Search results for: canine melanoma

Authors: Shabnam Abdi, Behzad Toosi

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Background: Melanoma is the most lethal type of malignant skin cancer in humans and dogs since it spreads rapidly throughout the body. Despite significant advances in treatment, cancer at an advanced stage has a poor prognosis. Hence, more effective treatments are needed to enhance outcomes with fewer side effects. Erythropoietin-producing hepatocellular receptors are the largest family of receptor tyrosine kinases and are divided into two subfamilies, EphA and EphB, both of which play a significant role in disease, especially cancer. Due to their association with proliferation and invasion in many aggressive types of cancer, Eph receptor tyrosine kinases (Eph RTKs) are promising cancer therapy molecules. Because these receptors have not been studied in canine melanoma, we investigated how EphA2 influences survival and tumorigenicity of melanoma cells. Methods: Expression of EphA2 protein in canine melanoma cell lines and human melanoma cell line was evaluated by Western blot. Melanoma cells were transduced with lentiviral particles encoding Eph-targeting shRNAs or non-silencing shRNAs (control) for silencing the expression of EphA2 receptor, and silencing was confirmed by Western blotting and immunofluorescence. The effect of siRNA treatment on cellular proliferation, colony formation, tumorsphere assay, invasion was analyzed by Resazurin assay Matrigel invasion assay, respectively. Results: Expression of EphA2 was detected in canine and human melanoma cell lines. Moreover, stably silencing EphA2 by specific shRNAs significantly and consistently decreased the expression of EphA2 protein in both human and canine melanoma cells. Proliferation, colony formation, tumorsphere and invasion of melanoma cells were significantly decreased in EphA2 siRNA-treated cells compared to control. Conclusion: Our data provide the first functional evidence that the EphA2 receptor plays a critical role in the malignant cellular behavior of melanoma in both human and dogs.

Keywords: ephA2, targeting, melanoma, human, canine

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Simona Perga, Chiara Beltramo, Floriana Fruscione, Isabella Martini, Federica Cavallo, Federica Riccardo, Paolo Buracco, Selina Iussich, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari, Paola Modesto

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Introduction: Human and canine melanoma have common clinical, histologic characteristics making dogs a good model for comparative oncology. The identification of specific genes and a better understanding of the genetic landscape, signaling pathways, and tumor–microenvironmental interactions involved in the cancer onset and progression is essential for the development of therapeutic strategies against this tumor in both species. In the present study, the differential expression of genes in spontaneously occurring canine melanoma and in paired normal tissue was investigated by targeted RNAseq. Material and Methods: Total RNA was extracted from 17 canine malignant melanoma (CMM) samples and from five paired normal tissues stored in RNA-later. In order to capture the greater genetic variability, gene expression analysis was carried out using two panels (Qiagen): Human Immuno-Oncology (HIO) and Mouse-Immuno-Oncology (MIO) and the miSeq platform (Illumina). These kits allow the detection of the expression profile of 990 genes involved in the immune response against tumors in humans and mice. The data were analyzed through the CLCbio Genomics Workbench (Qiagen) software using the Canis lupus familiaris genome as a reference. Data analysis were carried out both comparing the biologic group (tumoral vs. healthy tissues) and comparing neoplastic tissue vs. paired healthy tissue; a Fold Change greater than two and a p-value less than 0.05 were set as the threshold to select interesting genes. Results and Discussion: Using HIO 63, down-regulated genes were detected; 13 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Eighteen genes were up-regulated, 14 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Using the MIO, 35 down regulated-genes were detected; only four of these were down-regulated, also comparing neoplastic sample vs. paired healthy tissue. Twelve genes were up-regulated in both types of analysis. Considering the two kits, the greatest variation in Fold Change was in up-regulated genes. Dogs displayed a greater genetic homology with humans than mice; moreover, the results have shown that the two kits are able to detect different genes. Most of these genes have specific cellular functions or belong to some enzymatic categories; some have already been described to be correlated to human melanoma and confirm the validity of the dog as a model for the study of molecular aspects of human melanoma.

Keywords: animal model, canine melanoma, gene expression, spontaneous tumors, targeted RNAseq

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Authors: Stefan Bradu, Daniel Siegel, Jameson Loyal, Andrea Leaf, Alana Kurtti, Usha Alapati, Jared Jagdeo

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Compared with all other variants of nodular melanoma, patients with polypoid nodular melanoma have the lowest 5-year survival rate. The pathophysiology and management of polypoid melanoma are scarcely reported in the literature. Although surgical excision is the cornerstone of melanoma management, treatment of polypoid melanoma is complicated by several negative prognostic factors, including early metastasis. This report demonstrates the successful treatment of a rapidly developing red nodular polypoid melanoma with metastasis using surgery and adjuvant nivolumab in a SARS-CoV-2-positive patient who delayed seeking care due to the COVID-19 pandemic. In addition to detailing the successful treatment approach, the immunosuppressive effects of SARS-2-CoV and its possible contribution to the rapid progression of polypoid melanoma are discussed. This case highlights the complex challenges of melanoma diagnosis and management during the COVID-19 pandemic.

