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PURPOSE: For patients with advanced nonsquamous non-small cell lung cancer (NSCLC), immunotherapy or antiangiogenic therapy combined with pemetrexed and cisplatin/carboplatin have both shown significant efficacy at programmed cell death ligand 1 (PD-L1) levels of <1%. Our study aimed to compare two first-line regimens for patients with advanced nonsquamous NSCLC who were negative for PD-L1. METHODS: A retrospective cohort study was conducted comparing the outcomes of patients with advanced PD-L1(-) nonsquamous NSCLC who were treated with antiangiogenic therapy plus chemotherapy (A Group) to those who were treated with anti-PD-L1 monoclonal antibodies plus chemotherapy (mAbs) (B Group). Both regimens were evaluated for progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and side effects. RESULTS: 114 patients were enrolled in the study, 82 in Group A and 32 in Group B. Those in Group A had a longer median PFS (9.8 vs. 6.7 months, p = 0.025). The OS was also achieved (p = 0.058). No statistically significant difference was seen in ORR (52.4% vs. 50.0%, p = 0.815) or DCR (93.9% vs. 87.5%, p = 0.225) between the two groups. Patients in the A group who did not smoke and did not have specific metastases could benefit from survival. Adverse events (AEs) in both groups were tolerated. CONCLUSION: Bevacizumab plus chemotherapy outperformed immunotherapy plus chemotherapy in terms of PFS.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Pueblos del Este de Asia , Inmunoterapia , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Inhibidores de la Angiogénesis/efectos adversos , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéuticoRESUMEN
At present, medical education is rapidly evolving. Game-based learning (GBL) has been gradually used for education, and several innovations have emerged. The emergence of serious games and gamification provides alternative approaches for educators to improve the medical teaching process. Both serious games and gamification exert their education-promoting function by providing the possibility of combining learning activities such as feedback, testing, and spaced repetition with active participation and autonomy as well as positive experiences for students. Developing effective GBL modalities has the potential to bring immersive experiences for medical students and improve their study outcomes. Herein, we reviewed recent studies employing GBL in medical education, including serious games and gamification teaching. Furthermore, we also discussed the effectiveness and limitations of GBL to suggest future directions for the development and application of GBL in medical education.
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Educación Médica , Estudiantes de Medicina , Humanos , AprendizajeRESUMEN
Notch and Hedgehog signaling are involved in cancer biology and pathology, including the maintenance of tumor cell proliferation, cancer stem-like cells, and the tumor microenvironment. Given the complexity of Notch signaling in tumors, its role as both a tumor promoter and suppressor, and the crosstalk between pathways, the goal of developing clinically safe, effective, tumor-specific Notch-targeted drugs has remained intractable. Drugs developed against the Hedgehog signaling pathway have affirmed definitive therapeutic effects in basal cell carcinoma; however, in some contexts, the challenges of tumor resistance and recurrence leap to the forefront. The efficacy is very limited for other tumor types. In recent years, we have witnessed an exponential increase in the investigation and recognition of the critical roles of the Notch and Hedgehog signaling pathways in cancers, and the crosstalk between these pathways has vast space and value to explore. A series of clinical trials targeting signaling have been launched continually. In this review, we introduce current advances in the understanding of Notch and Hedgehog signaling and the crosstalk between pathways in specific tumor cell populations and microenvironments. Moreover, we also discuss the potential of targeting Notch and Hedgehog for cancer therapy, intending to promote the leap from bench to bedside.
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Tumors are comprised of both cancer cells and surrounding stromal components. As an essential part of the tumor microenvironment, the tumor stroma is highly dynamic, heterogeneous and commonly tumor-type specific, and it mainly includes noncellular compositions such as the extracellular matrix and the unique cancer-associated vascular system as well as a wide variety of cellular components including activated cancer-associated fibroblasts, mesenchymal stromal cells, pericytes. All these elements operate with each other in a coordinated fashion and collectively promote cancer initiation, progression, metastasis and therapeutic resistance. Over the past few decades, numerous studies have been conducted to study the interaction and crosstalk between stromal components and neoplastic cells. Meanwhile, we have also witnessed an exponential increase in the investigation and recognition of the critical roles of tumor stroma in solid tumors. A series of clinical trials targeting the tumor stroma have been launched continually. In this review, we introduce and discuss current advances in the understanding of various stromal elements and their roles in cancers. We also elaborate on potential novel approaches for tumor-stroma-based therapeutic targeting, with the aim to promote the leap from bench to bedside.
