Melanoma is a cancer of the neural crest-derived cells that provide pigmentation to skin and other tissues. Over the past 4 decades, the incidence of melanoma has increased more rapidly than that of any other malignancy in the United States. The National Cancer Institute reports a 2 percent increase in the incidence of melanoma between 1992 and 2002. New melanoma cases are diagnosed in about 60,000 people each year in the United States, and almost 8,000 die because of metastasized melanoma. Although melanoma accounts for only 4 percent of all dermatologic cancers, it is responsible for 80 percent of deaths from skin cancer; only 14 percent of patients with metastatic melanoma survive for five years.

Natural Options for Melatonin treatment of prevention
Research with vitamins or supplements for melanoma prevention or treatment is still very new, therefore no statements can be made with any confidence. However, it is interesting to point out that certain herbs or supplements have anti melanoma activity in test tubes. I have listed some of this melanoma research a few paragraphs below. Here are some options:

Curcumin is an extract from turmeric spice, see also Curcumin for information on natural curcumin supplements.
Cordyceps is a mushroom
Quercetin is a flavonoid
Rosemary extract which contains carnosol
Green tea extract has a potent extract EGCG, which is becoming very popular
Mistletoe herb
Tea tree oil

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Curry ingredient fights skin cancer
The compound that makes curry yellow could help fight skin cancer. Curcumin, found in the spice turmeric, interferes with melanoma cells. Tests in laboratory dishes show that curcumin made melanoma skin cancer cells more likely to self-destruct in a process known as apoptosis. The same research team has found that curcumin helped stop the spread of breast cancer tumor cells to the lungs of mice. The curcumin suppressed two proteins that tumor cells use to keep themselves immortal. People who eat plenty of turmeric have lower rates of some cancers.

Melanoma symptom and melanoma sign
Often, the first sign of melanoma is a change in the size, shape, color, or feel of an existing mole. Most melanomas have a black or blue-black area. Melanoma also may appear as a new, black, abnormal, or "ugly-looking" mole. Eye melanoma or ocular melanoma can also occur.
   Melanoma is much deadlier when it appears on the scalp or neck than somewhere else on the body.

Skin Melanoma Stage
Staging of malignant melanoma cancer is determined according to the level of invasion (Clark level) and vertical thickness (Breslow scale).

Melanoma Treatment
No current treatments substantially enhance patient survival once melanoma metastasis has occurred. Except for high-dose interferon as adjuvant therapy in stage III disease, little success has emerged over the last 20 years for metastatic melanoma. Besides operative therapy, which is the only effective treatment for malignant melanoma, postoperative adjuvant chemotherapy, immunotherapy, radiotherapy, and biologic therapy also are of great importance. In recent years, immunologic strategies including tumor vaccine and adjuvant therapy with interferon-alfa have been attempted to improve survival of patients with more advanced malignant melanoma.
     Melanoma survival rate or prognosis depends often on the severity of the melanoma and whether metastasis has occurred. Some people with melanoma are at increased risk of developing the skin cancer again in the future, especially if they have a family history of the disease.

Melanoma risk from medication
Patients with rheumatoid arthritis who are treated with methotrexate may have an elevated risk of developing melanoma compared with the general population.

Types of Melanoma
There are 4 major types of melanoma:
* Superficial spreading melanoma is the most common type of melanoma. It is usually flat and irregular in shape and color, with varying shades of black and brown. Superficial spreading melanoma may occur at any age or site and is most common in Caucasians.
* Nodular melanoma usually starts as a raised area that is dark blackish-blue or bluish-red, although some lack color.
* Lentigo maligna melanoma usually occurs in the elderly. Lentigo melanoma is most common in sun-damaged skin on the face, neck, and arms. The abnormal skin areas are usually large, flat, and tan with intermixed areas of brown.
* Acral lentiginous melanoma is the least common form of melanoma. It usually occurs on the palms, soles, or under the nails and is more common in African Americans.

