Vit D and melanoma - Part 2

The pendulum for and against, or neither, regarding whether Vitamin D levels matter in the development of....or outcomes in...melanoma patients...keeps swinging.  I posted these articles earlier:  Vitamin D and Melanoma

Now there is this:

Association of Vitamin D Levels With Outcome in Patients With Melanoma After Adjustment For C-Reactive Protein.  Fang, Sui, Wang, et al.  J Clin Oncol. 2016 Mar 21. 

To evaluate for an association between 25-hydroxyvitamin D levels (vitamin D) and outcome measures in patients with melanoma after evaluation is controlled for systemic inflammatory response (SIR) on the basis of simultaneous C-reactive protein (CRP) measurement.  Plasma samples from 1,042 prospectively observed patients with melanoma were assayed for vitamin D and CRP. The associations of demographics and CRP with vitamin D were determined, followed by a determination of the association between vitamin D and stage and outcome measures from the date of blood draw. The vitamin D level was considered sufficient if it was 30 to 100 ng/mL. Kaplan-Meier and Cox regression analyses were performed.  The median vitamin D level was 25.0 ng/mL. The median follow-up time was 7.1 years. A lower vitamin D was associated with the blood draw during fall/winter months, older age, increased CRP, increased tumor thickness, ulcerated tumor, and advanced melanoma stage. On univariate analysis, lower vitamin D was associated with poorer overall survival, melanoma-specific survival, and disease-free survival. The effect of vitamin D on these outcome measures persisted after adjustment for CRP and other covariates. Multivariable hazards ratios per unit decrease of vitamin D were 1.02 for OS, 1.02 for MSS, and 1.02 for DFS.  Lower vitamin D levels in patients with melanoma were associated with poorer outcomes. Although lower vitamin D was strongly associated with higher CRP, the associations of lower vitamin D with poorer OS, MSS, and DFS were independent of this association. Investigation of mechanisms responsible for these associations may be of value to patients with melanoma.

For what it's worth.  I happen to take 2000 units of Vitamin D daily.  Not saying you should....just say'n I do.  - c

Vitamin D and melanoma - folks with higher levesl do better - again!!!

Vitamin D and vitamin D levels of melanoma patients have long been discussed.  Here is a link to a couple of prior posts:  Vitamin D - low levels associated with a worse prognosis in melanoma...again...

Now there's this:

High serum vitamin D level correlates with better prognostic indicators in primary melanoma: A pilot study. Lim, Shayan, and Varigos. Australas J Dermatol. 2017 Mar 23.

Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level.

In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. 

Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex. Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours and in tumours with mitotic rate less than 1/mm² compared with greater than/= to 1/mm². A significant association was found between vitamin D level and tumour histological subtype. On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma, and SSM and acral lentiginous melanoma.  

A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings.

And again....  Take that Vitamin D, folks!!! - c

More evidence that Vitamin D matters for melanoma and cancer patients generally!

Not news, really.  Here are a zillion related posts!!!
2014:  Vitamin D and Melanoma 
2016:  Vit D and melanoma - Part 2 
Jan 2017:  Vitamin D - low levels associated with a worse prognosis in melanoma...again... 
June 2017:  Vitamin D and melanoma - folks with higher levesl do better - again!!! 
September 2017:  Vitamin D and melanoma

Now this:

Circulating 25-hydroxyvitamin D up to 3 decades prior to diagnosis in relation to overall and organ-specific cancer survival.  Weinstein, Mondul, Yu, et al.  Eur J Epidemiol. 2018 Aug 2.

While vitamin D has been associated with improved overall cancer survival in some investigations, few have prospectively evaluated organ-specific survival. We examined the accepted biomarker of vitamin D status, serum 25-hydroxyvitamin D [25(OH)D], and cancer survival in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Of 4616 cancer cases with measured serum 25(OH)D, 2884 died of their cancer during 28 years of follow-up and 1732 survived or died of other causes. Proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between pre-diagnostic 25(OH)D and overall and site-specific survival. Serum 25(OH)D was significantly lower among cases who subsequently died from their malignancy compared with those who did not (medians 34.7 vs. 36.5 nmol/L, respectively). Higher 25(OH)D was associated with lower overall cancer mortality. Higher 25(OH)D was related to lower mortality from the following site-specific malignancies: prostate, kidney, and melanoma, but increased mortality from lung cancer. Improved survival was also suggested for head and neck, gastric, pancreatic, and liver cancers, though not statistically significantly, and case numbers for the latter two organ sites were small. Higher 25(OH)D status years prior to diagnosis was related to improved survival for overall and some site-specific cancers, associations that should be examined in other prospective populations that include women and other racial-ethnic groups.

