Melanoma Treatment and Curcumin Benefits

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Questions and Answers

What is the primary purpose of sending a removed sample to a lab?

To confirm the presence of non-cancerous cells

To assess patient symptoms

To initiate consensus treatment

To determine if a wider excision is necessary (correct)

Which treatment is preferred for stage II or above melanoma if lymph nodes are positive?

Surgery and lymph node biopsy followed by target therapy or immunotherapy (correct)

Only palliative care

Surgery alone

Chemotherapy only

What combination produces better treatment outcomes compared to monotherapy with a BRAF inhibitor?

Combination of BRAF inhibitor and MEK inhibitor (correct)

CTLA4 inhibitor and PD-1 blocker

Surgery and immunotherapy

BRAF inhibitor and Tyrosine Kinase inhibitor

Which of the following is a common side effect of target therapy for melanoma?

Nausea (C) Signup and view all the answers

Which immunotherapy has demonstrated superior efficacy over chemotherapy?

CTLA4 inhibitor (ipilimumab) (B), Nivolumab (C) Signup and view all the answers

What effect does the combination of nivolumab and ipilimumab have compared to monotherapies?

It results in superior efficacy with more common irAEs (D) Signup and view all the answers

Which of the following is a possible immune-related adverse effect of immunotherapy?

Gastrointestinal issues (D) Signup and view all the answers

What is the most significant curcuminoid found in turmeric?

Curcumin (D) Signup and view all the answers

What does better safety and tolerability in target therapy imply?

Lower incidence of severe adverse effects compared to other treatments (D) Signup and view all the answers

Which of the following activities is NOT associated with curcumin?

Enhanced sedation (A) Signup and view all the answers

Which compound improves the bioavailability of curcumin?

Phosphatidylcholine phytosome complex (A) Signup and view all the answers

In the studies reviewed, what was observed regarding curcuminoids and pain management in knee osteoarthritis?

They resulted in significant reductions in rescue medication use (D) Signup and view all the answers

What was the overall risk of bias in the reviewed studies pertaining to curcuminoids?

Moderate (A) Signup and view all the answers

What was the primary efficacy measure in the systematic review and meta-analysis regarding curcuminoids?

Pain intensity or algofunctional status (B) Signup and view all the answers

How did the use of curcuminoids compare to ibuprofen in pain relief for knee OA?

Less effective than ibuprofen (A) Signup and view all the answers

What is a common limitation of the published RCTs reviewed regarding curcuminoids?

Small sample sizes (D) Signup and view all the answers

What role do autoreactive B cells play in the context of asymptomatic RA patients?

They can contribute to disease despite the absence of central tolerance. (D) Signup and view all the answers

What is a consequence of the excessive proliferation of fibroblast-like synoviocytes (FLS)?

Secretion of proteases that degrade cartilage. (A) Signup and view all the answers

Which of the following environmental factors is linked to the onset of RA?

Smoking. (C) Signup and view all the answers

What effect do autoantibodies like ACPA and RF have in rheumatoid arthritis?

ACPA triggers inflammation while RF exacerbates it. (D) Signup and view all the answers

How does macrophage activity contribute to joint erosion in RA?

They release cytokines to activate other immune cells. (A) Signup and view all the answers

What condition is characterized by microbiome dysbiosis and is also associated with increased risk for RA?

Psoriasis. (A), Crohn’s disease. (D) Signup and view all the answers

Which statement correctly describes the function of HLA-DRB1 in relation to RA risk?

It indicates a shared high risk for developing RA. (C) Signup and view all the answers

What is one of the main immune mechanisms involved in joint inflammation during RA?

Increased release of proteases from immune cells. (A) Signup and view all the answers

What percentage of all skin cancers do basal cell carcinomas (BCC) account for?

80% (C) Signup and view all the answers

Which of the following is NOT a risk factor for developing melanoma?

Chronic inflammation (D) Signup and view all the answers

What is the most common treatment method for basal cell carcinoma (BCC)?

