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1.
Clin. transl. oncol. (Print) ; 24(9): 1828–1830, septiembre 2022.
Article in English | IBECS | ID: ibc-JHG-515

ABSTRACT

PurposeTo evaluate the impact of cranial stereotactic radiotherapy (SRT) on overall survival (OS) of melanoma brain metastases (MBM) patients treated with combined nivolumab and ipilimumab (CNI) in a contemporary and real-world setting.Methods/patientsThe study was performed by using TriNetX, a global health network dataset of electronic medical records from patients in 49 healthcare organizations. We queried for patients with specific terms between January 2016 and December 2020 and run a propensity score matching (PSM) analysis. OS was estimated by Kaplan–Meier and log-rank test was applied.ResultsAfter initial query and PSM, 114 patients were selected in each cohort. Median OS was 327 days in CNI and not reached in the CNI + SRT cohort, with OS probability of 54.4 and 40.9%, respectively (log-rank P = .0057). CNI + SRT was associated with significantly decreased mortality (HR, 0.57; 95% CI 0.377-0.853; proportionality P = .0034).ConclusionsThis real-world analysis showed that CNI + SRT led to an improvement in OS compared to CNI. (AU)


Subject(s)
Humans , Brain Neoplasms/secondary , Immunotherapy , Ipilimumab/therapeutic use , Melanoma/pathology , Nivolumab/therapeutic use , Radiosurgery , Retrospective Studies
3.
J Extracell Vesicles ; 11(8): e12234, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35923105

ABSTRACT

Breast cancer cells release a large quantity of biocargo-bearing extracellular vesicles (EVs), which mediate intercellular communication within the tumour microenvironment and promote metastasis. To identify EV-bound proteins related to metastasis, we used mass spectrometry to profile EVs from highly and poorly metastatic breast cancer lines of human and mouse origins. Comparative mass spectrometry indicated that integrins, including αv and ß1 subunits, are preferentially enriched in EVs of highly metastatic origin over those of poorly metastatic origin. These results are consistent with our histopathological findings, which show that integrin αv is associated with disease progression in breast cancer patients. Integrin αv colocalizes with the multivesicular-body marker CD63 at a higher frequency in the tumour and is enriched in circulating EVs of breast cancer patients at late stages when compared with circulating EVs from early-stage patients. With a magnetic bead-based flow cytometry assay, we confirmed that integrins αv and ß1 are enriched in the CD63+ subsets of EVs from both human and mouse highly metastatic cells. By analysing the level of integrin αv on circulating EVs, this assay could predict the metastatic potential of a xenografted mouse model. To explore the export mechanism of integrins into EVs, we performed immunoprecipitation mass spectrometry and identified members of the galectin family as potential shuttlers of integrin αvß1 into EVs. In particular, knockdown of galectin-3, but not galectin-1, causes a reduction in the levels of cell surface integrins ß1 and αv, and decreases the colocalization of these integrins with CD63. Importantly, knockdown of galectin-3 leads to a decrease of integrin αvß1 export into the EVs concomitant with a decrease in the metastatic potential of breast cancer cells. Moreover, inhibition of the integrin αvß1 complex leads to a reduction in the binding of EVs to fibronectin, suggesting that integrin αvß1 is important for EV retention in the extracellular matrix. EVs retained in the extracellular matrix are taken up by fibroblasts, which differentiate into cancer associated fibroblasts. In summary, our data indicate an important link between EV-bound integrin αvß1 with breast cancer metastasis and provide additional insights into the export of integrin αvß1 into EVs in the context of metastasis.


