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1.
Neoplasma ; 69(2): 464-473, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35068159

RESUMO

Neuroblastoma (NB) is one of the most common extracranial malignant solid tumors in childhood, and over 90% of NBs are diagnosed in children under the age of 10 years old. For patients between 14 and 18 years old or older than 18 years, due to the rarity of NB, few studies have been performed in this population. Defined "adolescent cases" as individuals in 14-18 years old and "adult cases" as older than 18 years old, we reported five NB cases of adolescents and adults in our hospital. 137 cases presented a review of published literature on this topic. Clinicopathological factors and treatment modalities used of the 142 patients were assessed for their prognostic value. Better outcomes were found in adolescent patients rather than adult patients (p=0.012). Patients diagnosed with neuroblastoma or ganglioneuroblastoma (nodular type) (p=0.006) and with distant metastasis (p<0.001) were characterized by poor outcomes. Distant metastasis was an independent adverse influencing factor for overall survival in adolescent and adult NB patients. Regarding treatment modalities, complete surgical resection was a significant factor improving the survival for such patients (p<0.001). For patients with distant metastasis, a significantly longer progression-free survival with chemotherapy than without chemotherapy (p=0.038), whereas chemotherapy did not show an advantage on patients with localized disease (p=0.039). The prognosis of NB in adolescent and adult patients was worse than that in children. These two groups also showed heterogeneity in clinical factors, genetic factors, and treatment tolerance. The rarity of adolescent and adult NB can lead to misdiagnosis and incorrect management. Further optimization of chemotherapy regimens and dosage for adolescent and adult NB patients is needed. The anti-GD2 immunotherapy may be an effective approach for treatment.


Assuntos
Neuroblastoma , Adolescente , Adulto , Criança , Humanos , Imunoterapia , Lactente , Neuroblastoma/tratamento farmacológico , Neuroblastoma/terapia , Prognóstico
2.
Int J Med Sci ; 18(4): 1015-1023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456359

RESUMO

Huaier extract, the main active constituent proteoglycan, has anti-tumor activity in various experimental and clinical settings. However, the potential anti-neuroblastoma and associated mechanisms have not been investigated. Therefore, in this study, we aimed to elucidate the potential role of Huaier extract in 3 human neuroblastoma cell lines. Our study demonstrated that incubation with Huaier extract resulted in a marked decrease in cell viability in a dose-dependent manner. Huaier extract induced cell cycle arrest at G0/G1 phase in neuroblastoma and decreased the cell cycle related protein expression of cyclin D3. Western blotting analysis also showed that Huaier extract induced neuroblastoma cell apoptosis and autophagy. Signaling analysis indicated that Huaier extract suppressed the MEK/ERK and mTOR signaling pathways simultaneously. In conclusion, we verify that Huaier extract causes cell proliferation inhibition, apoptosis, autophagy, and cell cycle arrest in G0/G1 phase via MEK/ERK and mTOR signaling. Huaier extract may act as a complementary agent for treating neuroblastoma.


Assuntos
Misturas Complexas/farmacologia , Neuroblastoma/tratamento farmacológico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Misturas Complexas/isolamento & purificação , Misturas Complexas/uso terapêutico , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neuroblastoma/patologia , Serina-Treonina Quinases TOR/metabolismo , Trametes/isolamento & purificação
3.
Exp Cell Res ; 365(2): 177-184, 2018 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-29499203

RESUMO

Neuroblastoma (NB) is one of the most common solid tumors in children. High-risk NB remains lethal in about 50% of patients despite comprehensive and intensive treatments. Activation of PI3K/Akt/mTOR signaling pathway correlates with oncogenesis, poor prognosis and chemotherapy resistance in NB. Due to its central role in growth and metabolism, mTOR seems to be an important factor in NB, making it a possible target for NB. In this study, we investigated the effect of AZD8055, a potent dual mTORC1-mTORC2 inhibitor, in NB cell lines. Our data showed that mTOR signaling was extensively activated in NB cells. The activity of mTOR and downstream molecules were down-regulated in AZD8055-treated NB cells. Significantly, AZD8055 effectively inhibited cell growth and induced cell cycle arrest, autophagy and apoptosis in NB cells. Moreover, AZD8055 significantly reduced tumor growth in mice xenograft model without apparent toxicity. Taken together, our results highlight the potential of mTOR as a promising target for NB treatment. Therefore, AZD8055 may be further investigated for treatment in clinical trials for high risk NB.


Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Morfolinas/farmacologia , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Animais , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Camundongos Nus , Morfolinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Br J Haematol ; 169(2): 267-77, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25655921

RESUMO

This multicenter study used the Shanghai Children's Medical Center (SCMC)-ALL-2005 protocol for treatment of young patients (<2 years old) with acute lymphoblastic leukaemia (ALL), which was designed to improve treatment outcome in Chinese paediatric patients. These aims were pursued through risk-directed stratification based on presenting clinical and genetic features, minimal residual disease (MRD) levels and treatment response. All the patients achieved completed remission with 5-year event-free survivals of 82·6 ± 9·7% (low risk), 52·6 ± 8·4% (intermediate risk), 28·6 ± 17·1% (high risk). Disease recurrence was detected in bone marrow, bone marrow plus testis, testis alone and central nervous system in 16 (24·2%), 1 (1·5%), 1 (1·5%) and 1 (1·5%) patients respectively. No deaths were reported during induction. The SCMC-ALL-2005 trial for ALL patients <2 years old indicated high remission induction and low infection and treatment-related mortality rates.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Medula Óssea/patologia , Pré-Escolar , Feminino , Humanos , Lactente , Quimioterapia de Manutenção , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Indução de Remissão , Resultado do Tratamento
5.
World J Clin Cases ; 12(1): 148-156, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38292644

RESUMO

BACKGROUND: Elevated levels of cardiac troponin and abnormal electrocardiogram changes are the primary basis for clinical diagnosis of acute coronary syndrome (ACS). Troponin levels in ACS patients can often be more than 50 times the upper reference limit. Some patients with subarachnoid hemorrhage (SAH) also show electrocardiogram abnormalities, myocardial damage, and elevated cardiac biomarkers. Unlike ACS patients, patients with SAH only have a slight increase in troponin, and the use of anticoagulants or antiplatelet drugs is prohibited. Because of the opposite treatment modalities, it is essential for clinicians to distinguish between SAH and ACS. CASE SUMMARY: A 56-year-old female patient was admitted to the emergency department at night with a sudden onset of severe back pain. The final diagnosis was intraspinal hematoma in the thoracic spine. We performed an emergency thoracic spinal canal hematoma evacuation procedure with the assistance of a microscope. Intraoperatively, diffuse hematoma formation was found in the T7-T10 spinal canal, and no obvious spinal vascular malformation changes were observed. Postoperative head and spinal magnetic resonance imaging (MRI) showed a small amount of SAH in the skull, no obvious abnormalities in the cervical and thoracic spinal canals, and no abnormal signals in the lumbar spinal canal. Thoracoabdominal aorta computed tomography angiography showed no vascular malformation. Postoperative motor system examination showed Medical Research Council Scale grade 1/5 strength in both lower extremities, and the patient experienced decreased sensation below the T12 rib margin and reported a Visual Analog Scale score of 3. CONCLUSION: Extremely elevated troponin levels (more than 50 times the normal range) are not unique to coronary artery disease. SAH can also result in extremely high troponin levels, and antiplatelet drugs are contraindicated in such cases. Emergency MRI can help in the early differential diagnosis, as a misdiagnosis of ACS can lead to catastrophic neurological damage in patients with spontaneous spinal SAH.

