Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-07-22DOI: 10.1097/CMR.0000000000000991
Antonios Tsimpidakis, Ioannis-Alexios Koumprentziotis, Evanthia Mastoraki, Michaella Plaka, Helen Gogas, Alexander Stratigos, Vasiliki Nikolaou
{"title":"Exacerbation of Kaposi sarcoma following BRAF/MEK inhibitor therapy in a melanoma patient: a case report and mechanistic insight.","authors":"Antonios Tsimpidakis, Ioannis-Alexios Koumprentziotis, Evanthia Mastoraki, Michaella Plaka, Helen Gogas, Alexander Stratigos, Vasiliki Nikolaou","doi":"10.1097/CMR.0000000000000991","DOIUrl":"10.1097/CMR.0000000000000991","url":null,"abstract":"<p><p>We present a case of a 75-year-old male patient who experienced a severe exacerbation of his Kaposi sarcoma lesions, which have remained clinically stable for a year, following treatment with BRAF/mitogen-activated protein kinase inhibitors for his coexisting melanoma. In this case, we present the possibility that BRAF/MEK inhibition may be mechanistically associated with the progression of Kaposi sarcoma and briefly discuss the potential mechanisms behind this phenomenon.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"469-471"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-06-03DOI: 10.1097/CMR.0000000000000984
Federica Dini, Pietro Susini, Biancamaria Zuccaro, Giuseppe Nisi, Roberto Cuomo, Luca Grimaldi, Gabriella Perillo, Luca Tinunin, Pietro Antonini, Alessandro Innocenti, Giovanni Cecchi, Elisabetta Gambale, Laura Doni, Cinzia Mazzini, Nicola Santoro, Vincenzo De Giorgi
{"title":"Head and neck melanoma: the eyelid region has a better prognosis and easier management. A retrospective survey and systematic review.","authors":"Federica Dini, Pietro Susini, Biancamaria Zuccaro, Giuseppe Nisi, Roberto Cuomo, Luca Grimaldi, Gabriella Perillo, Luca Tinunin, Pietro Antonini, Alessandro Innocenti, Giovanni Cecchi, Elisabetta Gambale, Laura Doni, Cinzia Mazzini, Nicola Santoro, Vincenzo De Giorgi","doi":"10.1097/CMR.0000000000000984","DOIUrl":"10.1097/CMR.0000000000000984","url":null,"abstract":"<p><p>Eyelid melanoma (EM) is a malignant neoplasm accounting for around 1% of eyelid malignancies. Because of its rarity, most of our knowledge of EM is currently based on studies of cutaneous melanomas located elsewhere. Accordingly, this study aimed to specifically evaluate EM characteristics, management strategies, and prognosis. A retrospective study was carried out on patients diagnosed with EM at Careggi University Hospital, Florence between May 2012 and May 2022. In addition, a systematic review of relevant literature was conducted, encompassing studies published from 2013 to 2023. Clinical, histopathological, therapeutical, and prognostic data were analyzed to assess the metastasis rate and the 5-year survival rate of patients with EM. Separate data were extracted for in situ and invasive disease. Our original study included 19 patients diagnosed with EM with a 5-year survival rate of 100% for in situ and 83.3% for invasive EM. The literature review identified five poorly detailed large database reviews and 14 original studies on EM with an overall 5-year survival rate of 79.7%. The present research indicates that EM is a challenging malignancy, but has a relatively better prognosis and easier management than other melanomas of the head and neck region. These are probably related to the anatomical location which leads to early diagnosis. Therefore, EM should be considered as a specific disease requiring dedicated treatment. Based on the personal authors' experience and comprehensive overview of the current knowledge, a dedicated protocol is proposed.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"429-438"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141248252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-06-05DOI: 10.1097/CMR.0000000000000983
Pan Luo, Rui Guo, Dejin Gao, Qingguo Zhang