Subject(s)
Breast Neoplasms , Extracellular Vesicles , Animals , Breast Neoplasms/metabolism , Extracellular Vesicles/metabolism , Female , Galectin 3 , Humans , Integrin alphaV , Melanoma , Mice , Receptors, Vitronectin/metabolism , Skin Neoplasms , Tumor Microenvironment
4.
Front Public Health ; 10: 917119, 2022.
Article in English | MEDLINE | ID: mdl-35928495

ABSTRACT

Objective: This study aimed to describe the economic burden of Chinese patients with melanoma in Hunan province of China, and to investigate the factors for hospitalization spending and length of stay (LOS) in patients undergoing melanoma surgery. Methods: Data was extracted from the Chinese National Health Statistics Network Reporting System database in Hunan province during 2017-2019. Population and individual statistics were presented, and nonparametric tests and quantile regression were used to analyze the factors for spending and LOS. Result: A total of 2,644 hospitalized patients with melanoma in Hunan were identified. During 2017-2019, the total hospitalization spending was $5,247,972, and out-of-pocket payment (OOP) was $1,817,869, accounting for 34.6% of the total expenditure. The median spending was $1,123 [interquartile range (IQR): $555-2,411] per capita, and the median LOS was 10 days (IQR: 5-18). A total of 1,104 patients who underwent surgery were further analyzed. The non-parametric tests and quantile regression showed that women were associated with less spending and LOS than men. In general, patients aged 46-65 and those with lesions on the limbs had higher hospitalization costs and LOS than other subgroups. Conclusion: Melanoma causes heavy economic burdens on patients in Hunan, such that the median spending is close to 60% of the averagely annual disposable income. Middle-aged men patients with melanoma on the limbs present the highest financial burden of melanoma.


Subject(s)
Health Expenditures , Melanoma , China/epidemiology , Female , Hospitalization , Humans , Length of Stay , Male , Melanoma/surgery , Middle Aged
5.
Cell Mol Life Sci ; 79(9): 475, 2022 Aug 09.
Article in English | MEDLINE | ID: mdl-35943635

ABSTRACT

In malignant melanoma, a highly aggressive form of skin cancer, many microRNAs are aberrantly expressed contributing to tumorigenesis and progression. Further, deregulation of microRNA processing enzymes, like the miRNA-binding protein Argonaute 2, significantly impacts microRNA function. This study characterizes a novel splice variant of Argonaut 2, AGO2-ex1/3. AGO2-ex1/3 is substantially expressed in different melanoma cell lines and patient-derived tissue samples. It is a mature mRNA, which is translated into an N-terminally truncated Argonaute 2 protein form. Molecular dynamics simulations show that the PAZ, MID, and PIWI domain largely retain their structure in AGO2-ex1/3 and that the truncation of the N-terminus leads to an increased interdomain flexibility. Expression of AGO2-ex1/3 provides a survival advantage for melanoma cells while the knockdown causes significantly reduced proliferation and increases apoptosis. RNA-sequencing revealed that in cells lacking AGO2-ex1/3 expression many miRNA target genes are deregulated, implicating a considerable role of AGO2-ex1/3 for miRNA function. This study inaugurates insights into an important role of a so far unknown splice variant of Argonaute 2 for the miRNA pathway as well as the mechanisms which drive growth and survival of melanoma cells. This knowledge provides the basis for potential new promising therapeutic targets focusing on small RNA-mediated gene regulation in melanoma.


Subject(s)
Melanoma , MicroRNAs , Skin Neoplasms , Apoptosis/genetics , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , Humans , Melanoma/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , RNA Interference , Skin Neoplasms/genetics
6.
J Immunother ; 45(7): 303-306, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35947120

ABSTRACT

Preclinical studies show that ß-adrenergic activation suppresses the immune system and reduces the effectiveness of cancer immunotherapy. As a result, there is considerable interest in using ß-blockers (BBs), a cheap and safe class of medication, in combination with immunotherapy to improve outcomes in cancer. This study is a systematic review and meta-analysis of clinical studies. A comprehensive literature search was performed up to May 2022. Studies were included if they reported hazard ratios (HRs) of overall survival (OS), all-cause mortality or progression-free survival (PFS) associated with BBs in patients with solid organ cancer treated with immunotherapy. Study-specific HRs and 95% confidence intervals were pooled in random effects meta-analyses. Nine studies involving over 6350 patients with melanoma, lung, renal, urothelial, or other solid cancers treated with a range of immunotherapies met the inclusion criteria. Across all studies combined, there was no association between concomitant BB use and OS (HR 0.99, 0.83-1.18) or PFS (HR 0.97, 0.89-1.05). In subgroup analyses, BB use made no difference to OS or PFS in melanoma (OS HR 0.66, 0.33-1.34; PFS HR 0.81, 0.62-1.05) or to OS in lung cancer (OS HR 1.00, 0.49-2.07). In summary, this study found no evidence that BBs enhance immunotherapy effectiveness.


