This document provides background information on skin cancer and melanoma. It discusses the state of research on melanoma, including epidemiology, causes, diagnosis, prognosis, treatment options and molecular pathways. Ethical, legal and social aspects related to prevention, screening, treatment and research are also reviewed. The document is intended to help educators prepare lessons using multimedia resources on a skin cancer module.
Histopathological patterns of cutaneous malignant melanoma in Sudaniosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Histopathological patterns of cutaneous malignant melanoma in Sudaniosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Omid Hamid, MD, Alexander M.M. Eggermont, MD, PhD, and Ahmad Tarhini, MD, PhD, prepared useful practice aids pertaining to melanoma management for this CME activity titled "Tracing the Arc of Immunotherapy in Melanoma: Insights on the Current Role and Cutting-Edge Uses of Checkpoint Inhibitors for Patient Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2KC7j0k. CME credit will be available until July 10, 2019.
Alma 2016 Clinical Publication - Legato II Treats Scars Hamutal Gozlan
Clinical and histological results in the treatment of atrophic
and hypertrophic scars using a combined method of
radiofrequency, ultrasound and transepidermal drug delivery
Nanotechnology for cancer therapy recent developmentsroshan telrandhe
This paper is an overview of advances and prospects in applications of nanotechnology for cancer treatment. Nanotechnology is an use for prevention, diagnosis, and treatment. nanotechnology offers a promise for the targeted delivery of drugs, genes and protein to tumer tissue and therefore alleviating the toxicity of anticancer agent in healthy tissues. Cancer is one of the leading causes of death worldwide. Nanotechnology is one of the most rapidly growing fields in the 21st centuryThese mainly include arrays of nanocantilevers, nanotubes and nanowires for multiplexing detection, multifunctional injectable nanovectors for therapeutics and diagnostics. This article review current nanotechnology platforms for anticancer drug delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells, nuclear acid base nanoparticle [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO) ] The review increases awarnes of advantages in cancer therapy
We know that mesothelioma patients would rather stay local when receiving treatment,rnso we will review options for private medical centers, surgical consultants, clinical trials,rnand match you up with friendly, local physicians wherever we can.
We know that mesothelioma patients would rather stay local when receiving treatment,rnso we will review options for private medical centers, surgical consultants, clinical trials,rnand match you up with friendly, local physicians wherever we can.
Presentation from Southern California Chapter of the American College of Surgeons 2014 - "Extranodal Extension on Sentinel Lymph Node Dissection: Why Should We Treat It Differently?"
This data has since been published in The American Surgeon.
http://www.ncbi.nlm.nih.gov/pubmed/25264632
Omid Hamid, MD, Alexander M.M. Eggermont, MD, PhD, and Ahmad Tarhini, MD, PhD, prepared useful practice aids pertaining to melanoma management for this CME activity titled "Tracing the Arc of Immunotherapy in Melanoma: Insights on the Current Role and Cutting-Edge Uses of Checkpoint Inhibitors for Patient Care." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2KC7j0k. CME credit will be available until July 10, 2019.
Alma 2016 Clinical Publication - Legato II Treats Scars Hamutal Gozlan
Clinical and histological results in the treatment of atrophic
and hypertrophic scars using a combined method of
radiofrequency, ultrasound and transepidermal drug delivery
Nanotechnology for cancer therapy recent developmentsroshan telrandhe
This paper is an overview of advances and prospects in applications of nanotechnology for cancer treatment. Nanotechnology is an use for prevention, diagnosis, and treatment. nanotechnology offers a promise for the targeted delivery of drugs, genes and protein to tumer tissue and therefore alleviating the toxicity of anticancer agent in healthy tissues. Cancer is one of the leading causes of death worldwide. Nanotechnology is one of the most rapidly growing fields in the 21st centuryThese mainly include arrays of nanocantilevers, nanotubes and nanowires for multiplexing detection, multifunctional injectable nanovectors for therapeutics and diagnostics. This article review current nanotechnology platforms for anticancer drug delivery, including polymeric nanoparticles, liposomes, dendrimers, nanoshells, nuclear acid base nanoparticle [DNA, RNA interference (RNAi), and antisense oligonucleotide (ASO) ] The review increases awarnes of advantages in cancer therapy
We know that mesothelioma patients would rather stay local when receiving treatment,rnso we will review options for private medical centers, surgical consultants, clinical trials,rnand match you up with friendly, local physicians wherever we can.
We know that mesothelioma patients would rather stay local when receiving treatment,rnso we will review options for private medical centers, surgical consultants, clinical trials,rnand match you up with friendly, local physicians wherever we can.
Presentation from Southern California Chapter of the American College of Surgeons 2014 - "Extranodal Extension on Sentinel Lymph Node Dissection: Why Should We Treat It Differently?"
This data has since been published in The American Surgeon.
http://www.ncbi.nlm.nih.gov/pubmed/25264632
Nationale EuroCloud Monitor 2015 "Tussen Trotski en Troelstra"Peter Vermeulen
Drie jaar na de eerste Nationale EuroCloud Monitor blikken we terug en kijken we vooruit met behulp van nieuw onderzoek. Waar SaaS "revolutionair" om zich heen grijpt, ontwikkelt IaaS zich in het bedrijfsleven een stuk langzamer. En heeft het gebruik van de cloud nou wat opgeleverd of niet?
Early Detection of Melanoma and Other Skin CancersSummit Health
This lecture provides an overview of skin cancer including risks, early detection, and treatment. Learn to identify the early signs of skin cancer. Melanoma and non-melanoma skin tumors will be discussed and prevention of skin cancer will be emphasized.
We all Know that the most dangerous medical condition in our modern life is cancer!
There are two types of this awful condition, BENIGN and MALIGNANT. The first is safe
and can be removed by many ways without large effects on the patients, but the last
one is very killing and can cause a lot of consequences on the patient, even death.
In my report, I will discuss one of the cancer's types that occur in the human body,
which is "Melanocytes tumors".
