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Little is known about the adaption of community-based organizations (CBOs) during the COVID-19 crisis. This study aimed to study how HIV CBOs and their community health workers (CHWs) faced the COVID-19 outbreak. Semi-structured interviews (n = 53) were conducted among CHWs in Burundi, Mauritania, and Lebanon in 2021. A thematic content analysis was performed. Results showed that CBOs had succeeded in maintaining HIV services and integrated COVID-19 prevention and awareness in their activities. COVID-19 led to innovation in terms of HIV services (eg, telemedicine and online psychosocial support) and to opportunities to try new modalities of antiretroviral therapy dispensation. Field workers (a specific group among CHWs) were negatively impacted by the COVID-19 crisis and showed resilience in their adaptation to ensure the continuity of their activities. Considering the essential role of field workers during the crisis, their status and the sustainability of their activities should be clearly supported by health policies and programs.
Role of community health workers during the COVID-19 pandemicThis study explores how HIV community-based organizations (CBOs) and their community health workers (CHWs) adapted during the COVID-19 pandemic. We conducted interviews with 53 CHWs from Burundi, Mauritania, and Lebanon in 2021 to understand their experiences. We found that despite the challenges posed by COVID-19, CBOs managed to continue providing essential HIV services. They also incorporated COVID-19 prevention and awareness efforts into their work. The pandemic prompted innovation, such as the use of telemedicine and online psychosocial support, and provided opportunities to explore new ways of dispensing antiretroviral therapy (ART). However, field workers, a specific group of CHWs, faced significant negative impacts due to the pandemic. Despite these challenges, they showed remarkable resilience and adapted to ensure the continuity of their services. Given the critical role of field workers during the crisis, it is important for health policies and programs to support their status and ensure the sustainability of their activities.
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COVID-19 , Agentes Comunitários de Saúde , Infecções por HIV , Pesquisa Qualitativa , Populações Vulneráveis , Humanos , Infecções por HIV/epidemiologia , COVID-19/epidemiologia , COVID-19/prevenção & controle , Líbano/epidemiologia , Burundi/epidemiologia , Feminino , Masculino , Populações Vulneráveis/estatística & dados numéricos , Mauritânia/epidemiologia , Adulto , SARS-CoV-2 , Telemedicina/estatística & dados numéricos , Pessoa de Meia-Idade , Serviços de Saúde Comunitária/estatística & dados numéricosRESUMO
This study investigates the carcinogenic potential of chronic dermal exposure (16 weeks) to sulfuric acid (SA) in immunocompetent mice. Clinical assessments, histopathological analyses, immunohistochemical analyses and biochemical assays were conducted to evaluate skin irritation, oxidative stress biomarkers and the potential carcinogenic effect of SA. Results indicated that prolonged exposure to SA leads to various alterations in skin structure, notably inflammation, preneoplastic and neoplastic proliferation in hair follicles, as well as hyperkeratosis and acanthosis, resulting in an increased epidermal thickness of 98.50 ± 21.6 µm. Immunohistochemistry analysis further corroborates these observations, showcasing elevated nuclear expression of p53 and Ki-67, with a significant mitotic index of (57.5% ± 2.5%). Moreover, biochemical analyses demonstrate that SA induces lipid peroxidation in the skin, evidenced by a high level of Malondialdehyde and a consequential reduction in catalase activity. These findings suggest that prolonged exposure to SA can induce skin neoplasms, highlighting the need for stringent safety measures in environments where SA is frequently used. This study underscores the potential occupational health risks associated with SA exposure.
