Immune-related Bell’s palsy in melanoma patients treated with immune checkpoint inhibitors

xlomafota13 shared this article with you from Inoreader Immune-related Bell's palsy in melanoma patients treated with immune checkpoint inhibitors Via Melanoma Research - Current Issue Immune-checkpoint inhibitors (ICIs) exposed the oncology community to novel immune-related adverse events (irAEs). Here, we report on a retrospective analysis of patients with melanoma who developed an ICI-related, unilateral, acute and peripheral facial nerve paralysis (Bell's palsy).We retrospectively reviewed all the cases of ICI-related Bell's palsy in patients with melanoma treated at our institution from January 2015 to January 2020. A total of five cases of ICI-related Bell's palsy were identified. Median age was 63 years. Median time-to-onset of Bell's palsy from ICIs initiation was 15� ��weeks. Four patients were treated with prednisone alone, whereas one patient was treated with prednisone plus valaciclovir. All the patients completely recovered from Bell's palsy without neurological sequelae. In melanoma patients treated with ICIs, Bell's palsy is a rare, neurologic irAE with a favorable outcome following administration of oral corticosteroids. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model

xlomafota13 shared this article with you from Inoreader Metabolomic characterisation of progression and spontaneous regression of melanoma in the melanoma-bearing Libechov minipig model Via Melanoma Research - Current Issue Melanoma-bearing Libechov minipig (MeLiM) represents a large animal model for melanoma research. This model shows a high incidence of complete spontaneous regression of melanoma – a phenomenon uncommon in humans. Here, we present the first metabolomic characterisation of the MeLiM model comparing animals with progressing and spontaneously regressing melanomas. Plasma samples of 19 minipigs with progression and 27 minipigs with evidence of regression were analysed by a targeted metabolomic assay based on mass spectrometry detection. Differences in plasma metabolomics patterns were investigated by univari ate and multivariate statistical analyses. Overall, 185 metabolites were quantified in each plasma sample. Significantly altered metabolomic profile was found, and 42 features were differentially regulated in plasma. Besides, the machine learning approach was used to create a predictive model utilising Arg/Orn and Arg/ADMA ratios to discriminate minipigs with progressive disease development from minipigs with regression evidence. Our results suggest that progression of melanoma in the MeLiM model is associated with alteration of arginine, glycerophospholipid and acylcarnitines metabolism. Moreover, this study provides targeted metabolomics characterisation of an animal model of melanoma with progression and spontaneous regression of tumours. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment

xlomafota13 shared this article with you from Inoreader Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment Via Melanoma Research - Current Issue Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immunity by downregulating arginase 1 and inducible nitric oxide synthase production in MDSCs. Accordingly, decreased T cell anergy and helper to regulatory T cell conversion have been observed in the presence of NLGP, which ultimately augments T cell functions. M echanistically, NLGP-mediated rectification of T cell suppressive functions of MDSCs was primarily associated with downregulation of the interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling axis within the tumor microenvironment, as confirmed by knockdown of STAT3 (by STAT3-siRNA) and using IL-10−/− mice. Thus, NLGP-mediated suppression of MDSC functions in tumor hosts is appeared to be another associated effective mechanism for the eradication of murine melanoma by NLGP. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The efficacy of immunotherapy for in-transit metastases of melanoma: an analysis of randomized controlled trials

xlomafota13 shared this article with you from Inoreader The efficacy of immunotherapy for in-transit metastases of melanoma: an analysis of randomized controlled trials Via Melanoma Research - Current Issue Nearly 10% of patients with high-risk early-stage melanoma will develop satellite or in-transit metastases (ITM), classified as stage III disease similar to lymph node metastases. The pivotal registration trials of the CTLA-4 antibody ipilimumab, and the PD-1 antibodies nivolumab and pembrolizumab, also included patients with unresectable stage III disease. However, there has been no analysis of patients with ITM, and anecdotal retrospective small series have indicated a potential lesser effect. This study aimed to identify patients with unresectable ITM within the randomized trials, and to determine respon se, progression-free survival and overall survival. The pivotal phase III randomized intervention trials that included melanoma patients with ITM, with or without nodal metastasis, and were treated with ipilimumab, nivolumab or pembrolizumab was identified. The datasets from each trial were then searched to identify the specific details of the investigated patient population for a pooled analysis. The primary endpoint was complete response rate. Seven trials that included stage III patients, and with accessible datasets, were identified. There was a total of 4711 patients, however, no patients with ITM could be identified, as this data was not captured by the case report forms. Evidence from prospective clinical trials on the use of immunotherapy in patients with ITM is lacking. We recommend pooling data from multiple institutions to examine efficacy of available drug therapies in this patient population, but more importantly, prospective clinical trials of locoregional treatments w ith or without systemic drug therapies are required. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma

xlomafota13 shared this article with you from Inoreader BAP1 deletion abrogates growth and metastasis of murine cutaneous melanoma Via Melanoma Research - Current Issue Although germline mutations in BRCA-associated protein-1 (BAP1) predispose to cutaneous melanoma (CM), BAP1 is rarely mutated in primary CM outside the familial context. The role of BAP1 in the pathogenesis of CM remains obscure. Here, we discovered an unexpected role of BAP1 in suppressing CM growth and metastasis. BAP1 deletion by CRISPR-Cas9 system severely compromises colony-forming capability of murine CM cell line B16-F10 and human CM cell lines, SK-MEL-28 and A375. Furthermore, BAP1 loss abrogates tumor growth and lung metastasis in murine syngeneic tumor models. Deletion of BAP1 in B16-F10 cells leads to preferential downregulation of genes accompanied with increased H2A ubiquitination at lysine 119. Transcriptomic characterization of BAP1 deletion reveals multiple deregulated cellular functions including extracellular matrix-receptor interaction and MAPK signaling pathway which may contribute to BAP1's effect on metastasis and proliferation. Our findings indicate that BAP1 could be a potential therapeutic target for CM. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A case of sudden brain metastases progression after temporary targeted therapy discontinuation: when to regret a drug holiday

xlomafota13 shared this article with you from Inoreader A case of sudden brain metastases progression after temporary targeted therapy discontinuation: when to regret a drug holiday Via Melanoma Research - Current Issue Targeted therapy improves outcomes in BRAF V600-mutant metastatic melanoma with active brain metastases. We present the case of a patient with rapid brain disease progression upon temporary targeted therapy discontinuation and unusual rapid disease response upon treatment resumption. This report presents a 78-year-old woman with metastatic BRAF V600E positive melanoma (bladder and brain localizations). The patient started first-line dabrafenib and trametinib with good tolerability and evidence of complete response (CR). After 8 months of maintained CR, the patient took a drug holiday for 14 days. Brain MRI performed after treatment pause showed extensive disease progression, whereas extracranial staging was negative. The patient was asymptomatic: she restarted targeted therapy and underwent evaluation for whole-brain radiotherapy. Brain computed tomography scan and subsequent MRI performed to plan radiotherapy showed brain CR after only 10 days of targeted therapy resumption. The patient continued treatment, and radiotherapy indication was withheld. Repeated brain MRI confirmed maintained CR. Treatment with dabrafenib and trametinib is ongoing with excellent tolerability. Rapid intracranial progression is a well-known finding after discontinuation of combined targeted therapy in the case of extracranial progressive disease. This is the first report of documented disease progression upon temporary treatment discontinuation for reasons other than toxicity, with an unusual response after retreatment. Caution should be used in tailoring treatment during targeted therapy, allowing p auses for reasons other than toxicity. Strict adherence to treatment is paramount to guarantee disease control. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mapping sentinel lymph nodes in cutaneous melanoma: a vast array of perioperative imaging modalities

xlomafota13 shared this article with you from Inoreader Mapping sentinel lymph nodes in cutaneous melanoma: a vast array of perioperative imaging modalities Via Melanoma Research - Current Issue Sentinel lymph node biopsy (SLNB) is a decisive step in the staging process of melanoma, critically impacting patients' oncological outcome and driving the decision-making process. SLNB limits the extent of the dissection in cases where no metastases are found. Conversely, when metastases are detected, SLNB has the potential to improve regional control of the disease when complete lymphadenectomy or early administration of adjuvant treatment are indicated. Thus, accurately identifying sentinel lymph nodes represents an important prognostic factor. Several strategies have been studied, including novel procedur es that are not commonly used in the clinical setting. This review highlights the different tracers, preoperative and intraoperative imaging modalities studied to perform SLNB in cutaneous melanoma. The development of innovative modalities has been fueled by a need to optimize current approaches, offering new alternatives that can overcome some of the limitations of the standard method. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.