Keywords: covid-19, dermatology, immunotherapy, melanoma, nivolumab

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Authors: Chuan Yin

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Cancer stem cells (CSCs) represent a subpopulation of cancer cells that possess the characteristics associated with normal stem cells. CD133 is a phenotype of melanoma CSCs responsible for melanoma metastasis and drug resistance. Although adriamycin (ADR) is commonly used drug in melanoma therapy, but it is ineffective in the treatment of melanoma CSCs. In this study, we constructed CD133 antibody conjugated ADR immunoliposomes (ADR-Lip-CD133) to target CD133+ melanoma CSCs. The results showed that the immunoliposomes possessed a small particle size (~150 nm), high drug encapsulation efficiency (~90%). After 72 hr treatment on the WM266-4 melanoma tumorspheres, the IC50 values of the drug formulated in ADR-Lip-CD133, ADR-Lip (ADR liposomes) and ADR are found to be 24.42, 57.13 and 59.98 ng/ml respectively, suggesting that ADR-Lip-CD133 was more effective than ADR-Lip and ADR. Significantly, ADR-Lip-CD133 could almost completely abolish the tumorigenic ability of WM266-4 tumorspheres in vivo, and showed the best therapeutic effect in WM266-4 melanoma xenograft mice. It is noteworthy that ADR-Lip-CD133 could selectively kill CD133+ melanoma CSCs of WM266-4 cells both in vitro and in vivo. ADR-Lip-CD133 represent a potential approach in targeting and killing CD133+ melanoma CSCs.

Keywords: cancer stem cells, melanoma, immunoliposomes, CD133

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Authors: Jack S. Pullman, Daniel Wen, Avinash Sharma, Bert Van Der Werf, Richard Martin

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Background: New Zealand (NZ) melanoma incidence rates are amongst the highest in the world. Previous studies investigating the incidence of melanoma in NZ were performed for the periods 1995 – 1999 and 2000 – 2004 and suggested increasing melanoma incidence rates. Aim: The aim of the study is to provide an up-to-date review of trends in cutaneous melanoma in NZ from the New Zealand Cancer Registry (NZCR) 2010 – 2020. Methods: De-identified data were obtained from the NZCR, and relevant demographic and histopathologic information was extracted. Statistical analyses were conducted to calculate age-standardized incidence rates for invasive melanoma (IM) and melanoma in situ (MIS). Secondary results included Breslow thickness and melanoma subtype analysis. Results: There was a decline in the IM age-standardized incidence rate from 30.4 to 23.9 per 100,000 person-years between 2010 to 2020, alongside an increase in MIS incidence rate from 37.1 to 50.3 per 100,000 person-years. Men had a statistically significant higher IM incidence rate (p <0.001) and Breslow thickness (p <0.001) compared with women. Increased age was associated with a higher incidence of IM, presentation with melanoma of greater Breslow thickness and more advanced T stage. Conclusion: The incidence of IM in NZ has decreased in the last decade and was associated with an increase in MIS incidence over the same period. This can be explained due to earlier detection, dermoscopy, the maturity of prevention campaigns and/or a change in skin protection behavior.

Keywords: melanoma, incidence, epidemiology, New Zealand

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Authors: Peramachi Sathiyamoorthy, Jacop Gopas, Avi Golan Goldhirsh

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Corchorus olitorius is a leafy vegetable and an industrial crop. The herb has antioxidant, anti inflammatory, and anti-cancer properties. To assay the pharmaceutical properties, aqueous extracts of leaves and seeds from C. olitorius were tested against drug resistant melanoma cell line. The test showed LC50 of the extract was 0.08µg/ml. Aqueous seed extract exhibited higher melanoma inhibiting activity than leaf extract. Dialysis of seed extract showed that the active compound is less than 12 KDa. The compound with <3 KDa MW separated by microconcentration of seed extract showed 70.5 % inhibition of melanoma cell growth. Among the two fractions obtained by Gel filtration with G10 column, the first fraction at 1:2000 dilutions exhibited 100% inhibition of melanoma growth. The compound with Rf value 0.86 (MA4) isolated by TLC separation showed about 98% cytotoxicity against melanoma at 1: 1000 dilutions. Furthermore, HPLC separation of MA4 compound with Superdex 75 column resulted in 4 compounds. Out of 4, one compound showed melanoma inhibition. The active compound is identified by reagent methods as Strophanthidin. Further toxicological and clinical studies will lead to the development of a potential drug to treat drug resistant melanoma.