{"title":"Causal relationship between sex hormones and cutaneous melanoma: a two-sample Mendelian randomized study.","authors":"Pan Luo, Rui Guo, Dejin Gao, Qingguo Zhang","doi":"10.1097/CMR.0000000000000983","DOIUrl":"10.1097/CMR.0000000000000983","url":null,"abstract":"<p><p>This study aimed to elucidate the genetic aspects of the relationship between sex hormones and cutaneous melanoma risk, providing valuable insights into this complex association. In this study, we used estradiol, bioavailable testosterone, sex hormone-binding globulin, and total testosterone as the exposure and melanoma as the outcome for two-sample Mendelian randomization analysis. In this study, a random-effects inverse-variance weighting (IVW) model was used as the main analysis model, and the corresponding weighted median, simple mode, weighted mode, and Mendelian randomization‒Egger methods were used as supplementary methods. We assessed both heterogeneity and horizontal pleiotropy in our study, scrutinizing whether the analysis results were affected by any individual single nucleotide polymorphism. The random-effects IVW method indicated that estradiol [odds ratio (OR), 1.000; 95% confidence interval (CI), 0.998-1.003; P = 0.658], bioavailable testosterone (OR = 1.001, 95% CI, 0.999-1.003; P = 0.294), sex hormone-binding globulin (IVW: OR, 1.000; 95% CI, 0.998-1.003; P = 0.658), and total testosterone (IVW: OR, 1.002; 95% CI, 0.999-1.005; P = 0.135) were not genetically linked to cutaneous melanoma. No analyses exhibited heterogeneity, horizontal pleiotropy, or deviations. We were unable to find genetic evidence for a causal relationship between sex hormones and the occurrence of cutaneous melanoma in this study. These results are limited by sample size and population, so the causal relationship between sex hormones and cutaneous melanoma needs to be further studied.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"408-418"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-07-02DOI: 10.1097/CMR.0000000000000982
Claudia Fokken, Ivan Silbern, Orr Shomroni, Kuan-Ting Pan, Sergey Ryazanov, Andrei Leonov, Nadine Winkler, Henning Urlaub, Christian Griesinger, Dorothea Becker
{"title":"Interfering with aggregated α-synuclein in advanced melanoma leads to a major upregulation of MHC class II proteins.","authors":"Claudia Fokken, Ivan Silbern, Orr Shomroni, Kuan-Ting Pan, Sergey Ryazanov, Andrei Leonov, Nadine Winkler, Henning Urlaub, Christian Griesinger, Dorothea Becker","doi":"10.1097/CMR.0000000000000982","DOIUrl":"10.1097/CMR.0000000000000982","url":null,"abstract":"<p><p>Melanoma is the most serious and deadly form of skin cancer and with progression to advanced melanoma, the intrinsically disordered protein α-synuclein is upregulated to high levels. While toxic to dopaminergic neurons in Parkinson's disease, α-synuclein is highly beneficial for primary and metastatic melanoma cells. To gain detailed insights into this exact opposite role of α-synuclein in advanced melanoma, we performed proteomic studies of high-level α-synuclein-expressing human melanoma cell lines that were treated with the diphenyl-pyrazole small-molecule compound anle138b, which binds to and interferes with the oligomeric structure of α-synuclein. We also performed proteomic and transcriptomic studies of human melanoma xenografts that were treated systemically with the anle138b compound. The results reveal that interfering with oligomerized α-synuclein in the melanoma cells in these tumor xenografts led to a substantial upregulation and expression of major histocompatibility complex proteins, which are pertinent to enhancing anti-melanoma immune responses.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"393-407"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11361348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-07-22DOI: 10.1097/CMR.0000000000000992
Joseph B Elmes, Jessica M Davis, Laura W Musselwhite, Zane Chiad, Donald C Moore, Asim Amin