Subject(s)
Lung Neoplasms , Melanoma , Communication , Humans , Immunotherapy/adverse effects , Lung Neoplasms/drug therapy , Melanoma/etiology , Melanoma/therapy , Progression-Free Survival
7.
Immunity ; 55(8): 1336-1339, 2022 Aug 09.
Article in English | MEDLINE | ID: mdl-35947977

ABSTRACT

Fibroblasts strongly impact tumor progression, but whether they prime the pre-metastatic niche is poorly understood. In this issue of Immunity, Gong and Li et al. identify lung-specific immunosuppressive fibroblasts, which are hijacked by breast cancer cells to facilitate metastasis.


Subject(s)
Breast Neoplasms , Lung Neoplasms , Cell Line, Tumor , Female , Fertilizers , Fibroblasts/pathology , Humans , Lung/pathology , Lung Neoplasms/pathology , Melanoma , Neoplasm Metastasis/pathology , Skin Neoplasms , Soil , Tumor Microenvironment
8.
BMJ Case Rep ; 15(8)2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35948362

ABSTRACT

A woman with metastatic melanoma was treated with immunotherapy induction with ipilimumab and nivolumab and radiotherapy to liver metastases. The patient deteriorated shortly thereafter, becoming febrile and hypotensive and requiring admission to the intensie care unit (ICU) for inotrope support. Failure to respond to antibiotics and a negative septic screen prompted further investigation, which ultimately led to a diagnosis of haemophagocytic lymphohistiocytosis (HLH). The patient improved on high dose steroids and was discharged home. Months later, in the context of progressive melanoma, the patient was re-challenged with nivolumab monotherapy and subsequently experienced recurrence of HLH, confirming the aetiology as being immunotherapy related. This case serves as a reminder to consider HLH where there are fevers of unknown origin in an unwell patient receiving immune checkpoint inhibitor therapy and also highlights immunotherapy as a potential cause for HLH, which has rarely been reported in the literature to date.


Subject(s)
Antineoplastic Agents, Immunological , Lymphohistiocytosis, Hemophagocytic , Melanoma , Neoplasms, Second Primary , Antineoplastic Agents, Immunological/adverse effects , Female , Humans , Immune Checkpoint Inhibitors , Immunologic Factors/therapeutic use , Immunotherapy/adverse effects , Ipilimumab/adverse effects , Lymphohistiocytosis, Hemophagocytic/chemically induced , Lymphohistiocytosis, Hemophagocytic/drug therapy , Melanoma/pathology , Neoplasms, Second Primary/drug therapy , Nivolumab/adverse effects
9.
Cell Mol Life Sci ; 79(9): 478, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35948813

ABSTRACT

Melanoma is the most aggressive among all types of skin cancers. The current strategies against melanoma utilize BRAFV600E, as a focal point for targeted therapy. However, therapy resistance developed in melanoma patients against the conventional anti-melanoma drugs hinders the ultimate benefits of targeted therapies. A major mechanism by which melanoma cells attain therapy resistance is via the activation of microphthalmia-associated transcription factor-M (MITF-M), the key transcription factor and oncogene aiding the survival of melanoma cells. We demonstrate that tryptanthrin (Tpn), an indole quinazoline alkaloid, which we isolated and characterized from Wrightia tinctoria, exhibits remarkable anti-tumor activity towards human melanoma through the down-regulation of MITF-M. Microarray analysis of Tpn-treated melanoma cells followed by a STRING protein association network analysis revealed that differential expression of genes in melanoma converges at MITF-M. Furthermore, in vitro and in vivo studies conducted using melanoma cells with differential MITF-M expression status, endogenously or ectopically, demonstrated that the anti-melanoma activity of Tpn is decisively contingent on its efficacy in down-regulating MITF-M expression. Tpn potentiates the degradation of MITF-M via the modulation of MEK1/2-ERK1/2-MITF-M signaling cascades. Murine models demonstrate the efficacy of Tpn in attenuating the migration and metastasis of melanoma cells, while remaining pharmacologically safe. In addition, Tpn suppresses the expression of mutated BRAFV600E and inhibits Casein Kinase 2α, a pro-survival enzyme that regulates ERK1/2 homeostasis in many tumor types, including melanoma. Together, we point to a promising anti-melanoma drug in Tpn, by virtue of its attributes to impede melanoma invasion and metastasis by attenuating MITF-M.