Keywords: corchorus olitorius, melanoma, drug development, strophanthidin

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Authors: L. B. Naves, L. Almeida

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The development of Drugs Delivery System (DDS), has been wildly investigated in the last decades. In this paper, first a general overview of traditional and modern wound dressing is presented. This is followed by a review of what scientist have done in the medical environment, focusing the possibility to develop a new alternative for DDS through transdermal pathway, aiming to treat melanoma skin cancer.

Keywords: cancer therapy, dressing polymers, melanoma, wound healing

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Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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Authors: Shohreh Ghasemi

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Introduction: Melanoma is a complex disease with various clinical and histopathological features that impact prognosis and treatment decisions. Traditional methods of melanoma prognosis involve manual examination and interpretation of clinical and histopathological data by dermatologists and pathologists. However, the subjective nature of these assessments can lead to inter-observer variability and suboptimal prognostic accuracy. AI, with its ability to analyze vast amounts of data and identify patterns, has emerged as a promising tool for improving melanoma prognosis. Methods: A comprehensive literature search was conducted to identify studies that employed AI techniques for melanoma prognosis. The search included databases such as PubMed and Google Scholar, using keywords such as "artificial intelligence," "melanoma," and "prognosis." Studies published between 2010 and 2022 were considered. The selected articles were critically reviewed, and relevant information was extracted. Results: The review identified various AI methodologies utilized in melanoma prognosis, including machine learning algorithms, deep learning techniques, and computer vision. These techniques have been applied to diverse data sources, such as clinical images, dermoscopy images, histopathological slides, and genetic data. Studies have demonstrated the potential of AI in accurately predicting melanoma prognosis, including survival outcomes, recurrence risk, and response to therapy. AI-based prognostic models have shown comparable or even superior performance compared to traditional methods.

Keywords: artificial intelligence, melanoma, accuracy, prognosis prediction, image analysis, personalized medicine

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Authors: Warda Jabeen, Romaisa Shamim Khan, Osama Shakeel, Ahmed Faraz Bhatti, Raza Hussain

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Background: The worldwide incidence of cutaneous melanoma (CM) has been on the rise over the past few decades. Primary prevention and early treatment remain the focus of management to reduce the burden of disease. This entails identification of risk factors to prompt early diagnosis. In Pakistan, there is a scarcity of clinico-pathological data relating to cutaneous malignant melanoma. Objective: The purpose of this study was to analyze the epidemiological and clinical characteristics of patients presenting with cutaneous malignant melanoma in Pakistan, and to compare the results with other studies. Method: Shaukat Khanum Memorial Cancer Hospital and Research Centre is currently the only dedicated cancer hospital in the country, accepting patients from all over Pakistan. Majority of the patients, however, belong to the northern half of the country. From the recorded data of the hospital, all cutaneous melanoma cases were identified and evaluated. Results: Between 1997 and 2017, a total of 169 cutaneous melanoma patients were registered at Shaukat Khanum. Mean age was 47.5 years. The highest incidence of melanoma was seen in the age group 40-59 years (n=69, 40.8%). Most commonly reported clinical subtype was unspecified melanoma (n=154, 91%). Amongst those in which T stage was reported, the most frequently observed T-stage at presentation was T4 (n=23, 13.6%). With regards to body distribution, in our study CM was seen most commonly in the lower limb including the hip. The yearly incidence of melanoma has increased/remained stable from 2007 to 2017. Conclusion: cutaneous malignant melanoma is a fairly common disease in Pakistan. Patients tend to present at a more advanced stage as compared to patients in developed countries. Identification of risk factors and tumor characteristics is therefore of paramount importance to deal with these patients.

Keywords: epidemiology of cutaneous malignant melanoma, cutaneous malignant melanoma, Pakistan, skin cancer

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Authors: Firas Gerges, Frank Y. Shih

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Malignant melanoma, known simply as melanoma, is a type of skin cancer that appears as a mole on the skin. It is critical to detect this cancer at an early stage because it can spread across the body and may lead to the patient's death. When detected early, melanoma is curable. In this paper, we propose a deep learning model (convolutional neural networks) in order to automatically classify skin lesion images as malignant or benign. Images underwent certain pre-processing steps to diminish the effect of the normal skin region on the model. The result of the proposed model showed a significant improvement over previous work, achieving an accuracy of 97%.

