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1.
World J Surg Oncol ; 20(1): 287, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071438

RESUMO

BACKGROUND: Primary melanoma of the bladder is extremely rare and has been sporadically reported in case reports. Its incidence, diagnosis, treatment, and outcomes are still unclear. CASE PRESENTATION: We report a 67-year-old female patient who presented with hematuria and was diagnosed with primary melanoma of the bladder by transurethral resection. No distant metastasis was detected by fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT). After a multidisciplinary discussion, the patient received laparoscopic radical resection of the bladder tumor. There was no tumor recurrence or distant metastasis after 15 months of follow-up. CONCLUSION: Primary melanoma of the bladder is easily confused with urothelium carcinoma in morphology. The immunohistochemical is crucial in diagnosis. Because of a lack of in-depth understanding of primary melanoma of the bladder, the "gold standard" treatment has not been set. We would like to provide some rare information about it and discuss the proper treatment strategy for this rare disease.


Assuntos
Melanoma , Neoplasias da Bexiga Urinária , Idoso , Feminino , Humanos , Melanoma/patologia , Melanoma/cirurgia , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia
2.
Biomed Res Int ; 2022: 4864485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072469

RESUMO

Introduction: The purpose of this study is to use deep learning and machine learning to learn and classify patients with cutaneous melanoma with different prognoses and to explore the application value of deep learning in the prognosis of cutaneous melanoma patients. Methods: In deep learning, VGG-19 is selected as the network architecture and learning model for learning and classification. In machine learning, deep features are extracted through the VGG-19 network architecture, and the support vector machine (SVM) model is selected for learning and classification. Compare and explore the application value of deep learning and machine learning in predicting the prognosis of patients with cutaneous melanoma. Result: According to receiver operating characteristic (ROC) curves and area under the curve (AUC), the average accuracy of deep learning is higher than that of machine learning, and even the lowest accuracy is better than that of machine learning. Conclusion: As the number of learning increases, the accuracy of machine learning and deep learning will increase, but in the same number of cutaneous melanoma patient pathology maps, the accuracy of deep learning will be higher. This study provides new ideas and theories for computational pathology in predicting the prognosis of patients with cutaneous melanoma.


Assuntos
Aprendizado Profundo , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Prognóstico , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia
3.
Comput Intell Neurosci ; 2022: 6138490, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072725

RESUMO

One of the most prevalent diseases that can be initially identified by visual inspection and further identified with the use of dermoscopic examination and other testing is skin cancer. Since eye observation provides the earliest opportunity for artificial intelligence to intercept various skin images, some skin lesion classification algorithms based on deep learning and annotated skin photos display improved outcomes. The researcher used a variety of strategies and methods to identify and stop diseases earlier. All of them yield positive results for identifying and categorizing diseases, but proper disease categorization is still lacking. Computer-aided diagnosis is one of the most crucial methods for more accurate disease detection, although it is rarely used in dermatology. For Feature Extraction, we introduced Spectral Centroid Magnitude (SCM). The given dataset is classified using an enhanced convolutional neural network; the first stage of preprocessing uses a median filter, and the final stage compares the accuracy results to the current method.


Assuntos
Melanoma , Dermatopatias , Inteligência Artificial , Dermoscopia/métodos , Humanos , Melanoma/patologia , Pele/patologia
4.
J Int Adv Otol ; 18(5): 455-458, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36063100

RESUMO

Mucosal melanoma originating from the eustachian tube is very rare, and only 15 cases were reported so far. In this study, we report a case of mucosal melanoma from the eustachian tube which was surgically managed, followed by chemoradiotherapy. A 53-year-old man presented with a history of recurrent idiopathic hemotympanum and a dark red mass in the nasopharynx protruding from the eustachian tube orifice. Under an impression of mucosal melanoma from the eustachian tube, en-bloc surgical removal was performed using the infratemporal fossa approach type C combined with a transnasal endoscopic approach followed by postoperative chemoradiotherapy. However, the disease progressed to lung metastasis, and the patient died of the disease at 13 months postoperatively. The presenting case showed a poor progression despite a margin-free surgical resection followed by chemoradiotherapy. Additional trial of new treatment options is necessary to improve the poor prognosis.