For what it's worth.  - c

Vitamin D - low levels associated with a worse prognosis in melanoma...again...

These results are not exactly new.  Here are a couple of previous articles:  Vit D and melanoma - Part 2

Vitamin D deficiency is associated with a worse prognosis in metastatic melanoma. Timerman, McEnery-Stonelake,...Hodi, et al. Oncotarget. 2016 Dec 28.

Vitamin D deficiency (less than or = to 20 ng/mL) is associated with an increased incidence and worse prognosis of various types of cancer including melanoma. A retrospective, single-center study of individuals diagnosed with melanoma from January 2007 through June 2013 who had a vitamin D (25(OH)D3) level measured within one year of diagnosis was performed to determine whether vitamin D deficiency and repletion are associated with melanoma outcome. A total of 409 individuals diagnosed with histopathology-confirmed melanoma who had an ever measured serum 25(OH)D3 level were identified. 252 individuals with a 25(OH)D3 level recorded within one year after diagnosis were included in the study and the individual and melanoma characteristics such as age, sex, Breslow thickness, ulceration, stage, mitotic rate, and LDH were obtained from the medical record. A worse melanoma prognosis was associated with vitamin D deficiency, higher stage, ulceration, and higher mitotic rate. In patients with stage IV metastatic melanoma, vitamin D deficiency was associated with significantly worse melanoma-specific mortality. Patients with metastatic melanoma who were initially vitamin D deficient and subsequently had a decrease or less than or = to 20 ng/mL increase in their 25(OH)D3 concentration had significantly worse outcomes compared to non-deficient patients who had a greater than 20 ng/mL increase. Our results suggest that initial vitamin D deficiency and insufficient repletion is associated with a worse prognosis in patients with metastatic melanoma.

Take that Vitamin D, folks!!! - c

Vitamin D and melanoma

We've long known that higher vitamin D levels provide a better prognosis in melanoma.  Here is a link (with others within) discussing Vitamin D:  Vitamin D and melanoma - folks with higher levesl do better - again!!!

Now there is this ~

On the role of classical and novel forms of vitamin D in melanoma progression and management. Slominski, Brozyna, Skobowiat, et al. J Steroid Biochem Mol Biol. 2017 Jul 1.

Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)₂D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.

For what it's worth! - c

Vitamin D and Melanoma

Vitamin D level at diagnosis and its variation during follow up as prognostic factor of cutaneous melanoma.  Saiag, Aegerter, Vitous, et al.  June 2014 ASCO.

Low 25-hydroxyvitamin D3 serum concentration at diagnosis of melanoma might be associated with worse survival.   Patients were collected from Paris hospitals from 2003 -2008 as they were diagnosed with Stage I-IV melanoma and were followed until June 2011.  1,171 patients were included, with 411 relapses during f/u, and 303 deaths.  Median serum Vit D levels at inclusion were inversely correlated with prognostic factors such as AJCC stage, Breslow's thickness and ulceration, but were not associated with disease free survival.  Changes in Vit D levels during follow-up were significantly associated with worse disease free survival.  We show that Vit D variation during follow-up is an independent melanoma prognostic marker, but not its level at diagnosis.  Previously reported association between low Vit D level at diagnosis and poor prognosis were probably due to insufficient adjustment for prognostic factors.

I'm not sure what these peeps are saying in their last sentence.  That seems an odd conclusion for them to draw.  By their own admission, folks with lower levels of Vit D had increased Breslow thickness and ulceration.  So...we can't KNOW that the decreased Vit D levels CAUSED that...but....  And, we can't KNOW whether low Vit D or those known risk factors for worse prognosis (increased thickness and ulceration) did in fact, create the poor prognosis that did materialize....but....???