Keywords: deep learning, skin cancer, image processing, melanoma

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Authors: Kemka C. Ihemelandu, Chukwuemeka U. Ihemelandu

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The incidence of melanoma has been increasing rapidly over the past two decades, making melanoma a current public health crisis. Unfortunately, even as screening efforts continue to expand in an effort to ameliorate the death rate from melanoma, there is a need to improve diagnostic accuracy to decrease misdiagnosis. Artificial intelligence (AI) a new frontier in patient care has the ability to improve the accuracy of melanoma diagnosis. Convolutional neural network (CNN) a form of deep neural network, most commonly applied to analyze visual imagery, has been shown to outperform the human brain in pattern recognition. However, there are noted limitations with the accuracy of the CNN models. Our aim in this study was the optimization of convolutional neural network algorithms for the automated diagnosis of melanoma. We hypothesized that Optimal selection of the momentum and batch hyperparameter increases model accuracy. Our most successful model developed during this study, showed that optimal selection of momentum of 0.25, batch size of 2, led to a superior performance and a faster model training time, with an accuracy of ~ 83% after nine hours of training. We did notice a lack of diversity in the dataset used, with a noted class imbalance favoring lighter vs. darker skin tone. Training set image transformations did not result in a superior model performance in our study.

Keywords: melanoma, convolutional neural network, momentum, batch hyperparameter

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Authors: Małgorzata Drzewiecka, Tomasz Śliwiński, Maciej Radek

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The inhibition of histone deacetyles (HDACs) holds promise as a potential anti-cancer therapy because histone and non-histone protein acetylation is frequently disrupted in cancer, leading to cancer initiation and progression. Additionally, histone deacetylase inhibitors (HDACi) such as class I HDAC inhibitor - valproic acid (VPA) have been shown to enhance the effectiveness of DNA-damaging factors, such as cisplatin or radiation. In this study, we found that, using of VPA in combination with talazoparib (BMN-637 – PARP1 inhibitor – PARPi) and/or Dacarabazine (DTIC - alkylating agent) resulted in increased DNA double strand break (DSB) and reduced survival (while not affecting primary melanocytes )and proliferation of melanoma cells. Furthermore, pharmacologic inhibition of class I HDACs sensitizes melanoma cells to apoptosis following exposure to DTIC and BMN-637. In addition, inhibition of HDAC caused sensitization of melanoma cells to dacarbazine and BMN-637 in melanoma xenografts in vivo. At the mRNA and protein level histone deacetylase inhibitor downregulated RAD51 and FANCD2. This study provides that combining HDACi, alkylating agent and PARPi could potentially enhance the treatment of melanoma, which is known for being one of the most aggressive malignant tumors. The findings presented here point to a scenario in which HDAC via enhancing the HR-dependent repair of DSBs created during the processing of DNA lesions, are essential nodes in the resistance of malignant melanoma cells to methylating agent-based therapies.

Keywords: melanoma, hdac, parp inhibitor, valproic acid

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Authors: Lucas Bernardes Naves, Luis Almeida

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The paper includes a review concerning the use of some composites including poly(lactide-co-glycolide) (PGLA), zeolite and Gadopentetic acid (Gd-DTPA) loaded chitosan nanoparticles (Gd-nanoCPs) in order to establish a new alternative for the treatment of Melanoma Skin Cancer. The main goal of this paper it to make a review of what scientist have done in the last few years, as well as to propose a less invasive therapy for skin cancer, by using Hydrocolloid, based on PLGA coated with Gd-nanoCPs for Neutron Capture Therapy.

Keywords: cancer therapy, dressing polymers, melanoma, wound healing

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Authors: Natasha Goh, Sebastian Brown

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Purpose: This case report describes an unusual presentation of uveal melanoma. Method: Case notes, imaging, and histopathological specimen were reviewed for this case report. Result: The patient is a 62-year-old lady of Chinese heritage who had been receiving follow-up at the eye clinic of a tertiary hospital. She had a longstanding history of poor vision in her right eye after sustaining trauma to the eye at age 3. She was found to have a carotid-cavernous sinus fistula in the right eye in 2009 and underwent stenting in China. Unfortunately, this was unsuccessful and resulted in a painful blind eye. She had represented with headaches, worsening eye pain, and ptosis in Sydney in 2016. Her CT angiogram showed a calcified vascular structure in the orbit and globe, and she was offered a digital subtraction angiography by the neurosurgical team, which she ultimately declined. She had since been followed up at the eye clinic for the pthisical eye. Due to chronic ocular pain and recurrent conjunctivitis, the decision was made for an evisceration in 2021. The specimen was sent for routine histopathological examination and returned positive for uveal melanoma. The patient was subsequently referred to a melanoma center for further follow-up, which comprised serial imaging and radiotherapy treatment. Conclusion: Clinicians should bear in mind that uveal melanomas may present in a longstanding phthisical eye and in patients with no or little apparent risk factors.