Subject(s)
Melanoma , Microphthalmia-Associated Transcription Factor , Animals , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Melanoma/genetics , Mice , Microphthalmia-Associated Transcription Factor/genetics , Microphthalmia-Associated Transcription Factor/metabolism , Mitogen-Activated Protein Kinase Kinases/metabolism , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/metabolism , Quinazolines
10.
Biochem Biophys Res Commun ; 622: 170-176, 2022 Sep 24.
Article in English | MEDLINE | ID: mdl-35932528

ABSTRACT

Gene expression is tightly regulated by transcription factors (TFs) which play an important role in development and tumorigenesis. Abnormal transcriptional regulation leads to oncogene activation or tumor suppressor inhibition, thus promoting the occurrence and progression of tumors. MYBL2 (alias B-Myb), a ubiquitously expressed transcription factor of the MYB family, is a nuclear protein involved in cell cycle progression and overexpressed and associated with poor patient outcomes in numerous cancer entities. However, the further effectors of the MYBL2 downstream transcriptional network mediating its cancer-promoting properties remain not well elaborated. Here, we systemic investigated the global MYBL2 targets base on ChIP-seq data from melanoma, breast cancer, lung carcinoma, and liver cancer. Functional enrichment and further validation of MYBL2 downstream binding targets on melanoma cells demonstrated that genes in the Ras and ErbB signaling pathways were regulated by MYBL2. Moreover, when integrating breast cancer, lung carcinoma and liver cancer data, we identified HEB, ZEB1 and ASCL1 colocalized on Ras/ErbB signaling gene locus with MYBL2, indicating the regulatory complex on activating oncogenic expression. Taken together, this study provides a reference for a better understanding of the MYBL2 regulatory mechanism in tumorigenesis.


Subject(s)
Breast Neoplasms , Carcinoma , Liver Neoplasms , Lung Neoplasms , Melanoma , Basic Helix-Loop-Helix Transcription Factors/metabolism , Breast Neoplasms/genetics , Carcinogenesis/genetics , Carcinoma/genetics , Cell Cycle Proteins/metabolism , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , Lung Neoplasms/genetics , Melanoma/genetics , Trans-Activators/metabolism , Transcription Factors/metabolism , Zinc Finger E-box-Binding Homeobox 1/genetics , Zinc Finger E-box-Binding Homeobox 1/metabolism
11.
Cell Death Dis ; 13(8): 692, 2022 Aug 08.
Article in English | MEDLINE | ID: mdl-35941108

ABSTRACT

Metastatic malignant melanoma is the deadliest skin cancer, and it is characterised by its high resistance to apoptosis. The main melanoma driving mutations are part of ERK pathway, with BRAF mutations being the most frequent ones, followed by NRAS, NF1 and MEK mutations. Increasing evidence shows that the MST2/Hippo pathway is also deregulated in melanoma. While mutations are rare, MST2/Hippo pathway core proteins expression levels are often dysregulated in melanoma. The expression of the tumour suppressor RASSF1A, a bona fide activator of the MST2 pathway, is silenced by promoter methylation in over half of melanomas and correlates with poor prognosis. Here, using mass spectrometry-based interaction proteomics we identified the Second Mitochondria-derived Activator of Caspases (SMAC) as a novel LATS1 interactor. We show that RASSF1A-dependent activation of the MST2 pathway promotes LATS1-SMAC interaction and negatively regulates the antiapoptotic signal mediated by the members of the IAP family. Moreover, proteomic experiments identified a common cluster of apoptotic regulators that bind to SMAC and LATS1. Mechanistic analysis shows that the LATS1-SMAC complex promotes XIAP ubiquitination and its subsequent degradation which ultimately results in apoptosis. Importantly, we show that the oncogenic BRAFV600E mutant prevents the proapoptotic signal mediated by the LATS1-SMAC complex while treatment of melanoma cell lines with BRAF inhibitors promotes the formation of this complex, indicating that inhibition of the LATS1-SMAC might be necessary for BRAFV600E-driven melanoma. Finally, we show that LATS1-SMAC interaction is regulated by the SMAC mimetic Birinapant, which requires C-IAP1 inhibition and the degradation of XIAP, suggesting that the MST2 pathway is part of the mechanism of action of Birinapant. Overall, the current work shows that SMAC-dependent apoptosis is regulated by the LATS1 tumour suppressor and supports the idea that LATS1 is a signalling hub that regulates the crosstalk between the MST2 pathway, the apoptotic network and the ERK pathway.


