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From our LOJ Medical Sciences (LOJMS)


Monday 22 November 2021

Lupine Publishers| Diagnosis and Immunotherapy Strategies for Melanoma: A Review

 Lupine Publishers| Journal of Medical Sciences


Abstract

Melanoma is a type of skin cancer. Melanoma skin cancer is made up of abnormal pigment cells (melanocytes). Melanocytes are located at the bottom of the epidermis. These cells make melanin, which spreads to the top of the epidermis and gives skin its colour. Melanoma is usually brown or black in colour because the cell still makes melanin. Melanoma is more dangerous than other skin cancers because it more likely to spread if it is not found early. However, most melanomas about 84 out of 100 are found early before they have spread and so are likely to be cured with treatments. Melanoma can occur on any skin surface. In men, it’s often found on the skin on the head, on the neck, or between the shoulders and the hips. In women, it’s often found on the skin on the lower legs or between the shoulders and the hips. Melanoma is rare in people with dark skin. When it does develop in people with dark skin, it’s usually found under the fingernails, under the toenails, on the palms of the hands, or on the soles of the feet. Although one of the less common types of skin cancer, melanoma is considered the most serious type of skin cancer because it is more likely to spread to other parts of the body, especially if not detected early. The earlier melanoma is found, the more successful treatment is likely to be. Despite the many investigations in this field and a rapidly growing knowledge base, classification according to specific mutational profiles is not yet validated. Further investigations are required for validation and refinement, and to possibly identify additional factors.

Keywords: Melanoma; Melanocytes; Epidermis; Melanin

Introduction

Cancer is a disease of the cells, which are the body’s basic building blocks. The body constantly makes new cells to help us grow, replace worn-out tissue and heal injuries. Normally, cells multiply and die in an orderly way. Sometimes cells don’t grow, divide and die in the usual way. This may cause blood or lymph fluid in the body to become abnormal, or form a lump called a tumour. A tumour can be benign or malignant.

Benign tumour

Cells are confined to one area and are not able to spread to other parts of the body. This is not cancer.

Malignant tumour

Figure 1: How cancer starts?

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This is made up of cancerous cells, which sometimes also have the ability to spread by travelling through the bloodstream or lymphatic system (lymph fluid) (Figure 1). The cancer that first develops in a tissue or organ is called the primary cancer. A malignant tumour is usually named after the organ or type of cell affected. A malignant tumour that has not spread to other parts of the body is called localized cancer. A tumour may invade deeper into surrounding tissue and can grow its own blood vessels in a process called angiogenesis. If cancerous cells grow and form another tumour at a new site, it is called a secondary cancer or metastasis. A metastasis keeps the name of the original cancer. For example, melanoma that has spread to the bones is called metastatic melanoma, even though the person may be experiencing symptoms caused by problems in the bones (Figure 2).

Figure 2: How cancer spreads?

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The skin

The skin is the largest organ in the body. It acts as a barrier to protect the body from injury, control body temperature and prevent loss of body fluids. Skin, like all other body tissues, is made up of cells. The two main layers of the skin are the epidermis and the dermis. Below these is a layer of fatty tissue (subcutis). The epidermis is the top, outer layer of the skin. It contains three main kinds of cells:

Squamous cells - These flat cells are packed tightly together to make up the top layer of skin and form the thickest layer of the epidermis. These cells eventually die and become the surface of your skin. Over time our body sheds these dead skin cells.

Basal cells: These block-like cells make up the lower layer of the epidermis and multiply constantly. As they age, they move upwards in the epidermis and flatten out to form squamous cells.

Melanocytes: These cells sit between the basal cells of the skin and produce a dark pigment called melanin, the substance that gives skin its colour. When skin is exposed to ultraviolet (UV) radiation melanocytes make extra melanin to try to protect the skin from getting burnt. This is what causes skin to tan. Melanocytes are also in non-cancerous (benign) spots on the skin called moles or naevi. Most moles are brown, tan or pink in colour and round in shape [1].

Melanoma

All cancers involve the malfunction of genes that control cell growth and division. Most cancers are diagnosed in persons 55 and older. The lifetime risk for cancer is approximately 50% for men and approximately 33% for women.1 About 5% to 10% of all cancers are clearly hereditary; the other 90-95% of cancers are not hereditary but result from damage to genes (that is, somatic mutations) due to internal factors (that is, hormones, digestion of nutrients) or external factors (such as tobacco, chemicals, and sunlight). Cancer treatment includes surgery, radiation, chemotherapy, and vaccines. Some cancers are treated using various combinations of surgery, radiation, and chemotherapy [2]. Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers. The most serious common skin cancer is melanoma (malignant melanoma), which arises from neural crest-derived melanocytes located in the epidermis or dermis of the skin. Melanomas also can arise from melanocytes located in other regions of the body such as the eye, meninges, digestive tract, or lymph nodes. Melanocytes in the skin can give rise to a number of benign lesions such as nevi (moles), dysplastic nevi, Spitz nevi, blue nevi, solar lentigo, and seborrheic keratosis. When dealing with melanoma of the skin, establishing which pigmented lesions are malignant is the prime clinical problem, as the vast majority are benign.

Epidemiology and Aetiology

Exposure to the sun is the most commonly associated factor [3,4]. Predisposing factors that have been found to increase the risk of melanoma include skin that sunburns easily, poor tanning response, light-colored skin, history of severe sunburns, numerous nevi (more than 50), atypical nevi (that is, dysplastic nevi), a tendency toward freckling, a history of skin cancer, a family history of melanoma, the use of tanning salon, previous melanoma, and a weakened immune system (due to other cancers, transplant drugs, or HIV infection). Oral methoxsalen (psoralen) and ultraviolet A radiation is an effective treatment for psoriasis, but it is carcinogenic and increases the risk for melanoma. Individuals with recreational and vacation sun exposure may be at greater risk than those whose occupation exposes them to the sun constantly. In fact, continuous sun exposure appears to be a protective factor where melanoma is concerned.