I mentioned everything about Melanocytes tumor, starting with signs and symptoms,
and finishing with diagnosis and treatment.
The Melanocytes are found in two areas of the human body, (Eye and skin). It can be
hidden for a lot of time without discovering by patients or doctors, so all people need
to be checked every month or years to be sure that they are safe from this killing
condition.
Also, this condition can be normal without problems and found in all people
approximately, such we called it "Nevus" or "Shama" in Arabic language which is one of
the beauty sings.
Malignant melanoma is one of the most aggressive neoplasms of the skin. It originates from the melanocytes, which are cells derived embryologically from the neural crest and migrate to the epidermal basal layer. It is characterized by producing pigmentation as well as being susceptible to metastasis. We report the case of a 36-year-old female patient with advanced clinical stage and distant commitment. The biopsy confirmed the presence of Grade III invasive nodular cutaneous melanoma in the left subscapular region with lymph node metastasis with reactive hyperplasia. An exploratory research is carried out with the bibliographic review in scientific journals with evidence level II–IV. In portals PubMed, Redalyc, BVS, and UpToDate. 81241 met criteria 2248 of which 629 were chosen for having access to the full text and of these 496 are more current (as of 2008), and in the end, 27 articles were selected that met all the inclusion criteria to this article. Due to the increase in the incidence of this disease in recent years and its poor prognosis in short to medium term, it is important to know and follow-up on patients with known risk factors for this disease such as the presence of previous nevi, with emphasis on measures of prevention.
Melanoma Skin Cancer Detection using Image Processing and Machine Learningijtsrd
Dermatological Diseases are one of the biggest medical issues in 21st century due to its highly complex and expensive diagnosis with difficulties and subjectivity of human interpretation. In cases of fatal diseases like Melanoma diagnosis in early stages play a vital role in determining the probability of getting cured. We believe that the application of automated methods will help in early diagnosis especially with the set of images with variety of diagnosis. Hence, in this article we present a completely automated system of dermatological disease recognition through lesion images, a machine intervention in contrast to conventional medical personnel based detection. Our model is designed into three phases compromising of data collection and augmentation, designing model and finally prediction. We have used multiple AI algorithms like Convolutional Neural Network and Support Vector Machine and amalgamated it with image processing tools to form a better structure, leading to higher accuracy of 85 . Vijayalakshmi M M ""Melanoma Skin Cancer Detection using Image Processing and Machine Learning"" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-4 , June 2019, URL: https://www.ijtsrd.com/papers/ijtsrd23936.pdf
Paper URL: https://www.ijtsrd.com/engineering/other/23936/melanoma-skin-cancer-detection-using-image-processing-and-machine-learning/vijayalakshmi-m-m
SkinCure: An Innovative Smart Phone Based Application to Assist in Melanoma E...sipij
Melanoma spreads through metastasis, and therefore it has been proven to be very fatal. Statistical
evidence has revealed that the majority of deaths resulting from skin cancer are as a result of melanoma.
Further investigations have shown that the survival rates in patients depend on the stage of the infection;
early detection and intervention of melanoma implicates higher chances of cure. Clinical diagnosis and
prognosis of melanoma is challenging since the processes are prone to misdiagnosis and inaccuracies due
to doctors’ subjectivity. This paper proposes an innovative and fully functional smart-phone based
application to assist in melanoma early detection and prevention. The application has two major
components; the first component is a real-time alert to help users prevent skin burn caused by sunlight; a
novel equation to compute the time for skin to burn is thereby introduced. The second component is an
automated image analysis module which contains image acquisition, hair detection and exclusion, lesion
segmentation, feature extraction, and classification. The proposed system exploits PH2 Dermoscopy image
database from Pedro Hispano Hospital for development and testing purposes. The image database
contains a total of 200 dermoscopy images of lesions, including normal, atypical, and melanoma cases.
The experimental results show that the proposed system is efficient, achieving classification of the normal,
atypical and melanoma images with accuracy of 96.3%, 95.7% and 97.5%, respectively.
Ultraviolet radiation, Standard Erythema Dose(SED), Minimal Erythema Dose(MED), Sun Burns, Solar Dermatitis, Sun Burned Disease, DNA Damage, Cell Damage, Antiradiation UV Vaccine, Immune-Prophylaxis of Sun Burned Diseases, Immune-Prophylaxis of Sun Burns, Immune-Therapy of Sun-Burned Disease and Sun Burns, Basal Cell Carcinoma (BCC), Squamous Cell Carcinoma (SCC), Melanoma( MLN), Toxic Epidermal Necrolysis(TEN)
Dr Patrick Treacy on Diagnosis and Treatment of Malignant Melanoma Dr. Patrick J. Treacy
A 23-year-old Siberian female patient presented with a changing lesion on her abdomen. The patient stated the lesion was present for about two years and it started
off from within a freckle, which started to grow larger and somewhat darken in appearance. It had the clinical appearance of a melanoma and the dermoscopy three-point checklist (designed to allow non-experts not to miss detection of melanomas) was used to determine whether this had a high likelihood of malignancy. It included:
Asymmetry: asymmetry of colour and structure in one or
two perpendicular axes
Atypical network: pigment network with irregular holes
and thick lines
Blue-white structures: there was some evidence of blue-
white veil and regression structures
Dr Patrick Treacy shares some of his most challenging cases.