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Neoplasias Cutâneas , Ácidos Sulfúricos , Animais , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/metabolismo , Camundongos , Ácidos Sulfúricos/efeitos adversos , Ácidos Sulfúricos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Feminino , Malondialdeído/metabolismo , Imunocompetência , Catalase/metabolismo , Pele/patologia , Pele/metabolismo , Pele/efeitos dos fármacos , Antígeno Ki-67/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
In 2017, Morocco became the first Arab country to incorporate pre-exposure prophylaxis (PrEP) in its HIV-prevention program. Yet no research has been published on PrEP from Morocco. Although female sex workers are one of the target populations of PrEP in Morocco, their enrollment in PrEP is lower than men who have sex with men. In this study, we conducted 38 semi-structured interviews with female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. We also investigated preferences for daily oral, vaginal ring, and long-acting injectable PrEP. A reflexive thematic analysis revealed seven themes: PrEP stigma; stigmatization and criminalization of sex work; one size doesn't fit all; knowledge and misconceptions about PrEP; economic burden; inconvenience of PrEP pills; and preferred PrEP modalities. This paper discusses the implications of the findings for increasing access and use of PrEP in Morocco.
Factors that Influence Uptake of Oral PrEP among Female Sex Workers One of the most recent scientific advancements in the history of the HIV pandemic was the introduction of pre-exposure prophylaxis (PrEP). However, the uptake of PrEP in the Arab world is low. In this paper we interviewed female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. Several barriers were identified including stigma attached to PrEP, misconceptions about PrEP, and financial burden. Although most female sex workers in our study were interested in using PrEP, the delivery methods of PrEP should be tailored to fit the lifestyle and personal circumstances of potential users.
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Infecções por HIV , Profilaxia Pré-Exposição , Pesquisa Qualitativa , Profissionais do Sexo , Humanos , Marrocos , Profilaxia Pré-Exposição/estatística & dados numéricos , Feminino , Profissionais do Sexo/estatística & dados numéricos , Profissionais do Sexo/psicologia , Infecções por HIV/prevenção & controle , Adulto , Conhecimentos, Atitudes e Prática em Saúde , Estigma Social , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/administração & dosagem , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Masculino , Adulto Jovem , Pessoa de Meia-Idade , Administração OralRESUMO
The COVID-19 crisis had a global impact and many marginalised groups, such as people who use or inject drugs, are more vulnerable to the SARS-CoV-2 virus and its consequences due to their pre-existing health inequalities. Moreover, people who use/inject drugs are also criminalised in some countries such as Algeria. This analysis aimed to explore the psychosocial experience of the COVID-19 crisis among people who use/inject drugs in Algeria. Twenty-nine qualitative interviews were conducted in 2021 with a community-based approach. Results of the thematic content analysis showed the intersectional effects of the COVID-19 crisis among people who use or inject drugs through the experience of a double crisis: one related to COVID-19 and the second to their specific difficulties related to drug use. Addressing social inequalities in health of people who use or inject drugs, through better recognition of their rights and needs, is crucial to improving their health.
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Ganglioneuroma (GN) is a rare, benign neurogenic tumor that develops from sympathetic ganglion cells. It occurs mainly in the retroperitoneal region. Adrenal localization is rare. We report a case of adrenal ganglioneuroma in a 22-year-old woman with no previous history of the disease. The tumor was discovered incidentally on an entero scan ordered as part of the etiological assessment for chronic diarrhea. The diagnosis was confirmed by pathological examination.
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Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Standard treatments including surgical resection, radiotherapy, and chemotherapy, have failed to significantly improve the prognosis of glioblastoma patients. Currently, immunotherapeutic approaches based on vaccines, chimeric antigen-receptor T-cells, checkpoint inhibitors, and oncolytic virotherapy are showing promising results in clinical trials. The combination of different immunotherapeutic approaches is proving satisfactory and promising. In view of the challenges of immunotherapy and the resistance of glioblastomas, the treatment of these tumors requires further efforts. In this review, we explore the obstacles that potentially influence the efficacy of the response to immunotherapy and that should be taken into account in clinical trials. This article provides a comprehensive review of vaccine therapy for glioblastoma. In addition, we identify the main biomarkers, including isocitrate dehydrogenase, epidermal growth factor receptor, and telomerase reverse transcriptase, known as potential immunotherapeutic targets in glioblastoma, as well as the current status of clinical trials. This paper also lists proposed solutions to overcome the obstacles facing immunotherapy in glioblastomas.
