A rheumatological catastrophe: case of amyopathic juvenile dermatomyositis

Juvenile-onset amyopathic dermatomyositis is rare variant of juvenile-onset dermatomyositis (JDM), characterized by the hallmark cutaneous features of dermatomyositis without clinical or laboratory evidence of muscle disease. Dermatomyositis with positive anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody has a distinct phenotype associated with small hand joint arthritis, mucocutaneous ulceration in the absence of muscle involvement. In this article, we describe a 5-year-old child presented with mucocutaneous manifestations with no muscle weakness who responded to immunosuppressive therapy.

Recurrence factors in patients with cutaneous melanoma and positive sentinel lymph node treated in a single reference unit in Buenos Aires / Factores de recurrencia en pacientes con melanoma cu táneo y ganglio centinela positivo

Abstract Introduction : Although therapeutic advances have improved results of cutaneous melanoma (CM), senti nel node-positive patients still have substantial risk to develop recurrent disease. We aim to investigate prog nostic indicators associated with disease recurrence in positive-sentinel lymph node biopsy (SLNB) patients in a Latin-American population. Methods : Retrospective analysis of CM patients and positive-SLNB (2010-2020). Patients were divided into two groups: Group A (completion lymph node dissection, CLND), Group B (active surveillance, AS). Association of demographics, tumor data and SLN features with recurrence-free (RFS), distant metastases-free (DMFS) and melanoma specific (MSS) survival was analyzed. Results : Of 205 patients, 45 had a positive SLNB; 27(60%) belonged to Group A and 18(40%) to Group B. With a median follow-up of 36 months, 16 patients (12 in Group A and 4 in Group B) developed recurrent dis ease and estimated 5-yr RFS at any site was 60% (CI95%, 0.39 - 0.77) (44.5% in CLND group vs. 22% in AS group; P = 0.20). Estimated 5-yr DMFS and MSS: 65% (CI 95%, 0.44 - 0.81) and 73% (CI 95%, 0.59 - 0.89) with no differ ences between groups (p = 0.41 and 0.37, respectively). Independent predictors of poorer MSS were extranodal extension (ENE) and MaxSize > 2 mm of melanoma deposit in SLN. Factors independently associated with DMFS: Breslow depth > 2 mm, ENE, number (≥ 2) of posi tive SN and CLND status. Conclusion : Primary tumor and SN features in mela noma provide important prognostic information that help optimize prognosis and clinical management. AS is now the preferred approach for most positive-SLNB CM patients.

Resumen Introducción : Si bien los avances terapéuticos han permitido mejorar los resultados del melanoma cutáneo (MC), los pacientes con ganglio centinela positivo (BGCP) aún tienen riesgo elevado de desarrollar recurrencia de la enfermedad. Nuestro objetivo fue investigar in dicadores pronósticos asociados a dicho evento en una población latinoamericana. Métodos : Análisis retrospectivo de pacientes con MC y BGCP entre 2010-2020. Los pacientes se dividieron en 2 grupos: Grupo A (linfadenectomía terapéutica) y Grupo B (Vigilancia activa, VA). Se analizaron datos demográficos, tumorales y características del GC junto con sobrevida-libre de recurrencia (SLR), libre de metástasis a distancia (SLMD) y específica de melanoma (SEM). Resultados : De 205 pacientes, 45 presentaron BGCP; 27 (60%) perteneció al Grupo A y 18 (40%) al Grupo B. Con una mediana de seguimiento de 36 meses, 16 pa cientes (12 en Grupo A y 4 en Grupo B) desarrollaron enfermedad recurrente con una SLR a 5 años de 60% (IC95%: 0.39-0.77) (44.5% en Grupo B vs. 22% en Grupo A; P = 0.20). Las SLMD y SEM estimadas a 5 años fueron de 65% (CI 95%, 0.44 - 0.81) y 73% (CI 95%, 0.59 - 0.89) sin diferencias entre ambos grupos (p = 0.41 y 0.37, respec tivamente). Los predictores independientes de peor SEM fueron: extensión extranodal (ENE) y MaxSize > 2mm de depósito tumoral en GC. Los factores asociados de forma independiente con SLMD fueron Breslow >2mm, ENE, número (≥ 2) de GC positivos y el status (positividad) de la linfadenectomía. Conclusión : Características del tumor primario y del GC brindan información importante que ayuda a optimi zar el pronóstico y manejo clínico de los pacientes con MC. La VA es actualmente el abordaje de elección para la mayoría de los pacientes con BGCP.