This month he talks about treating Cutaneous Malignant Melanoma. Melanoma, also known as malignant melanoma, is a type of cancer that develops from the pigment-containing cells known as melanocytes. They typically occur in the skin but may rarely occur in the mouth, intestines, or eye. In women they most commonly occur on the legs, while in men they are most common on the back. Sometimes they develop from a mole with concerning changes including an increase in size, irregular edges, change in color, itchiness, or skin breakdown
RECOGNITION OF SKIN CANCER IN DERMOSCOPIC IMAGES USING KNN CLASSIFIERADEIJ Journal
The largest organ of the body is human skin. Melanoma is a fastest growing & deadliest cancer which starts in pigment cells (melanocytes) of the skin that mostly occurs on the exposed parts of the body. Early detection is vital in treating this type of skin cancer but the time and effort required is immense. Dermoscopy is a non invasive skin imaging technique of acquiring a magnified and illuminated image of a region of skin for increased clarity of the spots on the skin The use of machine learning and automation of the process involved in detection will not only save time but will also provide a more accurate diagnosis. The skin images collected from the databases cannot be directly classified by the automation techniques. The reason is twofold: (a) Lack of clarity in the features which is mainly due to the poor contrast of the raw image and (b) Large dimensions of the input image which causes the complexity of the system. Hence, suitable techniques must be adopted prior to the image classification process to overcome these drawbacks. The first drawback can be minimized by adopting suitable pre- processing techniques which can enhance the contrast of the input images. The second drawback is solved by incorporating the feature extraction technique which reduces the dimensions of the input image to high extent. Further, K-NN (K-Nearest Neighbor) classifier is used for classification of the given image into cancerous or non- cancerous.
Toward a malaria-free world - Lesson plansXplore Health
In this guide you will have suggestions of lesson plans that have been designed by the Education National Coordinators using the Xplore Health materials.
In this guide you will have suggestions of lesson plans that have been designed by the Education National Coordinators using the Xplore Health materials.
How are drugs developed? - Lesson plansXplore Health
In this guide you will have suggestions of lesson plans that have been designed by the Education National Coordinators using the Xplore Health materials.
Les cas d’obésité augmentent dans le monde. Préoccupés par la menace à long terme de l’obésité sur la santé, les médecins et les chercheurs tentent de comprendre ce qui rend obèse afin de créer un traitement plus efficace, ainsi que des stratégies de prévention.
Problem otyłości nasila się na całym świecie. Lekarze i naukowcy, zatroskani długoterminowym zagrożeniem dla zdrowia ze strony otyłości, próbują zrozumieć, co sprawia, że ludzie stają się otyli, aby dzięki tej wiedzy móc opracować bardziej skuteczne strategie leczenia i zapobiegania.
La obesidad es un fenómeno al alza en todo el mundo. Preocupados por la amenaza que supone a largo plazo para la salud, médicos y científicos intentan entender por qué la gente desarrolla obesidad y así poder diseñar estrategias de prevención y tratamiento más efectivas.
L’obesitat és un fenomen en alça arreu del món. Amoïnats per l’amenaça que suposa a llarg termini per a la salut, metges i científics intenten entendre què fa que la gent esdevingui obesa, de manera que puguin dissenyar estratègies de prevenció i tractament més efectives.
A crisis of fat? - Background informationXplore Health
This guide provides background information on obesity, its causes, consequences and treatment, as well as providing an insight into the ethical, legal and social aspects associated with this disease.
Inżynieria genetyczna - Poszukiwanie miejsca docelowego dla leku na miażdżycęXplore Health
Protocol for youngsters to carry out a bacterial transformation in a lab. The protocol follows a line of biomedical research which focuses on the study of a potential therapeutic target that could be recognised by a drug against atherosclerosis. The experiment protocol is an opportunity for science centres, museums and schools to replicate a real experiment done in a real lab doing research on drug discovery.
Génie génétique - À la recherche d’une cible pour le traitement de l’athérosc...Xplore Health
Protocol for youngsters to carry out a bacterial transformation in a lab. The protocol follows a line of biomedical research which focuses on the study of a potential therapeutic target that could be recognised by a drug against atherosclerosis. The experiment protocol is an opportunity for science centres, museums and schools to replicate a real experiment done in a real lab doing research on drug discovery.
Ingeniería genética - Buscando una diana para el tratamiento de la ateroscler...Xplore Health
Protocolo de experimento que permite a los estudiantes llevar a cabo una transformación bacteriana en el laboratorio. El protocolo se centra en una línea de investigación sobre el estudio de una potencial diana terapéutica que podría ser reconocida por un fármaco para la aterosclerosis. Este protocolo es una oportunidad para museos de la ciencia y escuelas de replicar un experimento que se está realizando en laboratorios reales para investigar nuevos fármacos.
Enginyeria genètica - Buscant una diana per al tractament de l’aterosclerosiXplore Health
Protocol d’experiment que permet als estudiants dur a terme una transformació bacteriana al laboratori. El protocol se centra en una línia de recerca sobre l’estudi d’una potencial diana terapèutica que podria ser reconeguda per un fàrmac per l’aterosclerosi. Aquest protocol és una oportunitat per museus de la ciència i escoles de replicar un experiment que s’està realitzant en laboratoris reals per investigar nous fàrmacs.
Acetabularia Information For Class 9 .docxvaibhavrinwa19
Acetabularia acetabulum is a single-celled green alga that in its vegetative state is morphologically differentiated into a basal rhizoid and an axially elongated stalk, which bears whorls of branching hairs. The single diploid nucleus resides in the rhizoid.
Biological screening of herbal drugs: Introduction and Need for
Phyto-Pharmacological Screening, New Strategies for evaluating
Natural Products, In vitro evaluation techniques for Antioxidants, Antimicrobial and Anticancer drugs. In vivo evaluation techniques
for Anti-inflammatory, Antiulcer, Anticancer, Wound healing, Antidiabetic, Hepatoprotective, Cardio protective, Diuretics and
Antifertility, Toxicity studies as per OECD guidelines
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
Honest Reviews of Tim Han LMA Course Program.pptxtimhan337
Personal development courses are widely available today, with each one promising life-changing outcomes. Tim Han’s Life Mastery Achievers (LMA) Course has drawn a lot of interest. In addition to offering my frank assessment of Success Insider’s LMA Course, this piece examines the course’s effects via a variety of Tim Han LMA course reviews and Success Insider comments.