Assuntos
Neoplasias da Orelha , Tuba Auditiva , Melanoma , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Endoscopia , Tuba Auditiva/cirurgia , Humanos , Masculino , Melanoma/patologia , Melanoma/radioterapia , Pessoa de Meia-Idade
6.
Clin. transl. oncol. (Print) ; 24(9): 1828–1830, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-206268

RESUMO

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)


Assuntos
Humanos , Neoplasias Encefálicas/secundário , Imunoterapia , Ipilimumab/uso terapêutico , Melanoma/patologia , Nivolumabe/uso terapêutico , Radiocirurgia , Estudos Retrospectivos
7.
Medicine (Baltimore) ; 101(35): e30471, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107519

RESUMO

Early diagnosis of malignant melanoma is critical for effective treatment and reduced patient mortality. However, current clinical and histological variables show limited accuracy in diagnosis. Serum or urine level of 5-S-cysteinyldopa (5-S-CD) is a commonly used melanoma biomarker in Japan owing to its increased sensitivity compared with other melanoma markers. However, its use as a diagnostic marker has shown some limitations. Therefore, here we examined the combination of 5-S-CD with melanoma inhibitory activity, which showed sensitivity in detecting melanoma comparable with that of 5-S-CD, and interleukin-8, a cytokine linked with melanoma progression, in a cohort of Japanese patients with melanoma. Our results revealed that the triple combination of 5-S-CD, melanoma inhibitory activity, and interleukin-8 showed high diagnostic accuracy in detecting melanoma compared with each of the individual factors. Importantly, the triple marker showed specificity and utility in detecting early-stage melanoma. Our results suggest the utility of the triple marker as a diagnostic biomarker for melanoma patients.


Assuntos
Cisteinildopa , Melanoma , Biomarcadores Tumorais , Citocinas , Humanos , Interleucina-8 , Melanoma/patologia , Neoplasias Cutâneas
8.
Medicine (Baltimore) ; 101(35): e30398, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107581

RESUMO

Advanced malignant melanoma (MM) is treated with immune checkpoint inhibitor (ICI) therapy, which often results in several immune-related adverse events. Fulminant type 1 diabetes mellitus (T1DM) is a rare, rapidly progressive, life-threatening disease. Here, we summarize 8 cases of MM with ICI-induced T1DM and describe one case that developed fulminant T1DM due to nivolumab therapy. We retrospectively reviewed patients treated with ICI from 2014 to 2021 at our hospital. The clinical features and risk factors of ICI-induced T1DM were discussed. ICIs were administered to 426 MM patients at our hospital. Among these, nivolumab was administered in 5 cases, pembrolizumab in 1 case, and the combination of nivolumab and ipilimumab in 2 cases. The frequency of ICI-associated T1DM was 1.88%. The mean glycated hemoglobin level at T1DM onset was 8.0 ± 1.0%. Of the patients, 75% were diagnosed with fulminant T1DM, 62.5% developed diabetic ketoacidosis, and 25% had glutamic acid decarboxylase (GAD) antibodies (an early predictive marker for T1DM). The mean interval between the first ICI administration and T1DM development was 201 ± 187 days. The mean duration of resumption was 13 ± 7 days. We should monitor for T1DM development following treatment with ICIs. ICI can be continued to be used to treat MM if insulin therapy successfully controls T1DM. A 67-year-old patient who received adjuvant nivolumab therapy developed fulminant T1DM and thyrotoxicosis 57 days later and tested positive for GAD antibodies. Subsequently, he developed hypophysitis and an isolated adrenocorticotropin deficiency. He continued receiving nivolumab along with self-injected insulin without developing recurrence.


