Malignant Melanoma and Vitamin D(3)
(may also apply to other cancers)
JNCI Journal of the National Cancer Institute 2005 97(3):195-199; doi:10.1093/jnci/dji019 "Sun Exposure and Mortality From Melanoma" (Author affiliations include Sloan-Kettering) "Results: Sunburn, high intermittent sun exposure, skin awareness histories, and solar elastosis were statistically significantly INVERSELY associated with death from melanoma. Melanoma thickness, mitoses, ulceration, and anatomic location on the head and neck were statistically significantly positively associated with melanoma death.


You probably heard the news stories in 2005 about sun exposure not being bad. They were very misleading at best and are based on a misinterpretation of some extremely important research which they may even have been intended to trivialize the news so people would not explore the information further.
The public was left with was a notion that sun exposure isn't bad and harried doctors who don't have the time, or perhaps the real information, will simply tell them to keep using sunblock without exploring the really critical information which is now available.
Yes, too much sun is very likely the cause of most skin cancer, but a chemical important to fighting cancer, and in some cases, the ONLY treatment for some cancers, is only created by direct sunlight on the unprotected skin, or obtained by prescription . This isn't my "opinion" it is the conclusion of many published medical studies (some of which I cite below).

Consider these facts:
Malignant Melanoma(MM) is a bigger killer in the north than near the equator.
MM is more deadly in indoor workers than outdoor workers.
This lends credence to the idea that too much sunblock and too little sun exposure can actually cause or make cancer worse. But what it really means is that you need to get a prescription vitamin supplement from your doctor if you have MM or some other cancers.
Why? Because studies show it can cut the mortality rate from MM by 50%, unlike kemotherapy which has little effect.

A Study
http://www.cfsan.fda.gov/~frf/forum05/H-PO-36.htm

A Melanoma Hypothesis: The Paradox of Outdoor and Indoor Solar UV Exposures.
D. E. Godar1 , J. C. Dowdy2 , S. G. Coelho3 , R. J. Landry3 , R. M. Sayre2 , J. C. Van der Leun4 , 1OSEL, CDRH, FDA, Silver Spring, MD, 2Rapid Precision Testing Laboratories, Cordova, TN, 3OSEL, CDRH, FDA, Rockville, MD, 4ECOFYS, Utrecht, The Netherlands
“Melanoma has been increasing at a steady logarithmic rate in fair-skinned, indoor workers since the mid 1930's. A paradox exists between indoor and outdoor workers because indoor workers get three to nine times less solar UV (290-400 nm) than outdoor workers, yet have a higher incidence of melanoma.”

The thrust of this paper is that outdoor workers are exposed to UVA and UVB while indoor workers only get UVA because UVB is filtered out by common window glass.

UVB is essential for the body to create Vitamin D3 while UVA causes Vitamin D3 to break down.

“Skin cells can convert vitamin D3 to the hormone, 1, 25-dihydroxyvitamin D3, or calcitriol, which causes growth inhibition and apoptotic cell death of melanoma cells in vitro and in vivo.” (That means both in the laboratory and in living animals.)

In other words, D3 helps prevent and stop the spread of cancer.

Explanation
OK, don’t run out and get a sunburn – that can cause cancer, but not getting an hour or two of unfiltered sunlight over a week’s time can lead to a Vitamin D3 deficiency and D3 is a treatment for cancer, a potent one according to some studies which show that D3 supplementation can cut the death rate for MM by half.
Considering that there is no real treatment for recurrent MM, that is rather significant (extreme understatement.)

More Evidence

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12174089&dopt=Abstract
British Journal of Dermatology
Volume 147 Issue 2 Page 197  - August 2002
doi:10.1046/j.1365-2133.2002.04960.x

Vitamin D and systemic cancer: is this relevant to malignant melanoma?

Says in part: “As in other cancers, there is evidence of a protective effect of vitamin D3 in MM, but ultraviolet radiation, which is a principal source of vitamin D3, is mutagenic. Further work is necessary on the influence of serum vitamin D3 levels on the occurrence and prognosis of MM, the effects of sun protection measures on serum vitamin D3 levels in temperate climates and epidemiological studies on geographical factors and skin type on the prognosis of MM. Meanwhile, it would seem mandatory to ensure an adequate vitamin D3 status if sun exposure were seriously curtailed, certainly in relation to carcinoma of breast, prostate and colon and probably also MM.”

