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Autologous peripheral blood stem cell (PBSC) transplantation is crucial in pediatric cancer treatment, and tandem transplantation is beneficial in certain malignancies. Collecting PBSCs in small children with low body weight is challenging. We retrospectively analyzed data of pediatric cancer patients weighing <15 kg who underwent autologous PBSC harvesting in our hospital. Collections were performed in the pediatric intensive care unit over 2 or 3 consecutive days, to harvest sufficient stem cells (goal ≥2 × 106 CD34+ cells/kg per apheresate). From April 2006 to August 2021, we performed 129 collections after 50 mobilizations in 40 patients, with a median age of 1.9 (range, 0.6-5.6) years and a body weight of 11.0 (range, 6.6-14.7) kg. The median CD34+ cells in each apheresate were 4.2 (range, 0.01-40.13) × 106/kg. 78% and 56% of mobilizations achieved sufficient cell dose for single or tandem transplantation, respectively, without additional aliquoting. The preapheresis hematopoietic progenitor cell (HPC) count was highly correlated with the CD34+ cell yield in the apheresate (r = 0.555, P < 0.001). Granulocyte colony-stimulating factor alone was not effective for mobilization in children ≥2 years of age, even without radiation exposure. By combining the preapheresis HPC count ≥20/µL and the 3 significant host factors, including age <2 years, no radiation exposure and use of chemotherapy, the prediction rate of goal achievement was increased (area under the curve 0.787).
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Gastric neoplasm is a high-mortality cancer worldwide. Chemoresistance is the obstacle against gastric cancer treatment. Mitochondrial dysfunction has been observed to promote malignant progression. However, the underlying mechanism is still unclear. The mitokine growth differentiation factor 15 (GDF15) is a significant biomarker for mitochondrial disorder and is activated by the integrated stress response (ISR) pathway. The serum level of GDF15 was found to be correlated with the poor prognosis of gastric cancer patients. In this study, we found that high GDF15 protein expression might increase disease recurrence in adjuvant chemotherapy-treated gastric cancer patients. Moreover, treatment with mitochondrial inhibitors, especially oligomycin (a complex V inhibitor) and salubrinal (an ISR activator), respectively, was found to upregulate GDF15 and enhance cisplatin insensitivity of human gastric cancer cells. Mechanistically, it was found that the activating transcription factor 4-C/EBP homologous protein pathway has a crucial function in the heightened manifestation of GDF15. In addition, reactive oxygen species-activated general control nonderepressible 2 mediates the oligomycin-induced ISR, and upregulates GDF15. The GDF15-glial cell-derived neurotrophic factor family receptor a-like-ISR-cystine/glutamate transporter-enhanced glutathione production was found to be involved in cisplatin resistance. These results suggest that mitochondrial dysfunction might enhance cisplatin insensitivity through GDF15 upregulation, and targeting mitokine GDF15-ISR regulation might be a strategy against cisplatin resistance of gastric cancer.
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Cisplatino , Neoplasias Gástricas , Humanos , Cisplatino/farmacología , Neoplasias Gástricas/patología , Regulación hacia Arriba , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/metabolismo , OligomicinasRESUMEN
BACKGROUND: Donor lymphocyte infusion (DLI) is effective for managing patients with hematologic malignancies after allogeneic hematopoietic stem cell transplant (HSCT). However, few studies have explored its optimal use in pediatric populations. Herein, we report our single-center experiences of DLI and factors for predicting its outcomes. METHODS: This retrospective study included pediatric patients who had received DLI (between June 1998 and December 2022) after allogeneic HSCT. Data regarding patient characteristics, preemptive DLI disease status, and DLI characteristics were collected. The primary outcomes were overall survival (OS), event-free survival (EFS), and graft-vs-host-disease (GVHD) development. RESULTS: The study cohort comprised 17 patients with acute leukemia, 3 with chronic leukemia, and 3 with lymphoma. Prophylactic, preemptive, and therapeutic DLI were used in seven, seven, and nine patients, respectively. Patients' median age and DLI dose were 9 years and 4.6 × 10 7 CD3 + cells/kg, respectively. The 5-year OS, EFS, and nonrelapse mortality were 43.5%, 38.3%, and 13.3%, respectively. Approximately 39% of the patients developed grade III or IV acute GVHD, whereas moderate/severe chronic GVHD (cGVHD) occurred in 30% of the evaluable patients. Patients' disease status before HSCT ( p = 0.009) and DLI ( p = 0.018) were the key factors influencing EFS. The implementation of a dose escalation schedule was associated with a marginal reduction in the risk of moderate/severe cGVHD ( p = 0.051). A DLI dose of ≥5 × 10 7 CD3 + cells/kg was significantly associated with a high moderate to severe cGVHD risk ( p = 0.002) and reduced OS ( p = 0.089). CONCLUSION: Patients' disease status before HSCT and DLI may help predict EFS. The use of DLI as a prophylactic and preemptive modality leads to a favorable 5-year EFS. To safely deliver DLI in children, clinicians must maintain vigilant monitoring and prepare patients in advance when escalating the dose to ≥5 × 10 7 CD3 + cells/kg.