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Introduction: Gliomas represent the most prevalent and aggressive tumors within the central nervous system. Despite the current standard treatments, the median survival time for glioblastoma patients remains dismal, hovering around 14 months. While attempts have been made to inhibit the PD-1/PD-L1 and CTLA-4/CD80-CD86 axes through immunotherapy, the outcomes have yet to demonstrate significant efficacy. The immune checkpoint Butyrophilin 3A1 (BTN3A1) can either be involved in advantageous or detrimental function depending on the cancer type. Methods: In our study, we utilized a Moroccan cohort to delve into the role of BTN3A1 in gliomas. A transcriptomic analysis was conducted on 34 patients, which was then corroborated through a protein analysis in 27 patients and validated using the TCGA database (n = 667). Results: Our results revealed an elevated expression of BTN3A1 in glioblastoma (grade 4), as evidenced in both the TCGA database and our cohort of Moroccan glioma patients. Within the TCGA cohort, BTN3A1 expression was notably higher in patients with wild-type IDH. We observed a positive correlation between BTN3A1 expression and immune infiltration of B cells, CD8+ T cells, naive CD4+ T cells, and M2 macrophages. Patients exhibiting increased BTN3A1 expression also presented elevated levels of TGF-ß, IL-10, and TIM-3 compared to those with reduced BTN3A1 expression. Notably, patients with high BTN3A1 expression were associated with a poorer prognosis than their counterparts with lower expression. Conclussion: Our findings suggest that BTN3A1 might promote the establishment of an immunosuppressive microenvironment. Consequently, targeting BTN3A1 could offer novel therapeutic avenues for the management of advanced gliomas.
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Biomarcadores Tumorais , Neoplasias Encefálicas , Butirofilinas , Glioma , Humanos , Masculino , Feminino , Prognóstico , Butirofilinas/genética , Butirofilinas/metabolismo , Glioma/imunologia , Glioma/genética , Glioma/mortalidade , Pessoa de Meia-Idade , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Biomarcadores Tumorais/genética , Adulto , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Idoso , Regulação Neoplásica da Expressão GênicaRESUMO
Visceral leishmaniasis (VL) is a potentially fatal infection caused by species of Leishmania. It is characterized by fever, weight loss, anemia, and enlargement of the spleen and liver. Hepatitis due to VL is one of the causes of granulomatous hepatitis rarely described in the literature. It poses a problem of differential diagnosis with other causes, notably infectious and autoimmune. Hence the need for a global clinical, biological, and histological evaluation to orientate this entity, especially in endemic countries like ours. In the present case study, a 2-year 8-month-old boy was diagnosed with VL and treated with meglumine antimoniate; the evolution was marked after 2 months by the persistence of a large liver; laboratory results showed elevated liver functions and anemia. A liver biopsy was performed, and the histological findings confirmed the diagnosis of granulomatous hepatitis.
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AIM: Our study aimed to perform on Moroccan patients' non-small cell lung carcinoma (NSCLC) concerning the relationship between PD-L1 tumor expression, clinicopathological features and tumor infiltrating immune cells (ICs). METHODS: This is a retrospective study (2019 to 2021) conducted on samples from Moroccan patients with NSCLC at the Pathological Anatomy Laboratory of Ibn Rochd University Hospital in Casablanca. Eligible participants for our study had to meet the following predefined criteria: age ≥18 years, histologically confirmed NSCLC, no prior therapeutic interventions, availability of clinical and pathological data, and a usable tumor sample for determining PD-L1 status. Exclusion criteria applied to patients with other types of lung cancer and unusable tumor samples. The evaluation of tumor and immune expression of PD-L1 was performed using immunohistochemistry (IHC), with the 22C3 clone on the Dako Autostainer Link 48 platform. Tumor PD-L1 expression was categorized into 3 levels: TPS <1% (negative expression), TPS 1-49% (low expression), and TPS ≥50% (high expression). ICs infiltrating the tumor expressing PD-L1 were considered positive when more than 1% of positive