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Melanoma

Category: Illness or disabilities

Type

Involuntary

Introduction and description

BEING EDITED ****************

 Melanoma, also known as malignant melanoma, is a type of cancer - abnormal cell growth - that develops from the pigment-containing cells known as melanocytes.  There are three main types of skin cancer - basal cell carcinoma (BCC) squamous cell carcinoma (SCC), and melanoma.  But the names are deceptive, because in reality these cancers are related to types of cell, some of which just happen to be in the skin

  • Basal cell carcinoma (BCC) – affects the stratum basale (basal layer, sometimes referred to as stratum germinativum) - the deepest layer of the five epidermis layers.  The stratum basale is primarily made up of basal keratinocyte stem cells, which can be considered the stem cells of the epidermis. Thus BCC is cancer of the basal keratinocyte stem cells.
  • Squamous cell carcinoma  - is a cancer of a kind of epithelial cell, the squamous cell. These cells are the main part of the epidermis of the skin, and this cancer is one of the major forms of skin cancer. However, squamous cells also occur in the lining of the digestive tract, lungs, and other areas of the body
  • Melanoma – occurs in melanocytes.  Although Melanomas typically occur in the skin, they can occur in any organ that has melanocytes

Thus all these cancers are distinguished by which cell they affect, not where they may occur in the body.  This is important, as different cells can be attacked by different pathogens, thus knowing which cell is affected helps us to home in on the possible pathogens. 

Although doctors talk about a cancer spreading, what is actually happening is that the pathogen is spreading, sometimes via the lymph system and sometimes via the blood circulatory system.  Thus if a pathogen attacks one type of cell, it is then known where the risk is in other organs from knowledge of where that type of cell is located in the body

Although most melanomas arise in the skin, they may also arise from mucosal surfaces or at other sites to which neural crest cells migrate.

Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm cell layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia.  As such melanoma can affect many parts of the body - the stratum basale of the skin's epidermis, the middle layer of the eye (the uvea), the inner ear, meninges, bones, and heart as well as a number of other organs.  We will look at this in more detail under symptoms. 

The present study retrospectively analyzed the data of 78 patients who were histopathologically diagnosed with MM in Dicle University Medical Faculty, Dermatology and Medical Oncology departments, Diyarbakir, Turkey between 2005 and 2014.  The study included 78 patients in total with 44 (56.4%) male and 34 (43.6%) female…. age range: 27 - 84 years. Of the patients,

  • 78.2% (n = 61) had cutaneous melanoma,
  • 8.9% had solid organ melanoma, and
  • 2.5% had ocular and mucosal melanoma.

The most common tumour localization among the patients was the lower extremities with 29.4% (n = 23). … Median overall survival in all patients was 14.9 months PMID:  27583086

Epidemiology

Skin cancer is the most common malignancy diagnosed in the United States, with 3.5 million cancers diagnosed in 2 million people annually. Melanoma represents less than 5% of skin cancers but results in most deaths. The incidence has been increasing over the past four decades. Elderly men are at highest risk; however, melanoma is the most common cancer in young adults aged 25 to 29 years and the second most common cancer in those aged 15 to 29 years.

And

Cancer Council of Australia
Approximately, two in three Australians will be diagnosed with skin cancer by the time they are 70, with more than 750,000 people treated for one or more non-melanoma skin cancers in Australia each year. Non-melanoma skin cancer is more common in men, with almost double the incidence compared to women….. melanoma is the third most common cancer in Australian women and the fourth most common cancer in men, and the most common cancer in Australians aged 15-44 years. In 2013, 12,744 Australians were diagnosed with melanoma.  Every year, in Australia:

  • skin cancers account for around 80% of all newly diagnosed cancers
  • GPs have over 1 million patient consultations per year for skin cancer
  • the incidence of skin cancer is one of the highest in the world, two to three times the rates in Canada, the US and the UK

Melanoma incidence in 2008

Symptoms

Melanoma can affect many parts of the body - the skin, eye, the inner ear, meninges, bones, and heart as well as a number of other organs.  For example:

  • Eye melanoma - The uvea (Lat. uva, grape) is the pigmented middle of the three concentric layers that make up an eye. Intraocular melanoma begins in the uvea. The uvea has three parts. The iris is the coloured area at the front of the eye. The ciliary body is a ring of muscle tissue that changes the size of the pupil and the shape of the lens. The choroid is a layer of blood vessels that brings oxygen and nutrients to the eye. Most intraocular melanomas begin in the choroid.   Ocular melanoma is the most common cancer of the eye in the USA, with approximately 2,000 cases diagnosed annually.
  • Heart melanoma - heart melanocytes are found in the valves (mitral, tricuspid, and aortic) and septa (ventricular and atrial). Moreover, the numbers of melanocytes in the heart appears to reflect that of the skin [PMID: 18627529]
  • Throat melanoma - Primary malignant melanoma of the esophagus (PMME) is a rare malignant neoplasm of the esophagus. In the majority of cases, the disease originates in the mucosal layer of the esophagus, which is similar to other types of esophageal cancer. [PMID: 27602062]
  • Lung melanoma - Primary malignant melanoma (MM) of the lung is very rare, but it does happen, indicating that the lung also contains melanocytes. [PMID:  27385996]
  • Urinary bladder melanoma - primary malignant melanomas of the urinary bladder present with hematuria, and dysuria, but some are only discovered via imaging studies. …. Pigmentation is prominent in most cases [ref  PMID:  27603550]
  • Brain melanoma - In the brain, tissues with melanin include the medulla and pigment-bearing neurons within areas of the brainstem, such as the locus coeruleus and the substantia nigra. It also occurs in the zona reticularis of the adrenal gland.  Primary brain melanomas are very infrequent and metastasis outside the central nervous system very uncommon, but they are not unknown.  In some cases they can occur in people where tests were negative for skin or mucous melanoma. [ref PMID: 27586680]
  • Skin melanomas - Melanoma in women occurs more commonly on the extremities, and in men it occurs most commonly on the trunk or head and neck.  Early signs in a nevus [skin lesion] that would suggest a malignant change include the following:
  • Darker or variable discoloration.
  • Itching.
  • An increase in size or the development of satellites.
  • Ulceration or bleeding (later signs).

This is not an exhaustive list. 

The roles of Melanin

Melanocytes are melanin-producing cells.  They produce melanin through a process called melanogenesis.  The melanocyte-stimulating hormones, known collectively as MSH, are produced by cells in the pituitary gland.  MSH stimulate the production and release of melanin - melanogenesis

Pigmentation

There are three basic types of Melanin: eumelanin, pheomelanin, and neuromelanin.

  • Eumelanin - The most common is eumelanin, of which there are two types—brown eumelanin and black eumelanin.
  • Pheomelanin is a cysteine-containing red polymer of benzothiazine units largely responsible for red hair, among other pigmentation.
  • Neuromelanin is found in the brain.

Melanin is thus a pigment and melanogenesis leads to the pigmentation in skin, eyes and hair.  Different levels of MSH are not the major cause of variation in skin colour. In many red-headed people, and other people who do not tan well, there are variations in their hormone receptors, usually they do not have as many.

There is the general assumption that since melanin is a broad term for a group of pigments and melanocytes produce melanin, then the role of these cells is to give them colour.  But this makes little sense if we look at the organs affected.    Why bother to colour the intestine?  Why bother to colour anything?  We assume that they have a role in skin and hair pigmentation, but even then why bother?  We could all be as white as snow.  Logic should show it cannot be the real role.

And the real role? Melanin also possesses radio-protective properties:

Protection against radiation

Ultraviolet (UV) radiation alters a number of metabolic functions in vivant. It produces damage to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals …., have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments …. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. PMID:  25516714

So melanin protects against UV radiation

  • UV-B - Exposure to UV-B radiation causes an increase in melanogenesis.  So we ‘tan’ as a form of protection against UV damage.  Melanin is a very effective absorber of light; the pigment is able to dissipate over 99.9% of absorbed UV radiation.
  • UV-B - The presence of melanin has no influence over cellular oxidative stress generation, but, in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage. [PMID: 22178978]

But it also protects against radiation in general:

Melanins possess numerous interesting physicochemical characteristics, including electromagnetic radiation absorption properties and ability to chelate metals. We have recently reported that melanin has remarkable ionizing-radiation-shielding properties, possibly because it can interact with photons via Compton scattering. …. melanin could play a beneficial role by scavenging various radionuclides, in addition to radiation shielding.  PMID: 18355691

Furthermore, melanins may protect against the radiation from mobile phones and laptops as well.  In some respects, all the brown and red non cancerous blotches and splotches [nevi] on a person’s skin may simply be a sign of the melanocytes increasing melanin production in the face of greatly increased radiation in general
[Nevus (plural: nevi) is a nonspecific medical term for a visible, chronic lesion of the skin or mucosa.]

Metal and toxin chelation

The heterogeneity of compounds that bind to melanin is large. Toxins, drugs, and several other compounds have what is called ‘melanin affinity’.
Compounds showing the highest affinity are mainly [but not exclusively] organic amines and metal ions.