Safalta Digital marketing institute in Noida, provide complete applications that encompass a huge range of virtual advertising and marketing additives, which includes search engine optimization, virtual communication advertising, pay-per-click on marketing, content material advertising, internet analytics, and greater. These university courses are designed for students who possess a comprehensive understanding of virtual marketing strategies and attributes.Safalta Digital Marketing Institute in Noida is a first choice for young individuals or students who are looking to start their careers in the field of digital advertising. The institute gives specialized courses designed and certification.
for beginners, providing thorough training in areas such as SEO, digital communication marketing, and PPC training in Noida. After finishing the program, students receive the certifications recognised by top different universitie, setting a strong foundation for a successful career in digital marketing.
How to Make a Field invisible in Odoo 17Celine George
It is possible to hide or invisible some fields in odoo. Commonly using “invisible” attribute in the field definition to invisible the fields. This slide will show how to make a field invisible in odoo 17.
Francesca Gottschalk - How can education support child empowerment.pptxEduSkills OECD
Francesca Gottschalk from the OECD’s Centre for Educational Research and Innovation presents at the Ask an Expert Webinar: How can education support child empowerment?
Operation “Blue Star” is the only event in the history of Independent India where the state went into war with its own people. Even after about 40 years it is not clear if it was culmination of states anger over people of the region, a political game of power or start of dictatorial chapter in the democratic setup.
The people of Punjab felt alienated from main stream due to denial of their just demands during a long democratic struggle since independence. As it happen all over the word, it led to militant struggle with great loss of lives of military, police and civilian personnel. Killing of Indira Gandhi and massacre of innocent Sikhs in Delhi and other India cities was also associated with this movement.
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
2. Table of contents
1. Introduction 3
2. State of the art 3
2.1. Introduction 3
2.2. Epidemiology of cutaneous melanoma 3
2.3. Aetiology of melanoma 4
2.4. Diagnosis 6
2.5. Prognosis 7
2.6. Treatment 7
2.7. Molecular pathways 10
2.8. Animal models 11
2.9. Clinical trials 12
3. Ethical, Legal and Social Aspects (ELSA) 13
3.1. Introduction 13
3.2. Prevention 13
3.3. Diagnosis and screening 14
3.4. Treatment 15
3.5. Research 16
Skin cancer exposed - 2 - Background information
3. 1. Introduction
This guide will provide you with background information on the Xplore Health module “Skin
cancer exposed” to enable you to prepare a lesson using the multimedia tools on the
website. The latest research into melanoma, the most severe form of skin cancer, and ethical,
legal and social aspects surrounding this disease are discussed.
2. State of the art
2.1. Introduction
The skin is the largest organ of the body and protects against heat, light, infection, and injury.
It is made up of two main layers: the epidermis (the top layer) and dermis (the inner layer).
Melanocytes are cells found in the epidermis and they contain melanin, which gives the skin
its colour. Melanoma is a cancer of the skin, that originates from melanocytes. It usually
occurs in adults and only occasionally occurs in children and adolescents, and is a very
serious form of skin cancer.
Melanoma can occur in sites other than the skin and this accounts for 5% of melanoma
cases including melanoma of the eyes or mucous membranes e.g. mouth. The cause,
outcome and treatment options of these rare forms of melanoma differ from that of skin
(cutaneous) melanoma.
It usually appears on the body as a new mole. Men most often get melanoma on the trunk or
on the head or neck; women most often get melanoma on the arms and legs. As with other
cancers, melanoma is best treated when it is found early. It can spread (metastasize) quickly
to other parts of the body through the blood or through the lymphatic system (a collection of
vessels which help the body to fight infection).
2.2. Epidemiology of cutaneous melanoma
The number of cases of melanoma is rising faster than that for any other major cancer. More
than 10,400 cases of melanoma are identified every year in the UK with over 2,000 deaths
from this disease. At present it occurs more commonly in females than males. The frequency
of melanoma cases increases with age but an unusually high number of melanomas is
observed among young people where almost a third of cases (31%) occur in people aged <
50 years. It is the commonest cancer type among 15-34 year olds.
Skin cancer exposed - 3 - Background information
4. Based on previous estimates, it is expected that almost 70,000 new cases of melanoma
were diagnosed in Europe during 2010-11.
Further information
European Cancer Observatory: This site presents the number of cases and deaths by cancer
in European countries and is updated regularly.
http://eu-cancer.iarc.fr/cancer-11-melanoma-of-skin.html,en
2.3. Aetiology of melanoma
There are several causes responsible for cutaneous melanoma and a number of risk factors
have been identified such as:
• Ultraviolet light (UVR) exposure
• Sensitivity to sunlight (e.g. Type of skin, eye colour, hair colour, number of moles)
• Genetic factors
• Previous history of a skin cancer
• A weakened immune system (immunosuppression)
Ultraviolet exposure
Ultraviolet light exposure results in a number of changes which together result in a weakened
protective system in the skin and an increased likelihood of developing a skin cancer. These
changes include DNA mutations, increased production of growth factors which stimulate cell
growth, reduced immunity, and formation of reactive oxygen species which are toxic and
dangerous molecules for the skin. There is also evidence that intermittent, high intensity
exposure to sunlight particularly during early life can result in an increased risk of developing
melanoma. A history of sunburn also doubles the risk of developing melanoma, and the use
of sun beds and sunlamps (an artificial source of sunlight used for tanning) also increases
the risk of melanoma in young adults.
Sun sensitivity
Fair skin burns easily resulting in freckles and tans with difficulty. This type of skin, blue eyes,
red hair and those individuals with a high number of moles are typical risk factors associated
with melanoma.
Skin cancer exposed - 4 - Background information
5. Genetic factors
A family history of melanoma is a significant risk factor and an estimated 10% of all
melanoma cases report a first- or second- degree relative with melanoma. In families where
members have many cases of melanoma, the inheritance appears to be due to a single gene
mutation. However, the majority of families show a complex pattern of inheritance suggesting
melanoma, which probably occurs through the interaction between genetic and
environmental factors. The genetic factors which predispose individuals to melanoma can be
divided into high penetrance genes and low penetrance alleles.
• High penetrance melanoma susceptibility genes.