AND

http://jnci.oxfordjournals.org/cgi/content/extract/97/3/161 "two independent epidemiologic studies (2,3) suggest that sunlight may reduce the risk of non-Hodgkin lymphoma (NHL) and may be associated with increased survival rates in patients with early-stage melanoma. In a large population-based case–control study of more than 3700 patients with incident lymphoma and nearly 3200 control subjects in Sweden and Denmark, Smedby et al. (2) reported a 20% to 40% reduction in the risk of this cancer."



http://jnci.oxfordjournals.org/cgi/reprint/jnci%3b97/3/161.pdf?ck=nck  "Sunlight and Reduced Risk of Cancer: Is the Real Story Vitamin D?" Egan, Sosman, Blot.

also http://jnci.oxfordjournals.org/cgi/content/full/97/3/161

Journal of the National Cancer Institute, Vol. 97, No. 3, 161-163, February 2, 2005
DOI: 10.1093/jnci/dji047

“In a follow-up study of more than 500 melanoma patients who participated in a U.S. case–control study in the 1990s, Berwick et al. (3) noted that subsequent mortality from melanoma was approximately one-half as high among those with signs of solar elastosis assessed by means of a standardized physical examination as among those without solar elastosis. The association of this biomarker of sun exposure and melanoma mortality persisted after adjustment for potential confounding factors, including thickness of the lesion and other established melanoma prognostic factors. The association was not confounded by early detection or various screening behaviors, including skin awareness, and skin self- or physician examination, or by social class.”

Translated into English, that means that sun exposure and therefore D3 is a big help in fighting cancers.

AND this quote from

British Journal of Dermatology
Volume 147 Issue 2 Page 197  - August 2002
doi:10.1046/j.1365-2133.2002.04960.x

Vitamin D and systemic cancer: is this relevant to malignant melanoma?

Osborne JE, Hutchinson PE.

Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, UK.

“Even more provocative is the observation of low 1,25-dihydroxyvitamin D3 serum levels in patients with malignant melanoma (13) and an association in some studies of specific vitamin D receptor polymorphisms with the development and outcome of melanoma (14). The incidence of melanoma of the skin on intermittently exposed sites is reduced among outdoor workers compared with indoor workers (15).”

In English that means that people with MM have low levels of D3, a very strong piece of evidence.

AND FINALLY

Journal of the National Cancer Institute, Vol. 97, No. 3, 161-163, February 2, 2005
DOI: 10.1093/jnci/dji047
“The notion that sun exposure might have a salutary influence for some types of cancers has been around for several decades. Among Caucasians in the United States, cancer mortality for several prominent cancers, including cancer of the breast, prostate, and colon, shows a striking latitudinal gradient, with increased mortality rates among individuals residing in the northern states compared with individuals residing the southern states (4). These patterns persist even after confounding variables like socioeconomic status, urban and rural residence, Hispanic heritage, and other risk factors are taken into account (5,6). In 1990, it was proposed that vitamin D, which is synthesized in the skin upon exposure to ultraviolet B light (UVB), might be the agent that accounts for these geographical patterns (7). 1,25-Dihydroxyvitamin D3 has multiple cellular effects, including inhibiting the G1/S cell cycle checkpoint, increasing expression of the cyclin-dependent kinase inhibitors p21 and p27, and potentially inducing apoptosis via a number of pathways (8–10). The ability to convert the provitamin to the active 1,25-dihydroxyvitamin D3 is much reduced at northern latitudes, and populations living far from the equator are at increased risk of vitamin D deficiency during the winter months (11).”

Vitamin D
There is some confusion in the online reports about Vitamin D, but the facts is that most supplements do not contain the vital component related to 1,25-dihydroxyvitamin D3.
You can only get that from a prescription supplement Chemical Name: CALCITRIOL (kal-si-TRYE-ole).
One good example is Rocaltrol (Roche).
This is relatively safe (certainly for those with recurrent MM for which there is no real treatment) but some caution is necessary for those with high calcium levels in the blood (hypercalcemia).
Tell your doctor your medical history, especially of: heart problems (e.g., arrhythmias, coronary artery disease), any allergies.

There are dozens of scientific and medical studies showing the importance of Vitamin D3 which I can provide if your doctor isn’t willing to let you try it based just on the reports cited above.

D3 is also an important weapon against rheumatoid arthritis.