ICs were present. RESULTS: Among the 316 analyzed samples, 56.6% showed a negative expression of PD-L1, 16.8% displayed a low expression of PD-L1, and 26.6% exhibited a strong expression. Regarding the histological type, among patients with TPS ≥ 50%, 25.8% had adenocarcinoma. Among patients with TPS ≥ 50%, 24.81% were smokers. PD-L1 was also strongly expressed in the lung (28.2%) and bronchi (26.5%). PD-L1 expression (TPS ≥ 50%) was observed in 35.29% of early-stage patients. Concerning tumor cells (TCs), 27.5% of tumors infiltrated by ICs had TPS ≥ 50%. Furthermore, coexpression of PD-L1 on both TCs and ICs infiltrating the tumor was found in 27.8% of tumors. Statistical analysis demonstrated a significant association between tumor PD-L1 expression and smoking status (P=0.019). However, no significant difference was observed between PD-L1 expression and the presence of ICs infiltrating the tumor (P=0.652), as well as the IHC expression of PD-L1 on ICs (P=0.259). CONCLUSION: Our results demonstrate a significant association between PD-L1 expression and smoking status. However, no significant association was observed between PD-L1 expression and the presence of infiltrating ICs, nor with the IHC expression of PD-L1 on ICs. Our data underscore the importance of participating in the study of specific factors influencing PD-L1 expression in patients with NSCLC.
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Antígeno B7-H1 , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/imunologia , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análise , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Linfócitos do Interstício Tumoral/metabolismo , Marrocos/epidemiologia , Adulto , Imuno-Histoquímica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Idoso de 80 Anos ou maisRESUMO
INTRODUCTION: Glioblastoma and astrocytoma, grade 4, are the most common and aggressive brain tumors. Several biomarkers, such as the isocitrate dehydrogenase mutation (IDH-1), alpha-thalassemia/mental retardation, and the X-linked mutation (ATRX), enable more accurate glioma classification and facilitate patient management. This study aimed to determine the prognostic value of clinical and molecular factors (IDH, TP53, and ATRX mutations). We also studied the relationship between these molecular markers and the overall survival (OS) of 126 patients with grade 4 glioblastoma/astrocytoma. METHODS: The immunohistochemical study was conducted using antibodies namely, IDH1, R132H, p53, and ATRX. Statistical tests were used to investigate factors that might influence overall survival using IBM SPSS Statistics, version 25.0 (IBM Corp., Armonk, NY). RESULTS: The median age at diagnosis was 51.5 years. Patients with a Karnofsky performance score (KPS) <70 presented less favorable survival outcomes compared to those with a KPS ≥70. The median OS for patients was found to be 11.17 months. Expression of IDH1 R132H was found in 13.5% of patients, p53 overexpression was identified in 55.6% of cases, and loss of ATRX expression was detected in 11.9%. The group of patients with IDH mutant/ATRX mutant/p53 wild-type had the best prognosis (OS = 27.393 months; p = 0.015). Our results were in line with previous studies. CONCLUSION: The clinical value of IDH and ATRX mutations in prognostic assessment was confirmed (p ≤0.05). The overexpression of p53 had no significant impact on OS (p = 0.726). Therefore, p53 alone cannot predict survival in glioblastoma patients. Based on the results, these biomarkers may be a potential therapeutic target to prolong patient survival, hence the need for further investigations.
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Kearns-Sayre syndrome (KSS) is a rare mitochondrial disease that affects young adults, due to a deletion of mitochondrial DNA and characterized by the triad: age of onset lower than 20 years, chronic progressive external ophthalmoplegia, and an atypical pigmentary retinopathy. It is also characterized by other endocrine, neurological, and especially cardiac impairment with a very high risk of cardiac complications during surgical procedures under all types of anesthesia. We report a case of KSS revealed by severe bilateral ptosis and confirmed by a muscle biopsy with "ragged red fibers." The ptosis was surgically managed by cautious Frontal suspension under local anesthesia "Frontal nerve block." Through this case, we discuss challenges in the management of KSS patients.