Assuntos
Diabetes Mellitus Tipo 1 , Insulinas , Melanoma , Hormônio Adrenocorticotrópico , Idoso , Diabetes Mellitus Tipo 1/induzido quimicamente , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glutamato Descarboxilase , Hemoglobina A Glicada , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Ipilimumab/efeitos adversos , Masculino , Melanoma/patologia , Nivolumabe/efeitos adversos , Estudos Retrospectivos , Neoplasias Cutâneas
9.
J Transl Med ; 20(1): 419, 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089578

RESUMO

BACKGROUND: This clinical trial evaluated a novel telomerase-targeting therapeutic cancer vaccine, UV1, in combination with ipilimumab, in patients with metastatic melanoma. Translational research was conducted on patient-derived blood and tissue samples with the goal of elucidating the effects of treatment on the T cell receptor repertoire and tumor microenvironment. METHODS: The trial was an open-label, single-center phase I/IIa study. Eligible patients had unresectable metastatic melanoma. Patients received up to 9 UV1 vaccinations and four ipilimumab infusions. Clinical responses were assessed according to RECIST 1.1. Patients were followed up for progression-free survival (PFS) and overall survival (OS). Whole-exome and RNA sequencing, and multiplex immunofluorescence were performed on the biopsies. T cell receptor (TCR) sequencing was performed on the peripheral blood and tumor tissues. RESULTS: Twelve patients were enrolled in the study. Vaccine-specific immune responses were detected in 91% of evaluable patients. Clinical responses were observed in four patients. The mPFS was 6.7 months, and the mOS was 66.3 months. There was no association between baseline tumor mutational burden, neoantigen load, IFN-γ gene signature, tumor-infiltrating lymphocytes, and response to therapy. Tumor telomerase expression was confirmed in all available biopsies. Vaccine-enriched TCR clones were detected in blood and biopsy, and an increase in the tumor IFN-γ gene signature was detected in clinically responding patients. CONCLUSION: Clinical responses were observed irrespective of established predictive biomarkers for checkpoint inhibitor efficacy, indicating an added benefit of the vaccine-induced T cells. The clinical and immunological read-out warrants further investigation of UV1 in combination with checkpoint inhibitors. Trial registration Clinicaltrials.gov identifier: NCT02275416. Registered October 27, 2014. https://clinicaltrials.gov/ct2/show/NCT02275416?term=uv1&draw=2&rank=6.


Assuntos
Melanoma , Telomerase , Humanos , Ipilimumab/farmacologia , Ipilimumab/uso terapêutico , Melanoma/patologia , Microambiente Tumoral , Vacinação
10.
J Immunother Cancer ; 10(9)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36113897

RESUMO

BACKGROUND: Tumor cells modulate host immunity by secreting extracellular vesicles (EV) and soluble factors. Their interactions with myeloid cells lead to the generation of myeloid-derived suppressor cells (MDSC), which inhibit the antitumor function of T and NK cells. We demonstrated previously that EV derived from mouse and human melanoma cells induced immunosuppressive activity via increased expression of programmed cell death ligand 1 (PD-L1) on myeloid cells that was dependent on the heat-shock protein 90α (HSP90α) in EV. Here, we investigated whether soluble HSP90α could convert monocytes into MDSC. METHODS: CD14 monocytes were isolated from the peripheral blood of healthy donors, incubated with human recombinant HSP90α (rHSP90α) alone or in the presence of inhibitors of TLR4 signaling and analyzed by flow cytometry. Inhibition of T cell proliferation assay was applied to assess the immunosuppressive function of rHSP90α-treated monocytes. HSP90α levels were measured by ELISA in plasma of patients with advanced melanoma and correlated with clinical outcome. RESULTS: We found that the incubation of monocytes with rHSP90α resulted in a strong upregulation of PD-L1 expression, whereas reactive oxygen species (ROS) and nitric oxide (NO) production as well as the expression of arginase-1, ectoenzymes CD39 and CD73 remained unchanged. The PD-L1 upregulation was blocked by anti-TLR4 antibodies and a nuclear factor-κB inhibitor. rHSP90α-treated monocytes displayed the downregulation of HLA-DR expression and acquired the resistance to apoptosis. Moreover, these monocytes were converted into MDSC as indicated by their capacity to inhibit T cell proliferation, which was mediated by TLR4 signaling as well as PD-L1 and indoleamine 2,3-dioxygenase (IDO) 1 expression. Higher levels of HSP90α in plasma of patients with melanoma correlated with augmented PD-L1 expression on circulating monocytic (M)-MDSC. Patients with melanoma with high levels of HSP90α displayed shorter progression-free survival (PFS) on the treatment with immune checkpoint inhibitors (ICIs). CONCLUSION: Our findings demonstrated that soluble rHSP90α increased the resistance of normal human monocytes to apoptosis and converted them into immunosuppressive MDSC via TLR4 signaling that stimulated PD-L1 and IDO-1 expression. Furthermore, patients with melanoma with high concentrations of HSP90α displayed increased PD-L1 expression on M-MDSC and reduced PFS after ICI therapy, suggesting HSP90α as a promising therapeutic target for overcoming immunosuppression in melanoma.