The binding of toxicants to melanin probably protects the cells initially. However, the binding is normally slowly reversible, and melanin may accumulate the toxicant and gradually release it into the cytosol.  And this may be where we have the true cause of melanoma, an overdose of toxins and radiation, which eventually damages the cell and its DNA.

Melanoma is thus not caused by exposure to radiation, per se, it is caused by an overload of toxins, drugs and other pharmaceuticals, food additives, heavy metals and radiation which the cell cannot handle.  The abnormal cell growth and runaway increase in the number of cells is a reflection of the body’s desperate attempt to produce more melanocytes capable of handling this influx of toxic waste.  The ‘cancer’ is a symptom not a cause.

 It is possible that in the midst of all this toxic waste there are some pathogens that simply damage the DNA of the melanocyte cells, causing them to malfunction – either over-producing melanin, or not producing enough, or malfunctioning in other ways – such as reproducing out of control.  Nanoparticles are key candidates here.

Once the cells are damaged or malfunctioning, the melanocytes can no longer produce melanin and once there is no melanin then we are at further risk from damage by radiation.  Alternatively the pituitary gland may be damaged so that it does not produce enough MSH or produces too much and the melanocytes produce melanin in abundance, in which case we are no longer at risk from radiation, but we get the characteristic large unpleasant black or dark brown moles symptomatic of melanoma.

The causes of melanoma

We thus now know in general what causes melanoma.  An overdose of all sorts of radiation, toxins, heavy metals, drugs and pharmaceuticals, insecticides and pesticides; and, for example, nanoparticles which might damage the DNA.

The pathogen may be an external one entering via the skin, BUT there is the real possibility that there is some internal melanocyte damaging pathogen, a pathogen in the body that is working its way round the body and has simply reached the surface; rather than the pathogen entering via the skin.

The link between Vitiligo and melanoma

Vitiligo is a long term skin condition characterized by patches of the skin losing their pigment. The patches of skin affected become white and usually have sharp margins. The hair from the skin may also become white. Inside the mouth and nose may also be involved. 

Vitiligo is thus a reduction by the body of melanin in melanocyte cells.  But why should the body do this?  The answer appears to be that the melanocytes are damaged and risk being a source of disease.  We know this from studies like the following:

Vitiligo-like depigmentation in patients with melanoma may be associated with more favourable clinical outcome. We conducted a systematic review of patients with stage III to IV melanoma treated with immunotherapy [stimulation of immune system] to determine the cumulative incidence of vitiligo-like depigmentation and the prognostic value of vitiligo development on survival.
One hundred thirty-seven studies were identified comprising 139 treatment arms (11 general immune stimulation, 84 vaccine, 28 antibody-based, and 16 adoptive transfer) including a total of 5,737 patients. The overall cumulative incidence of vitiligo was 3.4% …. In 27 studies reporting individual patient data, vitiligo development was significantly associated with both progression-free-survival …. and overall survival … indicating that these patients have two to four times less risk of disease progression and death, respectively, compared with patients without vitiligo development.  PMID:  25605840

In other words, we have the situation that a pathogen of some sort has attacked the melanocytes.  That pathogen has caused the melanocytes to malfunction.  On boosting the immune system, the body’s strategy is to actively reduce the production of melanin.  This indicates that the pathogen is targeting or attracted by the melanin as opposed to the cells as a whole, but in targeting the melanin it damages the melanocyte cells themselves.  ‘Starved’ of melanin, the pathogen then ceases its attack and can be flushed from the body by the immune system.

Causes

The principle causes of melanoma appear to be nanoparticles, pharmaceuticals, heavy metals and other toxins and a number of other man-made substances.  Another cause is also radiation of all types from laptops, mobile phones and so on.  In other words, melanoma is very largely a man-made disease.

 Pharmaceuticals

There is a link between pharmaceuticals - doctor prescribed drugs - and malignant melanoma.  The eHealthme site collects and analyses the Adverse Drug Reports submitted by doctors in the USA, to SEDA and the FDA.

They have a section called 'conditions', one of which is Malignant Melanoma.  In February 2017 there were about 750 pharmaceuticals implicated in causing Malignant melanoma.  This LINK takes you directly to this table and all the drugs implicated.  If the link has been broken, it should take you to the site anyway.  Search for Malignant Melanoma [this LINK may still work] in the conditions search box, scroll down and you will find a heading - drugs that could cause.  