See other types of skin cancer.

Risk of Melanoma with Skin Cancer
Women who've had common, highly curable forms of skin cancer may face a heightened risk of the deadlier skin tumor melanoma. A study of more than 67,000 white postmenopausal women found that those with a history of non- melanoma skin cancer were 70 percent more likely than other women to develop melanoma during the study period. The findings suggest that there are genetic influences that make some people vulnerable to both melanoma and non- melanoma skin cancers. Two forms of non-melanoma skin cancer -- basal cell and squamous cell -- account for the large majority of skin cancer cases, and are rarely fatal themselves. Based on the new findings, though, the diseases can be added to the list of risk factors for the deadlier melanoma. The results are based on data from the Women's Health Initiative, a large study of U.S. women begun in 1994 that collected detailed health and lifestyle information and followed up with participants annually. Women with a history of non- melanoma skin cancer should thorough skin examinations at frequent intervals to catch any new lesions early. SOURCE: Cancer, February 1, 2006.

Marathon runners may face an increased risk of skin cancer, Austrian researchers report. Based on the findings, they conclude, long-distance runners should make an effort to reduce their exposure to ultraviolet (UV) radiation by using sunscreen, wearing protective clothing, and organizing their training and competition routines accordingly. Dr. Christina M. Ambros-Rudolph of the Medical University of Graz in Austria and colleagues decided to investigate melanoma risk among long-distance runners after treating eight ultramarathon runners with the disease over a 10-year period. Along with sun exposure, immunosuppression due to intense training has been proposed as a potential trigger for melanoma. They recruited 210 marathon runners ranging in age from 19 to 71 years for the study, matching them by age and sex with a control group of non-marathoners. Even though men and women in the control group had more signs of sun sensitivity, such as light eye and skin color and more birthmarks, the marathoners were more likely to have changes in the skin that signal an increased malignant melanoma risk.

People who use tanning beds do not protect themselves from skin damage from subsequent sun exposure. In fact, use of sunbeds before age 35 substantially increases the risk of developing melanoma.

Sun-filled family vacations can leave children with more moles on their skin. These moles, also known as melanocytic nevi, are a precursor of melanoma.

Another melanoma risk?
Infants with hyperbilirubinemia who are treated with intensive phototherapy, the current standard treatment, have a significantly increased risk of melanocytic nevi. Given the link between such nevi and melanoma, dermatologic surveillance and preventive measures are important for these children. Archives Dermatolology 2006;142:1599-1604.

Recurrence of Melanoma
About 8% of patients with primary melanoma will have another primary melanoma diagnosed within 2 years.

Rapid growth of melanoma
Rapidly growing cutaneous melanomas exhibit a number of identifying characteristics including color and shape. Because of their rapid growth there is only a small window of opportunity to capture these melanomas in their early stage of development. Rapidly growing melanomas can occur in anyone, not necessarily those with large numbers of moles and freckles. In fact, they more often occur in those without large numbers of moles and freckles, and elderly men. Morphologically, they are more often red -- rather than brown and black -- symmetrical, elevated and symptomatic. Archives Dermatology 2006;142.

Melanoma Skin Cancer in Australia
Australia has the highest skin cancer rate in the world and despite decades of health campaigning the rate of melanoma, which is the most common kind of cancer, is soaring. The melanoma rate rose 12 percent in men and 15 percent in women in the last 10 years, and is expected to rise another 11 percent by 2011.

Prevalence of Melanoma
The increase in rates of melanoma, the most dangerous type of skin cancer, in the United States in recent years may reflect heightened diagnostic scrutiny rather than a true increase in new cases.
     However, the annual rate of occurrence of new melanomas in children in the United States is increasing rapidly.

Metastatic Melanoma Treatment
Patients with metastatic melanoma (MM) have new hope, says a published study by Mayo Clinic Cancer Center. The study, showed the combination of paclitaxel and carboplatin (PC) appears to be effective for metastatic melanoma when traditional treatments have failed.