Anal mucosal melanoma presenting as per rectal bleed: a case report

Anorectal mucosal melanoma is a rare, malignant and aggressive tumor that usually presents late. It primarily arises from the melanocytes but can also arise from the mucosal surface. It also carries poor survival rates. Early diagnosis of the disease and prompt treatment is necessary. Overall 5-year survival rate for anal melanoma is below 10%. We present a case of a 77 years old male patient who presented with chief complaints of per rectal bleeding and decreased appetite. Patient’s symptoms were initially confused for benign conditions like hemorrhoids. He was diagnosed with anal mucosal melanoma on per rectal biopsy. Patient’s radiological investigations including PET scan and MRCP were suggestive of liver and lung metastasis. In view of the advanced stage of the disease, the decision was taken to treat the patient conservatively. He was started on imatinib therapy and a regular follow up was kept and palliative care was provided.

Melanoma mucoso de la cavidad oral: Reporte de caso

El melanoma mucoso (MM) es un subtipo raro de malignidad que surge de la transformación maligna de los melanocitos. EL MM representa el 1% de todos los casos de melanoma, siendo un subtipo agresivo y con mal pronóstico, con supervivencia global a 5 años de 10-20%. El Melanoma mucoso de la cavidad oral corresponde al 0.5% de todos los tumores malignos en la cavidad oral y al 25% de los melanomas mucosos ubicados en cabeza y cuello. Tiene una distribución anatómica de predominio en el tracto sinunasal 70%, cavidad oral 20% y otras ubicaciones como larige y faringe. Algunos probables factores de riesgo descritos son: trauma mecánico crónico, etilismo, tabaquismo, formaldehído, Sin embargo su etiología permanece incierta. Presentamos el caso de una paciente Femenina de 77 años tratada exitosamente mediante maxilectomía inferior y disección selectiva cervical izquierda. (provisto por Infomedic International)

Mucosal melanoma (MM) is a rare subtype of malignancy arising from malignant transformation of melanocytes. MM accounts for 1% of all cases of melanoma, being an aggressive subtype with poor prognosis, with 5-year overall survival of 10-20%. Mucosal melanoma of the oral cavity corresponds to 0.5% of all malignant tumors in the oral cavity and 25% of mucosal melanomas located in the head and neck. It has an anatomical distribution of predominance in the sinonasal tract 70%, oral cavity 20% and other locations such as larynx and pharynx. Some probable risk factors described are chronic mechanical trauma, ethylism, smoking, formaldehyde, however its etiology remains uncertain. We present the case of a 77-year-old female patient successfully treated by inferior maxillectomy and selective left cervical dissection. (provided by Infomedic International)

Tumor maligno de la vaina nerviosa periférica: reporte de un caso / Malignant peripheral nerve sheath tumor, a case report

Resumen El tumor maligno de la vaina nerviosa periférica (TMVNP) es un sarcoma de alto grado de malignidad. Es poco frecuente, agresivo y generalmente se localiza en tronco y miembros inferiores. Se presenta mayormente en pacientes con neurofibormatosis tipo 1, aunque no siempre se encuentra esta asociación. Este tumorcomparte características histológicas e inmunohistoquímicas con el melanoma, lo que puede dificultar el diagnóstico. Presentamos el caso de un paciente con TMVNP, en el cual los hallazgos histológicos iniciales condujeron a un diagnósticoerróneode melanoma.

Abstract Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma. It is rare, aggressive and generally located on the trunk and lower limbs. It occurs in a high percentage of patients with neurofibormatosis type 1, although this association is not always found. This tumor shares histological and immunohistochemical characteristics with melanoma, which can make diagnosis difficult. We present the case of a patient with MPNST, in whom the initial histological findings led to an erroneous diagnosis of melanoma.