Surgical excision (C) Signup and view all the answers

Which melanoma type is characterized by rapid vertical growth and is often aggressive?

Nodular melanoma (B) Signup and view all the answers

Which joints are commonly affected first in rheumatoid arthritis (RA)?

Metacarpophalangeal joints (C) Signup and view all the answers

What is the recommended dosage of oral nicotinamide for reducing skin cancer risk?

500 mg twice daily (B) Signup and view all the answers

What percentage of rheumatoid arthritis cases are typically seropositive?

70% (B) Signup and view all the answers

Which type of skin cancer is most likely to develop in areas of chronic wounds or inflammation?

Squamous cell carcinoma (SCC) (B) Signup and view all the answers

Which of the following is a preferred treatment for patients with solid organ malignancy within the last five years?

Conventional DMARDs (C) Signup and view all the answers

Which screening method is recommended for individuals at increased risk of melanoma?

Screening at regular intervals (B) Signup and view all the answers

What is a common symptom of rheumatoid arthritis affecting larger joints?

Shoulder pain and stiffness (D) Signup and view all the answers

In comparison to surgical methods, which of the following is a primary characteristic of Mohs surgery?

It involves comprehensive dermatopathological examination. (C) Signup and view all the answers

What distinguishes target therapy from immunotherapy in the treatment of melanoma?

Target therapy specifically targets cancer mutations. (B) Signup and view all the answers

Which of the following is considered a complication of uncontrolled synovial tissue proliferation in RA?

Osteoporosis (A) Signup and view all the answers

Which of the following types of melanoma is primarily observed in people of color?

Acral lentiginous melanoma (A) Signup and view all the answers

What is indicated as a preferred treatment option for patients with an active serious infection?

Tofacitinib (B) Signup and view all the answers

What is a common feature in patients with rheumatoid arthritis?

Symptom asymmetry in joint involvement (A) Signup and view all the answers

Which of the following statements about the pathogenesis of RA is true?

It involves the proliferation of synovial tissues. (B) Signup and view all the answers

Which type of inflammation is commonly associated with rheumatoid arthritis?

Low-grade systemic inflammation (D) Signup and view all the answers

Which laboratory markers are often present in seropositive RA?

Anti-citrullinated protein antibody (ACPA) and rheumatoid factor (RF) (D) Signup and view all the answers

What was the significant finding related to curcuminoids in the reviewed RCTs?

They significantly reduce pain. (A) Signup and view all the answers

Which of the following is a noted risk associated with curcuminoid supplements?

Hepatotoxicity (C) Signup and view all the answers

What is a possible reason for the adverse reactions reported from curcuminoid supplements?

Use of unregulated supplements (C) Signup and view all the answers

How many RCTs were included in the review mentioned?

8 (B) Signup and view all the answers

What percentage of the hepatotoxicity cases assessed was classified as probable?

61% (B) Signup and view all the answers

What is suggested regarding further studies on curcuminoids?

They should rigorously define long-term efficacy and safety. (C) Signup and view all the answers

What proportion of hepatotoxicity cases involved piperine-containing medicines?

0% (D) Signup and view all the answers

What is one of the evaluations reported regarding curcuminoid usage?

It is considered safe and well tolerated. (D) Signup and view all the answers

Study Notes

Melanoma

Melanoma is a type of skin cancer that accounts for around 80% of all newly diagnosed cancers in Australia by the time people are 70.
Two in three Australians will be diagnosed with skin cancer by the time they are 70.
Basal cell carcinoma (BCC) is the most common type, making up 80% of skin cancers.
It has a low metastatic potential but can be locally destructive.
Squamous cell carcinoma (SCC) is the second most common skin cancer, comprising 20% of cases and can develop in sites of chronic wounds or scarring.