Melanoma Diagnosis in Blacks and Hispanics
Melanoma is diagnosed at a late stage more commonly among darker skinned individuals than in white patients. There are two broad possibilities for this. It's possible that melanoma is a faster, more aggressive disease in non-whites than whites; or, more likely, is a lack of education among patients and physicians. Black and hispanic patients at high risk are known to lack education about the disease and to engage in fewer self-protective behaviors, such as putting on sunscreen and staying out of the bright sun.

Statins and Melanama
Although there was thought to be an association between use of cholesterol-lowering statins and fibrates and a reduced risk of melanoma, a meta-analyses of trials of such drugs does not bear out this apparent connection.

Melanoma diagnosis from hair sample
Measuring the amount of melanin in a hair sample independently predicts an individual's risk for melanoma. Melanin is a natural substance that gives color to the hair, skin and iris of the eye, and also protects the skin from damaging rays of the sun. Determining the amount of melanin as an indication of an individual's skin type could be used to advise patients how often they should be screened for skin cancer and to also provide individualized patient advice. Hair concentrations of melanin can be measured by various means. Measuring 2,3,5-pyrroletricarboxylic acid (PTCA) levels, which forms after the oxidation of the pigment eumelanin, provides the strongest results. Subjects with a PTCA concentration below 85 ng/mg have more than four times the risk of developing melanoma. American Journal of Epidemiology, May 15, 2007.

Melanoma Cancer Research Update
Curcumin -induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IkappaB kinase and nuclear factor kappaB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway.
Cancer. 2005 Jul 11
Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R. Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Nuclear factor-kappaB (NF-kappaB) plays a central role in cell survival and proliferation in human melanoma; therefore, the authors explored the possibility of exploiting NF-kappaB for melanoma treatment by using curcumin, an agent with known, potent, NF-kappaB-inhibitory activity and little toxicity in humans. METHODS: Three melanoma cell lines (C32, G-361, and WM 266-4), all of which had B-raf mutations, were treated with curcumin, and the authors assessed its effects on viability ((3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay) and apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells). CONCLUSIONS: Curcumin has potent antiproliferative and proapoptotic effects in melanoma cells. These effects were associated with the suppression of NF-kappaB and IKK activities but were independent of the B-Raf/MEK/ERK and Akt pathways.

Low plasma coenzyme Q10 levels as an independent prognostic factor for melanoma progression.
J Am Acad Dermatol. 2006 Feb;54(2):234-41. Department of Dermatology, Catholic University of the Sacred Heart, Rome, Italy.
Abnormally low plasma levels of coenzyme Q10 (CoQ10) have been found in patients with cancer of the breast, lung, or pancreas. A prospective study of patients with melanoma was conducted to assess the usefulness of CoQ10 plasma levels in predicting the risk of metastasis and the duration of the metastasis-free interval. CONCLUSIONS: Analysis of our findings suggests that baseline plasma CoQ10 levels are a powerful and independent prognostic factor that can be used to estimate the risk for melanoma progression.

Association between pterostilbene and quercetin inhibits metastatic activity of B16 melanoma.
Neoplasia. 2005 Jan;7(1):37-47.
Inhibition of cancer growth by resveratrol (trans-3,5,4'-trihydroxystilbene; RESV), a phytoalexin present in many plant species, is limited by its low bioavailability. Pterostilbene (3,5-dimethoxy-4'-hydroxystilbene; PTER) and quercetin (3,3',4',5,6-pentahydroxyflavone; QUER), two structurally related and naturally occurring small polyphenols, show longer half-life in vivo. In vitro growth of highly malignant B16 melanoma F10 cells (B16M-F10) is inhibited (56%) by short-time exposure (60 min/day) to PTER (40 microm) and quercetin (20 microm) (approximate mean values of plasma concentrations measured within the first hour after intravenous administration of 20 mg/kg each polyphenol). Intravenous administration of PTER and QUER (20 mg/kg per day) to mice inhibits (73%) metastatic growth of B16M-F10 cell in the liver, a common site for metastasis development. The anti-metastatic mechanism involves: 1) a PTER-induced inhibition of vascular adhesion molecule 1 expression in the hepatic sinusoidal endothelium, which consequently decreases B16M-F10 cell adhesion to the endothelium through very late activation antigen 4; and 2) a QUER- and PTER-induced inhibition of Bcl-2 expression in metastatic cells, which sensitizes them to vascular endothelium-induced cytotoxicity. Our findings demonstrate that the association of PTER and QUER inhibits metastatic melanoma growth and extends host survival.