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Enfermedad Injerto contra Huésped , Neoplasias Hematológicas , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Humanos , Niño , Estudios Retrospectivos , Transfusión de Linfocitos , Enfermedad Crónica , Linfocitos , RecurrenciaRESUMEN
Methylmercury can interfere with the normal functioning of the nervous system, causing a variety of behavioral and physiological changes in fish. However, the influence of MeHg on the lateral line sensory and ion-regulatory functions of fish is not clear. Zebrafish embryos were utilized as a model to address this question. After exposure to water-borne MeHg (5, 10, 50, or 100 ppb) for 96 h (4-100 h post-fertilization), the survival rate declined by ca. 50 % at 100 ppb. However, MeHg at sublethal concentrations delayed hatching and decreased heart rates and body length. As to effects on the lateral line sensory system, MeHg at ≥10 ppb decreased the number of hair cells and impaired hair bundles and Ca2+-mediated mechanical transduction. As to ion regulation, MeHg at ≥10 ppb decreased the densities of skin stem cells and ionocytes, leading to declines in ion (Na+, K+, and Ca2+) contents and H+/NH4+ excretion levels. A gene expression analysis also revealed declines in messenger RNA levels of several ion-regulatory genes (ncc2b, trpv6v1a, trpv5/6, ncx1b, and rhcg1). This study demonstrated that the lateral line sensory and ion regulatory functions of fish are extremely sensitive to MeHg.
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Sistema de la Línea Lateral , Compuestos de Metilmercurio , Animales , Pez Cebra/metabolismo , Compuestos de Metilmercurio/toxicidad , PielRESUMEN
Gastric cancer is a common cancer worldwide, particularly in East Asia. Chemotherapy is used in adjuvant or palliative therapies for gastric cancer. However, subsequent chemoresistance often develops. Growth differentiation factor 15 (GDF15) links to several cancers, but its effect on chemoresistance in gastric cancer remains unclear. Here, we analyzed clinical samples from genetic databases and included patients with gastric cancer. We dissected the regulatory mechanism underlying GDF15-mediated resistance of cisplatin in human gastric cancer cells. We showed that GDF15 serum levels might be a valuable biomarker for predicting prognosis in gastric cancer. The expressions of GDF15 and its receptor glial cell-derived neurotrophic factor family receptor a-like (GFRAL) in gastric tumors are important for malignant progression. Moreover, GDF15 expression is increased in gastric cancer cells with cisplatin resistance, resulting from elevated intracellular glutathione (GSH) and antioxidant activities. Upregulated GDF15 could increase intracellular GSH content by activating the GFRAL-GCN2-eIF2α-ATF4 signaling, enhancing cystine-uptake transporter xCT expression, and contributing biosynthesis of GSH in human gastric cancer cells. In conclusion, our results indicate that GDF15 could induce chemoresistance by upregulating xCT expression and GSH biosynthesis in human gastric cancer cells. Targeting GDF15 could be a promising treatment method for gastric cancer progression.