Keywords: uveal melanoma, pthisical eye, carotid cavernous fistula, uveal melanoma risk factors

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Authors: Laila Seada, Nouf Al Gharbi, Shaimaa Dawa

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Although skin cancers are prevalent worldwide, it is uncommon in Ha’il region in the Kingdom of Saudi Arabia, mostly non-melanoma sub-type. During a 4-year period from 2014 to 2017, out of a total of 120 cases of skin lesions, 29 non-melanoma cancers were retrieved from histopathology files obtained from King Khalid Hospital. As part of the study, all cases of skin cancer diagnosed during 2014 -2017 have been revised and the clinicopathological data recorded. The results show that Basal cell carcinoma (BCC) was the most common neoplasm (36%), followed by cutaneous lymphomas (mostly mycosis fungoides 25%), squamous cell carcinoma (SCC) (21%) and dermatofibrosarcoma protuberans (DFSP) (11%). Only one case of metastatic carcinoma was recorded. BCC nodular type was the most prevalent, with a mean age 57.6 years and mean size 2.73 cm. SCC was mostly grade 2, with mean size 1.9 cm and an older mean age of 72.3 cm. Increased size of lesion positively correlated with older age (p = 0.001). Non-melanoma skin cancer in Ha’il region is not frequently encountered. BCC is the most frequent followed by cutaneous T-cell lymphomas and SCC. The findings in this study were in accordance with other parts of, but much lower than other parts of the world.

Keywords: non melanoma skin cancer, Hail Region, histopathology, BCC

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Authors: Kemka Ihemelandu, Chukwuemeka Ihemelandu

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Melanoma remains a public health crisis, with incidence rates increasing rapidly in the past decades. Improving diagnostic accuracy to decrease misdiagnosis using Artificial intelligence (AI) continues to be documented. Unfortunately, unintended racially biased outcomes, a product of lack of diversity in the dataset used, with a noted class imbalance favoring lighter vs. darker skin tone, have increasingly been recognized as a problem.Resulting in noted limitations of the accuracy of the Convolutional neural network (CNN)models. CNN models are prone to biased output due to biases in the dataset used to train them. Our aim in this study was the optimization of convolutional neural network algorithms to mitigate bias in the automated diagnosis of melanoma. We hypothesized that our proposed training algorithms based on a data augmentation method to optimize the diagnostic accuracy of a CNN classifier by generating new training samples from the original ones will reduce bias in the automated diagnosis of melanoma. We applied geometric transformation, including; rotations, translations, scale change, flipping, and shearing. Resulting in a CNN model that provided a modifiedinput data making for a model that could learn subtle racial features. Optimal selection of the momentum and batch hyperparameter increased our model accuracy. We show that our augmented model reduces bias while maintaining accuracy in the automated diagnosis of melanoma.

Keywords: bias, augmentation, melanoma, convolutional neural network

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Authors: Sri Suparwitri

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When an orthodontic force is applied to a tooth, an inflammatory response is initiated then lead to bone remodeling process, and the process accommodates tooth movement. One of cytokine that plays a prominent role in bone remodeling process was transforming growth factor-beta 1 (TGF-β1). The purpose of this study was to identify and compare changes of TGF-β1 in human gingival crevicular fluid during canine retraction using elastic chain and closed coil spring. Ten patients (mean age 20.7 ± 2.9 years) participated. The patients were entering the space closure phase of fixed orthodontic treatment. An upper canine of each patient was retracted using elastic chain, and the contralateral canine was retracted using closed coil spring. Gingival crevicular fluid samples were collected from the canine teeth before and 7 days after the force was applied. Transforming growth factor-beta 1 was determined by enzyme-linked immunosorbent assay (ELISA). The concentrations of TGF-β1 at 7 days were significantly higher compared to before canine retraction in both groups. In the evaluation of between-group difference, before retraction, the difference was insignificant, whereas at 7 days significantly higher values were determined in the closed coil spring group compared to elastic chain group. The result suggests that TGF-β1 is associated with the bone remodeling that occurs during canine distalization movement. Closed coil spring gave higher TGF-β1 concentrations thus more bone remodeling occurred and may be considered the treatment of choice.