Protective effect of quercetin and luteolin in human melanoma HMB-2 cells.
Mutat Res. 2005 Jan 3;565(2):105-12.
Multifunctional effects of flavonoids are reported to be markedly connected with their structure and the functional groups in the molecule. The important role in the activity play C2-C3 double bond, hydroxyl group at C3 and the number of hydroxyl groups at phenyl ring (B). In this paper, the DNA protective free radical scavenging potential of quercetin (QU) and luteolin (LU) against H2O2 and their clastogenic effect alone and in combination with melphalan (MH) were investigated in human melanoma HMB-2 cells. Elevated frequency of chromosomal aberrations induced by MH, that at high doses have shown a variety of toxic side effects, was statistically decreased by studied flavonoids regarding to control (QU at the concentration of 50 microM and LU already at the concentration of 20 microM). The results concerning DNA protective potential against free radicals in HMB-2 cells demonstrated that QU and LU have significant effect in dose dependent manner. The percentage of QU protective effect is 40% at the concentration 20 microM, resp. 80% at the concentration 100 microM. Comparable values were obtained with LU. Results are correlated to their structural arrangement and organization of the hydroxyl groups.

Antitumour activity of cordycepin in mice.
Clin Exp Pharmacol Physiol. 2004 Dec;31 Suppl 2:S51-3.
1. The antitumour effect of orally administered cordycepin, a component isolated from water extracts of Cordyceps sinensis, was examined in mice inoculated with B16 melanoma (B16-BL6) cells. 2. B16-BL6 (1 x 10(6)) cells were inoculated subcutaneously into the right footpad of mice. At 2 weeks after the cell inoculation, the enlarged primary tumour lump was weighed. Cordycepin (0, 5 and 15 mg/kg per day) was administered orally to the mice for 2 weeks from the date of tumour inoculation. Cordycepin (15 mg/kg per day) significantly reduced by 36% the wet weight of the primary tumour lump compared to that of the untreated control mice, without any loss of bodyweight or systemic toxicity. 3. Cordycepin (15 mg/kg per day) administered orally for 2 weeks inhibited the tumour enlargement in the right thigh inoculated with B16-BL6 cells premixed with extracellular matrix (Matrigel). 4. These results indicate that orally administered cordycepin inhibits melanoma cell growth in mice with no adverse effects.