Assuntos
Melanoma , Células Supressoras Mieloides , Animais , Arginase/metabolismo , Antígeno B7-H1/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas de Choque Térmico/uso terapêutico , Humanos , Inibidores de Checkpoint Imunológico , Imunossupressores/uso terapêutico , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Ligantes , Melanoma/patologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo
11.
Medicine (Baltimore) ; 101(35): e29390, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36107612

RESUMO

BACKGROUND: Melanoma is a cancerous tumor that develops from melanocytes in the epidermal basal layer of the skin. It is a fatal skin cancer and the third most common kind of cutaneous tumor. We aim to evaluate the effect of nivolumab in melanoma patients compared with other regimens. METHODS: This meta-analysis included only clinical trials, both randomized and nonrandomized. The main outcomes of interest were the response to treatment, overall survival (OS), progression-free survival, and adverse events. RESULTS: The overall effect estimates favored nivolumab group over the combination of nivolumab plus ipilimumab (HR 3.06, 95% CI 1.70-5.49) and chemotherapy group (HR 3.58, 95% CI 1.63-7.84) after 1 year. Compared to chemotherapy, nivolumab had lower rates of adverse events. CONCLUSION: Nivolumab monotherapy yields high progression-free survival rates and has the same efficacy when combined with ipilimumab in a 1-year OS. However, after 2 and 3 years of follow-up, the combined regimen has more OS rates.


Assuntos
Melanoma , Neoplasias Cutâneas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Humanos , Ipilimumab/efeitos adversos , Melanoma/patologia , Metanálise em Rede , Nivolumabe/efeitos adversos , Neoplasias Cutâneas/patologia
12.
Nat Commun ; 13(1): 5413, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109526

RESUMO

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and hence generating an immunologically hotter microenvironment. We find that inosine directly inhibits UBA6 in tumour cells, and lower level of UBA6 makes the tumour more immunogenic and this is reflected in favourable outcome following ICB therapy in human melanomas. Transplanted mouse melanoma and breast cancer cells with genetic ablation of Uba6 show higher sensitivity to ICB than wild type tumours. Thus, we provide evidence of an inosine-regulated UBA6-dependent pathway governing tumour-intrinsic immunogenicity and hence sensitivity to immune checkpoint inhibition, which might provide targets to overcome ICB resistance.


Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Animais , Terapia Combinada , Humanos , Inosina/farmacologia , Melanoma/patologia , Camundongos , Radioimunoterapia , Microambiente Tumoral , Enzimas Ativadoras de Ubiquitina
13.
Cancer Biol Ther ; 23(1): 336-347, 2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-36112948

RESUMO

Melanoma is a highly aggressive cancer that can metastasize at early stage. The aim of this study is to clarify the role of Piezo1 and its potential mechanism in regulating the malignant phenotypes of melanoma. In the present study, we first showed that Piezo1 was abnormally expressed in melanoma, which accelerated the malignant progression by activating AKT/mTOR signaling. Firstly, we found that Piezo1 was upregulated in melanoma and associated with poor survival. Additionally, Piezo1 knockdown significantly weakened intracellular calcium signal and viability of melanoma cells. Furthermore, Piezo1 knockdown inhibited the transendothelial migration and invasion in vitro, as well as metastasis in vivo. Mechanistically, we found that Piezo1 activated AKT/mTOR signaling to maintain malignant phenotypes of melanoma. Therefore, Piezo1 acts as an oncogene in melanoma cells and provides a novel candidate for melanoma diagnosis and treatment.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas c-akt , Cálcio , Humanos , Canais Iônicos/genética , Melanoma/genética , Melanoma/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
14.
Sci Rep ; 12(1): 15096, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064728

RESUMO

Scalp melanoma (SM) has a worse prognosis than melanoma in other locations likely because of late diagnosis due to hair coverage, difficulties in interpreting dermoscopy findings, and its unique molecular profile. We aimed to describe the clinical, histopathological, molecular, and dermoscopic patterns of SM and its relation to androgenetic alopecia/elastosis at the tumor site. Through a retrospective cross-sectional study, we identified all SM diagnosed at the A.C.Camargo Cancer Center between 2008 and 2018. In all, 48 SM were analyzed: 45.8% of which exhibited moderate/severe androgenetic alopecia and 54.1% exhibited elastosis. Androgenetic alopecia/elastosis at the site of the SM was associated with older age (p < 0.001), chronic sun damage (p < 0.001), lentigo maligna subtype (p = 0.029), and photodamaged dermoscopic pattern (p < 0.001). Additionally, 41 cases were evaluated with a 14-gene panel: 53.7% displayed mutations and 46.3% were wild-type. BRAF mutations were most common (77%), with BRAF V600K being more frequent (50%) than BRAF V600E (31.2%). The NF1 gene was evaluated in 40 samples, of which 20% exhibited mutations. SM presents differently in areas covered by hair compared to in areas with androgenetic alopecia. Patients without alopecia may have higher Breslow thickness due to late diagnosis because of hair concealment. The high frequency of detrimental mutations can also explain the poor prognosis of SM.


Assuntos
Alopecia , Melanoma , Proteínas Proto-Oncogênicas B-raf , Couro Cabeludo , Alopecia/genética , Alopecia/patologia , Estudos Transversais , Dermoscopia , Humanos , Melanoma/genética , Melanoma/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Couro Cabeludo/patologia
15.
Eur J Cancer ; 174: 251-260, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36067618

RESUMO

PURPOSE: Since molecular assays are not accessible to all uveal melanoma patients, we aim to identify cost-effective prognostic tool in risk stratification using machine learning models based on routine histologic and clinical variables. EXPERIMENTAL DESIGN: We identified important prognostic parameters in a discovery cohort of 164 enucleated primary uveal melanomas from 164 patients without prior therapies. We then validated the prognostic prediction of top important parameters identified in the discovery cohort using 80 uveal melanomas from the Tumor Cancer Genome Atlas database with available gene expression prognostic signature (GEPS). The performance of three different survival analysis models (Cox proportional hazards (CPH), random survival forest (RSF), and survival gradient boosting (SGB)) was compared against GEPS using receiver operating curves (ROC). RESULTS: In all three selection methods, BAP1 status, nucleoli size, age, mitotic rate per 1 mm2, and ciliary body infiltration were identified as significant overall survival (OS) predictors; and BAP1 status, nucleoli size, largest basal tumor diameter, tumor-infiltrating lymphocyte density, and tumor-associated macrophage density were identified as significant progression-free survival (PFS) predictors. ROC plots for the median survival time point showed that significant parameters in SGB studied model can predict OS better than GEPS. For PFS, SGB model performed similarly to GEPS. The time-dependent area under the curve (AUC) showed SGB model performing better than GEPS in predicting OS and metastatic risk. CONCLUSIONS: Our study shows that routine histologic and clinical variables are adequate for patient risk stratification in comparison with not readily accessible GEPS.