6.
World J Pediatr ; 2023 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-37770810

RESUMO

BACKGROUND: This study aimed to identify survival risk factors in Chinese children with hepatoblastoma (HB) and assess the effectiveness of the new treatment protocol proposed by the Chinese Children's Cancer Group (CCCG) in 2016. METHODS: A multicenter, prospective study that included 399 patients with HB from January 2015 to June 2020 was conducted. Patient demographics, treatment protocols, and other related information were collected. Cox regression models and Kaplan-Meier curve methods were used. RESULTS: The 4-year event-free survival (EFS) and overall survival (OS) were 76.9 and 93.5%, respectively. The 4-year EFS rates for the very-low-risk, low-risk, intermediate-risk, and high-risk groups were 100%, 91.6%, 81.7%, and 51.0%, respectively. The 4-year OS was 100%, 97.3%, 94.4%, and 86.8%, respectively. Cox regression analysis found that age, tumor rupture (R +), and extrahepatic tumor extension (E +) were independent prognostic factors. A total of 299 patients had complete remission, and 19 relapsed. Patients with declining alpha-fetoprotein (AFP) > 75% after the first two cycles of neoadjuvant chemotherapy had a better EFS and OS than those ≤ 75%. CONCLUSIONS: The survival outcome of HB children has dramatically improved since the implementation of CCCG-HB-2016 therapy. Age ≥ 8 years, R + , and E + were independent risk factors for prognosis. Patients with a declining AFP > 75% after the first two cycles of neoadjuvant chemotherapy had better EFS and OS.

7.
Theor Appl Genet ; 124(2): 249-59, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21971891

RESUMO

The high-density consensus map was constructed based on the GY14 × PI 183967 map from an inter-subspecific cross and the extended S94 × S06 map from an intra-subspecific cross. The consensus map was composed of 1,369 loci, including 1,152 SSR loci, 192 SRAP loci, 21 SCAR loci and one STS locus as well as three gene loci of fruit external quality traits in seven chromosomes, and spanned 700.5 cM, of which 682.7 cM (97.5%) were covered by SSR markers. The average genetic distance and physical interval between loci were 0.51 cM and ~268 kbp, respectively. Additionally, the physical position of the sequence-associated markers aligned along the assembled cucumber genome sequence established a relationship between genetic maps and cucumber genome sequence and to a great extent validated the order of markers in individual maps and consensus map. This consensus map with a high marker density and well-ordered markers is a saturated and reliable linkage map for genetic analysis of cucumber or the Cucurbitaceae family of plants.


Assuntos
Mapeamento Cromossômico , Cucumis sativus/genética , Marcadores Genéticos/genética , Polimorfismo Genético , Cruzamentos Genéticos , Biblioteca Gênica , Repetições de Microssatélites/genética , Sitios de Sequências Rotuladas
8.
J Int Med Res ; 50(4): 3000605221096161, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35485877

RESUMO

Waldenstrom's macroglobulinemia (WM) is a rare type of malignant B-cell lymphoma. The main feature of WM is elevated serum monoclonal immunoglobulin M, similar to multiple myeloma (MM). Unlike in MM, the rarity of destructive bone lesions in WM has been repeatedly emphasized. We report a unique case of WM with a vertebral compression fracture as the first symptom. This case highlights that the presence or absence of bone destruction may not clearly distinguish between WM and MM. The possibility of WM should be considered in patients with vertebral fracture and destruction as the first presentation. Performing vertebral bone marrow aspiration biopsy during percutaneous vertebroplasty is a convenient and effective method to assist in the diagnosis of WM.


Assuntos
Fraturas por Compressão , Linfoma de Células B , Mieloma Múltiplo , Fraturas da Coluna Vertebral , Macroglobulinemia de Waldenstrom , Humanos , Imunoglobulina M , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/diagnóstico por imagem , Macroglobulinemia de Waldenstrom/complicações , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/patologia
9.
Front Surg ; 9: 1066304, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684168

RESUMO

Background: Extraosseous Ewing's sarcoma/primary neuroectodermal tumor (EES/PNET) is a rare, malignant, small round blue cell tumor, which usually involves the larynx, kidneys, and esophagus. The most common metastatic sites are lung and bone. The incidence of epidural EES/PNET was 0.9%, and a detailed search of the PubMed literature found only 7 case reports of epidural ESS/PNET at the cervicothoracic junction in children. Case description: We report a case of epidural ESS/PNET at the cervicothoracic junction in a child with chest and back pain as the first symptom, which worsened after half a year and developed incomplete paralysis of both lower extremities and urinary incontinence. She underwent emergency surgery, chemotherapy and radiotherapy, and died of lung metastases 8 months after surgery. Conclusion: Primary epidural tumors are mostly benign, such as spinal meningiomas and neuromas. Contrary to what has been previously thought, we report a case of malignant epidural EES/PNET at the cervicothoracic junction without bone destruction; The rarity of epidural EES/PNET at the cervicothoracic junction in children has led to a lack of data, particularly on prognostic factors and recurrence patterns. Due to the difficulty of early diagnosis and high mortality, spine surgeons must explore and increase their awareness of this disease.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(6): 1963-1966, 2021 Dec.
Artigo em Zh | MEDLINE | ID: mdl-34893142