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Cisplatino , Neoplasias Gástricas , Humanos , Cisplatino/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Regulación hacia Arriba , Factor 15 de Diferenciación de Crecimiento/genética , Factor 15 de Diferenciación de Crecimiento/metabolismo , Glutatión/metabolismoRESUMEN
OBJECTIVES: To (1) modify the Mandarin-language 34-item Supportive Care Needs Survey-Adult Form into the Adolescent Form and (2) examine the psychometric properties of the Adolescent Form. DATA SOURCES: A multiphase, iterative scale validation process was used in this methodological study. Participants who were 13 to 18 years old and receiving cancer treatment in inpatient or outpatient settings, or receiving follow-up care in outpatient settings, were recruited using a convenience sampling method. Confirmatory factor analysis demonstrated good fitness of indices, and all factor loadings for the 18-item Adolescent Form were >0.50, which supported the scale's construct validity. The Adolescent Form score was significantly correlated with the symptom distress score (râ¯=â¯0.56, P < .01) and quality of life score (râ¯=â¯-0.65, P < .01), which indicated the scale's convergent validity. The correlated item-total correlations (0.30-0.78), Cronbach's alpha (.93), and test-retest reliability coefficient (0.79) confirmed the scale's stability. CONCLUSION: This study successfully modified the 34-item Adult Form into the 18-item Adolescent Form. Given its adequate psychometric properties, this concise scale has great promise as a useful, feasible, and age-appropriate tool for evaluating care needs among adolescents with cancer who speak Mandarin. IMPLICATIONS FOR NURSING PRACTICE: This scale can screen for unmet care needs in busy pediatric oncology settings or large-scale clinical trials. It allows for cross-sectional comparison of unmet care needs between adolescent and adult populations and for longitudinal follow-up into how unmet care needs change from adolescence into adulthood.
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Lenguaje , Calidad de Vida , Adulto , Niño , Humanos , Adolescente , Reproducibilidad de los Resultados , Estudios Transversales , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Malignant germ cell tumors (MGCTs) can develop either extracranially or intracranially. Growing teratoma syndrome (GTS) may develop in these patients following chemotherapy. Reports on the clinical characteristics and outcomes of GTS in children with MGCTs are limited. METHODS: We retrospectively collected the data, including the clinical characteristics and outcomes of five patients in our series and 93 pediatric patients selected through a literature review of MGCTs. This study aimed to analyze survival outcomes and risk factors for subsequent events in pediatric patients with MGCTs developing GTS. RESULTS: The sex ratio was 1.09 (male/female). In total, 52 patients (53.1%) had intracranial MGCTs. Compared with patients with extracranial GCTs, those with intracranial GCTs were younger, predominantly boys, had shorter intervals between MGCT and GTS, and had GTS mostly occurring over the initial site (all p < 0.001). Ninety-five patients (96.9%) were alive. However, GTS recurrence (n = 14), GTS progression (n = 9), and MGCT recurrence (n = 19) caused a substantial decrease in event-free survival (EFS). Multivariate analyses showed that the only significant risk factors for these events were incomplete GTS resection and different locations of GCT and GTS. Patients without any risk had a 5-year EFS of 78.8% ± 7.8%, whereas those with either risk had 41.7% ± 10.2% (p < 0.001). CONCLUSION: For patients with high-risk features, every effort should be made to closely monitor, completely remove, and pathologically prove any newly developed mass to guide relevant treatment. Further studies incorporating the risk factors into treatment strategies may be required to optimize adjuvant therapy.
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Neoplasias de Células Germinales y Embrionarias , Teratoma , Neoplasias Testiculares , Humanos , Niño , Masculino , Femenino , Teratoma/patología , Teratoma/cirugía , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/terapia , SíndromeRESUMEN
BACKGROUND: Taiwanese patients frequently experience severe hepatotoxicity associated with high-dose methotrexate (HD-MTX) treatment, which interferes with subsequent treatment. Drug-drug interactions occur when MTX is used in combination with proton pump inhibitors (PPIs), trimethoprim-sulfamethoxazole (TMP-SMX), or non-steroidal anti-inflammatory drugs (NSAIDs). In East Asia, real-world analyses on the effects of co-medication and other potential risk factors on the clinical course of HD-MTX-mediated acute hepatotoxicity in patients with osteogenic sarcoma (OGS) are limited. METHODS: This cohort study included patients with newly diagnosed OGS who were treated with HD-MTX between 2009 and 2017 at Taipei Veterans General Hospital. We collected data on the clinical course of HD-MTX-mediated acute hepatotoxicity, co-medications, and other potential risk factors, and analyzed the effects of these factors on the clinical course of HD-MTX-mediated acute hepatotoxicity. RESULTS: Almost all patients with OGS treated with HD-MTX developed acute hepatotoxicity with elevated alanine aminotransferase (ALT) levels. Most patients with Grade 3-4 ALT elevation failed to recover to Grade 2 within 7 days. Women and children are high-risk subgroups for HD-MTX-mediated elevation of ALT levels. Age is a factor that contributes to the pharmacokinetic differences of HD-MTX. However, the concurrent use of PPIs, TMP-SMX, or NSAIDs did not affect the elimination of MTX when administered with adequate supportive therapy. CONCLUSIONS: Co-administration of PPIs, TMP-SMX, or NSAIDs may have limited effects on acute hepatotoxicity in well-monitored and adequately pre-medicated patients with OGS undergoing chemotherapy with HD-MTX. Clinicians should pay particular attention to ALT levels when prescribing HD-MTX to children and women.