Keywords: closed coil spring, elastic chain, gingival crevicular fluid, TGF-β1

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Authors: Athanasia Eirini Zarkadi, Despoina Balli, Olga Elpis Kolokitha

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Objective: Impacted maxillary canines are a frequent condition and a common reason for patients seeking orthodontic treatment. Their simultaneous presence with dental anomalies raises a question about their possible connection. The aim of this study was to investigate the association of maxillary impacted canines with dental anomalies. Materials and Methods: Files of 874 patients from an orthodontic private practice in Greece were evaluated for the presence of maxillary impacted canines. From this sample, a group of 97 patients (39 males and 58 females) with at least one impacted maxillary canine were selected and consisted of the study group (canine impaction group) of this study. This group was compared to a control group of 97 patients (42 males and 55 females) that was created by random selection from the initial sample without maxillary canine impaction. The impaction diagnosis was made from the panoramic radiographs and confirmed from the surgery. The association between maxillary canine impaction and dental anomalies was examined with the chi-square test. A classification tree was created to further investigate the relations between impaction and dental anomalies. The reproducibility of diagnoses was assessed by re-examining the records of 25 patients two weeks after the first examination. Results: The found associated anomalies were cone-shaped upper lateral incisors and infraocclusion of deciduous molars. There is a significant increase in the prevalence of 12,4% of distal displacement of the unerupted mandibular second premolar in the canine impaction group compared to the control group that was 7,2%. The classification tree showed that the presence of a cone-shaped maxillary lateral incisor gave rise to the probability of an impacted canine to 83,3%. Conclusions: The presence of cone-shaped maxillary lateral incisors and infraocclusion of deciduous molars can be considered valuable early risk indicators for maxillary canine impaction.

Keywords: cone-shaped maxillary lateral incisors, dental anomalies, impacted canines, infraoccluded deciduous molars

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Authors: Shaira L. Kee, Michael Aaron G. Sy, Myles Joshua T. Tan, Hezerul Abdul Karim, Nouar AlDahoul

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Skin diseases are considered the fourth most common disease, with melanoma and non-melanoma skin cancer as the most common type of cancer in Caucasians. The alarming increase in Skin Cancer cases shows an urgent need for further research to improve diagnostic methods, as early diagnosis can significantly improve the 5-year survival rate. Machine Learning algorithms for image pattern analysis in diagnosing skin lesions can dramatically increase the accuracy rate of detection and decrease possible human errors. Several studies have shown the diagnostic performance of computer algorithms outperformed dermatologists. However, existing methods still need improvements to reduce diagnostic errors and generate efficient and accurate results. Our paper proposes an ensemble method to classify dermoscopic images into benign and malignant skin lesions. The experiments were conducted using the International Skin Imaging Collaboration (ISIC) image samples. The dataset contains 3,297 dermoscopic images with benign and malignant categories. The results show improvement in performance with an accuracy of 88% and an F1 score of 87%, outperforming other existing models such as support vector machine (SVM), Residual network (ResNet50), EfficientNetB0, EfficientNetB4, and VGG16.

Keywords: deep learning - VGG16 - efficientNet - CNN – ensemble – dermoscopic images - melanoma

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Authors: Soo Dong Cho, In-Ohk Ouh, Byeong Sul Kang, Seyeon Park, In-Soo Cho, Jae Young Song

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An VP2 gene from the current prevalent CPV (Canine Parvovirus) strain (new CPV-2a) in the Republic of Korea was expressed in a baculovirus expression system. Genomic DNA was extracted from the isolate strain CPV-2a. The recombinant baculovirus, containing the coding sequences of VP2 with the histidine tag at the N-terminus, were generated by using the Bac-to-Bac system. For production of the recombinant VP2 proteins, SF9 cells were transfection into 6 wells. Propagation of recombinant baculoviruses and expression of the VP2 protein were performed in the Sf9 cell line maintained. The proteins were detected to Western blot anlaysis. CPV-2a VP2 was detected by Western blotting the monoclonal antibodies recognized 6x His and the band had a molecular weight of 65 KDa. We demonstrated that recombinant CPV-2a VP2 expression in baculovirus. The recombinant CPV-2a VP2 may able to development of specific diagnostic test and vaccination of against CPV2. This study provides a foundation for application of CPV2 on the development of new CPV2 subunit vaccine.

Keywords: baculovirus, canine parvovirus 2a, Dog, Korea

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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Authors: Paula Buldres, Jorge Toledo

Abstract:

Objectives: This study aimed to characterize potential probiotic strains isolated from canine breast milk for use in dogs with enteropathies. Methodology: Six canine breast milk strains, one canine colostrum strain, and one control porcine breast milk strain were characterized. According to its functional properties of resistance to acids, different concentrations of bile salts, and pancreatin, its presumptive properties of safety and inhibitory effect on pathogens, non-cytotoxic characteristics, and adhesion to the intestine. The immunomodulatory effect of formulations with better probiotic characterization in vitro and in vivo was also analyzed. Results: Two strains characterized as potential probiotics were obtained, which corresponded to the canine strains (TUCO-16 and TUCO-17), presenting resistance to acidic pH, bile salts, and pancreatin, as well as an inhibitory effect on pathogenic Escherichia coli, Salmonella sp., and Clostridium perfringens. Strains TUCO-16 and TUCO-17 induced a significant increase in the expression of TNF-α and IL-8 in canine macrophages, respectively. Expression analyses of pattern recognition receptors in DH82 cells suggest that TUCO-16 and TUCO-17 might increase the TLR2 expression marker, and porcine strain (TUCO-4) increases the NOD2 expression marker. Based on the count obtained and the encapsulation yield, the best formulations correspond to FOS-Inulin for the TUCO-17 and TUCO-4 strains; Maltodextrin-Inulin for TUCO-16. All the strains are non-cytotoxic. The strain that showed the highest adhesion to intestinal epithelial cells was TUCO-17 with the FOS-Inulin formulation. On the other hand, the probiotics decreased the expression of pro-inflammatory markers in vivo, both in the intestine and in the spleen of mice. Conclusion: The combination of these three strains under study (TUCO-16, TUCO-17, and TUCO-4) would cover the probiotic properties in formulation and immunomodulation of all the markers under study.

