as an efficient delivery system for delivering specific molecular antitumor therapeutics in vivo could achieve a more excellent antitumor effect. Constitutive activation of signal transducer and activator of transcription 3 (Stat3) promotes survival in a wide spectrum of human cancers. In this paper, we study the in vivo behavior of graphene oxide chemically functionalized with polyethylenimine and polyethylene glycol (GO-PEI-PEG) as a plasmid-based Stat3-specific small interfering RNA (siRNA) carrier in mouse malignant melanoma. The in vivo results indicate significant regression in tumor growth and tumor weight after plasmid-based Stat3 siRNA delivered by GO-PEI-PEG treatment. Moreover, there was no significant side effect from GO-PEI-PEG treatment according to histological examination and blood chemistry analysis in mice. Thus, our work is the first success of using GO-PEI-PEG as a promising carrier for plasmid Stat3 siRNA delivery and down-regulation of Stat3 by a polymer-mediated vehicle and suggests the great promise of graphene in biomedical applications such as cancer treatment. (paper)

  8. Tumour response after hyperthermic isolated limb perfusion for locally advanced melanoma

    DEFF Research Database (Denmark)

    Paulsen, Ida Felbo; Chakera, A H; Drejøe, Jennifer Berg; Klyver, Helle; Dahlstrøm, Karin; Oturai, Peter Sandor; Mortensen, Jann; Hesse, Birger; Schmidt, Grethe; Drzewiecki, Krzysztof

    2014-01-01

    INTRODUCTION: The aim was to describe tumour response, complications, recurrence and survival after hyperthermic isolated limb perfusion (ILP) with melphalan or melphalan in combination with tumour necrosis factor-alpha in patients with melanoma metastases confined to an extremity. MATERIAL AND...

  9. Advanced head and neck cancer: Long-term results of chemo-radiotherapy, complications and induction of second malignancies

    OpenAIRE

    Munker, Reinhold; Purmale, L.; Aydemir, Ü.; Reitmeier, M.; Pohlmann, H.; Schorer, H.; Hartenstein, R.

    2001-01-01

    Background: Chemo-radiotherapy is superior to radiotherapy alone in the treatment of advanced, inoperable head and neck cancer. The long-term treatment results, the induction of second malignant tumors, and other long-term toxicities are not well defined. Patients and Methods: 100 consecutive patients with advanced head and neck cancer who were treated at our center were studied. Treatment results, survival, the occurrence of late complications, and second malignant tumors (SMT) were investig...

  10. Keeping a watch on melanoma.

    Science.gov (United States)

    Casparian, J Michael; Rodewald, Erin J

    2002-05-01

    When performing a total body skin examination, we discovered a melanoma in situ when a patient took off her wristwatch. This case illustrates the importance of removing jewelry when performing a complete skin examination. Furthermore, the location of this lesion highlights the association between malignant melanoma and intermittent sun exposure. PMID:12041820

  11. Safety, immunogenicity, and early evidence of antitumor response with the use of the vaccine formulation NeuGcGM3 / VSSPs in patients with advanced melanoma

    International Nuclear Information System (INIS)