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Neoplasias Óseas , Enfermedad Hepática Inducida por Sustancias y Drogas , Osteosarcoma , Niño , Humanos , Femenino , Metotrexato , Combinación Trimetoprim y Sulfametoxazol/efectos adversos , Estudios de Cohortes , Osteosarcoma/tratamiento farmacológico , Antiinflamatorios no Esteroideos , Inhibidores de la Bomba de Protones/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Factores de Riesgo , Enfermedad Hepática Inducida por Sustancias y Drogas/diagnóstico , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Progresión de la EnfermedadRESUMEN
This study aimed to describe and compare the differences in walking performance between adolescent patients in inpatient wards and outpatient units, and to identify factors that influence walking performance among adolescents receiving cancer treatment. The cross-sectional study with correlational research design recruited 32 adolescents with cancer between February 2015 and March 2017 in two teaching hospitals in Taiwan. Descriptive, bivariate, and multivariate regression analyses were used. Participants' age, treatment setting, and symptom distress were significantly associated with number of walking steps. All independent variables in the model together accounted for 82.1% of variance. This study addresses a gap in the existing literature to identify associated factors that affected walking performance among adolescents undergoing cancer treatment. Our findings represent a pathway toward generating knowledge to enhance well-being for this unique population.
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Neoplasias , Humanos , Adolescente , Estudios Transversales , Neoplasias/terapia , Caminata , Taiwán , HospitalesRESUMEN
BACKGROUND: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. METHODS: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. RESULTS: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS. CONCLUSIONS: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.
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Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Niño , Humanos , Adolescente , Recién Nacido , Lactante , Preescolar , Pronóstico , Cisplatino , Carboplatino/uso terapéutico , Estudios Retrospectivos , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/cirugía , Neoplasias del Mediastino/terapiaRESUMEN
Complement-mediated hemolytic uremic syndrome (CM-HUS) following chemotherapy for pediatric acute lymphoid neoplasms has rarely been reported. We report the case of an 8-year-old boy with T-lymphoblastic lymphoma (T-LBL) who developed CM-HUS with complement factor H (CFH) mutations (S1191L, V1197A) during induction therapy. Safe administration of chemotherapy after CM-HUS recovery was challenging. By closely monitoring hemolytic and renal parameters during the 2-year treatment period, we observed four episodes of microangiopathic hemolytic anemia (MAHA) with hypocomplementemia and low haptoglobin but no renal dysfunction or thrombocytopenia. Here, we describe the MAHA and CM-HUS episodes in the hopes of elucidating the complex pathophysiology of disorders associated with CFH mutation.
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Síndrome Hemolítico Urémico Atípico , Síndrome Hemolítico-Urémico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Púrpura Trombocitopénica Trombótica , Masculino , Humanos , Niño , Factor H de Complemento/genética , Factor H de Complemento/uso terapéutico , Hemólisis , Haptoglobinas/uso terapéutico , Síndrome Hemolítico-Urémico/genética , Síndrome Hemolítico-Urémico/patología , Síndrome Hemolítico-Urémico/terapia , Púrpura Trombocitopénica Trombótica/terapia , Proteínas del Sistema Complemento , Síndrome Hemolítico Urémico Atípico/tratamiento farmacológico , Síndrome Hemolítico Urémico Atípico/genéticaRESUMEN
Pharmaceuticals and personal care products are emerging environmental pollutants. Cisplatin, one of the most widely used platinum-based chemotherapeutic agents, has been found to contaminate aquatic environments. Using zebrafish embryos as a model, cisplatin was previously found to impair skin ionocytes and ion regulation. The purpose of this study was to further investigate how cisplatin damages ionocytes. Zebrafish embryos were exposed to cisplatin (0, 50, and 100 µM) for 96 h (4-100 h post-fertilization) and then stained with fluorescent dyes to reveal mitochondrial activity (rhodamine123), apoptosis (acridine orange), and oxidative stress (CellROX/MitoSOX) in ionocytes of living embryos. Results showed that cisplatin exposure decreased rhodamine 123-labeled ionocytes, induced oxidative stress in ionocytes, and promoted apoptosis in a concentration-dependent manner. Quantitative PCR analysis showed that mRNA levels of antioxidative genes (sod1, sod2, gpx1a, and cat) and an apoptotic gene (caps3a) were induced. In the time-course experiment at 96-98 h post-fertilization, cisplatin increased oxidative stress and apoptosis in ionocytes in a time-dependent manner. In conclusion, this study demonstrates that cisplatin exposure induces oxidative stress, mitochondrial damage, and apoptosis in ionocytes of zebrafish embryos.