The trend of pharmaceutical caused melanoma in the USA only is shown below:

 We have seen that the principal toxins causing melanoma are those showing melanin affinity.  One such chemical is chloroquine:

Chloroquine is an antimalarial drug but is also prescribed for conditions such as rheumatoid arthritis. Long-term users risk toxic side effects, including retinopathy, thought to be caused by chloroquine accumulation on ocular melanin….  chloroquine adsorption occurs via buffer cation displacement and is promoted by temperature-influenced secondary structure swelling. PMID:  26141438

 But as we can see above there may be many more, many not yet identified.  It is worth mentioning that a set of tests has been devised by one set of researchers that can check for melanin affinity:

Drugs possessing the ability to bind to melanin-rich tissue, such as the eye, are linked with higher ocular exposure, and therefore have the potential to affect the efficacy and safety profiles of therapeutics. A high-throughput melanin chromatographic affinity assay has been developed and validated, which has allowed the rapid melanin affinity assessment for a large number of compounds. Melanin affinity of compounds can be quickly assigned as low, medium, or high melanin binders. A high-throughput chromatographic method has [also] been developed and fully validated to assess melanin affinity of pharmaceuticals PMID:  26524700

 Nanoparticles

Sunscreens

 The topic of sunscreens has produced quite heated and even emotional debate for some time.  This paper best sums the overall conclusions reached

Sunscreens protect against sunburn, but there is no evidence that they protect against basal cell carcinoma or melanoma. …... Safety of sunscreens is a concern, and sunscreen companies have emotionally and inaccurately promoted the use of sunscreens.  PMID: 21170070

In effect, if the sunscreen has been properly labelled it may protect you from getting burnt, but melanoma and other forms of skin cancer are not caused by you getting burnt.

Int. J. Cancer 87:145–150, 2000. © 2000 - Sunscreen use and malignant melanoma
In a new population-based, matched, case-control study from southern Sweden of 571 patients with a first diagnosis of cutaneous malignant melanoma, between 1995 and 1997, and 913 healthy controls aged 16 to 80 years, the association between sunscreen use and malignant melanoma was evaluated. The median sun protection factor (SPF) used by both cases and controls was 6, range 2 to 25.
Sunscreen users reported greater sun exposure than non-users. Persons who used sunscreens did not have a decreased risk of malignant melanoma. Instead, a significantly elevated odds ratio (OR) for developing malignant melanoma after regular sunscreen use was found, adjusted for history of sunburns, hair colour, frequency of sunbathing during the summer, and duration of each sunbathing occasion. … The association appeared to hold for subjects who did not suffer from sunburns while using sunscreens, for subjects who used SPF of 10 or lower, and among men.

What is of major concern is what manufacturers put in sunscreens.

Bulkier particles of zinc oxide and titanium dioxide have been used in sunscreens for decades to reflect cancer-causing ultraviolet light. The reason traditional sunscreens look white when you rub them onto your skin is because particles of this size reflect visible light. But when these sunscreen ingredients are manufactured into nanoparticles – usually 25 to 50 nanometres wide – they behave differently. 

Nanoparticles of titanium dioxide and zinc oxide not only retain their UV light-absorbing capacity, but also absorb and scatter visible light, rendering them transparent on the skin.  And this is one of the main reasons they are used – appearance!

Megan Osmond-McLeod, researcher at Australia's Commonwealth Scientific and Industrial Research Organisation (CSIRO)
Another advantage is that, at the nanoscale, ZnO and TiO2 feel 'lighter' on the skin, rather than heavy and cakey.

In addition to these two compounds, silver nanoparticles, may be used as a form of anti-bacterial and anti-fungal preservative. 

Titanium dioxide nanoparticles have been proven to be dangerous by a number of research studies

Titanium dioxide nanoparticles (TiO2NPs), in the two crystalline forms, rutile and anatase, have been widely used in many industrial fields, especially in cosmetics. Therefore, a lot of details about their safety issues have been discussed by the scientific community. Many studies have led to a general agreement about TiO2NPs toxicity, in particular for anatase form, but no mechanism details have been proved yet. … Our study demonstrates that pH and sunlight are dominant factors to induce oxidative stress, TiO2NPs degradation and toxicity effects.  PMID:  27622577

But to rule out the role of any metal based nanoparticles would not be wise, as there is now a body of evidence showing that in simple terms all metallic nanoparticles are cytotoxic and can cause gene/DNA damage.