Carnosol inhibits the invasion of B16/F10 mouse melanoma cells by suppressing metalloproteinase-9 through down-regulating nuclear factor-kappa B and c-Jun.
Biochem Pharmacol. 2005 Jan 15;69(2):221-32. Epub 2004 Nov 23.
Carnosol, a constant constituent of Rosmarinus officinalis extracts, is a phenolic diterpene shown to have antioxidant and anticarcinogen properties. In our studies, carnosol inhibited the invasion of highly metastatic mouse melanoma B16/F10 cells in vitro. First, the antimetastatic potentials of carnosol were examined by soft agar colony formation assay. Second, carnosol dose-dependently inhibited B16/F10 cell migration and invasion by in vitro transwell assay. Third, the decreasing activity of metalloproteinase was observed by zymographic assay. The result revealed that the treatment of carnosol could diminish the activity of MMP-9 more than MMP-2. Next, we analyzed the amounts of MMP-9 and MMP-2 proteins in the cells. The data indicated MMP-9 protein was also suppressed by carnosol in the same manner. In accordance with the above data, the results of reverse transcriptase polymerase chain reaction (RT-PCR) analysis showed a reduced level of MMP-9 mRNA. Furthermore, carnosol significantly inhibited the tyrosine phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, AKT, p38, JNK and inhibition of activation of transcription factors NFkappa-B and c-Jun. These results lead us to conclude that carnosol could restrict the invasive ability of B16/F10 mouse melanoma cells by reducing MMP-9 expression and activity through suppressing (ERK) 1/2, AKT, p38, and JNK signaling pathway and inhibition of NF-kappaB and AP-1 binding activity. Taken together, these results indicate that carnosol targets MMP-mediated cellular events in cancer cells and provides a new mechanism for its anticancer activity.

Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma.
Int J Cancer. 2005 Apr 20;114(4):513-21.
Melanoma accounts for only about 4% of all skin cancer cases but most of skin cancer-related deaths. Standard systemic therapies such as interferon (IFN) have not been adequately effective in the management of melanoma. Therefore, novel approaches are needed for prevention and treatment of this disease. Chemoprevention by naturally occurring agents present in food and beverages has shown benefits in certain cancers including nonmelanoma skin cancers. Here, employing 2 human melanoma cell lines (A-375 amelanotic malignant melanoma and Hs-294T metastatic melanoma) and normal human epidermal melanocytes (NHEM), we studied the antiproliferative effects of epigallocatechin-3-gallate (EGCG), the major polyphenolic antioxidant present in green tea. EGCG treatment was found to result in a dose-dependent decrease in the viability and growth of both melanoma cell lines. Interestingly, at similar EGCG concentrations, the normal melanocytes were not affected. EGCG treatment of the melanoma cell lines resulted in decreased cell proliferation (as assessed by Ki-67 and PCNA protein levels) and induction of apoptosis (as assessed cleavage of PARP, TUNEL assay and JC-1 assay). EGCG also significantly inhibited the colony formation ability of the melanoma cells studied. EGCG treatment of melanoma cells resulted in a downmodulation of anti-apoptotic protein Bcl2, upregulation of proapoptotic Bax and activation of caspases -3, -7 and -9. Furthermore, our data demonstrated that EGCG treatment resulted in a significant, dose-dependent decrease in cyclin D1 and cdk2 protein levels and induction of cyclin kinase inhibitors (ckis) p16INK4a, p21WAF1/CIP1 and p27KIP1. Our data suggest that EGCG causes significant induction of cell cycle arrest and apoptosis of melanoma cells that is mediated via modulations in the cki-cyclin-cdk network and Bcl2 family proteins. Thus, EGCG, alone or in conjunction with current therapies, could be useful for the management of melanoma.

Influence of mistletoe lectins and cytokines induced by them on cell proliferation of human melanoma cells in vitro.
Toxicology. 2005 Feb 1;207(1):105-16.
Although aqueous mistletoe extracts are widely used in complementary cancer therapy, the precise mode of action of their main therapeutic agents, the three mistletoe lectins (MLs), is poorly understood as they act both as cytotoxic agents and as immunomodulators due to their cytokine release by mononuclear cells. Thus, this study aims to investigate both the direct and the indirect effects of MLs on the growth of human melanoma cells in vitro. Proliferation of six human melanoma cell lines under ML treatment and additionally under the influence of cytokines induced by them (TNF-alpha, IL-1, IL-6) was assessed by means of the tetrazolium derived reduction (XTT) assay. Furthermore, ML binding patterns were analysed and correlated with the biological effects. All three MLs inhibited melanoma cell proliferation in a dose-dependent manner starting at very low ML concentrations (0.001-100 ng/ml) with ML-I being the most cytotoxic lectin (significant inhibition of ultra-sensitive cell line MV3 at 1 x 10(-13) ng ML-I/ml). Even if applied in a broad concentration range (0.0001-100 ng/ml) cytokines had no influence on cell proliferation at all. For ML-I, no association between binding intensity and cytotoxicity was observed, while for ML-II and -III an association between binding and toxicity was established. In conclusion, this study emphasises the direct anti-proliferative effect of the mistletoe lectins on melanoma cells with ML-I being superior to MLs-II and -III. The observation of an ultra-sensitivity of one cell line towards ML-I toxicity may serve as an explanation for the therapeutic success in anecdotal case reports and needs further investigations.