Reflectance confocal microscopy - Consensus terminology glossary in Brazilian Portuguese for normal skin, melanocytic and non-melanocytic lesions

Abstract Background: Currently, there is no uniform and official terminology in Portuguese for reflectance confocal microscopy analysis, despite the increasing number of Brazilian dermatologists using this new tool. Objective: To present the terminology in Brazilian Portuguese for the description of reflectance confocal microscopy and establish the first Brazilian consensus on terms related to normal skin and cutaneous tumors. Methods: 10 Brazilian specialists from different institutions and states of Brazil were selected to evaluate the best corresponding terms in Portuguese for normal skin, melanocytic and non-melanocytic tumors. The terms used were translated from international consensuses in the English language. The modified Delphi method was used to create the consensus in 3 steps. Results: The terms considered the most appropriate in the Portuguese language to describe the findings of normal skin, melanocytic and non-melanocytic lesions in the reflectance confocal microscopy analysis were presented. Study limitations: The limitations of the present study include the number of participants and limited regional representation (only two of the five Brazilian regions were represented). Conclusion: This Brazilian consensus represents an opportunity for dermatologists and physicians specializing in cutaneous oncology to become familiar with reflectance confocal microscopy, propagating the technique in clinical and research environments to stimulate national and international publications on this subject.

Caracterización histológica del melanoma cutáneo en reportes de patología en la ciudad de Cali, 2016-2021 / Histological characterization of cutaneous melanoma in pathology reports in the city of Cali, 2016-2021

Introducción. El melanoma es la proliferación maligna de melanocitos asociado a un comportamiento agresivo. El objetivo de este estudio fue determinar las variables histológicas del melanoma cutáneo. Métodos. Estudio observacional retrospectivo, transversal descriptivo, realizado con reportes de patologías de pacientes con diagnóstico de melanoma cutáneo en un laboratorio de patología en Cali, Colombia, entre 2016-2021. Se incluyeron las variables edad, sexo, localización, subtipo, espesor de Breslow, ulceración, márgenes, mitosis, invasión linfovascular, neurotrofismo, regresión tumoral, nivel de Clark e infiltración tumoral por linfocitos. Resultados. Se obtuvieron 106 reportes y fueron excluidos 54 por duplicación. Se incluyeron 52 registros, la media de edad fue de 61 años, con una mayor frecuencia de mujeres (55,8 %). De los 33 casos donde se especificó el subtipo histológico, el más frecuente fue el de extensión superficial (66,6 %), seguido del acral lentiginoso (18,1 %) y nodular con (15,2 %). La localización más frecuente fue en extremidades (61,5 %). El espesor de Breslow más común fue IV (34,6 %) y el nivel de Clark más frecuente fue IV (34,6 %). La ulceración estuvo en el 40,4 %. El subtipo nodular fue el de presentación más agresiva, donde el 100 % presentaron espesor de Breslow IV. Conclusiones. El subtipo de melanoma más común en nuestra población fue el de extensión superficial; el segundo en frecuencia fue el subtipo acral lentiginoso, que se localizó siempre en extremidades. Más del 50 % de los melanomas tenían espesor de Breslow mayor o igual a III, lo que impacta en el pronóstico.

Background. Melanoma is the malignant proliferation of melanocytes associated with aggressive behavior. The objective of this study was to determine the histological variables of cutaneous melanoma. Methods. Observational, cross-sectional, descriptive, retrospective study carried out with reports of pathologies with a diagnosis of cutaneous melanoma in a pathology laboratory in Cali between 2016-2021. The variables were age, sex, location, subtype, Breslow thickness, ulceration, margins, mitosis, lymphovascular invasion, neurotropism, tumoral regression, Clark level and tumor infiltration by lymphocytes. Results. One hundred and six reports were obtained and 54 were excluded due to duplication. A descriptive analysis was made on the 52 records that were included, the mean age was 61 years, with a higher frequency in women with 55.8%. Of the 33 cases where the histological subtype was specified, the most frequent was superficial extension with 66.6%, followed by acral lentiginous with 18.1% and nodular with 15.2%. The most frequent location was in the extremities (61.5%); the most common Breslow was IV (34.6%), and the most frequent Clark was IV (34.6%). Ulceration was in 40.4%. The nodular subtype was the most aggressive presentation where 100% presented Breslow IV. Conclusions. The most common subtype of melanoma was that of superficial extension. In our population, the second most frequent was the acral lentiginous subtype, which was always located on the extremities. More than 50% of the melanomas had Breslow greater than or equal to III, which affects the prognosis.