These are mutations in the germline (i.e. in the lineage that in the body is responsible for
reproduction and therefore when transmitted, a germline mutation is incorporated in every
cell of the body, in contrast to a somatic mutation which is acquired in a single body cell).
Germline mutations can be passed from parent to child. Germline mutations in the
CDKN2A locus (40%) and cyclin-dependent kinase-4 (CDK4) (2%) are the only ones
identified in melanoma. These are essential genes which regulate the cell cycle, therefore
the speed of cell growth. Mutations of these genes make the cancer grow faster. In
addition, the frequency of the CDKN2A mutations are influenced by sunlight exposure,
demonstrating an important gene-environment interaction.
• Low penetrance melanoma susceptibility alleles
Epidemiological studies have established that the risk of developing melanoma could also
be directly related to pigmentation phenotype. Fair skin, poor tanning response, red or
blonde hair and freckles are all known melanoma risk factors. Studies analyzing all genes
in many different individuals have identified some genetic determinants of skin, hair and
eye colour variation. A single nucleotide change (known as single nucleotide
polymorphism) in some genes involved in the skin pigmentation pathway (melanocortin-1
receptor (MC1R), agouti stimulating protein (ASIP), tyrosinase (TYR) and tyrosinase-
related protein-1 (TYRP1)) can increase susceptibility to melanoma. These are mutations
that don’t occur frequently and are not inherited through the family.
Immunosuppression
A functional immune system is important to protect the body from melanoma; it is therefore
expected that immune-suppressed patients (e.g. patients who have been receiving an organ
transplant, need to reduce their immune-defense system in order to prevent a rejection
reaction, or HIV patients who have a weakened immune system) would be at a greater risk
Skin cancer exposed - 5 - Background information
6. for developing melanoma. The immune system may be important in both the development
and outcome of melanoma.
2.4. Diagnosis
The following features highly suggest that a skin lesion might be a melanoma:
• A new mole which is changing in shape, colour or size
• A longstanding mole which is changing in shape, colour or size
• Any mole which has three or more colours
• A mole which is itching or bleeding
• Any new persistent skin lesion especially if growing, if pigmented or red in
appearance, and if the diagnosis is not clear
• A new pigmented line in a nail especially where there is also damage to the nail
• A lesion growing under a nail
Suspicious pigmented lesions need to be removed in their entirety (excision biopsy) and then
analysed by a pathologist. The best outcome occurs when the correct diagnosis is made at
-
an early stage which can result in earlier treatment.
ABCDE criteria: In 1985, a group at New York University established the ABCDE criteria
(Asymmetry, Border irregularity, Colour variegation, Diameter <6 mm, Evolution, which
stands for change in size shape or colour over a short time) used as a simple tool to help
to identify melanoma from a harmless mole. Others factors have been also taken into
-
consideration such as inflammation (redness), crusting, or bleeding.
Dermoscopy: Hand held microscopes (dermoscopy) have been used to increase the
accuracy of making a diagnosis. These magnify the skin by 10-fold and help to identify
structures in the skin such as dots, streaks, veils, and pigment networks usually
undetectable by the naked eye. Changes in the pattern of these structures can help to
determine if a mole is harmless or a more likely to be melanoma.
Fig. 1: Comparison of early melanoma (top)
exhibiting the ABCDE features vs benign nevi
(bottom)
Skin cancer exposed - 6 - Background information
7. Fig. 2. Advanced melanomas demonstrate
ulcerative and nodular presentations. All of these
patients died within 1 year from when these
images were recorded
Fig. 3. Dermoscopic images of (left to right) a
normal nevus, a dysplastic nevus, and a
melanoma (note blue-white veil)
Credit for figs.1, 2 & 3: Rigel D. et al., CA Cancer J Clin 2010;60:301–316
2.5. Prognosis
The prognosis for melanoma is highly dependent on the stage it is at when it is found. If
caught early, melanoma can be cured. The risk of the cancer coming back increases with the
depth of the tumour - deeper tumours are more likely to come back. If the cancer has spread
to lymph nodes, there is a greater chance that the melanoma will come back. When left
untreated, it can and usually does spread (metastasize) to other organs in the body. The high
rate of metastasis is the main reason melanoma is considered the deadliest skin cancer.
Overall, males diagnosed with melanoma have a 5-year survival of 78%, for females this is
91% (Cancer Research UK) but advanced disease has a worse prognosis with only 11% of
individuals surviving 5-years. There are a few recognized features which determine the
outcome for melanoma and predict recurrence and survival, including
a) Breslow thickness (the vertical thickness of the tumour when analysed under the
microscope)
b) mitotic rate (the measure of the speed of cell growth in the dermis)
c) ulceration (as determined under the microscope)
d) the number of lymph nodes involved
e) if a patient is immunosuppressed.
2.6. Treatment
The first step in the treatment of melanoma is prevention. The best way to prevent melanoma
is to avoid sunburn and reduce sun exposure in both children and adults. Just getting one
bad, blistering, sunburn during childhood raises the risk of developing melanoma. Once
melanoma has developed, treatment is tailored around a variety of factors, including the
individual case, the type of melanoma and how much the melanoma has grown and spread.
Skin cancer exposed - 7 - Background information
8. Early detection of melanoma renders the disease curable in patients undergoing surgical
excision. Treatment therefore involves complete surgical removal of the cancerous mole or
area of skin. Local lymph nodes may be tested for the presence of cancer cells, indicating
whether melanoma has spread. Additional surgery, chemotherapy, radio- and/or immuno-
therapy may be needed if melanoma has spread beyond the skin to the lymph nodes and
other parts of the body. For most patients where the melanoma has spread beyond the skin,
there are no effective treatments and although many new treatments have been tested over
the past 30 years, the survival rates for this disease have not changed much. The future is
therefore to develop more effective treatments for this cancer.
