Malignant Neoplasms
Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang in Roxburgh's Common Skin Diseases, 2022
Overview: In 2017, there were an estimated 87,110 new cases of melanoma and 9,730 melanoma-related deaths in the United States. The mean age at the time of melanoma diagnosis is 55 years old, and men are more frequently diagnosed with melanoma in the United States. The strongest risk factors for the development of melanoma include ultraviolet light exposure, fair skin complexion, having over 100 nevi, and a family history of melanoma. Multiple genes, including CDKN2A, which serves as a tumor suppressor gene, have been associated with the development of familial melanoma. Multiple gene mutations have been implicated in cutaneous melanoma. The BRAF gene and pathway, which regulates cell differentiation, growth, and proliferation, is commonly mutated in melanoma and is the target of new therapeutic agents.
Clinical specialties
Andrew Schofield, Paul Schofield in The Complete SAQ Study Guide, 2019
A 27-year-old girl comes to you in the GP practice complaining of an ‘enlarging mole’ on her neck. State four questions you would want to ask about this ‘mole’? (2)Other than sun exposure, give two risk factors for developing malignant melanoma. (2)Name two types of malignant melanoma. (2)What is the most significant feature of a malignant melanoma in predicting prognosis? (1)Name two other sites at which malignant melanoma can occur. (2)What is the mainstay of treatment for these lesions? (1)
Malignant Melanoma
Pat Price, Karol Sikora in Treatment of Cancer, 2020
Patients with metastatic melanoma have a poor prognosis and until recently systemic treatment was largely ineffective. This has changed dramatically with the development of targeted agents and new immune regulating monoclonal antibodies. In patients of stage IV disease, defining the mutational status of the tumor (BRAF, c-KIT, and NRAS) is key to planning management. Surgery and radiotherapy offer palliation in certain circumstances, for example, radiotherapy for bone and brain metastases and surgery for other metastases.
Imiquimod-oleic acid prodrug-loaded cream reduced drug crystallinity and induced indistinguishable cytotoxicity and apoptosis in mice melanoma tumour
Published in Journal of Microencapsulation, 2019
Akanksha Sharma, Dharampal Sharma, Ashish Baldi, Kiran Jyoti, Ramesh Chandra, Jitender Madan
Melanoma with high metastatic potential is an aggressive form of skin cancer. Approximately 10% of the patients with locally advanced melanoma report 5-year survival (Coventry et al. 2015). Imiquimod (IMQ) has been categorised as antiviral and antitumour agent (Hanna et al. 2016). Besides, IMQ is a potent Toll-like receptor (TLR) agonist having high affinity for TLR-7 (Sioud 2006, Shojaei et al. 2009). Five per cent w/v IMQ dermal cream has demonstrated remarkable therapeutic efficacy in the treatment of non-melanoma in addition to malignant melanoma skin cancer (Amini et al. 2010, Bubna 2015). Topical dermal delivery of IMQ in mice activates dermal dendritic cells (DCs) and Langerhans cells and thus leads to maturation and migration of cutaneous DCs. In humans, IMQ drives pDCs (plasmacytoid dendritic cells) mobilisation and activation (Aspord et al. 2014, Singh et al. 2016). However, besides its excellent therapeutic efficacy in melanoma skin cancer, IMQ is also associated with serious side effect like severe skin inflammation (Varma et al. 2017) and physicochemical limitations (Chollet et al. 1998; Harrison et al. 2009). 5% w/v IMQ dermal cream exhibits crystallization upon storage (Chollet et al. 1998, Harrison et al. 2009). Moreover, IMQ has limited solubility of 0.79 µg/ml in aqueous phase owing to its basic structure and log p values of 2.7 (Statham and Nelson 2011a, Rehman et al. 2014).
Immunological responses to adjuvant vaccination with combined CD1c+ myeloid and plasmacytoid dendritic cells in stage III melanoma patients
Published in OncoImmunology, 2022
Martine Bloemendal, Kalijn F. Bol, Steve Boudewijns, Mark A.J. Gorris, Johannes H.W. de Wilt, Sandra A.J. Croockewit, Michelle M. van Rossum, Anna L. de Goede, Katja Petry, Rutger H.T. Koornstra, Carl Figdor, Winald R. Gerritsen, Gerty Schreibelt, I. Jolanda M. de Vries
We investigated vaccination with these improved and combined cDC2s and pDCs in lymph-node involved (stage III) melanoma patients. Cutaneous melanoma is an aggressive form of skin cancer due to its metastatic potential. Compared to patients with stage IV melanoma, patients with completely resected stage III melanoma harbor less tumor burden, hence less tumor-induced immune suppression27 which might hamper response to DC vaccination. As such, DC vaccination might be more successful in stage III melanoma patients. This is endorsed by superior induction of antigen-specific T cells by DC vaccination in stage III compared to stage IV melanoma patients.28,29 In addition, a retrospective analysis of stage III melanoma patients receiving adjuvant moDC vaccination showed improved overall survival (OS) compared to their matched controls.30 Stage III melanoma is treated with surgical resection with curative intent. Unfortunately, despite complete surgical resection, patients have a high risk of recurrence resulting in 5-year OS rates between 40 and 78%.31 Therefore, effective adjuvant therapy for this group of patients is warranted. At time of trial enrollment, no adjuvant therapy significantly impacting survival was registered and for this reason, we included patients with completely resected stage III melanoma to receive adjuvant nDC therapy. In the meantime, after completion of the enrollment phase, several drugs were approved for use as an adjuvant therapy.32–35
Clinical correlates and prognostic value of different metastatic sites in patients with malignant melanoma of the skin: a SEER database analysis
Published in Journal of Dermatological Treatment, 2018
In this study, cutaneous melanoma patients with metastatic disease were classified according to the site of metastases [distant skin/subcutaneous lesions, distant (non regional) lymph nodes, lung, bone, liver, and brain]. For the sake of this analysis, distant lymph nodes were those groups not labeled as N1, N2, or N3 in the TNM 7th edition. Primary end points include overall survival (OS) (defined as the time from diagnosis till death due to any reason) and MSS (defined as the time from diagnosis till death due to cutaneous melanoma). Chi-square test was utilized to compare the correlation between different clinico-pathological characteristics and different metastatic sites. Kaplan–Meier analysis and log-rank testing were used for survival comparisons. Cox proportional hazard model was conducted to produce multivariate analyses and hazard ratios with corresponding 95% CI were generated for prognostic factors affecting overall and MSS. Statistical significance was considered if a two-sided p value <0.05 was achieved. All of the statistical analyses were performed using SPSS Statistics 20.0 (IBM, NY).