Study on the Effect of Liuwei Dihuang Pills on Regulating the Antigen Cross-Presenting Ability of Dendritic Cells by Interfering with Gap Junctional Communication Function / 广州中医药大学学报

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Regulatory Effect and Mechanism of Yichang Sanjie Granules on Intestinal Flora and Immune Function in Mice with Colon Cancer / 广州中医药大学学报

Objective To observe the regulating effect and mechanism of Yichang Sanjie Granules on intestinal flora and immune function in mice with colon cancer.Methods Sixty mice were randomly divided into six groups,i.e.,the normal group,the model group,the low-,medium-and high-dose groups of Yichang Sanjie Granules,and the overexpression of melanoma absent gene 2(AIM2)plasmid(pcDNA-AIM2)intervention group,with 10 mice in each group.Colorectal cancer model was prepared by oxidized azomethine(AOM)/dextran sulfate sodium(DSS)induction method in all groups except normal group.After drug administration,the survival curves of mice in each group were plotted and the tumor volume was calculated;serum levels of immunoglobulin(Ig)G,IgM,interleukin(IL)-1β and IL-18 were detected by enzyme-linked immunosorbent assay(ELISA);peripheral blood levels of CD3+,CD4+,CD8+ T cells were detected by flow cytometry;the splenic index was determined;Hematoxylin-eosin(HE)staining was used to observe the pathological changes in colon tissues;16S-rDNA intestinal flora sequencing was used to detect the α-diversity of intestinal flora and the structure of intestinal flora communities;and protein immunoblotting(Wetsern Blot)was used to detect the protein expressions of AIM2,apoptosis-associated speckled-like protein containing a CARD(ASC),and cystatinase-1(caspase-1)in colon tissues.Results Compared with the normal group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the model group were significantly decreased,and the tumor volume,serum levels of IL-1β and IL-18,peripheral blood level of CD8+,and splenic index were significantly increased(all P＜0.05),and the HE staining results showed the characteristic manifestations of colon cancer;compared with the model group,the survival rate,serum levels of IgG and IgM,peripheral blood levels of CD3+ and CD4+ and CD4+/CD8+ ratio,protein expression levels of colon tissue AIM2,ASC and caspase-1 in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group were significantly increased,and the tumor volume,serum levels of IL-1β and IL-18,level of peripheral blood CD8+,and splenic index were significantly decreased(all P＜0.05),and the HE staining results showed the manifestations of colon cancer were improved.Compared with the normal group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group,and Ruminiclostridium in the model group were significantly decreased,while the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was increased in the model group(P＜0.05);compared with the model group,the Observed index,Chao1 index,Shannon index,the relative abundance of Bacteroidetes,Proteobacteria,Muribaculaceae,Lachnospiraceae-NK4A136group and Ruminiclostridium were significantly increased,and the relative abundance of Firmicutes,Actinobacteria,Patescibateria,Lactobacillus,Odoribacter,Alistipes,Ruminococcaceae-uncultured and Bacteroides was decreased in the low-,medium-and high-dose groups of Yichang Sanjie Granules and the pcDNA-AIM2 group(all P＜0.05).Conclusion Yichang Sanjie Granules can increase autoimmunity and improve intestinal flora structure in mice with colon cancer,and its mechanism is related to the activation of AIM2 inflammatory vesicles.

A Review of Research Status for the Anti-tumor Mechanism of Shanxian Granule / 广州中医药大学学报

In this article,the mechanism of Shanxian Granule in inhibiting liver cancer,lung cancer,sarcoma,melanoma and other tumors was reviewed,with a view to providing a theoretical basis for the clinical research of Shanxian Granules in the treatment of malignant tumors.Shanxian Granule are the pure Chinese medicine preparation for counteracting malignant tumor developed by the Oncology Research Team of Shaanxi University of Chinese Medicine on the basis of the theory of traditional Chinese medicine syndrome differentiation and treatment combined with decades of clinical experience as well as the achievements of modern pharmacological research.Shanxian Granule are mainly composed of Crataegi Fructus,Agrimoniae Herba,Panacis Quinquefolii Radix,Curcumae Rhizoma,Testudinis Carapax et Plastrum,Trionycis Carapax,Corydalis Rhizoma,and Polyporus,and have the actions of benefiting qi and nourishing yin,supporting healthy-qi and cultivating the essence,activating blood and removing stasis,and eliminating swelling and counteracting cancer.The compatibility of Shanxian Granule embodies the principle of supporting healthy-qi but avoiding maintaining pathogens,and eliminating pathogens but avoiding injuring healthy-qi.The granules can effectively inhibit the growth and metastasis of liver cancer,lung cancer,sarcoma,melanoma and other tumors both in vivo and in vitro,alleviate the clinical symptoms of tumor patients,and improve their prognosis.The anti-tumor mechanism of Shanxian Granules is related to the enhancement of body immune function,inhibition of tumor cell proliferation,enhancement of tumor cell apoptosis,inhibition of tumor cell invasion and metastasis as well as the tumor angiogenesis.