Low Serum 25-Hydroxyvitamin D Concentrations are Associated with Increased Risk for Melanoma and unfavorable Prognosis.  Bade, Zdebik, Wagenpfeil, et al.  PLoS One.  Dec 2014.

Low vitamin D status (Serum 25(OH)D concentration is associated with increased incidence and unfavorable outcome of various types of cancer.  Serum Vit D concentrations were retrospectively analyzed in 324 melanoma patients and 141 healthy controls.  Vit D levels were significantly lower in melanoma patients (med = 13.6 ng/ml) vs controls (med = 15.6 ng/ml).  When looking at Vit D levels in the melanoma patients:  those with lower levels of Vit D had greater Breslow thickness and inferior survival (med = 80 months) vs the melanoma patients with higher levels (med = 195 months).  Our data support that concept that serum Vit D concentrations are associated with risk and prognosis of melanoma.  Whether normalizing serum Vit D in these patients improves outcomes will require testing in future clinical trials.

This report is at least consistent within its own data.  Clearly, there is much related to Vit D and its effects on cancer that we don't understand.

For what it's worth! - c

The latest anti-oxidant controversy

Medscape article re selenium/Vit E and Prostate cancer - 2014

This article from last year notes..."data from the much publicized Selenium and Vitamin E Cancer Prevention Trial (SELECT), which sought to determine whether these supplements could protect against the development of prostate cancer, confirm that both antioxidants can be risky business for men.  ...men receive no preventive benefit from either selenium or vitamin E supplements; in fact, for certain men, these supplements actually increased the risk for prostate cancer."  A researcher interviewed noted, "Many people think that dietary supplements are helpful or at the least innocuous. This is not true."

"The cohort of 4856 men was culled from SELECT, the larger phase 3 placebo-controlled trial in which more than 35,000 men were randomized to high-dose vitamin E (400 IU/day) and/or selenium (200 µg/day) supplements.  SELECT began in 2001 and was expected to run for 12 years, but it was stopped early, in 2008, after participants had been on the supplements for an average of 5 years. The results demonstrated that there was no protective effect from selenium and suggested that vitamin E increased prostate cancer risk.  Although the use of the supplements stopped, the study actually continued. After 2 years of follow-up, the men who took vitamin E had a statistically significant 17% increased risk for prostate cancer.  Notably, the rate of prostate cancer detection was higher in the groups that received either supplement alone or a combination of the 2 than in the placebo group (but the difference was significant only in the vitamin E group)."


Medscape re antioxidants and melanoma - 2015

This article published October 23 reports...."though the data are preliminary, findings from a new study may shed some light on why supplementing with antioxidants may be a bad idea for patients with cancer." 
"Our data suggest cancer cells benefit more from antioxidants than do normal cells," said lead author Sean Morrison, PhD, director of the Children's Research Institute and Mary McDermott Cook Chair in Pediatric Genetics at UT Southwestern Medical Center in Dallas, Texas. "It raised the concern that people with cancer may want to think twice before they supplement their diet with large doses of antioxidants."
In their study, human melanoma cells taken from several patients were [grafted into mice] In mice that were given the antioxidant N-acetyl-cysteine, cancer spread was accelerated. It significantly increased the frequency of melanoma cells in the blood of some of the mice and significantly increased metastatic disease burden in all of them.  "At least in the mice, the antioxidants promoted the capacity of the cancer cells to spread and metastasize," he said.

The authors found that that metastasizing melanoma cells experience very high levels of oxidative stress, which in turn leads to the death of most of these cells. Oxidative stress therefore limits distant metastasis by melanoma cells. But by administering antioxidants to the mice, more of the metastasizing melanoma cells were able to survive and increase the metastatic disease burden.
Even though this study was done in mice, Dr Morrison feels that the results can be extrapolated to humans. "We have previously shown that the behavior of human melanomas in mice are predictive of how melanoma behaves in humans.  ...  But it is important to remember that our study was performed in mice and not in actual human patients."

The report goes on to reference the report above as well as one in which patients with lung cancer were given selenium or not.  Those who were given the supplement had a greater incidence of a second tumor, "but it was not statistically significant and therefore could have been due to chance."