    Introduction. Melanoma is now considered an epidemic around the world. Its high lethality, constitutes a serious problem despite the continuous pharmacological and technological advances. NeuGcGM3/VSSP is a vaccine formulation containing ganglioside NeuGcGM3 incorporated in the acting of Neisseria meningitidis. It may be a choice therapeutic given this ganglioside in primary melanoma expression and immunogenicity and safety demonstrated by this vaccine in advanced breast cancer. This study evaluated the safety, immunogenicity and the anti-tumor response in patients with advanced melanoma to manage it via IM or SC. Material and methods: The expression of ganglioside in primary melanomas and its metastases was identified by immunohistochemical methods with the AcM 14F7 (anti-NGCGM3). 2 clinical trials Phase Ib/IIa escalation of doses with NeuGcGM3 /VSSP were conducted in patients with melanoma Advanced IM and SC routes. Safety and anti-tumour response were evaluated with the CTC and RECIST criteria. The statistical analysis was performed with the SPSS statistical package. Results: NeuGcGM3 is expressed in primary tumors and the studied lymph nodes metastases. NeuGcGM3/VSSP was safely managed by the SC and IM, roads without limiting toxicity. Immunogenic with IgM and IgG isotype antibody response resulted in 75% patients. There was anti-tumoral response in 38.5% with increase in median SV mainly associated with anti-tumor response. The appearance of vitiligo and the response of antibodies against other not present in the vaccine formulation gangliosides may be considered a manifestation of immune restoration. Conclusions. NeuGcGM3/VSSP managed IM and SC in patients with advanced melanoma was safe, immunogenic and antitumor activity associated with overall survival advantage. (author)

  12. 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

  13. Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary metastases from malignant melanoma

    International Nuclear Information System (INIS)

    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

  14. 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

    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

  15. 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

  16. Cheek-neck advancement-rotation flaps following Mohs excision of skin malignancies.

    Science.gov (United States)

    Katz, A E; Grande, D J

    1986-09-01

    The cheek-neck advancement-rotation flap has proved extremely useful for delayed reconstruction of the face following the microscopically controlled surgical excision (MCSE) of skin malignancies. We have recently used these flaps successfully to repair combined defects of the cheek and nose in eight patients, isolated cheek defects in six patients, combined defects of the cheek and lips in two patients, and isolated defects of the nose, temple, and an antral cutaneous fistula in each of three patients. Defects as large as 6.0 X 10.0 cm have been closed in one stage with this flap. This flap is extremely hearty and its scars can be well concealed. It is especially valuable in the elderly patient and should always be considered as one of the options for reconstruction of the face following MCSE of skin malignancies. PMID:3745621

  17. Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods

    International Nuclear Information System (INIS)

    Malignant gliomas consist of glioblastomas, anaplastic astrocytomas, anaplastic oligodendrogliomas and anaplastic oligoastrocytomas, and some less common tumors such as anaplastic ependymomas and anaplastic gangliogliomas. Malignant gliomas have high morbidity and mortality. Even with optimal treatment, median survival is only 12–15 months for glioblastomas and 2–5 years for anaplastic gliomas. However, recent advances in imaging and quantitative analysis of image data have led to earlier diagnosis of tumors and tumor response to therapy, providing oncologists with a greater time window for therapy management. In addition, improved understanding of tumor biology, genetics, and resistance mechanisms has enhanced surgical techniques, chemotherapy methods, and radiotherapy administration. After proper diagnosis and institution of appropriate therapy, there is now a vital need for quantitative methods that can sensitively detect malignant glioma response to therapy at early follow-up times, when changes in management of nonresponders can have its greatest effect. Currently, response is largely evaluated by measuring magnetic resonance contrast and size change, but this approach does not take into account the key biologic steps that precede tumor size reduction. Molecular imaging is ideally suited to measuring early response by quantifying cellular metabolism, proliferation, and apoptosis, activities altered early in treatment. We expect that successful integration of quantitative imaging biomarker assessment into the early phase of clinical trials could provide a novel approach for testing new therapies, and importantly, for facilitating patient management, sparing patients from weeks or months of toxicity and ineffective treatment. This review will present an overview of epidemiology, molecular pathogenesis and current advances in diagnoses, and management of malignant gliomas

  18. Long-Term Treatment Outcome after Only Popliteal Lymph Node Dissection for Nodal Metastasis in Malignant Melanoma of the Heel: The Only “Interval Node” Dissection Can Be an Adequate Surgical Treatment

    Directory of Open Access Journals (Sweden)