Effect and mechanism of Sitravatinib combined with Niraparib on proliferation,apoptosis and autophagy in mucosal melanoma cell lines / 基础医学与临床

Objective To investigate the effect of anti-angiogenic drug Sitravatinib combined with poly(adenosine diphosphate[ADP]-ribose)polymerase inhibitor(PARPi)Niraparib on mucosal melanoma cell lines and its possible mechanism.Methods The CCK8 assay was used to detect the maximal half inhibitory concentration(IC50)of Sitravatinib and Niraparib targeting at mucosal melanoma(MM)cell lines.CompuSyn was used to detect the Combination Index(CI)in different concentrations of the two drugs.Flow cytometry was used to detect the effect of drugs on cell apoptosis.Colony formation assay was used to detect the effect of drugs on cell proliferation.Western blot was used to detect the protein expressions and RT-qPCR was used to detect mRNA expression.Results CI values was respectively 0.19 and 0.15 for Sitravatinib(2 μmol/L)in combination with Niraparib(20 μmol/L)in a human vaginal maligant melanoma cell line(HMVII)and a metastasis inguinal lymph node of vulvar malignant melanoma cell line(GAK).Compared with the control group and single-drug groups,the cell proliferation of the combination group was significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).The cell apoptosis rate was signifi-cantly increased(P＜0.01 or P＜0.001).The protein and mRNA expression of apoptosis-related biomarkers signifi-cantly increased(P＜0.001);In addition,the protein and mRNA expression of cell autophagy biomarkers signifi-cantly increased(P＜0.01 or P＜0.001).The protein expression of DNA damage marker significantly increased.Moreover,compared with the control group,The expression of radiation sensitive protein 51(RAD51)recombinase in the Sitravatinib single-drug group and combination group significantly reduced.As the dose of Sitravatinib gradu-ally increased up to 2 μmol/L,the protein and mRNA expression of RAD51 both significantly reduced(P＜0.05 or P＜0.01),the mRNA expression of BRCA1 and BRCA2 also significantly reduced(P＜0.05 or P＜0.01 or P＜0.001).Conclusions Sitravatinib combined with Niraparib inhibits the proliferation of mucosal melanoma cells,induces cell apoptosis and promotes autophagy.The mechanism is potentially related to the inhibition of ho-mology-dependent recombination repairs(HRR).

Expert consensus on cryoablation therapy of oral mucosal melanoma / 实用口腔医学杂志

Cryoablation therapy with explicit anti-tumor mechanisms and histopathological manifestations has a long history.A large number of clinical practice has shown that cryoablation therapy is safe and effective,making it an ideal tumor treatment method in theory.Previously,its efficacy and clinical application were constrained by the limitations of refrigerants and refrigeration equipment.With the development of the new generation of cryoablation equipment represented by argon helium knives,significant progress has been made in refrigeration efficien-cy,ablation range,and precise temperature measurement,greatly promoting the progression of tumor cryoablation technology.This consensus systematically summarizes the mechanism of cryoablation technology,indications for oral mucosal melanoma(OMM)cryotherapy,clinical treatment process,adverse reactions and management,cryotherapy combination therapy,etc.,aiming to provide reference for carrying out the standardized cryoablation therapy of OMM.

Therapeutic effect of recombinant Salmonella SGN1 on melanoma in mice and its mechanism of action / 中国生物制品学杂志

@#Objective To investigate the therapeutic effect of recombinant Salmonella SGN1 on murine melanoma model and the action mechanism,and to provide reference for clinical treatment of melanoma with SGN1.Methods The recombinant Salmonella SGN1 and control strain VNP-V were co-cultured with mouse melanoma B16F10 cells,and the effect of SGN1 on the proliferation of B16F10 cells in vitro was detected by cell counting method. The B16F10 subcutaneous tumor transplantation model in mice was constructed. SGN1,VNP-V and PBS(control group)were injected into the tumor at a single dose,with five mice in each group,and the inhibitory effect of SGN1 on tumor growth was observed. The pathological changes of tumor tissues in mice were observed by HE staining. The distribution of SGN1 in tumor tissues was observed by plate counting. Flow cytometry was used to evaluate the proportion of infiltrating T lymphocyte subsets. The expression of T-cell marker CD3 was detected by immunofluorescence and immunohistochemical staining.Results Compared with the control group,recombinant Salmonella SGN1 significantly inhibited the proliferation of mouse melanoma B16F10 cells in vitro(t = 6. 935,P < 0. 01). In tumor-bearing mice,SGN1 was tumor-targeted and significantly inhibited the growth of B16F10 subcutaneous transplanted melanoma in mice(t = 7. 566,P < 0. 001). HE staining showed that SGN1 significantly induced the necrosis of subcutaneous transplanted melanoma cells in mice. The results of immunofluorescence,immunohistochemistry and flow cytometry confirmed that SGN1 significantly increased tumor-infiltrating CD3~+ T-cells(t = 11. 91,8. 873 and 5. 300,respectively,each P < 0. 01).Conclusion The recombinant Salmonella SGN1 can significantly inhibit the proliferation of B16F10 cells and exert anti-tumor effects by promoting tumor cell necrosis and elevating CD3~+ tumor-infiltrating T-cells,providing a theoretical basis for the clinical treatment of melanoma with SGN1