Another study looked at [genetics] to shed more light on which population of men who already have prostate cancer might be most harmed by selenium. Among men with the AA genotype, higher selenium levels were associated with a 40% reduced risk of presenting with aggressive disease, whereas among men with the V allele, higher selenium levels were associated with an almost doubling of the risk for aggressive disease.  Phillip Kantoff, MD, director of the Lank Center for Genitourinary Oncology, and vice chair and chief, Division of Solid Tumor Oncology, Department of Medical Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts, was the senior author on the genetic study.  [When interviewed, he noted:]  "The study is interesting. There is a fair amount of data supporting this. In fact, there are 2 follow-up studies of SELECT study showing that over time the arms that got vitamin E or selenium had more or more aggressive cancers."
"The underlying mechanism is still not clear but this is one possible one," Dr Kantoff added.

And then there was this about Vitamin D:  Vitamin D and melanoma 

Bottom line:  I think there is much we don't understand about many things....and that certainly includes the behavior of cancer cells .  I have NEVER been one to recommend boat loads of vitamins and supplements; just because a little is good doesn't mean a lot is better!  As a rather brilliant nursing professor I had noted, "Americans have the most expensive urine in the world."  Referencing the fact that most water soluble vitamins are simply excreted by the body and the money we paid for them is literally dollars down the drain.  These reports as well as other previously existing data warn that supplements can also cause harm.  If I were a man with prostate cancer, I certainly wouldn't be taking selenium and Vitamin E supplements. On the other hand, I see no need to panic.  We have also long known that folks who eat a well balanced diet, heavy in fruits and vegetables, and get regular exercise, lead longer, healthier lives with less incidence of heart disease, cancer, and dementia than those who do otherwise.  I see nothing scary in an orange.  And, melanoma or no, that is the path I will continue to follow.

Eat your colors! - c

Everything cures melanoma...redux....#5?????

Lord knows I have covered 'most' everything that folks have tested and came away saying would cure melanoma:  coffee, curcumin, strawberry extract, wine, doxycycline, beta blockers, snake venom, shitakes, eggplant, potatoes, tomatoes, cimetadine, NSAID's, Vitamin D, Vietnamese Sophora root, exercise, sandalwood...I did leave off sea urchin snot....just seemed a bridge too far!!!!  Here are those posts if you'd like to see the data for yourself:

From 2013:  Everything cures melanoma, so why do we have it?

Be Better in 2013: Jump up, jump around and get down!

2014: Red, red wine boosts radiation effect

Also from 2014:  For melanoma: eat that curry again we just don't know why!

2015: Everything kills melanoma: Take 4

Now we have these reports touting the benefits of dill and parsley, coffee and curcumin again, anti-cholesterol meds and stress control! Here you go:

Efficient Synthesis of Glaziovianin A Isoflavone Series from Dill and Parsley Extracts and Their in Vitro/in Vivo Antimitotic Activity.  Semenov, Tsyganov, Semenova, et al.  J Nat Prod. 2016 Apr 21. 

A concise six-step protocol for the synthesis of isoflavone glaziovianin A (GVA) and its alkoxyphenyl derivatives 9 starting with readily available plant metabolites from dill and parsley seeds was developed. The reaction sequence involved an efficient conversion of the key intermediate epoxides 7 into the respective β-ketoaldehydes 8 followed by their Cu(I)-mediated cyclization into the target series 9. The biological activity of GVA and its derivatives was evaluated using a panel of seven human cancer cell lines and an in vivo sea urchin embryo assay. Both screening platforms confirmed the antimitotic effect of the parent GVA (9cg) and its alkoxy derivatives. Structure-activity relationship studies suggested that compounds 9cd and 9cf substituted with trimethoxy- and dillapiol-derived B-rings, respectively, were less active than the parent 9cg. Of the evaluated human cancer cell lines, the A375 melanoma cell line was the most sensitive to the tested molecules. Notably, the target compounds were not cytotoxic against human peripheral blood mononuclear cells up to 10 μM concentration. Phenotypic readouts from the sea urchin assay unequivocally suggest a direct microtubule-destabilizing effect of isoflavones 9cg, 9cd, and 9cf.

Higher Caffeinated Coffee Intake Is Associated with Reduced Malignant Melanoma Risk:  A Meta-analysis study.  Liu, Shen, Shi, Cai, PLoS One.  2016 Jan 27.