Learning Outcomes

Identify the prevalence of different types of skin cancers
Know the risk factors for skin cancers
Recognise symptoms of BCC and SCC
Know the prevention and treatments for BCC and SCC
Understand the pathogenesis of cutaneous melanoma
Appreciate treatments for cutaneous melanoma
Compare and contrast target therapy with immunotherapy
Know drug classes, names, and mode of action in cutaneous melanoma

Risk Factors

Non-melanoma: UV exposure (especially early childhood), Male > Female
Melanoma: UV, fair skin type, multiple atypical moles, family history of melanoma, genetic predisposition

BCC and SCC Manifestations

Images of BCC and SCC are included showing the physical manifestations, including characteristics such as a locally destructive and slow-growing nature.

BCC/SCC Prevention and Treatments

Prevention: Sun protection, oral nicotinamide (Vitamin B3), topical fluorouracil
Treatment: Surgical excision, Mohs surgery, curettage and electrodesiccation, photodynamic therapy (PDT), cryosurgery, topical fluorouracil/imiquimod, radiation

Melanoma Manifestations

Different types of melanoma are shown and their associated features
Includes superficial spreading, nodular, lentigo maligna, acral lentiginous and mucosal melanoma

Melanoma Screening and Diagnosis

People at increased risk for melanoma should be screened regularly.
Screening involves a total body skin examination supported by dermoscopy or other imaging techniques.
Screening is useful for early detection of all skin cancers.

Melanoma Pathophysiology

Genetic level: Activating BRAF mutation, telomerase reverse transriptase mutation, cell cycle controlling genes mutations and their effect on the development of melanoma.
Protein level: Over-stimulation of MAPK pathway, deletion, mutations in PTEN or tumour protein p53.

Target Therapy C-KIT

A small number of melanomas have changes in the C-KIT gene.
Clinical trials are testing drugs such as imatinib, dasatinib, and nilotinib as target therapy for C-KIT changes.
Drug resistance is associated with the frequent presence of brain and central nervous system metastases.

Target Therapy Table

Shows various types of inhibitors and their associated dosages.
Includes dabrafenib combined with trametinib, Vemurafenib combined with cobimetinib, encorafenib combined with binimetinib, imatinib combined with nilotinib.

Pathophysiology- Adaptive Immune Resistance

Checkpoint inhibition: Monoclonal antibodies such as ipilimumab against CTLA-4, enhancing T cell response against melanoma cells to prevent negative feedback

Immunotherapy Table

Lists various immunotherapy agents and their respective approvals/phases of development
Includes ipilimumab for CTLA-4, pembrolizumab, Nivolumab, Pidilizumab, Durvalumab, Atezolimab

Melanoma Genetic Alterations

Four different genetic melanoma subtypes: BRAF mutant melanomas (50%), N-Ras, K-Ras, and H-Ras-mutant melanomas (25%), NF1-mutant (15%) and Triple-wild-type (10%) .
Activating TERT-promoter mutations (30-80%)
Altered tumor suppressors - CDKN2A, PTEN, P53

Melanoma Treatment By Stage

Treating stage 0-1 melanoma: Surgery to remove the melanoma and a small margin of normal skin around.
Treating stage II or above melanoma: Surgery + lymph node biopsy; If lymph node positive, target therapy/immunotherapy is required.

Target Therapy Considerations

Rapid response within days to a few weeks.
Favourable treatment outcomes with BRAF inhibitor + MEK inhibitor compared to monotherapy with a BRAF inhibitor.
Good safety and tolerability profile, common side effects include nausea, diarrhoea, vomiting, arthralgia, fatigue, photosensitivity, increase in creatine kinase and liver transaminases, peripheral oedema, alopecia, and hyperkeratosis.

Immunotherapy Considerations

CTLA4 inhibitor (ipilimumab): Demonstrated superior efficacy compared to chemotherapy, but caused a range of immune related adverse events (irAE)
PD-1 blockers (nivolumab, pembrolizumab): Showed superior efficacy compared to ipilimumab and chemotherapy, with lower toxicity rates

Management- Challenge

Multiple mechanisms of resistance against BRAF and MEK inhibitors have been identified.
Immune inhibition of lymphocyte activation gene-3 (LAG-3) is often linked to managing PD-1 immunotherapy tolerance.