Nodular melanoma in a 53-year-old male with glioblastoma multiforme: A rare case report

@#Although melanoma only accounts for 1% of skin cancers, it is responsible for most skin cancer deaths. Glioblastoma multiforme, a high-grade astrocytoma, is the most aggressive and devastating primary brain tumor. These two diseases remain to be the biggest therapeutic challenge in both specialties of dermatology and neuro-oncology. A 53-year-old Filipino male who presented with a 2-year history of generalized dark brown and black patches on the body developed weakness and numbness of the left extremities. Biopsy and immunohistochemical staining of the skin revealed nodular melanoma with adjacent regressing melanoma. Biopsy of the intracranial mass showed glioblastoma multiforme. One month after the partial excision of the intracranial mass, the patient expired due to brain herniation. Nodular melanoma and glioblastoma multiforme may occur concomitantly in a patient. A review of the literature suggests a shared genetic predisposition. Its existence carries a poor prognosis and requires early detection to start aggressive treatment.

Research progress of m6A methylation modification in ocular diseases / 国际眼科杂志(Guoji Yanke Zazhi)

N6-methyladenosine(m6A), the most common, abundant, and conserved RNA modification in eukaryotic cells, regulates RNA splicing, stability, output, degradation and translation through m6A methyltransferase, m6A demethylase, and m6A methylated binding proteins. Recent studies have found that abnormal m6A methylation may mediate a variety of pathological processes in eyes and participate in the occurrence and development of metabolic, inflammatory, degenerative ocular diseases and ocular tumors, such as diabetic retinopathy, cataract, age-related macular degeneration and uveal melanoma. This review aims to summarize the roles of m6A methylation modification in ocular cells and ocular diseases, elucidate the potential molecular mechanisms of m6A methylation in ocular diseases, so as to encourage innovative approaches in the treatment of these ocular diseases.

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Inhibitory effect of curcumin on malignant biological behavior and Wnt/β-catenin pathway of uveal melanoma cells / 中华实验眼科杂志