In vitro and in vivo anti-tumoral effect of curcumin against melanoma cells.
Int J Cancer. 2004 Sep 1;111(3):381-7.
Curcumin, the active ingredient from the spice turmeric (Curcuma longa Linn), is known to be an anti-oxidant and an anti-inflammatory agent. It has been demonstrated recently to possess anti-angiogenic effects and pro-apoptotic activities against Ehrlich ascites tumor cells. In the current study, curcumin was found to be cytotoxic in vitro for B16-R melanoma cells resistant to doxorubicin either cultivated as monolayers or grown in three-dimensional (3-D) cultures (spheroids). We have demonstrated that the cytotoxic effect observed in the 2 culture types can be related to the induction of programmed cell death. In our in vivo studies, we examined the effectiveness of a prophylactic immune preparation of soluble proteins from B16-R cells, or a treatment with curcumin as soon as tumoral appearance, alone or in combination, on the murine melanoma B16-R. The combination treatment resulted in substantial inhibition of growth of B16-R melanoma, whereas each treatment by itself showed little effect. Moreover, animals receiving the combination therapy exhibited an enhancement of their humoral anti-soluble B16-R protein immune response and a significant increase in their median survival time (> 82.8% vs. 48.6% and 45.7% respectively for the immunized group and the curcumin-treated group). Our study shows that curcumin may provide a valuable tool for the development of a therapeutic combination against the melanoma.

Dietary supplementation with high-selenium soy protein reduces pulmonary metastasis of melanoma cells in mice.
J Nutr. 2004 Jun;134(6):1536-40.
The effect of high-selenium (Se) soy protein on pulmonary metastasis of murine B16BL6 melanoma cells was investigated in male C57BL6 mice. Isolated soy proteins (ISP) from soybeans grown with and without Se foliar application during seed development were compared. Five diets were studied, a basal AIN-93G diet or a basal diet containing 10% low-Se ISP, 5% low-Se + 5% high-Se ISP, 10% high-Se ISP, or 10% low-Se ISP supplemented with Se equivalent to that of the 10% high-Se ISP diet. The Se concentrations of the 5 diets were 0.13, 0.13, 1.9, 3.6, and 3.0 microg/g, respectively. Mice were fed the diet for 2 wk before and 2 wk after an i.v. injection of 5 x 10(4) viable cells. At necropsy, the number and size of tumors that had developed in the lungs were determined. In the control group, 13/18 mice exhibited > or = 50 tumors. The numbers of mice with > or = 50 tumors were 8/18, 7/18, 3/18, and 6/17 in the ISP-fed groups, respectively. The differences between the 10% high-Se ISP group, the Se-supplemented 10% low-Se group, and the control were significant (P < 0.05). Dietary supplementation with 10% low-Se ISP significantly decreased the mean number of tumors per group and the tumor size compared with the control. A greater reduction in these variables occurred in mice fed the 10% high-Se ISP diet. The inhibition by the Se-supplemented 10% low-Se ISP diet was similar to that by the 10% high-Se ISP diet. The whole-blood Se concentration was inversely related to the tumor number (R = -0.87, P = 0.052), tumor cross-sectional area (R = -0.91, P < 0.05), and tumor volume (R = -0.93, P < 0.05). These findings suggest that Se is responsible for the greater antimetastatic effect of the high-Se ISP. We conclude that the high-Se soy protein has a greater inhibitory effect than the low-Se soy protein on pulmonary metastasis of melanoma cells in mice.