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 for those with highest versus lowest quantity of intake. In the dose-response analysis, the RR of MM was 0.955 for per 1 cup/day increment of caffeinated coffee consumption and linearity dose-response association was found. Strikingly, no significant association was found between the decaffeinated coffee intake level and MM risk.  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.


Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism.  Yang, Bai, Xiong, et al.  Nature. 2016 Mar 16. 

CD8⁺ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment. Reactivating the cytotoxicity of CD8⁺ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8⁺ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme, led to potentiated effector function and enhanced proliferation of CD8⁺ but not CD4⁺ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8⁺ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8⁺ T cells were better than wild-type CD8⁺ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy.

Curcumin:  A new candidate for melanoma therapy?  Mirzaei, Naseri, Reazee, et al.  Int J Can.  2016 Jun 9.  

Melanoma remains among the most lethal cancers and, in spite of great attempts that have been made to increase the life span of patients with metastatic disease, durable and complete remissions are rare. Plants and plant extracts have long been used to treat a variety of human conditions; however, in many cases, effective doses of herbal remedies are associated with serious adverse effects. Curcumin is a natural polyphenol that shows a variety of pharmacological activities including anti-cancer effects, and only minimal adverse effects have been reported for this phytochemical. The anti-cancer effects of curcumin are the result of its anti-angiogenic, pro-apoptotic, and immunomodulatory properties. At the molecular and cellular level, curcumin can blunt epithelial-to-mesenchymal transition and affect many targets that are involved in melanoma initiation and progression (e.g. BCl2, MAPKS, p21 and some microRNAs). However, curcumin has a low oral bioavailability that may limit its maximal benefits. The emergence of tailored formulations of curcumin and new delivery systems such as nanoparticles, liposomes, micelles and phospholipid complexes has led to the enhancement of curcumin bioavailability. Although in vitro and in vivo studies have demonstrated that curcumin and its analogues can be used as novel therapeutic agents in melanoma, curcumin has not yet been tested against melanoma in clinical practice. In this review, we summarized reported anti-melanoma effects of curcumin as well as studies on new curcumin formulations and delivery systems that show increased bioavailability. Such tailored delivery systems could pave the way for enhancement of the anti-melanoma effects of curcumin.

Association of stress coping strategies with immunological parameters in Melanoma Patients.  Trapp, Trapp, Avian, et al.  Acta Derm Venereol. 2016 Jun 9.

In this exploratory case control study the association between stress coping strategies and lymphocyte subpopulations was calculated in 18 non-metastatic melanoma patients and 18 controls with benign skin diseases. Coping strategies were assessed using the German version of the stress-coping questionnaire (SVF 120). While in the control group patients showed significant negative correlations of lymphocyte subpopulations (CD3+, CD4+, CD8+, CD19+, CD45+ cells) with coping strategies that refer to defence, in melanoma patients significant positive correlations between lymphocyte subpopulations (CD3+, CD4+, CD19+, CD45+ cells) were found with regard to coping strategies that are characterized by diversion from stress and focusing on stress-compensating situations. The present data, in melanoma patients and controls, show contrary correlations between stress coping strategies and lymphocyte subpopulations. The interconnection between stress coping and immunologic alterations in malignant melanoma is a field deserving further multiprofessional investigation in order to provide new therapeutical approaches in the treatment and understanding of melanoma patients.

Supercritical Fluid Extract of Spent Coffee Grounds Attenuates Melanogenesis through Downregulation of the PKA, PI3K/Akt, and MAPK Signaling Pathways.  Huang, Wei, Siao, et al.  Evid Based Complement Alternat Med. June 2016.

The mode of action of spent coffee grounds supercritical fluid CO2 extract (SFE) in melanogenesis has never been reported. In the study, the spent coffee grounds were extracted by the supercritical fluid CO2 extraction method; the chemical constituents of the SFE were investigated by gas chromatography-mass spectrometry (GC-MS). The effects of the SFE and its major fatty acid components on melanogenesis were evaluated by mushroom tyrosinase activity assay and determination of intracellular tyrosinase activity and melanin content. The expression level of melanogenesis-related proteins was analyzed by western blotting assay. The results revealed that the SFE of spent coffee grounds (1-10 mg/mL) and its major fatty acids such as linoleic acid and oleic acid (6.25-50 μM) effectively suppressed melanogenesis in the B16F10 murine melanoma cells. Furthermore, the SFE decreased the expression of melanocortin 1 receptor (MC1R), microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2). The SFE also decreased the protein expression levels of p-JNK, p-p38, p-ERK, and p-CREB. Our results revealed that the SFE of spent coffee grounds attenuated melanogenesis in B16F10 cells by downregulation of protein kinase A (PKA), phosphatidylinositol-3-kinase (PI3K/Akt), and mitogen-activated protein kinases (MAPK) signaling pathways, which may be due to linoleic acid and oleic acid.
 