Objective:To explore the inhibitory effect of curcumin on the malignant biological behavior of uveal melanoma (UM) and its possible mechanism.Methods:M23 cells were cultured in curcumin medium with different concentrations (0, 20, 40 and 80 μmol/L) for 48 hours, respectively.The morphological changes of cells were observed under an inverted microscope.The cell survival rate was detected by the cell counting kit-8 (CCK-8) method.The apoptosis, colony formation, migration and invasion of cells were detected by flow cytometry, plate clone formation experiment, cell scratch experiment and Transwell assay, respectively.The relative expressions of genes related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin and matrix metallo proteinase 9 ( MMP-9) mRNA in cells were detected by real-time fluorescence quantitative PCR.The relative expressions of proteins related to Wnt/β-catenin pathway, c-Myc, Cyclin D1, Survivin, MMP-9 and β-catenin, glycogen synthase kinase 3β (GSK-3β), phosphorylated GSK-3β (p-GSK-3β) and axis inhibition protein 2 (Axin2) proteins were detected by Western blot.Another 20 female BALB/c mice were selected and injected with M23 cell suspension under the subcutaneous fat pad in the left posterior abdomen to establish the in vivo M23 transplanted tumor model.The mice successfully modeled were randomly divided into model group, low-dose curcumin group, medium-dose curcumin group and high-dose curcumin group according to the random number table method, which was intraperitoneally injected with 0, 10, 20 and 40 mg/kg curcumin physiological saline solution respectively.After a continuous injection for 30 days, the subcutaneous tumor was stripped and weighed.The animal experiment process followed the 3Rs principle of animal research and was approved by the Laboratory Animal Ethics Committee of Inner Mongolia Baotou Steel Hospital (No.2021MER-023). Results:The cell survival rate, the number of colony formation, the apoptosis rate, the cell invasion rate and the cell migration rate were (100.00±0.00)%, 128.67±9.18, (1.33±0.29)%, (89.76±4.57)% and 148.33±8.18 in 0 μmol/L curcumin group, (83.78±4.59)%, 100.33±8.73, (14.53±2.04)%, (65.43±3.70)% and 125.33±7.41 in 20 μmol/L curcumin group, (66.09±3.92)%, 58.67±6.55, (27.23±3.56)%, (34.83±2.19)% and 73.67±6.34 in 40 μmol/L curcumin group, and (47.16±3.63)%, 31.67±4.92, (44.73±4.36)%, (18.82±1.99)% and 45.67±5.31 in 80 μmol/L curcumin group.There were statistically significant differences in the survival rate, colony formation number, cell apoptosis rate, migration rate and invasion rate of M23 cells among the four groups ( F=125.321, 97.941, 72.516, 277.097, 139.006; all at P<0.001). With the increase of curcumin concentration, the cell survival rate, colony formation number, cell migration rate and cell invasion number decreased obviously, and the cell apoptosis rate increased obviously, and the pairwise comparisons showed significant differences (all at P<0.05). With the increase of curcumin concentration, the relative expression levels of c-Myc, Cyclin D1, Survivin, MMP-9 mRNA and proteins, β-catenin and p-GSK-3β proteins decreased significantly, while the relative expression level of Axin2 protein increased significantly, showing significant differences in pairwise comparisons (all at P<0.05). The tumor tissue weight of mice decreased with the increase of curcumin dosage, and the pairwise comparisons were statistically significant (all at P<0.05). Conclusions:Curcumin can inhibit the proliferation, migration, invasion and other malignant biological behaviors of UM M23 cells, inhibit tumor growth and promote cell apoptosis.Its mechanism may be related to blocking the activation of Wnt/β-catenin pathway.

Effect of interfering hsa_circ_0103232 on the biological behavior of uveal melanoma cells / 中华实验眼科杂志

Objective:To investigate the effects of interference with hsa_circ_0103232 on the proliferation, metastasis, cell cycle and apoptosis of melanoma cells C918 and MUM2B.Methods:C918 and MUM2B cells were cultured, and the interference efficiency of three small interfering RNA (siRNA) targeting hsa_circ_0103232 were detected by real-time fluorescent quantitative polymerase chain reaction (PCR).The siRNA with the highest interference efficiency was used for the following experiment.Both C918 and MUM2B cells were divided into negative control transfection (siCtrl) groups and interference (si-hsa_circ_0103232) groups.The proliferation of C918 and MUM2B cells was examined by cell counting kit-8 (CCK-8) assay and cell colony formation assay.The migration of C918 and MUM2B cells was determined by transwell assay.The cell cycle distribution and apoptosis rate of C918 and MUM2B cells were detected by flow cytometry.The localization of hsa_circ_0103232 in C918 and MUM2B cells was tested by the fluorescence in situ hybridization experiment (FISH).Results:The results of real-time quantitative PCR showed that among the three siRNAs targeting hsa_circ_0103232, si-hsa_circ_0103232#1 had the best effect, which reduced the expression level of gene in C918 and MUM2B cells to 0.263±0.016 and 0.469±0.028, significanthy lower than 1.013±0.008 and 1.004±0.108 of control groups (both at P<0.001).CCK-8 results showed that the proliferation activity of C918 and MUM2B cells was significantly lower in si-hsa_circ_0103232 group than in siCtrl group after transfection (all at P<0.05).The results of cell clone formation showed that the clone number of C918 and MUM2B cells in si-hsa_circ_0103232 group were 12±1 and 45±7, which were significantly lower than 28±4 and 83±3 in siCtrl group, and the differences were statistically significant ( t=4.93, 7.42; both at P<0.05).Transwell assay results showed that the number of migrating C918 and UM2B cells in si-hsa_circ_0103232 group were 4±1 and 24±2, respectively, which were significantly lower than 37±12 and 57±3 in siCtrl group, and the differences were statistically significant ( t=3.91, 10.80; both at P<0.05).The results of flow cytometry showed that compared with siCtrl group, the proportion of G1 phase cells in C918 and MUM2B cells in si-hsa_circ_0103232 group increased significantly, the proportion of G2/M phase cells decreased significantly, and the number of apoptotic cells increased significantly (all at P<0.05).FISH experiment showed that hsa_circ_0103232 was located in the nuclei of C918 and MUM2B cells. Conclusions:Interference with hsa_circ_0103232 can inhibit the proliferation, migration and cycle progression of C918 and MUM2B cells, and promote their apoptosis.hsa_circ_0103232 may be a new therapeutic target for uveal melanoma.