Combination Therapy

Combining PD1 and PD-L1 leads to longer progression-free survival but has a higher rate of grade 3/4 adverse events compared with doublet therapies.
Sequencing approach (giving one drug after the other) might result in similar survival as full combination therapy with less toxicity.

Sample Exam Questions

Questions regarding each topic are presented in a sample exam format.

Rheumatoid Arthritis

Learning Outcomes: describe inflammatory and immunological mechanisms, identify drug targets, understand DMARD drug selection, define mechanisms of action and toxicity of DMARDs.
Practice Point: Advice for pharmacists' role in RA management
Background: Symmetric polyarthritis of hands, wrists, and feet. Low-grade fevers, anemia (fatigue). Joint erosion and destruction may occur in RA, alongside systemic inflammation.
Symptoms: Primarily affects the joints, with possible first symptoms in metacarpophalangeal, proximal interphalangeal, and wrist joints, leading to prolonged morning stiffness and pain.
Common Presentations: Swollen, tender, stiff multiple symmetrical joints lasting for more than an hour in the morning or after inactivity. Chronic fatigue + fever + weight loss. Possible joint destruction and systemic inflammatory symptoms including fatigue and fever.
Joint Changes: X-ray images showing the effects of RA on the joints, including joint swelling, destruction, and loss of joint space.
Common Sites: Images illustrating common locations affected by RA, including the distal interphalangeal joints (DIP), proximal interphalangeal joints (PIP), and metacarpophalangeal joints (MCP).
Risk Factors: Age (most common >60 years), Sex (women > men), Genetics (HLA genes encoding MHCII protein), Smoking (current or former), History of nulliparous births, Early life exposure to smoking or infections, and Obesity.
Pathogenesis: The description of the underlying disease mechanisms, particularly the role of citrullination in immune system dysfunction and subsequent inflammatory response leading to joint damage from uncontrolled synovial tissues proliferation. Also includes the role of APCs, CD4+ T cells, and resulting autoantibodies (ACPA, RF) in disease progression.
Pathogenesis Overview: Video showing the mechanistic details of RA (presumably a New England Journal of Medicine video)
Induction of RA Pathogenesis: Specific diagram depicting stages of RA pathogenesis, including citrullination, macrophage presentation, B cell proliferation, and plasma cell production of autoantibodies.
RA Pathogenesis: Diagram showing key cells (macrophages, T cells, B cells, fibroblast-like synoviocytes, osteoclasts) and cytokines (TNF, IL-1, IL-6) involved in the pathophysiology of RA.
Antigen Presentation Dysfunction in Autoimmunity: Diagram highlighting the role of HLA-DRB1 variants in enhancing citrulline binding and leading to stronger T cell activation.
Early B Cell Antigen Recognition and Autoantibody Production: Diagram showing the process of autoreactive B cell activation and the lack of central tolerance in RA patients.
Microbiome Linkages with RA: Environmental risk factors such as respiratory diseases, smoking exposure, and periodontal/dental issues can contribute to tissue damage and further disease. High risk of disease with HLADRb1. Many bacteria can cause post-translational modification (PTM) such as citrullination, leading to autoantibodies (ACPA and IgG) in the sputum of RA patients.
Joint Erosion: Diagram showing the mechanism of joint erosion, including inflammation with macrophage activation, excessive protease secretion damaging cartilage, bone erosion (osteoclast activity), and synovial hyperplasia.
Linkages Between Cytokines and Symptoms: Diagram depicting the connection between various cytokines and clinical symptoms like inflammation, destructive changes, and systemic inflammation.
Management of RA: Goals of therapy include symptom relief, modifying disease course, inducing and maintaining remission, and preventing relapses. Special considerations for pregnancy and co-morbidities.
Considerations: Symptom relief, disease modification, induction of remission, maintaining remission, preventing relapses, and treatments for pregnancy and co-morbidities.
Why is treatment of early RA Important?: Early treatment leads to reduced joint damage, reduced bone mineral density loss, and prevents disability.
How to Differentiate Between MSK Conditions: Differentiating factors between RA and other joint diseases, including clinical history, disease extent, extra-articular symptoms, blood results, and joint aspiration.
Treatment Strategy: Symptomatic treatments (non-pharmacological, analgesics, anti-inflammatory drugs, corticosteroids.) and Disease-Modifying Anti-Rheumatic Drugs (DMARDs) are initiated early, often in combination to improve long-term outcome and slow disease progression. This includes synthetic DMARDs (methotrexate, leflunomide, sulphasalazine, hydroxychloroquine) and biologics (antibodies to cellular processes or ligands).
Methotrexate: Mechanism of action, dosages, adverse events, precautions, and practice points.
Leflunomide: Mechanism of action, dosages, adverse events, precautions, and practice points.
Sulfasalazine: Mechanism of action, dosages, adverse events, precautions, and practice points.
Hydroxychloroquine: Mechanism of action, dosages, adverse events, precautions, and practice points.
Efficacy Comparison: Comparison of various DMARD efficacy on the use of the PBS.
Combination Rx: Risk and benefit of combining DMARDs including MTX, Hydroxychloroquine, and Sulfasalazine.
Criteria for Biologics: Specific criteria are listed for use of biologics for rheumatoid arthritis treatment.
Choice of First bDMARD for RA: Selection of a first-line biologic DMARD in rheumatoid arthritis patients, taking into consideration approval guidelines, patient characteristics and adherence factors. Cost of medication and prescription consideration are also included.
Immunologic Targeting: Includes specific examples of biologics targeting different systems within the immune response (e.g. anti-CD19, anti-TNF).