{"title":"Hemophagocytic lymphohistiocytosis induced by dabrafenib-trametinib in a patient with metastatic melanoma: a case report and pharmacovigilance analysis.","authors":"Joseph B Elmes, Jessica M Davis, Laura W Musselwhite, Zane Chiad, Donald C Moore, Asim Amin","doi":"10.1097/CMR.0000000000000992","DOIUrl":"10.1097/CMR.0000000000000992","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) has been reported rarely with BRAF/MEK inhibitor combinations, including dabrafenib/trametinib. Postmarketing pharmacovigilance analyses evaluating outcomes associated with dabrafenib/trametinib-induced HLH are also lacking. Herein, we report a case of dabrafenib/trametinib-induced HLH in a patient with metastatic melanoma. Recovery of HLH-related symptoms was observed following drug discontinuation, supportive care, and corticosteroids. We also conducted a pharmacovigilance analysis of the USA Food and Drug Administration Adverse Event Reporting System (FAERS) to describe postmarketing cases of HLH with dabrafenib/trametinib exposure. There were 50 reports of HLH with dabrafenib/trametinib in FAERS. Most cases occurred in the setting of melanoma ( n = 39; 78%) and most were reported in Europe ( n = 39; 74%). Hospitalization was the most common outcome ( n = 39; 78%) of this adverse event per FAERS. HLH is a rare complication of dabrafenib/trametinib, and clinicians should be aware and monitor for signs of this potentially serious and life-threatening adverse event.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"465-468"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-10-01Epub Date: 2024-08-28DOI: 10.1097/CMR.0000000000000996
{"title":"Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma: Erratum.","authors":"","doi":"10.1097/CMR.0000000000000996","DOIUrl":"10.1097/CMR.0000000000000996","url":null,"abstract":"","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":"34 5","pages":"473"},"PeriodicalIF":1.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-08-01Epub Date: 2024-05-20DOI: 10.1097/CMR.0000000000000975
Mark R Albertini, Cindy L Zuleger, Erik A Ranheim, Oyewale Shiyanbola, Paul M Sondel, Zachary S Morris, Jens Eickhoff, Michael A Newton, Irene M Ong, Rene Welch Schwartz, Rubi Hayim, Ilene D Kurzman, Michelle Turek, David M Vail
{"title":"Administration of intratumoral GD2-directed interleukin-2 immunocytokine and local radiation therapy to activate immune rejection of spontaneous canine melanoma.","authors":"Mark R Albertini, Cindy L Zuleger, Erik A Ranheim, Oyewale Shiyanbola, Paul M Sondel, Zachary S Morris, Jens Eickhoff, Michael A Newton, Irene M Ong, Rene Welch Schwartz, Rubi Hayim, Ilene D Kurzman, Michelle Turek, David M Vail","doi":"10.1097/CMR.0000000000000975","DOIUrl":"10.1097/CMR.0000000000000975","url":null,"abstract":"<p><p>Canine malignant melanoma provides a clinically relevant, large animal parallel patient population to study the GD2-reactive hu14.18-IL-2 immunocytokine as it is similar to human melanoma and expresses GD2. The objectives of this study were to evaluate safety, radiation fractionation, and identify informative biomarkers of an in-situ tumor vaccine involving local radiation therapy plus intratumoral-immunocytokine in melanoma tumor-bearing dogs. Twelve dogs (six dogs/arm) with locally advanced or metastatic melanoma were randomized to receive a single 8 Gy fraction (arm A) or three 8 Gy fractions over 1 week (arm B) to the primary site and regional lymph nodes (when clinically involved) with the single or last fraction 5 days before intratumoral-immunocytokine at 12 mg/m 2 on 3 consecutive days. Serial tumor biopsies were obtained. All 12 dogs completed protocol treatment, and none experienced significant or unexpected adverse events. Evidence of antitumor activity includes one dog with a complete response at day 60, one dog with a partial response at day 60, and four dogs with mixed responses. Histology of serial biopsies shows a variably timed increase in intratumoral lymphocytic inflammation in some dogs. Canine NanoString analyses of serial biopsies identified changes in gene signatures of innate and adaptive cell types versus baseline. There were no significant differences in NanoString results between arm A and arm B. We conclude that intratumoral-immunocytokine in combination with local radiation therapy in canine melanoma is well tolerated and has antitumor activity with the potential to inform clinical development in melanoma patients.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"307-318"},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-08-01Epub Date: 2024-06-07DOI: 10.1097/CMR.0000000000000980