Assuntos
Melanoma , Neoplasias Uveais , Humanos , Aprendizado de Máquina , Melanoma/patologia , Prognóstico , Transcriptoma , Neoplasias Uveais/genética , Neoplasias Uveais/patologia
16.
Front Immunol ; 13: 952220, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052068

RESUMO

Introduction: B cells are key regulators of immune responses in melanoma. We aimed to explore differences in the histologic location and activation status of B cell follicles in sentinel lymph nodes (SLN) of melanoma patients. Methods: Flow cytometry was performed on fresh tumor draining lymph nodes (LN). Paraffin slides from a separate cohort underwent NanoString Digital Spatial Profiling (DSP)®. After staining with fluorescent markers for CD20 (B cells), CD3 (T cells), CD11c (antigen presenting cells) and a nuclear marker (tumor) was performed, regions of interest (ROI) were selected based on the location of B cell regions (B cell follicles). A panel of 68 proteins was then analyzed from the ROIs. Results: B cell percentage trended higher in patients with tumor in LN (n=3) compared to patients with nSLN (n=10) by flow cytometry. B cell regions from a separate cohort of patients with tumor in the (pSLN) (n=8) vs. no tumor (nSLN) (n=16) were examined with DSP. Within B cell regions of the SLN, patients with pSLN had significantly higher expression of multiple activation markers including Ki-67 compared to nSLN patients. Among 4 patients with pSLN, we noted variability in arrangement of B cell follicles which were either surrounding the tumor deposit or appeared to be infiltrating the tumor. The B cell follicle infiltrative pattern was associated with prolonged recurrence free survival. Conclusion: These data suggest a role for B cell follicles in coordinating effective adaptive immune responses in melanoma when low volume metastatic disease is present in tumor draining LN.


Assuntos
Melanoma , Neoplasias Cutâneas , Biologia , Humanos , Excisão de Linfonodo , Metástase Linfática , Melanoma/patologia , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia
17.
Front Immunol ; 13: 914612, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072600

RESUMO

Yutao Wang, China Medical University, ChinaThe tumor microenvironment (TME) has been shown to impact the prognosis of tumors in patients including cutaneous melanoma (CM); however, not all components of TME are important. Given the aforementioned situation, the functional immune cell contents correlated with CM patient prognosis are needed to optimize present predictive models and reflect the overall situation of TME. We developed a novel risk score named core tumor-infiltrating immune cell score (cTICscore), which showed certain advantages over existing biomarkers or TME-related signatures in predicting the prognosis of CM patients. Furthermore, we explored a new gene signature named cTILscore-related module gene score (cTMGs), based on four identified TME-associated genes (GCH1, GZMA, PSMB8, and PLAAT4) showing a close correlation with the cTICscore, which was generated by weighted gene co-expression network analysis and least absolute shrinkage and selection operator analysis to facilitate clinical application. Patients with low cTMGs had significantly better overall survival (OS, P = 0.002,< 0.001, = 0.002, and = 0.03, respectively) in the training and validating CM datasets. In addition, the area under the curve values used to predict the immune response in four CM cohorts were 0.723, 0.723, 0.754, and 0.792, respectively, and that in one gastric cohort was 0.764. Therefore, the four-gene signature, based on cTICscore, might improve prognostic information, serving as a predictive tool for CM patients receiving immunotherapy.cutaneous melanoma, tumor microenvironment, prognosis, immunotherapy, cTICscore.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Imunoterapia , Melanoma/genética , Melanoma/patologia , Melanoma/terapia , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Microambiente Tumoral/genética
18.
Cell Commun Signal ; 20(1): 141, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096820