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Fibroblastos Asociados al Cáncer , Células Madre Mesenquimatosas , Neoplasias , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Microambiente Tumoral , Fibroblastos Asociados al Cáncer/patología , Matriz Extracelular , Células Madre Mesenquimatosas/patología , Células del Estroma/patologíaRESUMEN
Background: Pancreatic squamous cell carcinoma (PSCC) is a rare pancreatic malignancy compared to most common pancreatic adenocarcinoma (PAC). Aims: To analyze the prognostics factors of PSCC and compare PAC with PSCC in demographic patterns, clinicopathologic characteristics and treatment modalities. Methods: Data of PSCC and PAC patients from January 1, 2004 to December 31, 2015 were extracted from Surveillance, Epidemiology and End Results (SEER) database for case-control study. Kaplan-Meier method and Cox proportional hazards analysis were used in survival analysis. A 1:3 propensity-score matching (PSM) was performed to compare the overall survival (OS) and cancer specific survival (CSS) between PAC and PSCC in each variable. Results: PAC patients (n = 38â 968) and PSCC patients (n = 124) were analyzed. After PSM, 372 PAC patients and 124 PSCC patients were obtained. PSCC tends to happen to elders, white and female with a predilection site of pancreatic head, followed by tail, then body. PSCC have a higher proportion to be poorly differentiated and metastatic when diagnosed. The prognosis of PSCC patients was significantly worse than PAC patients in both univariate and multivariate analyses. Surgery and chemotherapy were independent prognostic factors for PSCC. Conclusions: PSCC patients were identified associated with a worse prognosis than PAC patients. PSCC tend to be poorly differentiated and more easily to be metastatic. Surgery and chemotherapy may be effective therapies to improve the OS of PSCC significantly.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Pancreáticas , Adenocarcinoma/epidemiología , Adenocarcinoma/terapia , Anciano , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/terapia , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/terapia , Pronóstico , Puntaje de Propensión , Programa de VERF , Neoplasias PancreáticasRESUMEN
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 receptor/ligand have revolutionized cancer treatment, achieving unprecedented efficacy in numerous malignancies. Despite the excellent therapeutic effects of ICIs, medications, such as pembrolizumab, ipilimumab, nivolumab, atezolizumab, avelumab, and durvalumab, typically cause a broad spectrum of toxicity events termed as immune-related adverse events (irAEs). Out of all irAEs, ophthalmic adverse events occur infrequently and are not comprehensively recognized. The current understanding of ophthalmic irAEs is mainly derived from case reports and case series. In this review, based on relevant articles in the literature and current evidence, we summarize the incidences, manifestations, diagnoses, underlying mechanisms, treatments, and outcomes of ophthalmic irAEs and discuss possible management strategies. A better understanding of these features is critical for managing patients with ICI-associated ophthalmic adverse events.
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Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of multiple malignancies, especially in non-small cell lung cancer (NSCLC). With the extensive application of ICIs in clinical practice, clinicians have to manage their toxicities, which are often termed immune-related adverse events (irAEs). Several ICIs, such as nivolumab, pembrolizumab, atezolizumab, and durvalumab, have been approved by the US Food and Drug Administration (FDA) to treat advanced NSCLC, accompanied by a broad spectrum of toxicity reactions. However, ICIs-associated neurological toxicities, regarding polyneuropathy, Bell palsy, encephalopathy, and myasthenia gravis, as uncommon emerging toxicities have not been well recognized, present a challenge for clinicians to improve awareness of supervision, recognition, and management before death from them. Herein, we have summarized the incidence, diagnosis, clinical manifestations, potential mechanisms, treatments, and outcomes of ICIs-related neurotoxicity and optimized the management approach for NSCLC patients. Prompt recognition and proper management are indispensable to reduce the morbidity of these patients with immune-related neurological toxicities.
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Ikaros is a zinc finger transcription factor (TF) of the Krüppel family member, which significantly regulates normal lymphopoiesis and tumorigenesis. Ikaros can directly initiate or suppress tumor suppressors or oncogenes, consequently regulating the survival and proliferation of cancer cells. Over recent decades, a series of studies have been devoted to exploring and clarifying the relationship between Ikaros and associated tumors. Therapeutic strategies targeting Ikaros have shown promising therapeutic effects in both pre-clinical and clinical trials. Nevertheless, the increasingly prominent problem of drug resistance targeted to Ikaros and its analog is gradually appearing in our field of vision. This article reviews the role of Ikaros in tumorigenesis, the mechanism of drug resistance, the progress of targeting Ikaros in both pre-clinical and clinical trials, and the potential use of associated therapy in cancer therapy.
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The chemokine ligand CCL2 and its receptor CCR2 are implicated in the initiation and progression of various cancers. CCL2 can activate tumour cell growth and proliferation through a variety of mechanisms. By interacting with CCR2, CCL2 promotes cancer cell migration and recruits immunosuppressive cells to the tumour microenvironment, favouring cancer development. Over the last several decades, a series of studies have been conducted to explore the CCL2-CCR2 signalling axis function in malignancies. Therapeutic strategies targeting the CCL2- CCR2 axis have also shown promising effects, enriching our approaches for fighting against cancer. In this review, we summarize the role of the CCL2-CCR2 signalling axis in tumorigenesis and highlight recent studies on CCL2-CCR2 targeted therapy, focusing on preclinical studies and clinical trials.