RESUMO

Platelets are key participants in many pathophysiological processes, play a broad role in tissue regeneration and repair, and interact closely with tumor cells. Platelets have active and passive migration in the human body, and they play different biological meanings, including antimicrobial host defense, inflammation, autoimmune response, tumor growth and metastasis, etc. Therefore, in-depth understanding of the structure and function of platelets, and targeted platelets as biomarkers have become particularly important in the field of modern medical research and treatment. This review provides an overview of platelet physiology, focusing on the biological characteristics of platelet polarity movement and its significance in diseases.


Assuntos
Plaquetas , Hemostasia , Humanos , Inflamação
11.
In Vivo ; 34(5): 2381-2388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32871763

RESUMO

BACKGROUND/AIM: Huaier extract, whose main active constituent is the proteoglycan, has anti-tumor activity in several types of malignancies. In this study, we aimed to elucidate the effect of Huaier extract in hepatoblastoma cells. MATERIALS AND METHODS: The effect of Huaier extract on the proliferation of human hepatoblastoma cell lines HepG2 and HuH-6, was examined. RESULTS: Incubation with Huaier extract resulted in a marked, dose-dependent decrease in hepatoblastoma cell viability. Huaier extract induced S phase arrest in hepatoblastoma cells and upregulated the expression of the cell cycle related proteins cyclin D1 and cyclin D3. It also induced apoptosis in hepatoblastoma cells. Additionally, it significantly suppressed the activity of p-ERK and p-MEK. CONCLUSION: Huaier extract inhibits proliferation, and induces cell apoptosis and cell cycle arrest via the MEK-ERK pathway in hepatoblastoma cells. Huaier extract may act as a complementary agent for treating hepatoblastoma.


Assuntos
Hepatoblastoma , Neoplasias Hepáticas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Misturas Complexas , Hepatoblastoma/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno , Extratos Vegetais/farmacologia , Transdução de Sinais , Trametes
12.
Nagoya J Med Sci ; 82(2): 323-333, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32581411

RESUMO

Environmental endocrine disruptors (EEDs) are natural or synthetic chemical compounds that interfere with normal endocrine function in both wildlife and humans. Previous studies have indicated that EEDs may contribute to oncogenesis. This study explores the relationship between EEDs and pediatric germ cell tumors (GCTs). A case-control study was conducted in 84 pediatric patients from 2014 to 2017, including 42 subjects with immature teratoma, yolk sac tumor, or germinoma, and 42 controls who experienced pneumonia or trauma. Serum PFASs, including PFBS, PFHpA, PFHxS, PFOA, PFOS, PFNA, PFDA, PFUA, PFOSA, and PFDoA, were measured in each subject, and their history of possible EED exposure was reviewed. Six of the 10 measured PFASs were significantly increased in the GCT group relative to the control group. With respect to lifestyle history, only PFHxS levels were statistically significantly associated with GCTs as determined by logistic regression analysis. The odds ratio for a 1 ng/L increase in PFHxS was 19.47 (95% CI: 4.20-90.26). Furthermore, in the GCT and control groups, both parental consumption of barbecued foods and hair dye use among parents were significantly correlated with elevated serum PFHxS levels (ρ = 0.383, 0.325 in the patient group and ρ = 0.370, 0.339 in the control group; p < 0.05). Our study confirmed that children with GCTs from our institute had relatively high serum levels of PFASs relative to those of tumor-free pediatric patients. Serum PFHxS levels were independently associated with germ cell tumor occurrence.