The Human body can be exposed to metal nano materials through multiple pathways, nano metals follow the blood stream in the circulatory system and are distributed to organs. Metal nano particles are mainly taken up into cells by endocytosis, and direct or indirect damages to genes can be induced by these particles after metabolism in cells. These damages would affect the course of cell cycle and the stability of the genome, resulting in gene mutation or chromosome aberration, and even leading to the death or malignant transformation of cells. PMID: 26733143

Cosmetics

The cosmetics industry has been very quick in using nanoparticles (NPs) because they believe it results ”in products with better efficacy and functionality”. Or if we put this another way, they spread more easily and appear smoother.  The companies concerned have done this despite the fact that numerous papers on the subject of molecular toxicology have revealed that NP exposure can promote cytotoxicity and oxidative damage.  “Numerous health concerns have been raised in the use of NPs in personal care products”. But they are still being sold and marketed without any label to indicate nanoparticles have been used.

The goal of the study was to determine the cytotoxicity and intracellular distribution of titanium dioxide (TiO2) NPs containing fatty acid composites (palmitoleic acid, palmitic acid, stearic acid and oleic acid) commonly used in cosmetic products. Two types of cells, human fibroblast skin cells and adenocarcinoma lung cells, were exposed to either bare TiO2 NPs or TiO2 NPs mixed with fatty acids for up to 48 hr.. …... TiO2 NPs containing fatty acids posed reduced cytotoxicity (80-88% decreases) than bare NPs in both cell types. PMID: 27432239

So the fatty acids protect you up to a point, and it is these sorts of findings that have prompted manufacturers to say cosmetics are ‘safe’.  But of course they are not ‘safe’, it is only that there is slightly less intracellular penetration of the NPs containing fatty acid composites compared with bare NPs. The NPs are still entering your cells and the extent of penetration depends on the ratio of fatty acids to nanoparticles.

Food

According to a report by Friends of the Earth in 2014, many popular foods contain nanoparticles, including Kraft Singles, Trix, and Hershey’s. The report found that the number of food products with ‘nano-ingredients’ is up tenfold since their report on this topic in 2008. These products are made by major companies including Kraft, General Mills, Hershey, Nestle, Mars, Coca-Cola, Unilever, Smucker’s and Albertsons. They state that due to a lack of labelling and disclosure, it is likely that a far greater number of food products with undisclosed nanomaterials are currently on the market.

The report, “Tiny Ingredients, Big Risks: Nanomaterials rapidly entering food and farming,” documents 94 food and beverage products on the market known to contain nanomaterials — including brand name products, such as Jet Puffed Marshmallows, Nestle Original Coffee Creamer, PowerAde and Trix cereal.

Nanoparticles of silver, titanium dioxide, zinc and zinc oxide  - melanin affinity chemicals - are used in nutritional ‘supplements’, in artificial flavourings, to prolong shelf life, in food packaging and food contact materials, and as preservatives.

 Antiperspirants and cosmetics containing aluminium

Aluminum salts such as aluminum chlorohydrate (ACH) are known for use as an active antiperspirant agent that blocks the secretion of sweat.  Aluminium phosphate (AlPO4) is used in the manufacture of cosmetics.  In general aluminium compounds do not cross the dermal barrier.  But where they are in nanoparticle form, or where the dermal barrier is compromised or damaged in some way they do. 

…. the aim of this study with an in vitro Franz™ diffusion cell was to measure aluminum uptake from three cosmetic formulations of antiperspirant: the base for an "aerosol" (38.5% of ACH), a "roll-on" emulsion (14.5% ACH), and a "stick" (21.2%), by samples of intact and stripped human skin (5 donors). … Following contacts lasting 6, 12 and 24h, the Al assays showed only insignificant transdermal absorption of Al …. On stripped skin, for which only the "stick" formulation was tested, the measured uptake was significantly higher PMID:  22459170

Aluminium in general does a great deal of harm in the body.  It is one chemical able to damage the blood brain barrier and it is also implicated in breast cancer.  Thus these products are causing harm generally in the body. 

The potential toxicity of Al has been clearly shown and recent works convincingly argue that Al could be involved in cancerogenic processes. Nowadays, for example, Al is suspected of being involved in breast cancer. Recent work in cells in culture has lent credence to the hypothesis that this metal could accumulate in the mammary gland and selectively interfere with the biological properties of breast epithelial cells, thereby promoting a cascade of alterations reminiscent of the early phases of malignant transformation. PMID: 24418462

But this study found that aluminium compounds may also cause melanoma

A cohort of employees of 1 large aluminium company since 1983 was assembled (n = 6,485, 5,828 men). Deaths and incident cancers to 2002 were ascertained by linkage to national and state cancer and death registries. …. ….The only significant increased mortality risk was from pleural mesothelioma. …. The cohort had a …higher risk of melanoma PMID: 18478567

 

 

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