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Contaminantes Químicos del Agua , Pez Cebra , Animales , Apoptosis/genética , Cisplatino/metabolismo , Cisplatino/toxicidad , Embrión no Mamífero/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo/genética , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/genéticaRESUMEN
BACKGROUND: Patients with childhood cancer are at increased risk for the development of second cancers. METHODS: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. RESULTS: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. CONCLUSION: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.
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Neoplasias Primarias Secundarias , Neoplasias , Niño , Humanos , Neoplasias/epidemiología , Neoplasias Primarias Secundarias/epidemiología , Estudios Retrospectivos , Taiwán/epidemiologíaRESUMEN
Silver nanoparticles (AgNPs) are increasingly used in our daily life and have become a potential environmental hazard. However, the toxic effects of AgNPs on the early stages of fish are not fully understood, and little is known about their effects on specific types of ionocytes. Using zebrafish embryos as a model, this study examined the effects (changes in cell number, morphology, NH4+ secretion and gene expression) of sublethal concentrations of AgNPs (0.1, 1, and 3 mg/L) on two major types of ionocytes: H+ pump-rich (HR) ionocytes, and Na+ pump-rich (NaR) ionocytes in the skin of embryos. After exposure to AgNPs for 96 h, the number of HR ionocytes significantly declined by 30% and 41% in the 1 and 3 mg/L AgNP groups, respectively. In addition, the apical opening of HR ionocytes became smaller, suggesting that AgNPs impaired the critical structure for ion transport. NH4+ secretion by HR ionocytes of embryos also declined significantly after AgNP exposure. In contrast, the number of NaR ionocytes increased by 29% and 43% in the 1 and 3 mg/L AgNP groups, respectively, while these cells deformed their shape. AgNPs altered mRNA levels of several ion channel and transporter genes involved in the functions of HR ionocytes and NaR ionocytes, and influenced hormone genes involved in regulating calcium homeostasis. This study shows that AgNPs can cause differential adverse effects on two types of ionocytes and the effects can threaten fish survival.
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Embrión no Mamífero/efectos de los fármacos , Nanopartículas del Metal/química , Mitocondrias/efectos de los fármacos , Plata/toxicidad , Animales , Transporte Iónico , Plata/química , Contaminantes Químicos del Agua/toxicidad , Pez CebraRESUMEN
Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.
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Leucemia Mieloide Aguda/tratamiento farmacológico , Adolescente , Antineoplásicos/uso terapéutico , Niño , Preescolar , Análisis Citogenético , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Incidencia , Lactante , Recién Nacido , Leucemia Mieloide Aguda/genética , Masculino , Proteínas de Neoplasias/metabolismo , Recurrencia Local de Neoplasia/patología , Supervivencia sin Progresión , Estudios Retrospectivos , Taiwán , Factores de Tiempo , Resultado del TratamientoRESUMEN
We herein report the case of a girl with PRETEXT III hepatoblastoma (HB) developing recurrent lung metastases despite multiple chemotherapy regimens, aggressive tumor excision, multiple lung metastasectomies, and autologous peripheral blood stem cell transplantation. High tumor mutation burden (TMB) was identified through targeted next-generation sequencing, and pembrolizumab was administered post-operatively as a last resort. A complete and sustained response to the immune checkpoint inhibitor was achieved for 22 months. Although the majority of HB have a low TMB, immune checkpoint inhibitor therapy may be useful for patients with refractory HBs with a high TMB.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Hepatoblastoma/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/secundario , Preescolar , Femenino , Hepatoblastoma/patología , Humanos , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Trasplante de Células Madre , Resultado del TratamientoRESUMEN
Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.