Huasheng Liu, Hong Jiang, Qianqian Shan
{"title":"Reflectance confocal microscopy versus dermoscopy for the diagnosis of cutaneous melanoma: a head-to-head comparative meta-analysis.","authors":"Huasheng Liu, Hong Jiang, Qianqian Shan","doi":"10.1097/CMR.0000000000000980","DOIUrl":"10.1097/CMR.0000000000000980","url":null,"abstract":"<p><p>This meta-analysis aimed to evaluate the comparative diagnostic performance of reflectance confocal microscopy (RCM) and dermoscopy in detecting cutaneous melanoma patients. An extensive search was conducted in the PubMed and Embase databases to identify available publications up to December 2023. Studies were included if they evaluated the diagnostic performance of RCM and dermoscopy in patients with cutaneous melanoma. The quality of the included studies was assessed using the Quality Assessment of Diagnostic Performance Studies (QUADAS-2) tool. A total of 14 articles involving 2013 patients were included in the meta-analysis. The overall sensitivity of RCM was 0.94 [95% confidence interval (CI), 0.87-0.98], while the overall sensitivity of dermoscopy was 0.84 (95% CI, 0.71-0.95). These results suggested that RCM has a similar level of sensitivity compared with dermoscopy ( P = 0.15). In contrast, the overall specificity of RCM was 0.76 (95% CI, 0.67-0.85), while the overall specificity of dermoscopy was 0.47 (95% CI, 0.31-0.63). The results indicated that RCM appears to have a higher specificity in comparison to dermoscopy ( P < 0.01). Our meta-analysis indicates that RCM demonstrates superior specificity and similar sensitivity to dermoscopy in detecting cutaneous melanoma patients. The high heterogeneity, however, may impact the evidence of the current study, further larger sample prospective research is required to confirm these findings.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"355-365"},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-08-01Epub Date: 2024-05-20DOI: 10.1097/CMR.0000000000000981
Alice Indini, Rossana Gueli, Michele Cerati, Erika Rijavec, Marco Parravicini, Sabrina Casagrande, Cristina Rovelli, Paolo Antonio Grossi, Francesco Grossi
{"title":"Cytomegalovirus gastritis as a rare adverse event during combined ipilimumab and nivolumab in a patient with melanoma.","authors":"Alice Indini, Rossana Gueli, Michele Cerati, Erika Rijavec, Marco Parravicini, Sabrina Casagrande, Cristina Rovelli, Paolo Antonio Grossi, Francesco Grossi","doi":"10.1097/CMR.0000000000000981","DOIUrl":"10.1097/CMR.0000000000000981","url":null,"abstract":"<p><p>Immunotherapy has improved survival outcomes of patients with advanced melanoma. Lower gastrointestinal tract immune-related adverse events (irAEs) are common during treatment; however, gastritis is not frequently observed. Herein, we report a case of severe cytomegalovirus (CMV)-related gastritis in a patient treated with ipilimumab and nivolumab for metastatic melanoma. This report presents a 60-year-old woman with stage IV BRAF wild-type melanoma. After the second course of ipilimumab-nivolumab, the patient reported epigastric discomfort after meals, anorexia, and subsequent nausea, vomiting, epigastric pain, and weight loss. Disease staging with PET/CT scan showed very good partial response and diffuse gastroduodenitis. The patient underwent esophagogastroduodenoscopy, showing severe esophageal candidiasis and diffuse hemorrhagic, edematous, and ulcerative mucosa in the whole gastric wall. Biopsies