While most of these...coffee, curcumin, and becoming a bit more zen most certainly....are likely to do no harm, do keep this word of warning in mind should you be determine to cure yourself:   Combining alternative and conventional treatments can be a risky business!

For what it's worth! - c

"Alternative" treatment for melanoma

I started this blog in 2010 (or rather, Rosie did!!) as a way to communicate my personal story to family and friends.  Around the end of 2011, it began to change.  As I was contacted by melanoma patients and their families, I began researching better answers to their questions. Suddenly I realized, if there was one who found me seeking information...there must be many more who also needed to know.  This blog has become my message board to all those families.  Those who read this strange conglomeration will still find my general random craziness, a glimpse into my passions (reading, cooking, sewing, family, running, music), the best research I can find regarding melanoma, and...extreme honesty!  While I put out the latest and greatest about every single development in melanoma, I work hard to include context about what is actually known, what we can hope the treatment will provide, and when I can find the info....how it all turns out. I admit complete hatred of insurance companies...every single one of them!!!  There is so much that needs to be repaired in the way medicine, Big Pharma, clinical trials and the FDA work that I could dedicate every post to those topics alone.  I have absolutely no tolerance for medical providers who treat patients badly, quacks who are no more than elaborate con artists taking advantage of fear and desperation, or legitimate researchers who continue to use FDA approved medications instead of  better, more effective ones.  So, lets start there!

Folks can be very protective of the medicine "they" took.  They seem to take it as a personal insult when treatments they utilized turn out to be lacking.  Interferon is a classic example.  It has little to no effect on melanoma, has been clearly proven to have absolutely NO positive influence on survival, yet docs still use it both as treatment and as a comparative arm in trials, and some of those who took it go into attack mode when it is criticized.  When the good news about ipi was just coming out in 2011, I noted this:  Is interferon still an appropriate treatment?  Though dacarbazine offers at least a bit more help for those who are running out of better options, many of the same criticisms can be applied to its use.  Ribas and Robert had this discussion in 2013:  No more dacarbazine!  I took peptide vaccines as part of my nivo trial.  Since then we have learned - Peptide vaccines do NOT trigger an effective immune response!  Thankfully, they are no longer used in my trial!  (Although one of my fellow ratties bemoaned the fact that patients in the trial currently don't "go through what I went through" as though it was unfair!  OMG!!!  Learning from mistakes made on fellow ratties is the ONLY thing that IS fair in a clinical trial!!!!)  ADC's (antibody drug conjugates) sound great, but so far leak too much nasty chemo into the patient's body (rather than just in the tumor). Hopefully, they will get better.  The Cure Tech anti-PD1 product was a dismal failure and despite the suffering of the ratties (Love you, J!!!) who participated in that trial, it was ended and hopefully will never be heard from again.

All this to say, that melanoma patients can only do the best we can.  We can research things to the best of our ability, find the best care we can afford to get to, and choose!  Sometimes it feels no better than throwing a dart at a board....with your eyes closed!  Educated guesses and desperate decisions.  I am certain I owe my existence to the clinical trial I was lucky enough to be in.  However, there were many ways in the course of that experience in which I was used and treated unfairly.  I think many people fear speaking out....lest they not be allowed to continue or be punished in some other way.  Not me:  Patient rights in a clinical trial. An oxymoron???  I also have no timidity whatsoever when it comes to medical providers who do not serve their patients as they should:  The Jerk!  I did end up getting an apology, as my letter was forwarded to the Jerk in question, perhaps he learned something...we can only hope.  I have even less tolerance for folks who pose as reputable medical providers, when in reality they are nothing more than con artists taking money from desperate, suffering, and frightened patients.  Even when their "treatments" do no harm (though many actually do) they all waste time and treasure as the patient adopts ineffective care, often until it is too late.  My heart will never forget Mike Brockey and the time he lost on Gerson.  Even when you are minding your own business, the Snake Oil Salesmen will even try to attack via blogs!!!  Fredda Branyon, posing as a doctor offering stem cell therapy, was already CONVICTED and facing jail time when she (or her minions) began commenting on every blog they could find with the word 'cancer' in the title:  Dr. Fredda Branyon is a CRIMINAL!  Yes, the conversations I had with many other bloggers were very interesting!