Some studies show that Vitamin D doesn’t help against cancer, but they don’t isolate D3 and you don’t get D3 from milk or ordinary supplements so those studies are essentially meaningless.




A new report seen in the Hindustani Times, but based on research done at The University of Texas A&M Anderson Cancer Center, says that the yellow curcumin spice found in curry and tumeric powders has very strong anti-cancer properties especially for malignant melanoma.

A recent study listed in PubMed (Anticancer Res. 2003 Jan-Feb;23(1A):363-98.) says:

"Aggarwal BB, Kumar A, Bharti AC.

Cytokine Research Section, Department of Bioimmunotherapy, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Box 143, Houston, TX, USA. aggarwal@mdanderson.org

Curcumin (diferuloylmethane) is a polyphenol derived from the plant Curcuma longa, commonly called turmeric. Extensive research over the last 50 years has indicated this polyphenol can both prevent and treat cancer. The anticancer potential of curcumin stems from its ability to suppress proliferation of a wide variety of tumor cells, down-regulate transcription factors NF-kappa B, AP-1 and Egr-1; down-regulate the expression of COX2, LOX, NOS, MMP-9, uPA, TNF, chemokines, cell surface adhesion molecules and cyclin D1; down-regulate growth factor receptors (such as EGFR and HER2); and inhibit the activity of c-Jun N-terminal kinase, protein tyrosine kinases and protein serine/threonine kinases. In several systems, curcumin has been described as a potent antioxidant and anti-inflammatory agent. Evidence has also been presented to suggest that curcumin can suppress tumor initiation, promotion and metastasis. Pharmacologically, curcumin has been found to be safe. Human clinical trials indicated no dose-limiting toxicity when administered at doses up to 10 g/day. All of these studies suggest that curcumin has enormous potential in the prevention and therapy of cancer. The current review describes in detail the data supporting these studies."


The latest study  (Cancer. 2005 Jul 11; [Epub ahead of print]) says:


Siwak DR, Shishodia S, Aggarwal BB, Kurzrock R.

Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

BACKGROUND: 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). Curcumin-treated cells also were examined for NF-kappaB binding activity (electrophoretic mobility shift assay) and for the activity of its upstream regulator, IkappaB kinase (IKK) (immune complex kinase assay). In addition, relevant signaling, as reflected by B-Raf kinase activity (kinase cascade assay), and steady-state levels of activated, downstream effectors, as reflected by mitogen-activated signal-regulated protein kinase (MEK), extracellular signal-regulated protein kinase (ERK), and Akt phosphorylation levels (immunoblots), were assessed. RESULTS: Curcumin treatment decreased cell viability of all 3 cell lines in a dose-dependent manner (50% inhibitory concentration = 6.1-7.7 muM) and induced apoptosis. NF-kappaB and IKK were active constitutively in all melanoma cell lines examined, and curcumin, under apoptosis-inducing conditions, down-regulated NF-kappaB and IKK activities. However, curcumin did not inhibit the activities of B-Raf, MEK, or ERK, and Akt phosphorylation was enhanced. Furthermore, in the presence of curcumin, the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-[(R)-2-O-methyl-3-O-octadecylcarbonate] no longer suppressed Akt phosphorylation. 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. Cancer 2005. (c) 2005 American Cancer Society."




Translated into English, curcumin has shown a remarkable and possibly unique ability to restrict the growth of melanoma cells in laboratory tests. This does not PROVE it will work in people (in viva) but, since the spice has no known toxic effects even in what would be massive doses, it seems like it would be a very good idea to take it.





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Copyright, 2005, John A. McCormick, Inc.

RSS PubMED MELANOMA news FEED
HubMED/PubMED news feed "MELANOMA"
HubMED/PubMED news feed "MELANOMA AND Vitamin D"
If RSS feed not working properly, go to http://www.hubmed.org/search.cgi?q=melanoma+vitamin+d
If RSS feed not working properly, go to http://www.hubmed.org/search.cgi?q=melanoma
Breaking news on melanoma July 15, 2005
Breaking news on melanoma December 13, 2005
Effective chemotherapy
A new and effective chemo offers hope for those with Inoperable Metastatic Melanoma

Chemotherapy hasn't been effective for melanoma but a new clinical trial has shown an average of 13 months increase in life expectancy with a low-dose outpatient
chemobiotherapy combination of temozolomide, the granulocyte macrophage colony
stimulating factor (GM-CSF) LEUKINE(R) (sargramostim), Interferon-alpha-2b and
interleukin-2. The study was on only 31 Stage IV patients but it is very encouraging, especially since 4 went into complete remission.