Chemotherapy for melanoma
Chemotherapy uses anti-cancer drugs to destroy the growth of cancer cells. As they circulate
in the blood, they can reach cancer cells wherever they are in the body. Chemotherapy may
be used for an advanced melanoma that has spread to another part of the body (metastatic
disease). There are several newer types of chemotherapy and combinations of drugs being
evaluated in clinical trials both for metastatic disease and as an additional treatment for
people with local lymph node spread. In addition, the combination of chemotherapy and anti-
angiogenesis inhibitors (substances that prevent the formation of new blood vessels that
tumours need to grow and spread) or immunotherapy is also being explored.
Side effects
Different drugs have different side effects. Some common side effects of chemotherapy
include a drop in the number of blood cells, feeling sick, diarrhoea, hair loss or thinning, sore
mouth, feeling tired, and loss of fertility.
Radiotherapy for melanoma
Radiotherapy uses high energy rays to kill cancer cells. Radiotherapy could be used for
advanced melanoma, to shrink the tumours and help control symptoms, for example when
melanoma has spread to the brain or bones.
Side effects
The side effects will vary depending on which part of the body has been treated.
Radiotherapy just to the skin does not have very many side effects. The skin may become
slightly red and sore.
Skin cancer exposed - 8 - Background information
9. Biological therapy for melanoma
Biological therapies are treatments that use substances naturally produced by the body.
Some of these treatments are called immunotherapy as the drugs stimulate the immune
system. The most common immunotherapy used to treat melanoma is interferon. Interferon
helps the body attack cells that the body recognises as abnormal, for example cancer cells.
Interferon treatment has been tested in melanoma for some years. But it is still an
experimental treatment and has not been proven to help cure melanoma.
Currently, melanoma vaccines are being intensely evaluated in clinical trials for patients with
both localized and advanced melanoma. The vaccines are made using certain proteins found
only on a melanoma tumour and are given as an injection; the person’s immune system then
recognizes the proteins and destroys melanoma cancer cells.
An example, ipiluminab is a promising new experimental immunotherapy for the treatment of
patients with melanoma. Ipiluminab is a monoclonal antibody directed against CTLA-4
(cytotoxic T-lymphocyte associated molecule-4). This new approach works by taking the
brakes off the immune system. Ongoing clinical trials of ipiluminab for patients with advanced
melanoma will provide further guidance regarding the role of this drug in the treatment of
melanoma.
Side effects
In particular the immunotherapy could eventually trigger “autoimmune” side effects in which
the patient’s own immune system attacks normal cells in their body.
Targeted therapy
Targeted therapy is a treatment that targets specific genes or proteins. It is a major area of
research for melanoma. Ongoing research has identified a number of molecular pathways
and activated or mutated genes in melanoma. This includes the most commonly mutated
gene BRAF as well as activation of the MAP kinase pathway. Ongoing laboratory and clinical
research confirms the importance of these genes and pathways in melanoma.
There are several drugs in development that target BRAF and the MAP kinase pathway. This
includes BRAF inhibitors (PLX4032, also known as RO5185426), GSK BRAF inhibitors, and
MEK inhibitors. There are many ongoing clinical trials exploring these new approaches.
Ongoing clinical trials are evaluating the optimum dose and schedule and combining targeted
therapies with other pathway inhibitors, as well as combining these therapies with
immunotherapy. Another important focus is the development of agents which target the C-kit
Skin cancer exposed - 9 - Background information
10. gene, which is mutated or associated with extra copies of the gene in certain subtypes of
melanoma including lentigo maligna melanoma, mucosal melanoma, and acral lentiginous
melanoma (melanoma of the palms, soles, and nail beds).
2.7. Molecular pathways
Genes involved in the development of melanoma are critical to maintain cell proliferation,
differentiation and apoptosis (cell death). It is thought that some melanomas arise from
melanocytes or from harmless moles. There is evidence that a specific combination of
changes and abnormalities in genes from these different pathways can result in the
development of melanoma. Among the main forces limiting the ability of melanoma cells to
die to their appropriate and physiological levels and promoting an uncontrolled mechanism of
cell proliferation and survival are the Raf/MAPK pathways. These signaling cascades are
organized in intricate networks, and multiple genetic alterations of them occur in melanoma,
including mutations that activate Ras and two of its effectors cascades, Raf and
phosphoinositide 3-kinase (PI3K).
Here we highlight the most studied molecular targets in melanoma:
MAPK (mitogen-activated protein kinase): MAPKs are a family of enzymes that form an
integrated network influencing cellular functions such as differentiation, proliferation, and cell
death. These cytoplasmic proteins modulate the activities of other intracellular proteins by
adding phosphate groups to their serine/threonine amino acids.
BRAF: BRAF is an isoform of RAF. Raf proteins (Raf-1, A-Raf, B-Raf) are intermediate to
RAS and MAPK in the cellular proliferative pathway. Raf proteins are typically activated by
RAS via phosphorylation, and activated Raf proteins in turn activate MAPK via
phosphorylation. However, Raf proteins may also be independently activated by other
kinases.
RAS: The RAS gene family consists of H-RAS, N-RAS, and K-RAS. The RAS proteins are
typically small triphosphate-binding proteins, and are the common upstream molecule of
several signaling pathways that play a key role in signal transduction, which results in cellular
proliferation and transformation.
MITF: Microphthalmia-associated transcription factor is an early marker for melanocyte
lineage and essential for normal melanocyte development. It induces transcription of genes
important for melanin production, including tyrosinase. Currently, there is contradictory data
regarding MITF, both supporting and negating a role in melanomagenesis.
Skin cancer exposed - 10 - Background information
11. 2.8. Animal models
A wide variety of animal models of malignant melanoma are currently available to
researchers who are interested in the process of this disease: including Sinclair swine and
Camargue horses. Although neither example generates melanoma with a sunlight aetiology
the swine represents an interesting model, as the skin of the pig resembles the structure of
the human skin. Angora goats, develops in response to a chronic sunlight exposure,
lentiginous melanoma comparable to a form of melanoma described in the elderly.