RESUMO

Breast cancer is the most common cancer in females, and to date, the mortality rate of breast cancer metastasis cannot be ignored. The metastasis of breast cancer is a complex, staged process, and the pattern of metastatic spread is not random. The pre-metastatic niche, as an organ-specific home for metastasis, is a favourable environment for tumour cell colonization. As detection techniques improve, the role of the pre-metastatic niche in breast cancer metastasis is being uncovered. sEVs (small extracellular vesicles) can deliver cargo, which is vital for the formation of pre-metastatic niches. sEVs participate in multiple aspects of creating a distant microenvironment to promote tumour invasion, including the secretion of inflammatory molecules, immunosuppression, angiogenesis and enhancement of vascular permeability, as well as regulation of the stromal environment. Here, we discuss the multifaceted mechanisms through which breast cancer-derived sEVs contribute to pre-metastatic niches. In addition, sEVs as biomarkers and antimetastatic therapies are also discussed, particularly their use in transporting exosomal microRNAs. The study of sEVs may provide insight into immunotherapy and targeted therapies for breast cancer, and we also provide an overview of their potential role in antitumour metastasis. Video Abstract.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Melanoma , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Comunicação Celular , Vesículas Extracelulares/patologia , Feminino , Humanos , Melanoma/patologia , Neoplasias Cutâneas , Microambiente Tumoral
19.
Urologiia ; (4): 56-59, 2022 Sep.
Artigo em Russo | MEDLINE | ID: mdl-36098591

RESUMO

A rare case of primary renal pelvis melanoma in 47-year-old man is presented in the article. Before surgery a patient was considered to have metastatic urothelial carcinoma. A diagnosis of malignant melanoma was based on immunophenotyping and detection of intracellular melanin pigment both in pelvis tumor and lung metastasis. The primary localization in the pelvis was proven by the presence of scattered melanocytes within urothelium.The patient had no previous history ofskin or mucosa melanoma. This is the sixth case of renal pelvis melanoma published in PubMed.


Assuntos
Carcinoma de Células de Transição , Melanoma , Neoplasias Cutâneas , Neoplasias da Bexiga Urinária , Carcinoma de Células de Transição/patologia , Humanos , Pelve Renal/diagnóstico por imagem , Pelve Renal/patologia , Pelve Renal/cirurgia , Masculino , Melanoma/diagnóstico , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Neoplasias da Bexiga Urinária/patologia
20.
Int J Mol Sci ; 23(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36077308

RESUMO

Regardless of the significant improvements in treatment of melanoma, the majority of patients develop resistance whose mechanisms are still not completely understood. Hence, we generated and characterized two melanoma-derived cell lines, primary WM793B and metastatic A375M, with acquired resistance to the RAF inhibitor vemurafenib. The morphology of the resistant primary WM793B melanoma cells showed EMT-like features and exhibited a hybrid phenotype with both epithelial and mesenchymal characteristics. Surprisingly, the vemurafenib-resistant melanoma cells showed a decreased migration ability but also displayed a tendency to collective migration. Signaling pathway analysis revealed the reactivation of MAPK and the activation of the PI3K/AKT pathway depending on the vemurafenib-resistant cell line. The acquired resistance to vemurafenib caused resistance to chemotherapy in primary WM793B melanoma cells. Furthermore, the cell-cycle analysis and altered levels of cell-cycle regulators revealed that resistant cells likely transiently enter into cell cycle arrest at the G0/G1 phase and gain slow-cycling cell features. A decreased level of NME1 and NME2 metastasis suppressor proteins were found in WM793B-resistant primary melanoma, which is possibly the result of vemurafenib-acquired resistance and is one of the causes of increased PI3K/AKT signaling. Further studies are needed to reveal the vemurafenib-dependent negative regulators of NME proteins, their role in PI3K/AKT signaling, and their influence on vemurafenib-resistant melanoma cell characteristics.


Assuntos
Melanoma , Proteínas Proto-Oncogênicas B-raf , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Indóis/farmacologia , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/patologia , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Vemurafenib/farmacologia , Vemurafenib/uso terapêutico
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