With some regularity, folks contact me here, or post on forums, asking what diet or 'alternative' treatment they could use to 'fight' their melanoma.  While I believe in a healthy diet and exercise, sadly, so far, no particular diet or food has been found to prevent or cure melanoma.  But, I cover them all:  Sugar free, Ketogenic, Gerson, Cellect  There's Strawberry Juice, Eggplant, potatoes, and tomatoes, Red wine, Coffee, doxycycline, curcumin, cimetidine, NSAID's and shitakes, Vitamin D, Snake venom, beta blockers and Vietnamese sophora root, exercise, Curry again!!!  and today there are these:

Anticancer effects of Sandalwood.  Santha and Dwivedi.  Anticancer Research, June 2015.
Effective management of tumorigenesis requires development of better anticancer agents with greater efficacy and fewer side effects.  Natural products are important sources for the development of chemotherapeutic agents and almost 60% of anticancer drugs are of natural origin.  Alpha-Santlol, isolated from Sandalwood, is known for a variety of therapeutic properties.  Our laboratory identified its anticancer effects in chemically-induced carcinogenesis in [special] mice and in vitro models of melanoma, non-melanoma, breast and prostate cancer.

Good to know.  However, that's a long way from peeps.  Not sure what "non-melanoma" is!  And, while I will be the first to laud the lowly periwinkle (the source of one of the best and most effective chemotherapy drugs, Vincristine) and work to protect the rain forest, nature also provides us with poison ivy, oleander, and hemlock!

Coffee drinking and cutaneous melanoma risk in the NIH-AARP diet and health study.  Loftfield, Freedman, Graubard, et al.  J Natl Cancer Inst.  Jan 2015.
Cutaneous melanoma is the fifth most common cancer in the US.  Modifiable risk factors, with the exception of exposure to ultraviolet radiation, are poorly understood.  Coffee contains numerous bioactive compounds and may be associated inversely with melanoma.  Coffee intake was assessed at baseline with a food frequency questionnaire in the NIH-AARP prospective cohort study.  Among 447,356 non-Hispanic whites who were cancer-free at baseline, 2,904 cases of malignant melanoma were id'd during a median 10.5 year follow-up.  After statistical analysis, the highest category of coffee intake (more than or equal to 4 cups a day) was inversely associated with malignant melanoma, but only if was caffeinated.

Though the authors admit they are not sure if the effect was from the coffee or the caffeine, guess I'll have another cup!!!

No matter how strange the findings, when it comes to melanoma, I will certainly put it all out there!!!  You never know!  But, if it walks like a duck, quacks like a duck, smells like a duck, seems just a little too easy, too crazy, or too good to be true....it probably is!!!!  Don't let desperation trick you into doing something that could prevent you from getting the best REAL help you can.  This oped/report on cancer therapy by QuackWatch 
provides good analysis of particular treatment scams as well as basic information about how treatments and programs are analyzed to determine their real value and how quacks twist the 'data' and prey on the fears of frightened folks.  This paragraph really hit home:
    "Quacks typically charge that the medical profession, drug companies, the food industry, government agencies, and/or other "vested interests" are conspiring against "natural" cancer cures. No such conspiracy has ever been exposed. Yet many patients—especially those whom standard medicine cannot cure—embrace the notion that a small but dedicated band of rebels is defying the medical establishment by making natural cures available. And desperate patients may find it more comfortable to believe that cures are being suppressed than to feel that their situation is hopeless."

Don't let jerks take advantage of you.  Melanoma is fight enough. There are more viable treatments (as lame as they are!!!) for melanoma than ever before.  It is not easy, but don't let fear and denial rule your decisions.  I hope this helps.  I wish you well. - c