The report was by Lynn E. Spitler, M.D., study investigator and director of the Northern
California Melanoma Center, San Francisco.

" The treatment regimen consisted of temozolomide at 200 mg/m(2) (at 150
mg/m(2) daily for patients with a previous history of chemotherapy) given
orally days one through five, followed by 12 days of subcutaneous daily
biotherapy with LEUKINE at 125 mcg/m(2) to a maximum 250 mcg,
Interferon-alpha-2b at 5 MU and interleukin-2 at 4 MU/m(2). This 28-day
treatment cycle was repeated as clinically indicated with the same treatment
sequence and dosage of each individual medication, or adjusted per-dosing
modifications based on adverse events and the investigator's judgment.
Response and progression were evaluated in this study using the international
criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST)
Committee."

See the Journal of Clinical Oncology for December, 2005.

There are many misleading or downright WRONG TV reports on skin cancer, Vitamin D, and sun exposure - once again all the TV news channels will probably have it  WRONG! ONLY Vitamin D-3 reduces cancer risk as I've been reporting for years! This is not found in the over the counter  vitamin D supplements, ONLY by prescription or direct sun exposure
Useful, but outdated Vitamin D information on an official Canadian government medical site. Please be sure to note the date the page was created.

http://www.bccancer.bc.ca/PPI/UnconventionalTherapies/VitaminDCholecalciferolCalcitriol.htm
University of Texas M. D. Anderson Cancer Center
Melanoma risk only partially associated vith exposure to UVB from sunlight
Researchers at The University of Texas M. D. Anderson Cancer Center have found that the risk of developing melanoma, the most deadly form of skin cancer, is only partially associated with exposure to ultraviolet B (UVB) radiation, the rays in sunlight that increase in summer and cause sunburn.
The report in the Dec. 21 issue of the Journal of the National Cancer Institute also indicates that only nonmalignant skin cancers (basal and squamous cell carcinoma) are strongly associated with exposure to UVB radiation.
That does not mean, however, that sunbathing poses a minimal risk of developing melanoma. Researchers say that ultraviolet A (UVA) radiation, the rays in sunlight that reach the deeper layers of skin and are associated with signs of aging, can damage the DNA in melanocytes, the pigment-producing cells that give rise to melanoma.


This report is only included for reasons of completeness, it has no currently significent useful information for patients.

American Society for Photobiology Journal 81:1276–1286 (2005)
doi: 10.1562/2005-01-24-RA-424
Photochemistry and Photobiology: Vol. 81, No. 6, pp. 1276–1286.
Comparisons of Estimated Economic Burdens due to Insufficient Solar Ultraviolet Irradiance and Vitamin D and Excess Solar UV Irradiance for the United States
William B. Grant,1, * Cedric F. Garland,2 and Michael F. Holick3


ABSTRACT
Vitamin D sufficiency is required for optimal health, and solar ultraviolet B (UVB) irradiance is an important source of vitamin D. UVB and/or vitamin D have been found in observational studies to be associated with reduced risk for over a dozen forms of cancer, multiple sclerosis, osteoporotic fractures, and several other diseases. On the other hand, excess UV irradiance is associated with adverse health outcomes such as cataracts, melanoma, and nonmelanoma skin cancer. Ecologic analyses are used to estimate the fraction of cancer mortality, multiple sclerosis prevalence, and cataract formation that can be prevented or delayed. Estimates from the literature are used for other diseases attributed to excess UV irradiation, additional cancer estimates, and osteoporotic fractures. These results are used to estimate the economic burdens of insufficient UVB irradiation and vitamin D insufficiency as well as excess UV irradiation in the United States for these diseases and conditions. We estimate that 50 000–63 000 individuals in the United States and 19 000–25 000 in the UK die prematurely from cancer annually due to insufficient vitamin D. The U.S. economic burden due to vitamin D insufficiency from inadequate exposure to solar UVB irradiance, diet, and supplements was estimated at $40–56 billion in 2004, whereas the economic burden for excess UV irradiance was estimated at $6–7 billion. These results suggest that increased vitamin D through UVB irradiance, fortification of food, and supplementation could reduce the health care burden in the United States, UK, and elsewhere. Further research is required to confirm these estimates."