Terpinen-4-ol, the main component of Melaleuca alternifolia (tea tree oil) inhibits the in vitro growth of human melanoma cells.
J Invest Dermatol. 2004 Feb;122(2):349-60.
The search for innovative therapeutic approaches based on the use of new substances is gaining more interest in clinical oncology. In this in vitro study the potential anti-tumoral activity of tea tree oil, distilled from Melaleuca alternifolia, was analyzed against human melanoma M14 WT cells and their drug-resistant counterparts, M14 adriamicin-resistant cells. Both sensitive and resistant cells were grown in the presence of tea tree oil at concentrations ranging from 0.005 to 0.03%. Both the complex oil (tea tree oil) and its main active component terpinen-4-ol were able to induce caspase-dependent apoptosis of melanoma cells and this effect was more evident in the resistant variant cell population. Freeze-fracturing and scanning electron microscopy analyses suggested that the effect of the crude oil and of the terpinen-4-ol was mediated by their interaction with plasma membrane and subsequent reorganization of membrane lipids. In conclusion, tea tree oil and terpinen-4-ol are able to impair the growth of human M14 melanoma cells and appear to be more effective on their resistant variants, which express high levels of P-glycoprotein in the plasma membrane, overcoming resistance to caspase-dependent apoptosis exerted by P-glycoprotein-positive tumor cells.

[Retrospective study of malignant melanoma patients treated with mistletoe extracts]
Forsch Komplementarmed Klass Naturheilkd. 2003 Oct;10(5):248-55.
OBJECTIVE: The aim of the present investigation was to analyze survival time and survival rate of all patients with malignant melanoma who had been counseled at the Tumorambulanz Herdecke of the Community Hospital Herdecke. PATIENTS AND METHODS: 284 melanoma patients were included in a retrospective questionnaire study. Only those patients were considered for analysis in whom the prognostic factors histology, tumor localization, and Clark level were known. The data of the study population were compared with patient data obtained from the literature. RESULTS: 94 patients were included in the analysis. 66 of whom had received and 7 had not received mistletoe treatment, in the remaining 21 patients there was no information whether or not mistletoe treatment had been given. Thus, we did our study without a clearly defined internal control group. The median survival time among patients treated with mistletoe had been 14.1 years. The 5- and 10-year survival rates were 80 and 68% for the mistletoe-treated patients, respectively. DISCUSSION: The 5-year survival rate of the mistletoe-treated patients is comparable to that of patients without mistletoe therapy while the 10-year survival rate is a little bit lower. This may be due to the fact that, in contrast to the patients from the relevant literature, 33.3% of the patients suffered from lymph node and/or distant metastases already before counseling the Tumorambulanz Herdecke. Moreover, 50% of our patients had melanoma of Clark level IV in contrast to 22.2% or 31% in the relevant literature. CONCLUSIONS: In spite of the theoretical reservations against mistletoe treatment in melanoma patients, our retrospective analysis did not show any clues about disadvantages of mistletoe treatment in melanoma patients. A controlled prospective study therefore should prove the efficacy of a mistletoe therapy in patients with malignant melanoma.

Tanning beds and melanoma
Dr. George Hollenberg, M.D., a New York-area pathologist and founder of Acupath Laboratories says: "Young Americans are frequenting tanning salons at the brisk rate of 1 million visits per day. Researchers have confirmed that the long-term results are anything but healthy. A study published in the March 2007 issue of the International Journal of Cancer found that tanning bed use before age 35 increases the risk of developing melanoma, the deadliest form of skin cancer, by up to 75 percent. The most significant known risk factor for melanoma cancer is unprotected exposure of the skin to ultraviolet light -- essentially, the modus operandi of a tanning bed -- which makes the link between the two hardly surprising." Dr. George Hollenberg, M.D. is an authority in the fields of pathology, clinical pathology and dermatopathology with expertise in the areas of dysplastic nevi, melanoma, prostate and gastrointestinal cancer. Board-certified in Pathology and Dermatopathology, Dr. Hollenberg is a Fellow of the College of American Pathologists, The American Society of Dermatopathology and the AMA.