Melanoma is a common cancer. In early 2005, the American Cancer Society estimated that approximately 59,500 individuals would be diagnosed with melanoma, the projected number of deaths was 7,770. The prevalence of melanoma is 13:1,000 Caucasian Americans. During the 1970s, the incidence rate of melanoma showed a marked increase of approximately 6.0% per year, although this rate slowed to approximately 3.0% a year beginning in 1981. There is some data to suggest that superficial spreading melanoma has been found more frequently during the last 30 years. Five-year survival rates for melanoma of the skin have increased from 80% in 1976 to 85% in 1985 to 91% in 2000 [5].

Types of melanoma

Superficial spreading melanoma: It begins with an intraepidermal horizontal or radial growth phase, appearing first as a macule that slowly evolves into a plaque, often with multiple colours and pale areas of regression. Secondary nodular areas may also develop. This is the most common type of melanoma, making up 55-60% of all cases. It is more common in younger people and is often related to a pattern of irregular high sun exposure, including episodes of sunburn. It can start as a new brown or black spot that spreads within the outer layer of the skin (epidermis), or an existing spot, freckle or mole that changes size, colour or shape. It can develop on any part of the body. This type of melanoma often grows slowly and becomes more dangerous when it invades the lower layer of the skin (dermis) [6].

Nodular melanoma

Is a primarily nodular, exophytic brown-black, often eroded or bleeding tumour, which is characterized by an aggressive vertical phase, with a short or absent horizontal growth phase. This type makes up about 10-15% of melanomas. It usually appears as a round, raised lump on the surface of the skin that is often red, pink, brown or black and feels firm to touch. It may develop a crusty surface that bleeds easily. It is most commonly found in older people on severely sun-damaged skin on the head and neck. It is a fast growing and aggressive form of melanoma, spreading quickly into the lower layer of the skin (dermis) [7].

Lentigo maligna melanoma: Arises often after many years from a lentigo maligna (melanoma in situ) located predominantly on the sun-damaged faces of older individuals. This type of melanoma is most common in older people. It makes up about 10-15% of melanomas and begins as a large freckle (lentigo maligna) in an area of sun-damaged skin, such as the face, ears, neck and head. It may grow slowly and superficially over many years before it penetrates more deeply into the skin. Acral lentiginous melanoma: is typically palmoplantar or subungual. In its initial intraepidermal phase (which may be protracted), there is irregular, poorly circumscribed pigmentation; later a nodular region reflects the invasive growth pattern. This is an uncommon type of melanoma (around 1-2% of all cases). It is most commonly found on the hairless skin on the soles of the feet or palms of the hands, or under the fingernails or toenails. It commonly appears as a colourless or lightly pigmented area, which can be mistaken for a stain or bruise. In the nails, it most often presents as a long streak of pigment in the nail or discoloration in the skin around the nail. It may grow slowly before it becomes invasive.

Desmoplastic melanoma

This is another uncommon type of melanoma (around 1-2% of cases) that presents as a firm, progressively growing lump, often on the head or neck. Many are skin-coloured and not pigmented and can be difficult to diagnose. There are some other rarer types of non-skin melanoma. Mucosal melanomas start in the tissues in the mouth, nervous system, anus, urethra, vagina, and nasal passages. Ocular melanomas start in the eye. Recent molecular studies have shown the genetic heterogeneity of melanoma, with distinct molecular signatures identified in tumours at different anatomical locations and with different associations with reported sun exposure.

Symptoms of Melanoma

Often the first sign of melanoma is a change in the shape, color, size, or feel of an existing mole. Melanoma may also appear as a new mole. Thinking of “ABCDE” can help you remember what to look for

a) Asymmetry: The shape of one half does not match the other half.

b) Border that is irregular: The edges are often ragged, notched, or blurred in outline. The pigment may spread into the surrounding skin.

c) Color that is uneven: Shades of black, brown, and tan may be present. Areas of white, gray, red, pink, or blue may also be seen

d) Diameter: There is a change in size, usually an increase. Melanomas can be tiny, but most are larger than the size of a pea (larger than 6 millimeters or about 1/4 inch).

e) Evolving: The mole has changed over the past few weeks or months.

f) Risk and prevention: Exactly what cause of melanoma is unknown? But many risk factors for melanoma are known. A risk factor for melanoma is known. A risk factor is anything that increases the chance of getting a disease. Some risk factors are passed down from parent to child through genes. Other risk factors are activities that people do. Having one or more risk factors does not mean you will get melanoma. Likewise, melanoma occurs in some people who have no risk factors. Key melanoma risk factors are described next.

g) Ultraviolet energy: Melanoma often occurs on parts of the body exposed to UV energy. UV energy is an invisible light energy. The main source of UV energy or rays is sunlight. Tanning beds also expose the skin to UV rays and are known to cause skin cancer, including melanoma. Both UVA (ultraviolet A) and UVB (Ultraviolet B) rays contribute to the development of Melanoma and skin cancer. Too much exposure damages the skin and increases the risk for skin cancer. Whether sun exposure was too much depends on UV intensity, length of exposure, and how well the skin was protected [8].

Read More Lupine Publishers Medical science Journal Articles: https://lupine-publishers-medical-sciences.blogspot.com/


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