Subject(s)
Caspases , Melanoma , Apoptosis , Caspases/metabolism , Hippo Signaling Pathway , Humans , Melanoma/genetics , Melanoma/metabolism , Mitochondria/metabolism , Protein Serine-Threonine Kinases/genetics , Proteomics , Proto-Oncogene Proteins B-raf/metabolism
12.
Cir Cir ; 90(4): 525-528, 2022.
Article in English | MEDLINE | ID: mdl-35944435

ABSTRACT

BACKGROUND: Lymph mapping with sentinel node biopsy is the standard procedure for lymph node staging in patients with cutaneous melanoma with a tumor thickness of 1 mm or greater. Patients who have metastases in sentinel node must undergo complementary lymphadenectomy; however, it has not been shown to improve survival. OBJECTIVE: To know the prevalence in our setting of metastases in the product of complementary lymphadenectomy in patients with metastatic sentinel node. METHOD: Evaluation of a descriptive, retrospective, observational and analytical cohort of patients with metastatic sentinel node submitted to lymphadenectomy. Multivariate analysis of tumor thickness, neural invasion, location, sentinel node number, serum DHL level, lymph nodes dissected and extracapsular spread. RESULTS: 67 patients, 35 women and 32 men with a mean of 66 years, 22% had metastases in lymph nodes from complementary lymphadenectomy, 19% of them with extracapsular spread; no relationship with the Breslow level. Extracapsular spread in the sentinel node, lymphadenectomy time, and perineural invasion in the primary tumor were prognostic factors for non-sentinel node metastasis. CONCLUSIONS: In this series, 22% of the patients with a sentinel node-positive have metastases in the non-sentinel nodes, 19% of them with extracapsular spread, which justifies complementary lymphadenectomy.


ANTECEDENTES: El mapeo linfático con biopsia del ganglio centinela es el procedimiento estándar de estadificación ganglionar en pacientes con melanoma cutáneo con grosor tumoral de 1 mm o mayor. Los pacientes que tienen metástasis en él deben ser sometidos a linfadenectomía complementaria; sin embargo, esta no ha mostrado mejorar la superviviencia. OBJETIVO: Conocer la prevalencia en nuestro medio de metástasis en el producto de linfadenectomía complementaria en pacientes con ganglio centinela metastásico. MÉTODO: Evaluación de una cohorte descriptiva, retrospectiva, observacional y analítica de pacientes con ganglio centinela metastásico sometidos a linfadenectomía, con análisis multivariado de grosor tumoral, invasión neural, localización, número de ganglios centinela, concentración sérica de deshidrogenasa láctica, ganglios disecados en linfadenectomía y ruptura capsular. RESULTADOS: Hubo 67 pacientes (35 mujeres y 32 hombres), con una media de 66 años de edad, en el 22% hubo metástasis en ganglios de linfadenectomía complementaria y en el 19% ruptura capsular; sin relación con el nivel de Breslow. La ruptura capsular en el ganglio centinela, el tiempo de linfadenectomía y la invasión perineural fueron factores pronóstico de metástasis en ganglios no centinela. CONCLUSIONES: En esta serie, el 22% de los pacientes tuvieron metástasis en ganglios no centinela, el 19% de ellos con ruptura capsular, lo cual justifica la linfadenectomía complementaria.