Keywords: probiotics, gastrointestinal infec, dog, probiotic formulation, immunomodulatory probiotics

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Authors: Max Butler

Abstract:

Melanoma accounts for 80% of skin cancer-related deaths globally. The poor prognosis and increasing incidence of melanoma impose a significant burden on global healthcare systems. Early detection, precise diagnosis, and preventative strategies are critical to improving patient outcomes. Dermoscopy is the gold standard for specialist assessments of pigmented skin lesions, as it can differentiate between benign and malignant growths with greater accuracy than visual inspection. In the United Kingdom, guidelines from the National Institute of Clinical Excellence (NICE) state dermoscopy should be used in all specialist assessments of pigmented skin lesions. Compliance with this guideline is low, resulting in missed and delayed melanoma diagnoses. To address this problem, a quality improvement project was initiated at Buckinghamshire Healthcare Trust (BHT) within the plastic surgery department. The target group was a trainee and consultant plastic surgeons conducting outpatient skin cancer clinics. Analysis of clinic documentation over a one-month period found that only 62% (38/61) of patients referred with pigmented skin lesions were examined using dermoscopy. To increase dermoscopy rates, teaching was delivered to the department highlighting national guidelines and the evidence base for dermoscopic examination. In addition, clinic paperwork was redesigned to include a text box for dermoscopic examination. Reauditing after the intervention found a significant increase in dermoscopy rates (52/61, p = 0.014). In conclusion, implementing a quality improvement project with targeted teaching and documentation template templates successfully increased dermoscopy rates. This is a promising step toward improving early melanoma detection and patient outcomes.

Keywords: melanoma, dermoscopy, plastic surgery, quality improvement

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Authors: Roberto Coppo, Francesca Orso, Daniela Dettori, Elena Quaglino, Lei Nie, Mehran M. Sadeghi, Daniela Taverna

Abstract:

Malignant melanoma is currently the fifth most common cancer in the white population and it is fatal in its metastatic stage. Several research studies in recent years have provided evidence that cancer initiation and progression are driven by genetic alterations of the tumor and paracrine interactions between tumor and microenvironment. Scattered data show that the Endothelial and Smooth muscle cell-Derived Neuropilin-like molecule (ESDN) controls cell proliferation and movement of stroma and tumor cells. To investigate the role of ESDN in the tumor microenvironment during melanoma progression, murine melanoma cells (B16 or B16-F10) were injected in ESDN knockout mice in order to evaluate how the absence of ESDN in stromal cells could influence melanoma progression. While no effect was found on primary tumor growth, increased cell extravasation and lung metastasis formation was observed in ESDN knockout mice compared to wild type controls. In order to understand how cancer cells cross the endothelial barrier during metastatic dissemination in an ESDN-null microenvironment, structure, and permeability of lung blood vessels were analyzed. Interestingly, ESDN knockout mice showed structurally altered and more permeable vessels compared to wild type animals. Since cell surface molecules mediate the process of tumor cell extravasation, the expression of a panel of extravasation-related ligands and receptors was analyzed. Importantly, modulations of N-cadherin, E-selectin, ICAM-1 and VAP-1 were observed in ESDN knockout endothelial cells, suggesting the presence of a favorable tumor microenvironment which facilitates melanoma cell extravasation and metastasis formation in the absence of ESDN. Furthermore, a potential contribution of immune cells in tumor dissemination was investigated. An increased recruitment of macrophages in the lungs of ESDN knockout mice carrying subcutaneous B16-F10 tumors was found. In conclusion, our data suggest a functional role of ESDN in the tumor microenvironment during melanoma progression and the identification of the mechanisms that regulate tumor cell extravasation could lead to the development of new therapies to reduce metastasis formation.