of the gastric wall were obtained. Before receipt of the final pathology report, the patient was empirically started on corticosteroids based on the clinical suspicion of immune-related gastritis, without improvement of symptoms. The hematoxylin-eosin staining demonstrated active gastritis with diffuse nuclear cytopathic viral inclusions in epithelial and interstitial cells; CMV infection was confirmed with immunohistochemical staining. The patient started ganciclovir and fluconazole, with rapid improvement of symptoms. This case presents a rare instance of CMV gastritis in a patient receiving combined anti-PD1 and anti-CTLA4 , in the absence of immune-suppression to manage an irAE. In the case of suggestive symptoms of irAEs, a high index of clinical suspicion is required to rule out concomitant or isolated infective disease. Guidelines for prophylaxis and treatment of these patients are needed, to optimize treatment results.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"386-389"},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141070532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melanoma ResearchPub Date : 2024-08-01Epub Date: 2024-06-07DOI: 10.1097/CMR.0000000000000964
Prisca Bustamante, Jacqueline Coblentz, Christina Mastromonaco, Emma Youhnovska, Hiroaki Ito, Rita Pinto Proença, Cristina Fonseca, Kyle Dickinson, Emily Marcotte, Myriam MacDonald, Ana-Beatriz Toledo-Dias, Sabrina Bergeron, Alicia Goyeneche, Rafaella Atherino Schmidt Andujar, Thupten Tsering, Alexander Laskaris, Eva Jin, Amélie Nadeau, Tiffany Porraccio, Miguel N Burnier, Julia V Burnier
{"title":"Comprehensive clinical imaging, histopathological analysis and liquid biopsy-based surveillance of human uveal melanoma in a prolonged rabbit xenograft model.","authors":"Prisca Bustamante, Jacqueline Coblentz, Christina Mastromonaco, Emma Youhnovska, Hiroaki Ito, Rita Pinto Proença, Cristina Fonseca, Kyle Dickinson, Emily Marcotte, Myriam MacDonald, Ana-Beatriz Toledo-Dias, Sabrina Bergeron, Alicia Goyeneche, Rafaella Atherino Schmidt Andujar, Thupten Tsering, Alexander Laskaris, Eva Jin, Amélie Nadeau, Tiffany Porraccio, Miguel N Burnier, Julia V Burnier","doi":"10.1097/CMR.0000000000000964","DOIUrl":"10.1097/CMR.0000000000000964","url":null,"abstract":"<p><p>Uveal melanoma is the most common intraocular tumor in adults. Our group has previously developed a human uveal melanoma animal model; however, adverse effects caused by the immunosuppressive agent, cyclosporine A, prevented animals from surviving more than 12 weeks. In this study, we tested multiple cyclosporine A doses over an extended disease course up to 20 weeks, providing complete clinical imaging of intraocular tumors, histopathological analysis and liquid biopsy biomarker analysis. Twenty albino rabbits were divided into four groups with different daily cyclosporine A schedules (0-10 mg/kg) and inoculated with human uveal melanoma cell lines, 92.1 or MP41, into the suprachoroidal space. Rabbits were monitored with fundoscopy, ultrasound and optical coherence tomography. Intraocular tumors (macroscopic or microscopic) were detected in all study animals. Tumor size and growth were correlated to cyclosporine A dose, with tumors regressing when cyclosporine A was arrested. All tumors expressed HMB-45 and MelanA; however, tumor size, pigmentation and cell morphology differed in 92.1 vs. MP41 tumors. Finally, across all groups, circulating tumor DNA from plasma and aqueous humor was detected earlier than tumor detection by imaging and correlated to tumor growth. In conclusion, using three clinically relevant imaging modalities (fundoscopy, ultrasonography and optical coherence tomography) and liquid biopsy, we were successfully able to monitor tumor progression in our rabbit xenograft model of human uveal melanoma.</p>","PeriodicalId":18550,"journal":{"name":"Melanoma Research","volume":" ","pages":"285-295"},"PeriodicalIF":1.5,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}