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BACKGROUND: Ankylosing spondylitis (AS) is a type of chronic inflammation that is most prevalent in young adults and is characterized by an inflammatory enthesiopathy that gradually develops toward ossification and ankylosis. If inflammation is left unchecked, it can potentially lead to complications such as secondary amyloidosis, also known as AA amyloidosis, involving the deposition of amyloid serum A protein. Our case presents with a thyroid localization of AA amyloidosis which is secondary to this AS. Such a case has been described in only four cases in the literature. Cardiac localization of AA amyloidosis has been exceptionally described in the literature. CASE PRESENTATION: We report the case of a young patient with severe AS complicated by secondary amyloidosis with thyroid, cardiac, and probably renal localization. He was treated with anti-TNF therapy, and his condition improved significantly. CONCLUSIONS: Our case presents several localizations of AA amyloidosis secondary to this AS. Although cardiac involvement is rare in secondary AA amyloidosis, it should always be screened for, even in a cardiacly asymptomatic patient.
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Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, recommended for persons at substantial risk for HIV, such as female sex workers (FSW) and men who have sex with men (MSM). We present Morocco's and the Middle East/North Africa's first PrEP demonstration project. Our pilot aimed to assess the feasibility and acceptability of a community-based PrEP program for FSW and MSM in Morocco's highest HIV prevalence cities: Agadir, Marrakech, and Casablanca. From May to December 2017, 373 eligible participants engaged in a 5-9 month program with daily oral TDF/FTC and clinic visits. Of these, 320 initiated PrEP, with 119 retained until the study's end. We report an 86% PrEP uptake, 37% overall retention, and 78% retention after 3 months. No seroconversions occurred during follow-up. These results underscore PrEP's need and acceptability among MSM and FSW and demonstrate the effectiveness of a community-based PrEP program in Morocco. These findings informed Morocco's current PrEP program and hold potential for the wider region with similar challenges.
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Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Profissionais do Sexo , Minorias Sexuais e de Gênero , Masculino , Humanos , Feminino , Homossexualidade Masculina , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Marrocos , Profilaxia Pré-Exposição/métodosRESUMO
Ammi visnaga (A. visnaga) is an annual herb that has been used in traditional medicine to treat various ailments attributed to the presence of its bioactive compounds. The purpose of this study was to identify and examine the phytochemical properties of the hydroalcoholic extract of A. visnaga using in vitro and in vivo models. Our findings demonstrated that the extract contained a variety of beneficial components, including phenols, flavonoids, tannins, coumarins, saponins, khellin, and visnagin. The total polyphenolic content and total flavonoid content were 23.26 mg/GAE/g dry weight and 13.26 mg/GAE/g dry weight, respectively. In vitro tests demonstrated that the extract possessed antioxidant properties as evidenced by the ability to scavenge free radicals, including DPPH, ABTS, nitric oxide (NO), phosphomolybdate, and ferric-reducing antioxidant power (FRAP). Further, the extract was found to inhibit hydrogen peroxide (H2O2)-induced hemolysis. In a 90-d in vivo study, female Wistar rats were administered 1 g/kg of A. visnaga extract orally resulting in a significant increase in total white blood cell count. Although morphological changes were observed in the liver, no marked alterations were noted in kidneys and spleen. In a female Swiss albino mice model of acetic acid-induced vascular permeability, A. visnaga significantly inhibited extravasations of Evans blue at doses of 0.5 or 1 g/kg with inhibition percentages of 51 and 65%, respectively, blocking tissue necrosis. The extract also demonstrated potential immunomodulatory properties in mice by enhancing antibody production in response to antigens. In silico molecular docking studies demonstrated a strong affinity between khellin or visnagin and immunomodulatory proteins, NF-κB, p52, and TNF-α. These findings suggest that A. visnaga may be considered a beneficial antioxidant with immunomodulatory properties and might serve as a therapeutic agent to combat certain diseases.