Expression of miR-205 and miR-367 in cutaneous malignant melanoma tissue and their clinical significances / 局解手术学杂志

Objective To study the expression of miR-205 and miR-367 in cutaneous malignant melanoma(CMM)tissue and their relationships with clinicopathological characteristics and prognosis.Methods The tumor tissues from 85 patients with CMM who were admitted to our hospital from May 2013 to December 2019 were selected as the CMM group,and the nevus tissue samples from 80 patients with benign pigmented nevi who were treated in our hospital during the same period were selected as the control group.The expression level of miR-205 and miR-367 of two groups were detected by qRT-PCR.The clinical and pathological data of patients with CMM were collected,and the relationships between the expression of miR-205 and miR-367 and clinicopathological characteristics were analyzed.Kaplan-Meier was used to draw the survival curves of patients 3 years after surgery,and the survival rate of patients was analyzed by Log-rank test.The influencing factors of prognosis was analyzed by COX proportional risk regression model.Results The expression level of miR-205 of patients in the CMM group was lower than that in the control group,and the expression level of miR-367 was higher than that in the control group(P<0.05).The proportions of patients with ulceration,high clinical stage,tumor invasion,low KPS score,thick primary lesion,high Clark grade,lymph node metastasis in the miR-205 low-expression group were higher than those in the miR-205 high-expression group(P<0.05),the proportions of patients with the above indexes in the miR-367 high-expression group were higher than those in the miR-367 low-expression group(P<0.05).Patietns were followed up for 3 years,with a median time of 28.3 months,and 1 case was lost to followed-up.The Kaplan-Meier survival curve showed that the 3-year survival rate of patients in the miR-205 high-expression group was higher than that in the miR-205 low-expression group(P<0.05),and the 3-year survival rate of patients in the miR-367 low-expression group was higher than that in the miR-367 high-expression group(P<0.05).COX multivariate regression analysis showed that the high clinical stage,low KPS score,high Clark grade,lymph node metastasis,and high expression of miR-367 were the risk factors for prognosis of patients,while high expression of miR-205 was a protective factor(P<0.05).Conclusion Low expression of miR-205 and high expression of miR-367 in CMM tissue are associated with ulceration,high clinical stage,tumor invasion,low KPS score,thick primary lesion,high Clark grade,lymph node metastasis,and poor prognosis.These two indicators may serve as potential biomarkers for prognostic evaluation in CMM patients.

Safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma:Meta-analysis / 中国免疫学杂志

Objective:To analyze the safety and efficacy of PD-1 inhibitors versus chemotherapy or ipilimumab in advanced melanoma.Methods:PubMed,CNKI,VIP and Wanfang databases were searched to collect randomised controlled trials of PD-1 inhibi-tors in treatment of advanced melanoma.The search time was from the establishment of the database to May 1,2022.Two reviewers independently screened the literature,extracted data,and assessed risk of bias of included studies.Meta-analysis was performed using RevMan5.4 and STATA16 software.Results:A total of 7 studies were included.Meta-analysis results show that:①Safety:Compared with chemotherapy,PD-1 inhibitor treatment had fewer adverse events,especially in the blood system;compared with ipilimumab alone,PD-1 inhibitor combined with ipilimumab had more adverse events,especially liver function indicators;there was no signifi-cant difference in the incidence of total adverse events between PD-1 inhibitor monotherapy and ipilimumab monotherapy.②Efficacy:The PFS,OS and ORR of PD-1 inhibitor versus chemotherapy or ipilimumab were HR=0.54,95%CI(0.45,0.62),P<0.05,HR= 0.69,95%CI(0.58,0.80),P=0.03 and OR=3.16,95%CI(2.59,3.86),P<0.05,respectively.Conclusion:PD-1 inhibitors have good efficacy in treatment of advanced melanoma,while different combination methods and different control treatments may have different efficacy.Limited by the quantity and quality of included studies,more research evidence is needed to support this.