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Quimiocina CCL2/metabolismo , Neoplasias/metabolismo , Receptores CCR2/metabolismo , Transducción de Señal/fisiología , Animales , Carcinogénesis/metabolismo , Movimiento Celular/fisiología , Proliferación Celular/fisiología , HumanosRESUMEN
PURPOSE: This aim of this study was to provide a comprehensive understanding of the clinical characteristics, treatment, and prognosis of patients with small bowel adenocarcinoma (SBA), mucinous small bowel adenocarcinoma (MSBA), and signet ring cell carcinoma of the small bowel (SRCSB). METHODS: Information on patients with SBA, MSBA, and SRCSB (2004-2015) was obtained from the Surveillance, Epidemiology and End Results (SEER) database. Cox proportional hazards models and Kaplan-Meier curves were used for the survival analyses. Propensity-score matching (PSM) was implemented to determine the differences among these tumors. RESULTS: In all, 3697 patients with SBA (n = 3196), MSBA (n = 325) and SRCSB (n = 176) were ultimately eligible for this study. Poor differentiation, local invasion, and lymph node metastasis were more likely to be observed in SRCSB than in SBA and MSBA. Surgery was the most common treatment modality in all groups. The prognosis of SBA was similar to that of MSBA, but better than that of SRCSB in both unmatched and matched cohorts. M stage, surgery, and chemotherapy were identified as independent predictors of survival in all patients. Surgery and chemotherapy could significantly improve outcomes in all groups before and after PSM. Radiotherapy was associated with a survival benefit in patients with SBA, but this trend was not maintained after PSM. Survival advantages of SBA and MSBA were remarkable in the stratified analysis of surgery after PSM. CONCLUSION: Patients with SRCSB had the worst prognosis among all histological types examined. However, surgery and chemotherapy could improve patients survival, regardless of histological type.
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Adenocarcinoma Mucinoso/patología , Adenocarcinoma/patología , Carcinoma de Células en Anillo de Sello/patología , Neoplasias Duodenales/patología , Neoplasias del Íleon/patología , Neoplasias del Yeyuno/patología , Adenocarcinoma/mortalidad , Adenocarcinoma/terapia , Adenocarcinoma Mucinoso/mortalidad , Adenocarcinoma Mucinoso/terapia , Adulto , Anciano , Antineoplásicos/uso terapéutico , Neoplasias Óseas/secundario , Neoplasias Encefálicas/secundario , Carcinoma de Células en Anillo de Sello/mortalidad , Carcinoma de Células en Anillo de Sello/terapia , Procedimientos Quirúrgicos del Sistema Digestivo , Neoplasias Duodenales/mortalidad , Neoplasias Duodenales/terapia , Femenino , Humanos , Neoplasias del Íleon/mortalidad , Neoplasias del Íleon/terapia , Neoplasias del Yeyuno/mortalidad , Neoplasias del Yeyuno/terapia , Estimación de Kaplan-Meier , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Programa de VERFRESUMEN
Hepatoid adenocarcinoma of the stomach (HAS) is a rare malignant tumor, accounting for only 0.17-15% of gastric cancers. Patients are often diagnosed at an advanced disease stage, and their symptoms are similar to conventional gastric cancer (CGC) without specific clinical manifestation. Morphologically, HAC has identical morphology and immunophenotype compared to hepatocellular carcinoma (HCC). This is considered to be an underestimation in diagnosis due to its rare incidence, and no consensus is reached regarding therapy. HAS generally presents with more aggressive behavior and worse prognosis than CGC. The present review summarizes the current literature and relevant knowledge to elaborate on the epidemic, potential mechanisms, clinical manifestations, diagnosis, management, and prognosis to help clinicians accurately diagnose and treat this malignant tumor.
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BACKGROUND: Thyroid function abnormality (TFA) is a common immune-related adverse event (irAEs), but the association between it and the efficacy of programmed cell death protein 1 (PD-1) inhibitor in advanced non-small cell lung cancer (NSCLC) is finitely understood. MATERIALS AND METHODS: We conducted a single center, retrospective study of advanced NSCLC patients who were treated with PD-1 inhibitors between 10 October 2016 and 1 April 2020. TFA was characterized as new onset subclinical hypothyroidism, overt hypothyroidism, subclinical hyperthyroidism and overt hyperthyroidism. Frequency of development of TFA-irAEs, and its relationship with overall survival (OS) and progression free survival (PFS) were evaluated. RESULTS: In our study, 191 patients were treated with PD-1 inhibitors. Among them, forty patients (20.9%) developed TFA, of whom 10 (5.2%) presented with subclinical hypothyroidism, 15 (7.9%) with overt hypothyroidism, 6 (3.1%) with subclinical hyperthyroidism and 9 (4.7%) with overt hyperthyroidism. Survival analysis showed that the OS (16.8 months vs. 11.1 months, p < 0.001) and PFS (10.4 months vs. 5.5 months, p < 0.001) were significantly longer in patients with TFA-irAEs than in those without TFA-irAEs. In subgroup analysis of hypothyroidism and hyperthyroidism groups, similar trends were also obtained for both OS and PFS. After adjusting for potential confounding variables, patients with TFA-irAEs had a lower mortality risk (HR 0.334, 95%CI 0.196-0.571) than those without TFA-irAEs. CONCLUSIONS: TFA-irAEs is associated with enhanced PD-1 inhibitor efficacy in advanced NSCLC patients and it may be a biomarker for antitumor immune response.