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Antineoplásicos/farmacología , Calcio/metabolismo , Proteínas de Peces/farmacología , Mitocondrias/efectos de los fármacos , Proteínas Citotóxicas Formadoras de Poros/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sarcoma Sinovial/tratamiento farmacológico , Tilapia/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Humanos , Mitocondrias/fisiología , Sarcoma Sinovial/metabolismoRESUMEN
Environmental contamination by anticancer pharmaceuticals has been widely reported. These drugs are not readily biodegradable, and their parent compounds and/or metabolites have been detected in surface waters and groundwater throughout the world. Adverse effects of anticancer drugs occur frequently in cancer patients, and a large body of clinical knowledge has accumulated. However, the effects of these drugs on aquatic organisms have not been thoroughly studied. This study aimed to investigate the effects of acute exposure to a common anticancer drug, vincristine (VCR), on zebrafish embryonic development and skin function. After 96 h of VCR exposure (0, 1, 10, 15, and 25 mg/L), significant teratogenic effects were observed, including growth retardation, pericardial edema, spine, tail, and yolk sac malformations (VCR ≥ 15 mg/L), a decreased heart rate, and ocular malformations (VCR ≥ 10 mg/L). The value of the half lethal concentration for zebrafish embryos was 20.6 mg/L. At ≥10 mg/L VCR, systemic ion contents and acid secretion in the skin over the yolk-sac decreased, and these findings were associated with decreases in skin ionocytes (H+-ATPase-rich cells and Na+-K+-ATPase-rich cells). Also, the microridge-structure of skin keratinocytes was significantly damaged. The number of lateral line hair cells was reduced when VCR was ≥10 mg/L, and functional impairment was detected when VCR was as low as 1 mg/L. Results of this in vivo study in zebrafish embryos indicate that acute exposure to VCR can lead to developmental defects, impairment of skin functions, and even fish death.
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Embrión no Mamífero/efectos de los fármacos , Células Ciliadas Auditivas/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Sistema de la Línea Lateral/efectos de los fármacos , Piel/efectos de los fármacos , Vincristina/toxicidad , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/crecimiento & desarrollo , Animales , Desarrollo Embrionario/efectos de los fármacos , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/patología , Humanos , Queratinocitos/metabolismo , Queratinocitos/patología , Piel/metabolismo , Piel/patología , Pez Cebra/metabolismo , Proteínas de Pez Cebra/metabolismoRESUMEN
OBJECTIVE: To provide strategies for monitoring and treating severe lung involvement in Gaucher disease. STUDY DESIGN: We reviewed the chart of a 5-year-old boy who developed rapidly progressive, severe infiltrative lung involvement of Gaucher disease (GD) and improved after allogeneic hematopoietic stem cell transplant (HSCT), along with other case studies reported before December 2019. He was diagnosed with GD (homozygous mutation at c.1448 T > C, p.L483P), and started receiving enzyme replacement therapy (ERT) at 17 months old. He developed respiratory distress symptoms after 45 months of ERT; chest imaging reported diffuse interstitial infiltration of the bilateral lungs and consolidations at the right lungs. Allogeneic HSCT using cells from a matched unrelated donor was performed four months upon progressive respiratory symptoms. RESULTS: His respiratory symptoms subsided in one month; chest imaging improvement, pulmonary function test improvement, and normalized activity of ß-glucocerebrosidase were reported in three months. CONCLUSION: This is the first report of a patient who received early and regular ERT but developed severe infiltrative lung involvement and recovered after allogeneic HSCT. Based on study results, we suggest regular chest imaging, even for asymptomatic patients. For patients with severe lung involvement, rapid deterioration, and unresponsive to higher ERT dosages, allogeneic HSCT should be considered.
RESUMEN
Ammonia (including NH3 and NH4+) is a major pollutant of freshwater environments. However, the toxic effects of ammonia on the early stages of fish are not fully understood, and little is known about the effects on the sensory system. In this study, we hypothesized that ammonia exposure can cause adverse effects on embryonic development and impair the lateral line system of fish. Zebrafish embryos were exposed to high-ammonia water (10, 15, 20, 25, and 30 mM NH4Cl; pH 7.0) for 96 h (0-96 h post-fertilization). The body length, heart rate, and otic vesicle size had significantly decreased with ≥15 mM NH4Cl, while the number and function of lateral-line hair cells had decreased with ≥10 mM NH4Cl. The mechanoelectrical transduction (MET) channel-mediated Ca2+ influx was measured with a scanning ion-selective microelectrode technique to reveal the function of hair cells. We found that NH4+ (≥5 mM NH4Cl) entered hair cells and suppressed the Ca2+ influx of hair cells. Neomycin and La3+ (MET channel blockers) suppressed NH4+ influx, suggesting that NH4+ enters hair cells via MET channels in hair bundles. In conclusion, this study showed that ammonia exposure (≥10 mM NH4Cl) can cause adverse effects in zebrafish embryos, and lateral-line hair cells are sensitive to ammonia exposure.