More accessible to experimentation, however, are the non-mammalian Xiphophorus fish
model and the marsupial opossum, Monodelphis domestica both of which develop
melanomas in response of UV exposure and which spontaneously metastasize to other
organs. Melanomas arise spontaneously in dogs, and this model has been used to evaluate
novel cytokine combinations and gene-therapy protocols.
The most exploited model for studying melanomas is the mouse one, also due to the
increasing understanding of mouse genetics. Melanomas initiation in mice is not a
spontaneous event therefore induction of it is obtained via application of physical agents or
specific genetic manipulations (transgenic mice) as well as the inoculation of mice with
tumour-cell lines.
These models have the advantage of an intact immune system, which allows the
investigators to study not only the molecular events within the tumours, but also to look into
the immune responses against these tumours.
Finally, the more recently described models which employ immunodeficient mice (SCID)
provide a method for studying human tumours under controlled conditions. These mice have
been genetically manipulated in order to compromise the immuno-response and allow
injection or incorporation of material from human origin without any rejection problem. For
example these models allow injection under the skin or into the tail vein of cells isolated from
human metastatic tumours. Although the incidence of spontaneous metastasis from primary
tumours to other organs is pretty low, tumorigenicity (tumour formation) can be established
few weeks later by quantitative measure of lung colonies (number of tumours aggregate in
the lung, typically one of the primary targets of metastatic melanoma cells).
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12. 2.9. Clinical trials
A new treatment for melanoma is showing promising results in patients with a particular gene
mutation. In a study recently published in the New England Journal of Medicine, patients with
metastatic melanoma were treated orally with a drug called PLX4032, which targets a gene
mutation (BRAFV600E) associated with an increased risk of melanoma. Abnormal changes
in what is known as the BRAF gene are found in 40-60% of all melanomas. Mutated versions
of BRAF can become stuck in the “on” position, promoting uncontrolled (cancerous) growth.
PLX4032 is a novel BRAF “inhibitor” that can slow or even halt this growth. In a group of 32
metastatic melanoma patients with the BRAF mutation, PLX4032 resulted in tumour
shrinking in 81% patients. Responses have lasted anywhere from 2-18 months. It is not yet
clear whether treatment with PLX4032 will lead to improved overall melanoma survival rates,
but the authors are currently investigating this in a larger trial. Around 30% of the patients
treated with PLX4032 developed squamous cell carcinomas (a milder form of skin cancer).
PLX4032 provides the first evidence that therapy targeting tumours containing activating
BRAF-V600E mutations can significantly reduce tumour size in melanoma. This is the first
example of successful targeting of an intracellular signaling molecule which has an activating
mutation. Although there has been impressive success with the selective kinase-targeted
therapies, the long-term outcome is still awaited. Initially treatment-responsive patients
ultimately develop resistance to the treatment and relapse. By understanding how this occurs
a rational basis for combination therapy or second-generation drugs may then be developed
to combat this resistance.
Further information:
GenoMel is an international research consortium. Their website includes interactive resources about
melanoma. http://www.genomel.org/index.php
http://www.genomel.org/patient_information.php
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13. 3. Ethical, Legal and Social Aspects (ELSA)
In this section you will find a number of opinions and incentives for discussion in class on
ethical, legal and social aspects (ELSA) related to skin cancer:
3.1. Introduction
Melanoma is a common cancer, and one that is reasonably well known to the public. But this
familiarity can be misleading: it may not be taken as seriously as other cancers, because it is
thought to be easily treatable, and because people may think of melanomas as being little
different from harmless moles until it is perhaps too late. Prevention, early detection, and
early treatment are crucial, but this may not be well understood, particularly in countries, like
the UK, where sunshine is thought to be entirely beneficial and relatively unusual, where tans
are fashionable, and where sunburn is discussed with amusement!
3.2. Prevention
Prevention of melanomas is a public health issue. Public education campaigns about the
risks of intermittent, high intensity exposure to ultraviolet radiation, particularly sunlight and
artificial ultraviolet light in sunbeds, can make a significant difference to people’s awareness
of the risks, and to their behaviour. Public awareness of the risks of sunburn and overuse of
sunbeds is relatively low, as is the public understanding of the efficacy of preventive
measures such as covering up, use of suncreams and sunblocks, UV filtering glass in
windows, and so on. The marketing and sale of suncreams and sunblocks with reference to
“sun protection factors” is neither especially clear, nor is the evidence-base (if any)
underlying these indices ever explained to the public, and although more publicity has been
given to how best to apply creams, how long their protective effect lasts, and how it is
modified by sweat or bathing, this is again not well grasped by most users.
There has been some recent controversy about the safety of sunbed use, and calls for tighter
regulation of this industry, especially where the clients are under 18 years of age. But the
regulation of the industry is not risk-based. Overall, while a “healthy tan” remains
fashionable, there will be significant public communication difficulties about the need to be
sensible in the sun. And focussing on the risks of UV exposure can be controversial and
counterproductive in light of people’s enjoyment of outdoor work and leisure, and the known
health benefits.
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14. So far as biomedical prevention is concerned, there are no genetic tests that are sensitive
and specific enough to guide clinical decision-making, preventive strategies, or reproductive
choices. But in future it may be possible to give advice to would-be parents who have family
histories of melanoma: this would be subject to the usual ethical worries about the use and
abuse of genetic tests in reproductive medicine. It might also be possible to use medical
interventions that are protective against the effects of genes known to be involved in
biological pathways that lead to melanoma formation. There would then be an ethical debate
about the relative merits of pharmaceutical prevention and behaviour change. However, this
type of treatment might be especially useful in patients at high risk of melanoma (in
particular, those who are immunosuppressed).
A final consideration in terms of prevention concerns the impact of environmental change.
Climate change and ozone layer depletion are having a significant impact in terms of
people’s exposure to harmful levels of UV radiation. The Australian experience of rising
melanoma rates due to the Ozone hole, high summer temperatures, and a highly outdoor-
oriented culture is illustrative here. But it also illustrates the effects of widespread culture
change (“Slip on a T-shirt, slop on the suncream, slap on a hat” and a change in attitudes to
sunburn from amusement to disapproval), in combination with early diagnosis (through
primary care screening and patient self-monitoring) and treatment in reducing melanoma
incidence.