Metastatic Melanoma
Patients with metastatic melanoma have new hope: the combination of paclitaxel and carboplatin appears to be effective for metastatic melanoma when traditional treatments have failed.

Melanoma questions
Q. I was wondering if you might review the information on melanoma at your site and consider adding some information that has stirred controversy, but may be life-saving. While early sunburns appear to correlate with a higher
risk, there is evidence that vitamin D deficiency is a factor later on. The research that you referenced in your article about melanoma indicates that those who have had other types of skin cancer seem to be at higher risk of melanoma.
Could it be that, in accordance with their dermatologist's recommendations, they are using sunscreens more judiciously (which block vitamin D production by over 95% even at low SPFs), and have unwittingly increased melanoma incidence and recurrence? Because of this type of research, I am concerned that people with risk will get the impression that ideally they should avoid the sun entirely. I have been reading with great interest Dr. Michael
Holick's work at Boston University. A short article referencing highlights is at:
http://www.bu.edu/phpbin/researchbriefs/display.php?id=562&group=research
   It just seems a little too coincidental to me that melanoma has been increasing, even as judicious use of sunscreen has also been increasing. Since we already know that many cancers, cardiovascular disease, diabetes, MS, and possibly autism (decreased activated vitamin D in brain) seem to be hindered/prevented by adequate vitamin D levels, it would seem to be a safe recommendation, if not a life-saving measure, to prescribe at least some unprotected sunshine exposure and vitamin D supplementation for those with skin cancer risk, especially melanoma. I can also see a potential problem for someone who has melanoma risk and who has been placed on a statin drug..... I would like to see a research study analyzing data to see if manipulation of this increases risk for melanoma, or other conditions
typically resulting from vitamin D deficiency. Thank-you for your informative website. I visit often.
   A. There are many factors involved in melanoma formation including genetics, early life heavy sun exposure, diet, smoking, use of sunscreens, skin color, latitude and country where the person lives, atmospheric changes over time on this planet, etc. It is possible that vitamin D deficiency may be an additional factor and this would be an interesting topic for research.
      Q.  I am aware of the various risk factors that have been named as probable. In fact, the latitude and country / location factors you mentioned may directly relate to the vitamin D issue, as they have already connected this with M.S.  However, I was referring to a specific statement at the web site that folks that have had other types of skin cancer are at greater risk for melanoma. My comment about this observation is that since people who have had basal cell or squamous cell cancers are the same people who most avoid the sun, use the most sunscreen and so are at great risk for vitamin D deficiency -- and since we already know that vitamin D deficiency increases melanoma occurrence and
recurrence -- I was asking if Dr. Sahelian would consider mentioning this and suggesting that these folks be extra diligent in supplementing their vitamin D accordingly (that they at least have their levels tested), since vitamin D deficiency in this group is almost certain. It might also protect this subpopulation from other cancers, as well, and improve their risk with respect to cardiovascular disease and diabetes.

Q. Are the herbs and supplements ashwagandha herb, tongkat ali herb, or saw palmetto herb helpful in melanoma?
   A. I have not seen any studies regarding these herbs and their influence on melanoma.

Q. In completing research on tyrosine supplement I came across a reference to melanoma skin cancer. The reference stated that individuals with melanoma should not take L-Tyrosine. Is this a valid statement with some basis in fact?
   A. We have not seen any research that would support the viewpoint that tyrosine supplement use has harmful effects on melanoma.