Subject(s)
Melanoma , Skin Neoplasms , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Melanoma/pathology , Neoplasm Staging , Retrospective Studies , Sentinel Lymph Node Biopsy , Skin Neoplasms/pathology
13.
Mol Med Rep ; 26(4)2022 Oct.
Article in English | MEDLINE | ID: mdl-35946460

ABSTRACT

Melanoma is the most aggressive form of skin cancer with the poorest prognosis and its pathogenesis has yet to be fully elucidated. As key factors that regulate cellular homeostasis, both reactive oxygen species (ROS) and autophagy are involved in the development of melanoma, from melanomagenesis to progression and drug resistance. However, the interaction between ROS and autophagy in the etiology and treatment of melanoma is not well characterized. The present review examined the production of ROS and the role of oxidative stress in melanoma, and summarized the role of ROS­mediated autophagy in melanomagenesis and melanoma cell fate decision following treatment with various anticancer drugs. The present findings may lead to a better understanding of the pathogenesis and progression of melanoma, and suggest promising treatment options for this disease.


Subject(s)
Antineoplastic Agents , Melanoma , Antineoplastic Agents/pharmacology , Autophagy , Humans , Melanoma/pathology , Oxidative Stress , Reactive Oxygen Species
14.
ACS Appl Mater Interfaces ; 14(31): 35309-35318, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35913267

ABSTRACT

Systemic administration of immune checkpoint blockade agents can activate the anticancer activity of immune cells; however, the response varies from patient to patient and presents potential off-target toxicities. Local administration of immune checkpoint inhibitors (ICIs) can maximize therapeutic efficacies while reducing side effects. This study demonstrates a minimally invasive strategy to locally deliver anti-programmed cell death protein 1 (anti-PD-1) with shear-thinning biomaterials (STBs). ICI can be injected into tumors when loaded in STBs (STB-ICI) composed of gelatin and silicate nanoplatelets (Laponite). The release of ICI from STB was mainly affected by the Laponite percentage in STBs and pH of the local microenvironment. Low Laponite content and acidic pH can induce ICI release. In a murine melanoma model, the injection of STB-ICI significantly reduced tumor growth and increased CD8+ T cell level in peripheral blood. STB-ICI also induced increased levels of tumor-infiltrating CD4+ helper T cells, CD8+ cytotoxic T cells, and tumor death. The STB-based minimally invasive strategy provides a simple and efficient approach to deliver ICIs locally.


Subject(s)
Immune Checkpoint Inhibitors , Melanoma , Animals , Biocompatible Materials/pharmacology , CD8-Positive T-Lymphocytes , Humans , Mice , T-Lymphocytes, Cytotoxic , Tumor Microenvironment
16.
BMC Med Imaging ; 22(1): 143, 2022 08 09.
Article in English | MEDLINE | ID: mdl-35945505

ABSTRACT

BACKGROUND: Skin cancer continues to be the most frequently diagnosed form of cancer in the U.S., with not only significant effects on health and well-being but also significant economic costs associated with treatment. A crucial step to the treatment and management of skin cancer is effective early detection with key screening approaches such as dermoscopy examinations, leading to stronger recovery prognoses. Motivated by the advances of deep learning and inspired by the open source initiatives in the research community, in this study we introduce Cancer-Net SCa, a suite of deep neural network designs tailored for the detection of skin cancer from dermoscopy images that is open source and available to the general public. To the best of the authors' knowledge, Cancer-Net SCa comprises the first machine-driven design of deep neural network architectures tailored specifically for skin cancer detection, one of which leverages attention condensers for an efficient self-attention design. RESULTS: We investigate and audit the behaviour of Cancer-Net SCa in a responsible and transparent manner through explainability-driven performance validation. All the proposed designs achieved improved accuracy when compared to the ResNet-50 architecture while also achieving significantly reduced architectural and computational complexity. In addition, when evaluating the decision making process of the networks, it can be seen that diagnostically relevant critical factors are leveraged rather than irrelevant visual indicators and imaging artifacts. CONCLUSION: The proposed Cancer-Net SCa designs achieve strong skin cancer detection performance on the International Skin Imaging Collaboration (ISIC) dataset, while providing a strong balance between computation and architectural efficiency and accuracy. While Cancer-Net SCa is not a production-ready screening solution, the hope is that the release of Cancer-Net SCa in open source, open access form will encourage researchers, clinicians, and citizen data scientists alike to leverage and build upon them.