3.3. Diagnosis and screening
The first step in diagnosis will normally lie with the patient coming forward to her GP with a
concern. Physician-initiated screening will be relatively unusual except in high-incidence
countries or in specific high risk-groups (such as the immuno-suppressed): the normal
considerations of effectiveness and cost-effectiveness will control how and when a screening
programme could be initiated. Since the consequences of a false positive in primary care
treatment or referral are relatively minor (mild anxiety in the patient and very minor physical
discomfort during and for a short while after biopsy), the main concern here will normally be
with avoiding false negatives in patients who do present with a mole or skin lesion of concern
to them, and with encouraging patients to present and not to ignore what may be warning
signs of melanoma.
However, the best ways to encourage patients to seek diagnosis are not entirely clear, and
the benefits must be traded off against the costs in terms of resources diverted from other
Skin cancer exposed - 14 - Background information
15. uses, and against the adverse consequences in terms of health behaviour of inducing
excessive anxiety or caution.
Although false positives may be of relatively little concern from a medical point of view, from
a public health point of view they could become quite costly if they were relatively frequent,
and undermine the confidence of the public in the reliability and utility of seeking diagnosis,
and the quality of clinical care more generally. This speaks to a need to ensure that
diagnostic criteria are simple, robust, easy to validate, and useable by non-specialists – who
must also have access to appropriate training. Similar remarks apply to the development of
patient/user tests of the checklist or home diagnostics type. While tests that can usefully
encourage patients to seek professional advice can be beneficial, medical devices and
testing kits could be quite damaging if unreliable, hard to interpret, or understood to be
definitive, clinical grade, testing protocols.
The most serious difficulty in fact may be the usual problem in healthcare that patients who
could benefit from screening, diagnosis or treatment fail to come forward – and for many
years it has been known that people’s willingness to seek medical help is lower in poorer
socioeconomic groups, for various reasons. If melanoma is also commoner in poorer
socioeconomic groups, this can lead to significant health inequalities and healthcare
provision inequities.
3.4. Treatment
The ethical challenges of treatment are perhaps better understood than those of treatment:
good communication is the key, so that the patient and their family understand the nature of
the illness, the treatment options and their associated risks and benefits, and the likely
prognosis. In some cultural groups there may be less willingness to disclose a cancer
diagnosis to the patient herself, but this may be less difficult in the case of melanoma (at
least in its early stages) once it is understood that it is usually a highly treatable illness.
Patients (or their families) may focus on the word “cancer” and become fatalistic or decline
treatment or disclosure of diagnosis. Yet the treatment would under normal circumstances be
very highly effective.
The two main difficult issues relating to treatment are availability and research. In advanced
disease, where available treatments are rather ineffective, rather costly, or both, there can be
serious difficulties in terms of the affordability and cost-effectiveness of treatment. Therefore
there can be difficult judgements for commissioners of treatment about whether to offer
particular courses of treatment – or for clinicians, about whether to disclose that a course of
Skin cancer exposed - 15 - Background information
16. treatment may exist but which the NHS or private provider will not pay for. These decisions
about cost-effectiveness, be they made in general terms by the National Institute of Health
and Clinical Excellence (NICE) or specifically by doctors or primary care trusts (or their
successors), are hard to challenge.
3.5. Research
There are significant open questions relating to the design and evaluation of health
promotion and health education programmes in melanoma. The same applies to the
evaluation of preventive strategies, especially those involving products (such as creams) that
are more the province of the cosmetic, than the pharmaceutical, industry. Given the
importance of prevention in controlling melanoma, this points to a serious ethical problem
relating to the proper allocation of resources for research. And as with any medical or quasi-
medical product, it may require a significant regulatory push to force the industries in
question to subject their products to appropriate, unbiased testing, and to ensure that the
information they use to promote their product and guide users is reliable, accurate and open
to verification.
The ethics of research into treatments is much better understood, since the regulatory
system for drugs and devices is very much better developed and subject to clear guidelines
and principles. This is true both in animal and human subjects research. Although
controversy does stalk both animal research in dermatology (particularly in the case of use of
genetically modified animals as model animals in cancer research) and healthy volunteer
studies in humans (there was a long period in which prisoners were prime subjects for
dermatological research, in the US particularly), the guidelines and supervision of such
research are broadly robust and respected.
Some difficulties may arise in clinical trials proper (Phase II and III studies involving patients).
In particular, some patients may find it impossible to get a treatment unless it is in a clinical
trial (even if it is a licensed product), on cost grounds – yet being in a clinical trial may mean
assignment (by randomisation or otherwise) to the control group anyway. Since no research
study is entirely without risk, it may be that some people are almost coerced into taking such
risks simply because they have no other way of accessing the drug their clinician believes
that they need.
Other problems, relating to consent, can arise: one such is the therapeutic misconception,
such that the patient believes that they are getting “the best treatment for my disease” when
the clinician is actually enrolling research participants precisely because he doesn’t know
Skin cancer exposed - 16 - Background information
17. what is the best treatment for the disease, and allocation to a treatment may have nothing to
do with the specifics of any individual patient (obviously so, when allocation is randomised).
Patients may also believe that the experimental treatment is by definition the best treatment,
simply because it is the most up to date. Equally, some patients may seek to cheat the
protocol or to go overseas to destinations where the treatment is available outside any trial
protocol, at great expense and, sometimes, great risk (both from the untested treatment and
from unscrupulous or otherwise poor quality care in the destination clinic and after).
Authors:
The State of the Art document has been developed by Dr Daniele Bergamaschi, Centre for
Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and
Dentistry, Queen Mary University, London.
The ELSA document has been developed by Richard Ashcroft, Professor of Bioethics at
Queen Mary, University of London.
Skin cancer exposed - 17 - Background information
18. FUNDED BY: PROJECT PARTNERS:
Skin cancer exposed - 18 - Background information