Keywords: melanoma, tumor microenvironment, extravasation, cell surface molecules

Procedia PDF Downloads 305

Authors: Awf A. Al-Khan, Michael J. Day, Judith Nimmo, Mourad Tayebi, Stewart D. Ryan, Samantha J. Richardson, Janine A. Danks

Abstract:

Osteosarcoma (OS) is the most common type of malignant primary bone tumour in dogs. In addition to their critical roles in bone formation and remodeling, parathyroid hormone-related protein (PTHrP) and its receptor (PTHR1) are involved in progression and metastasis of many types of tumours in humans. The aims of this study were to determine the localisation and expression levels of PTHrP and PTHR1 in canine OS tissues using immunohistochemistry and to investigate if this expression is correlated with survival time. Formalin-fixed, paraffin-embedded tissue samples from 44 dogs with known survival time that had been diagnosed with primary osteosarcoma were analysed for localisation of PTHrP and PTHR1. Findings showed that both PTHrP and PTHR1 were present in all OS samples. The dogs with high level of PTHR1 protein (16%) had decreased survival time (P<0.05) compared to dogs with less PTHR1 protein. PTHrP levels did not correlate with survival time (P>0.05). The results of this study indicate that the PTHR1 is expressed differently in canine OS tissues and this may be correlated with poor prognosis. This may mean that PTHR1 may be useful as a prognostic indicator in canine OS and could represent a good therapeutic target in OS.

Keywords: dog, expression, osteosarcoma, parathyroid hormone receptor 1 (PTHR1), parathyroid hormone-related protein (PTHrP), survival

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

Abstract:

Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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Authors: Sushila Jaiswal, Awadhesh Kumar Jaiswal

Abstract:

Background: Primary melanocytic tumors of the central nervous system (CNS) are uncommon lesions and arise from the melanocytes located within the leptomeninges. Aim and objective: The aim of the study was to evaluate the clinical details, histomorphology of the primary melanocytic tumor of CNS. Method: The study was performed by the retrospective review of the case records of the primary melanocytic tumors of CNS diagnosed in our department. The formalin-fixed, paraffin embedded tissue blocks and tissue sections were retrieved and reviewed. Results: Seven cases (6 males, 1 female; age range- 16-40 years; mean age- 27 years) of primary melanocytic tumors of CNS were retrieved over last seven years. The tumor was intracranial (n=5; frontal – 1 case, parietal – 1 case, cerebello-pontine angle- 1 case, occipital -1 case, foramen magnum-1 case) and intra spinal (n=2; cervical – 2 cases). All patients presented with the neurological deficits related to the location of the tumor. Four cases were malignant melanoma; two were melanocytoma of intermediate grade and remaining one was melanocytoma. On histopathology, melanocytoma and melanoma both displayed sheets of well-differentiated melanocytes having round to oval nuclei with finely dispersed chromatin, occasional single eosinophilic nucleoli and a moderate amount of cytoplasm with abundant granular melanin pigment. The absence of mitosis and macronucleoli was noticed in melanocytoma while melanoma showed frequent mitosis and macronucleoli. On immunohistochemistry, both showed diffuse strong HMB45 and S-100 immunopositivity. Conclusion: Primary melanocytic tumors of CNS are rare and predominantly seen in males. It is important to differentiate melanoma from melanocytoma as prognosis of later is good.

Keywords: melanocytoma, melanoma, brain tumor, melanin

Procedia PDF Downloads 193

Authors: Olivier de Backer, Alexis Khelfi, Olivier Svensek, Axelle Nolmans, Dominique Desnoeck

Abstract:

The SMC5-SMC6 complex helps replication and repair of DNA double-strand breaks. Nse1, Nse3 and Nse4 are non-SMC components of the complex in which Nse3 stimulates the E3 ubiquitin ligase activity of Nse1 and is required for recruiting the complex on DNA. In most eukaryotes, Nse3 is a single protein, but in eutherians (placental mammals), it belongs to a large family of proteins called MAGE (Melanoma antigen) that share a conserved domain of about 200 aa known as MHD (Mage homology domain). MAGE assembles specific RING and HECT ubiquitin ligases and determines new substrates for ubiquitination. The MHD is required for the interaction with the cognate E3 ligase. Some MAGEs (referred to as Type I) are exclusively expressed in germ cells of the testis but are often expressed ectopically in cancer cells as the result of epigenetic modifications. The 12 MAGE-A genes belong to this category. Serval MAGE-A proteins could promote tumorigenesis by targeting tumor suppressor proteins (including p53) for ubiquitination and degradation. We showed that depletion of MAGE-A proteins in melanoma cells results in impaired DNA damage response and increased double-strand breaks after exposure to camptothecin. Moreover, it was shown that other actors of the DNA Damage Response were impacted when cells were depleted of MAGEA proteins.

Keywords: DNA damage response, melanoma, camptothecin, new role, MAGEA

Procedia PDF Downloads 55