INTRODUCTION  and selected quotes:

"There is rapidly mounting evidence that vitamin D has many important health benefits and that adequate serum levels of 25-hydroxyvitamin D (25(OH)D) are required for optimal health (1–12). There are also studies indicating that solar ultraviolet B (UVB) exposure is the primary source of vitamin D for most people outside the near-polar regions (13). However, despite this evidence, public health leaders have been slow to accept the role of solar UVB irradiance and vitamin D in maintaining optimal health, in part, because of widespread concern regarding the risk of cutaneous malignant melanoma (CMM) and nonmelanoma skin cancer (NMSC) due to solar UV irradiance.

In this study, we estimate the economic burden of insufficient solar UVB irradiance and vitamin D in the United States and compare this estimate with the economic burden from excess UV irradiation over either short (sunburning) or long periods. The approach is to consider diseases for which a strong geographic variation in the United States can be identified for disease outcome and to then use these variations to estimate the fraction of the disease burden in the United States that can be attributed to insufficient UVB irradiance and/or vitamin D or to excess solar UV irradiance. For some diseases that are linked to vitamin D deficiency but for which geographical variations are not apparent within the United States, results in the literature are used. Following that, the results for the United States are extrapolated to the United Kingdom."



"Risk of hip fracture in elderly cut by 50% with Vitamin D supplementation (low 25(OH)D serum levels."

"Vitamin D recommendations
The consensus of scientific understanding defines vitamin D deficiency as serum 25(OH)D levels below 16 ng/mL (40 nmol/L), insufficiency in the range 20–32 ng/mL, and sufficiency in the range 32–80 ng/mL, with normal in sunny countries (54–90 ng/mL), and excess greater than 100 ng/mL (85–90). To obtain high enough serum 25(OH)D levels now considered optimal, oral intakes of 1000 I.U. (25 μg) or more per day of vitamin D3 in the absence of UVB irradiance may be required."

Massive Study On Consequences of Widespread Vitamin D Deficiency in the U.S. Population 50,000+ premature cancer-related deaths caused by lack of Vitamin D
Calcitriol in cancer treatment: From the lab to the clinic

Mol Cancer Ther. 2004;3:373-381
© 2004 American Association for Cancer Research

Tomasz M. Beer and Anne Myrthue
Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR
Requests for Reprints: Tomasz M. Beer, Department of Medicine, Oregon Health and Science University, Mail Code CR-145, 3181 SW Sam Jackson Park Road, Portland, OR 97239.

1,25-Dihydroxyvitamin D (calcitriol), the most active metabolite of vitamin D, has significant antineoplastic activity in preclinical models. Several mechanisms of activity have been proposed. These include inhibition of proliferation associated with cell cycle arrest and, in some models, differentiation, reduction in invasiveness and angiogenesis, and induction of apoptosis.
This site does NOT provide medical advice, it provides summaries and links to information in medical journals and my aim is to provide medical professionals and patients with vital information which can be used to guide medical professionals in the treatment of various difficult-to-treat conditions.
Does sunlight have a beneficial influence on certain cancers?

Prog Biophys Mol Biol. 2006 Feb 28;
Kricker A, Armstrong B
http://www.hubmed.org/display.cgi?uids=16595142

Apperly [1941. The relation of solar radiation to cancer mortality in North America. Cancer Research 1, 191-195] first proposed that increased mortality from cancer in the north than in the south of the USA might be due to the south to north decrease in ambient solar radiation. This inverse association between ambient solar radiation and cancer mortality has been subsequently reported for cancers of the colon, breast, ovary and prostate. While the evidence that sunlight might be related to lower incidence or more favourable outcomes from cancer came initially from ecological studies, case-control and cohort studies have now shown a similar association of sun exposure with risks of colon, breast and prostate cancers in individuals, and other studies in individuals have found that serum and dietary vitamin D levels are associated with reduced risks of colorectal cancer and, less certainly, prostate cancer. Studies in individuals have recently also suggested an effect of sun exposure to reduce risk of non-Hodgkin lymphoma and to increase survival after a diagnosis of melanoma. Data on variation in survival from cancer by season of diagnosis suggest that sun exposure may also improve outcome from cancers of the breast, colon and prostate and Hodgkin lymphoma.

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STA-4783 has been fast tracked for MM treatment and may double survival time to 12 months.
Journal National Cancer Institute: " Two Studies Find Evidence That Sunlight May Have Beneficial Influence on Cancer"


This page was last updated: March 26, 2010