Subject(s)
Melanoma , Skin Neoplasms , Dermoscopy/methods , Humans , Melanoma/diagnostic imaging , Neural Networks, Computer , Skin Neoplasms/diagnostic imaging
17.
Medicine (Baltimore) ; 101(31): e29979, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35945708

ABSTRACT

INTRODUCTION: Mucosal melanoma (MM) is a rare disease, accounting for approximately 1.4% of all melanomas and only 0.03% of all new cancer diagnoses. Traditionally, it has been associated with a poor prognosis, with an overall 5-year survival rate of <25%. Progress in treatment has been hindered by its rarity and lack of evidence. However, studies on the treatment of subcutaneous melanoma with immunotherapy have demonstrated significant improvement in survival rates and have become a core part of oncological strategies. This paper discusses the revision of the evidence for the use of immunotherapy in the head and neck. METHODS: This systematic review was conducted on January 19, 2019. The Medline and Embase databases were searched. In total, 509 articles were collated and screened. Inclusion criteria for the study included treatment-naive cohorts, cohorts with recurrent disease, primary outcomes with overall survival and disease-free survival at 5 years and at the longest follow-up, and studies of adults with MM in whom immunotherapy was reported as a treatment strategy. The exclusion criteria included duplicate papers, anatomical sites other than the head and neck, case reports, and those not published in English. RESULTS: Fifty-two papers out of the 509 collated papers met the inclusion criteria. The results are shown as a comparison of yearly survival rates following different treatment modalities (immunotherapy vs nonimmunotherapy) at 2, 3, and 5 years. It was found that, with immunotherapy, survival rates at all intervals were higher than those without immunotherapy. DISCUSSION: Immunotherapy outcomes in small studies have shown good data for increasing survival rates at yearly intervals in MM of the head and neck. Larger clinical trials are needed to accurately distinguish the efficacy and survival outcomes of immunotherapy when compared with treatment modalities, excluding immunotherapy. However, the ability to perform larger trials is limited by the rarity of MM of the head and neck.


Subject(s)
Head and Neck Neoplasms , Melanoma , Adult , Disease-Free Survival , Head and Neck Neoplasms/therapy , Humans , Immunotherapy/methods , Melanoma/therapy , Survival Rate
18.
Medicine (Baltimore) ; 101(31): e29473, 2022 Aug 05.
Article in English | MEDLINE | ID: mdl-35945730

ABSTRACT

RATIONALE: The introduction of immune-checkpoint inhibitors (ICPI) in recent years has changed the natural course of many neoplasms. However, patients receiving these medications may present immune-mediated adverse events; management includes temporary or permanent cessation of treatment and corticosteroids, occasionally combined with other immunomodulators. Such immunosuppression, however, also has numerous adverse events and even if it is effective in controlling toxicity, it delays immunotherapy reinitiation, as current evidence requires dose tapering to ≤10 mg prednisolone equivalent before rechallenge. Enteric-coated budesonide is a corticosteroid formulation acting primarily to the intestine and liver, as a result of its extensive first-pass hepatic metabolism. PATIENT CONCERNS: A 76-year-old woman treated with ipilimumab for metastatic melanoma presented with abdominal pain, vomiting, and diarrhea for at least the previous 4 days. Laboratory tests, among others, revealed elevated aminotransferases and C-reactive protein. During hospitalization, the patient also developed fever. DIAGNOSIS: The patient, after excluding alternative causes of aminotransferase elevation, was diagnosed with grade 3 ipilimumab-associated hepatotoxicity. INTERVENTIONS: Budesonide monotherapy was administered; initial daily dose was 12 mg. OUTCOMES: Fever subsided after the first dose of budesonide. Aminotransferases returned to normal-near normal approximately 1 month after the first dose of budesonide. After this point, daily dose was reduced by 3 mg every 2 weeks, with no clinical or biochemical relapse. CONCLUSIONS: This case of ICPI hepatitis is, to our knowledge, the first in the literature managed with budesonide monotherapy. Therefore, budesonide may be a potentially attractive option for the management of ICPI-associated liver injury in cases where corticosteroid treatment is necessary due to its safety profile and the potential advantage of faster immunotherapy rechallenge in selected patients without requiring dose tapering, in contrast to systemically acting corticosteroids. Clinical trials should be conducted in the future in order to validate or refute these findings.