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Ammi , Quelina , Ratos , Feminino , Camundongos , Animais , Extratos Vegetais/química , Ammi/química , Quelina/química , Quelina/farmacologia , Antioxidantes/farmacologia , Peróxido de Hidrogênio , Simulação de Acoplamento Molecular , Ratos Wistar , Flavonoides/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
Introduction: There has been increased interest in HER2-low breast tumors recently, as these tumors may have distinct clinical and molecular characteristics compared to HER2-negative and HER2-positive tumors. A new nomenclature has been proposed for HER2 1+ and HER2 2+ tumors that are confirmed negative according to fluorescence in situ hybridization (FISH). These tumors are now referred to as HER2-low, and it is thought that they may represent a distinct subtype of breast cancer that warrants further investigation. In this study, we aimed to evaluate the clinicopathological characteristics and prognostic impact of this particular subtype in a North-African context where HER2-low breast cancer is a relatively understudied subtype, particularly in non-Western populations. Methods: We conducted a retrospective cohort study on 1955 breast tumors in Moroccan patients over 10 years, collected at the Pathology Department of Ibn Rochd University Hospital in Casablanca and at the pathology department of Hassan II University Hospital in Fes. We elaborated on their complete immunohistochemical profile based on the main breast cancer biomarkers: Ki-67, HER2, estrogen, and progesterone receptors. Their overall survival and disease free survival data were also retrieved from their respective records. Results: Out of 1955 BC patients, 49.3% were classified as HER2-low; of which 80.7% and 19.2% were hormone receptors positive and negative, respectively. The clinicopathologic features indicate that HER2-low subtype tumors behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-low subtype-belonging patients present significantly the poorest prognosis in disease-free survival (p = 0.003) in comparison with HER2-negative ones. When considering the hormonal status, hormonal-dependent tumors show a significant difference according to HER2 subtypes in disease-free survival (p < 0.001). Yet no significant difference was shown among hormonal negative tumors. Moreover, patients with hormonal positive tumors and simultaneously belonging to the HER2-low subgroup present a significantly good prognosis in overall survival compared to the ones with hormonal negative tumors (p = 0.008). Conclusion: Our study has shown that the HER2-low phenotype is common among hormone-positive patients. The clinicopathological features and prognostic data indicate that the hormonal receptors effect and HER2 heterogeneity are crucial factors to consider. It is important to note that this particular subgroup is different from the HER2-negative one and should not be treated in the same way. Therefore, this study offers a new perspective in the management of HER2-low patients and can serve as a basis for future prospective analyses.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Prognóstico , Biomarcadores Tumorais/análise , Receptor ErbB-2/análise , Estudos Retrospectivos , Hibridização in Situ Fluorescente , Receptores de ProgesteronaRESUMO
PURPOSE: Peripheral neuroblastic tumors are the most common extracranial cancers found in children, and they are characterized by a diverse spectrum of clinical manifestations and heterogeneous behaviors. This study aimed to investigate the epidemiological and clinical characteristics of children with peripheral neuroblastic tumors admitted to the Department of Pediatric Hematology and Oncology of the Hospital August 20 in Casablanca. METHODS: The medical files of 48 children with peripheral neuroblastic tumors addressed to our department between February 2018 and February 2023 were reviewed. The clinical and demographic characteristics of patients were analyzed by the Statistical Package for the Social Sciences (SPSS), survival curves were obtained by Kaplan-Meier technique, and we assigned the tumor stage to patients based on the International Neuroblastoma Risk Group Staging System (INRGSS). RESULTS: The median age of diagnosis was 30 months (1-174), with a ratio F/M of 1.28. 93.75% of patients had neuroblastoma, and the rest had ganglioneuroma. About 64.6% of patients had at their initial presentations stage M of peripheral neuroblastic tumors. The adrenal region made up 71% of the primary tumor site. The bone was one of the most prevalent metastatic sites (54.2%). The five-year overall survival rate was 35.4%. CONCLUSION: Overall, this study revealed a high stage of peripheral neuroblastic tumors in the majority of the diagnosed patients in our Department of Pediatric Hematology and Oncology. Moreover, the heterogeneity of peripheral neuroblastic tumors makes clinical recognition difficult and, in general, too late.