    Kentaro Tanaka

    2013-01-01

    Full Text Available We present a patient with malignant melanoma on his heel. Wide local excision was performed, along with sentinel lymph node biopsy of the inguinal and popliteal lesions. The primary site was clear of tumor at all margins; the inguinal nodes were negative, but the popliteal node was positive for metastatic melanoma. Only radical popliteal lymph node dissection was performed. The patient went on to receive adjuvant chemoimmunotherapy. There was no recurrence or complication until the long-term followup. Popliteal drainage from below the knee is uncommon, and the rate of popliteal-positive and inguinal-negative cases is estimated to be less than 1% of all melanomas. There is no established evidence about how to treat lymph nodes in these cases. Because we considered popliteal nodes as a regional, not interval, lymph node basin, only popliteal lymph node dissection was performed, and good postoperative course was achieved. The first site of drainage is the sentinel node, and the popliteal node can be a sentinel node. The inguinal node is not a sentinel node in all lower extremity melanomas. This case illustrates the importance of individual detailed investigation of lymphatic drainage patterns from foot to inguinal and popliteal nodes.

  19. Visual outcome of accelerated fractionated radiation for advanced sinonasal malignancies employing photons/protons

    International Nuclear Information System (INIS)

    Purpose: To investigate the visual outcomes of patients with advanced sinonasal malignancies treated with proton/photon accelerated fractionated radiation (AFR). Patients and methods: Between 1991 and 2001, AFR was used to treat 36 patients with advanced stage primary (n = 33) or recurrent (n = 3) nasal or paranasal malignant tumors. Full ophthalmologic follow-up was documented. The median dose to the gross tumor volume (GTV) was 69.6 CGE (range 60.8-77). Visual complications were graded according to the National Cancer Institute Common Toxicity Criteria (CTC) and the late effects of normal tissue (LENT) scoring systems. The median follow-up was 52.4 months (range 17-122.8). Results: Thirteen patients developed late visual/ocular toxicity. Cataracts were LENT grade 1 and 3 in 2 patients and 1 patient, respectively. One LENT grade 1 vascular retinopathy and 1 optic neuropathy were also observed. Three and five patients presented with nasolacrimal duct stenosis (CTC grade 2, 2 patients; CTC grade 3, 1 patient) and dry-eye syndrome (CTC grade 1, 1 patient; CTC grade 2, 4 patients), respectively. The 3- and 5-year probability of LENT/CTC grade ≥2 visual toxicity were 15.8 ± 6.7% and 20.7 ± 7.8%, respectively. Conclusions: AFR for locally advanced nasal cavity and paranasal sinus tumors enables delivery of 70 CGE to the tumor with acceptable ophthalmologic complications

  20. Cholangiocarcinoma and malignant bile duct obstruction: Areview of last decades advances in therapeutic endoscopy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    In the last decades many advances have been achievedin endoscopy, in the diagnosis and therapy ofcholangiocarcinoma,however blood test, magneticresonance imaging, computed tomography scan mayfail to detect neoplastic disease at early stage, thus thediagnosis of cholangiocarcinoma is achieved usuallyat unresectable stage. In the last decades the roleof endoscopy has moved from a diagnostic role toan invaluable therapeutic tool for patients affectedby malignant bile duct obstruction. One of the majorissues for cholangiocarcinoma is bile ducts occlusion,leading to jaundice, cholangitis and hepatic failure.Currently, endoscopy has a key role in the work upof cholangiocarcinoma, both in patients amenable tosurgical intervention as well as in those unfit for surgeryor not amenable to immediate surgical curative resectionowing to locally advanced or advanced disease, withpalliative intention. Endoscopy allows successful biliarydrainage and stenting in more than 90% of patientswith malignant bile duct obstruction, and allows rapidreduction of jaundice decreasing the risk of biliary sepsis.When biliary drainage and stenting cannot be achievedwith endoscopy alone, endoscopic ultrasound-guidedbiliary drainage represents an effective alternativemethod affording successful biliary drainage in morethan 80% of cases. The purpose of this review is tofocus on the currently available endoscopic managementoptions in patients with cholangiocarcinoma.