Subject(s)
Chemical and Drug Induced Liver Injury , Lymphoma, Follicular , Melanoma , Aged , Budesonide/adverse effects , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/etiology , Female , Humans , Immune Checkpoint Inhibitors , Ipilimumab/adverse effects , Lymphoma, Follicular/drug therapy , Melanoma/pathology , Transaminases
19.
J Int Med Res ; 50(8): 3000605221116758, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35942551

ABSTRACT

OBJECTIVE: This study aimed to investigate the correlation between KAI1 (CD82) and miR-633 expression and prognosis and survival time of patients with melanoma combined with colorectal cancer (CRC). METHODS: Clinical and follow-up data of melanoma and CRC patients were recorded, and the expression levels of KAI1 and miR-633 were detected. Pearson chi-square tests and Spearman correlation coefficient were used to analyze the relationship between prognosis and related parameters in these patients. Cox proportional risk regression and receiver operating characteristic curve analyses were used. RESULTS: Overall, 195 patients were included. KAI1 and miR-633 expression levels were significantly correlated with the prognosis of patients with melanoma combined with CRC. Spearman correlation analysis showed that the expression levels of KAI1 and miR-633 were significantly correlated with the prognosis of patients. Multivariate Cox regression analysis suggested that low expression levels of KAI1 and high expression levels of miR-633 indicated shorter survival time for patients. CONCLUSIONS: KAI1 expression was significantly correlated with melanoma and CRC patient prognosis. When KAI1 expression levels were low, the patient survival time was poor.


Subject(s)
Colorectal Neoplasms , Melanoma , MicroRNAs , Biomarkers, Tumor/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Humans , Kangai-1 Protein/analysis , Kangai-1 Protein/genetics , Kangai-1 Protein/metabolism , Melanoma/genetics , Melanoma/pathology , MicroRNAs/genetics , Neoplasm Staging , Prognosis
20.
World J Surg Oncol ; 20(1): 256, 2022 Aug 10.
Article in English | MEDLINE | ID: mdl-35948931

ABSTRACT

Gastrointestinal melanoma is usually metastatic in origin, and primary melanoma within the gastrointestinal tract is rarely reported. Colon is considered to be an extremely uncommon site for primary melanomas. Herein, we report the first case of a large primary melanoma within the transverse colon with gastric involvement. CT scan found a mass within the colon, which seemed to connect to the gastric antrum. Esophagogastroscopy showed an ulcerated lesion in the greater curvature of the stomach. Subsequent colonoscopy identified a large ulcerated lesion rendering significant stenosis of the transverse colon. Biopsy following colonoscopy indicated a diagnosis of colonic melanoma based on pathological findings, which identified submucosal malignant melanoma cells with epithelioid and spindle features. Immunohistochemical stains were positive for S-100, HMB-45, Vimentin, and Melan-A. A series of clinical and imaging examinations revealed no suspicious primary cutaneous or ocular lesions. The diagnosis of primary colonic melanoma was considered. A radical transverse colectomy with subtotal gastrectomy were conducted subsequently. Definite diagnosis of primary colonic melanoma can be established after ruling out the possibility of being a metastasis from other more common primary sites. Primary colonic melanomas are a challenge to diagnose and often need a multidisciplinary treatment approach, including surgery, BRAF-targeted therapy, and immunotherapy.


Subject(s)
Colonic Neoplasms , Melanoma , Colectomy , Colonic Neoplasms/pathology , Humans , Melanoma/surgery , S100 Proteins
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