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Ganglioneuroma , Neuroblastoma , Criança , Humanos , Neuroblastoma/epidemiologia , Neuroblastoma/patologia , Ganglioneuroma/epidemiologia , Ganglioneuroma/patologia , Proteínas Repressoras , Taxa de SobrevidaRESUMO
Background: The crosstalk between the immune system and cancer cells has aroused considerable interest over the past decades. To escape immune surveillance cancer cells evolve various strategies orchestrating tumor microenvironment. The discovery of the inhibitory immune checkpoints was a major breakthrough due to their crucial contribution to immune evasion. The A2AR receptor represents one of the most essential pathways within the TME. It is involved in several processes such as hypoxia, tumor progression, and chemoresistance. However, its clinical and immunological significance in human breast cancer remains elusive. Methods: The mRNA expression and protein analysis were performed by RT-qPCR and immunohistochemistry. The log-rank (Mantel-Cox) test was used to estimate Kaplan-Meier analysis for overall survival. Using large-scale microarray data (METABRIC), digital cytometry was conducted to estimate cell abundance. Analysis was performed using RStudio software (7.8 + 2023.03.0) with EPIC, CIBERSORT, and ImmuneCellAI algorithms. Tumor purity, stromal and immune scores were calculated using the ESTIMATE computational method. Finally, analysis of gene set enrichment (GSEA) and the TISCH2 scRNA-seq database were carried out. Results: Gene and protein analysis showed that A2AR was overexpressed in breast tumors and was significantly associated with high grade, elevated Ki-67, aggressive molecular and histological subtypes, as well as poor survival. On tumor infiltrating immune cells, A2AR was found to correlate positively with PD-1 and negatively with CTLA-4. On the other hand, our findings disclosed more profuse infiltration of protumoral cells such as M0 and M2 macrophages, Tregs, endothelial and exhausted CD8+ T cells within A2ARhigh tumors. According to the Single-Cell database, A2AR is expressed in malignant, stromal and immune cells. Moreover, it is related to tumor purity, stromal and immune scores. Our results also revealed that CD8+T cells from A2ARhigh patients exhibited an exhausted functional profile. Finally, GSEA analysis highlighted the association of A2AR with biological mechanisms involved in tumor escape and progression. Conclusion: The present study is the first to elucidate the clinical and immunological relevance of A2AR in breast cancer patients. In light of these findings, A2AR could be deemed a promising therapeutic target to overcome immune evasion prevailing within the TME of breast cancer patients.
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Neoplasias da Mama , Neoplasias Mamárias Animais , Humanos , Animais , Feminino , Neoplasias da Mama/genética , Adenosina , Microambiente Tumoral/genética , AlgoritmosRESUMO
Introduction: Uveal melanoma (UM) is a rare yet deadly tumor. It is known for its high metastatic potential, which makes it one of the most aggressive and lethal cancers. Recently, immune checkpoints such as Programmed cell Death protein-1 (PD1) and Cytotoxic T-Lymphocyte-Associated significantly increasing patient survival in multiple human cancers, especially cutaneous melanoma. However, patients with UMs were excluded from these studies because of their molecular characteristics, which tend to be widely different from those of cutaneous melanoma. This study aimed to analyze the expression of V domain Ig Suppressor T-cell Activation (VISTA), a novel immune checkpoint, to evaluate its prognosis significance and its correlation with PD1 and CTLA-4. Methods: Evaluation of VISTA, CTLA-4, and PD1 expression was performed through TCGA database analysis and immunohistochemistry using two independent cohorts with primary malignant UM. Results and discussion: Our results showed that VISTA expression was associated with tumor aggressiveness, T cell exhaustion, and the shortest median overall survival among patients. Surprisingly, PD1 protein expression was negative in all patients, whereas CTLA-4 expression was high in patients with advanced stages. Our findings suggest that VISTA may be a prognostic marker and an attractive treatment strategy for immunotherapy in patients with UM. Exploring its expression profile may predict response to immunotherapy and may lead to the improvement of precision therapy in malignant uveal melanoma patients.