Additional Topics

Sample Exam Questions: Sample exam questions for both Melanoma and Rheumatoid Arthritis.
Evidence-based Complementary Medicines for Osteoarthritis Pain and Disability 2024: Specific information on evidence and safety regarding CM use in osteoarthritis management and treatment.
Glucosamine: Description of glucosamine sulfate and its naturally occurring source from synovial fluid as a supplementary aid in osteoarthritis treatment.
Chondroitin: Overview of chondroitin, its source, proposed mechanisms of action, efficacy evidence (specifically in Cochrane review updated 2009), and safety considerations.
Indian Frankincense (Boswellia serrata): Description of the composition of Indian frankincense, its active components, efficacy (specifically in clinical trials shown in the lecture), and safety precautions.
Turmeric (Curcumin) : Overview of curcumin as an active constituent of the turmeric rhizome, the effect on inflammation, efficacy, clinical trials, adverse effects (particularly hepatotoxicity from recent data), and drug interactions.
Pycnogenol: Overview of Pycnogenol, derivation, effects on matrix metalloproteinases (MMPs), and evidence regarding benefits in osteoarthritis patients.
Methylsulfonylmethane (MSM): Characteristics of the compound, its application in osteoarthritis and its effect on inflammatory cytokines.
Omega-3 Fatty Acids: Overview of the mechanism of action of Omega-3 fatty acids and its effects of inflammatory conditions.
Case Studies (2023 and 2024): Specific cases of individuals who present to a pharmacy with distinct skin or joint conditions with specific details and the required questions to evaluate and provide advice.
Contact Dermatitis: Definition, causes, typical symptoms, and treatment.
Topical Corticosteroids: Indications, application, precautions, and commonly available types.
Cutaneous Drug Reactions: An overview of the potential for a drug reaction to the skin based on their mechanism, type of response, severity, common triggers, and how to recognize clinical features and when to refer to the GP or dermatologist.

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Description

Test your knowledge on melanoma treatment options, including immunotherapy and targeted therapies. Additionally, explore the health benefits of curcuminoids, particularly curcumin found in turmeric, and its implications in pain management and bioavailability. Each question will deepen your understanding of cancer treatment and nutritional science.