Assuntos
Disruptores Endócrinos/sangue , Fluorocarbonos/sangue , Neoplasias Embrionárias de Células Germinativas/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Estudos de Casos e Controles , Pré-Escolar , Tumor do Seio Endodérmico/sangue , Tumor do Seio Endodérmico/epidemiologia , Exposição Ambiental , Feminino , Germinoma/sangue , Germinoma/epidemiologia , Humanos , Lactente , Masculino , Exposição Materna , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Teratoma/sangue , Teratoma/epidemiologia
13.
Oncotarget ; 8(50): 87455-87471, 2017 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-29152094

RESUMO

To identify cellular and molecular changes that driver pediatric low grade glioma (PLGG) progression, we analyzed putative cancer stem cells (CSCs) and evaluated key biological changes in a novel and progressive patient-derived orthotopic xenograft (PDOX) mouse model. Flow cytometric analysis of 22 PLGGs detected CD133+ (<1.5%) and CD15+ (20.7 ± 28.9%) cells, and direct intra-cranial implantation of 25 PLGGs led to the development of 1 PDOX model from a grade II pleomorphic xanthoastrocytoma (PXA). While CSC levels did not correlate with patient tumor progression, neurosphere formation and in vivo tumorigenicity, the PDOX model, IC-3635PXA, reproduced key histological features of the original tumor. Similar to the patient tumor that progressed and recurred, IC-3635PXA also progressed during serial in vivo subtransplantations (4 passages), exhibiting increased tumor take rate, elevated proliferation, loss of mature glial marker (GFAP), accumulation of GFAP-/Vimentin+ cells, enhanced local invasion, distant perivascular migration, and prominent reactive gliosis in normal mouse brains. Molecularly, xenograft cells with homozygous deletion of CDKN2A shifted from disomy chromosome 9 to trisomy chromosome 9; and BRAF V600E mutation allele frequency increased (from 28% in patient tumor to 67% in passage III xenografts). In vitro drug screening identified 2/7 BRAF V600E inhibitors and 2/9 BRAF inhibitors that suppressed cell proliferation. In summary, we showed that PLGG tumorigenicity was low despite the presence of putative CSCs, and our data supported GFAP-/Vimentin+ cells, CDKN2A homozygous deletion in trisomy chromosome 9 cells, and BRAF V600E mutation as candidate drivers of tumor progression in the PXA xenografts.

14.
J Neurosurg Pediatr ; 17(1): 49-56, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26451721

RESUMO

OBJECT The purpose of this study was to explore the clinical features and outcome of medulloblastoma in Chinese children. The authors analyze the reasons that treatment is abandoned and attempt to provide evidence-based recommendations for improving the prognosis of medulloblastoma in this population. METHODS A total of 67 pediatric cases of newly diagnosed medulloblastoma were included in this study. All of the children were treated at Xinhua Hospital between January 2007 and June 2013. The authors retrospectively analyzed the clinical data, treatment modalities, and outcome. The male-to-female ratio was 2:1, and the patients' median age at diagnosis was 51.96 months (range 3.96-168.24 months). The median duration of follow-up was 32 months (range 3-70 months). RESULTS At the most recent follow-up date, 31 patients (46%) were alive, 30 (45%) had died, and 6 (9%) had been lost to follow-up. The estimated 3-year overall survival and progression-free survival, based on Kaplan-Meier analysis, were 55.1% ± 6.4% and 45.6% ± 6.7%, respectively. Univariate analysis showed that standard-risk group (p = 0.009), postoperative radiotherapy (RT) combined with chemotherapy (p < 0.001), older age (≥ 3 years) at diagnosis (p = 0.010), gross-total resection (p = 0.012), annual family income higher than $3000 (p = 0.033), and living in urban areas (p = 0.008) were favorable prognostic factors. Multivariate analysis revealed that postoperative RT combined with chemotherapy was an independent prognostic factor (p < 0.001). The treatment abandonment rate in this cohort was 31% (21 of 67 cases). CONCLUSIONS There was a large gap between the outcome of medulloblastoma in Chinese children and the outcome in Western children. Based on our data, treatment abandonment was the major cause of therapeutic failure. Parents' misunderstanding of medulloblastoma played a major role in abandonment, followed by financial and transportation difficulties. Establishment of multidisciplinary treatment teams could improve the prognosis of medulloblastoma in Chinese children.


Assuntos
Neoplasias Cerebelares , Meduloblastoma , Resultado do Tratamento , Adolescente , Neoplasias Cerebelares/epidemiologia , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/terapia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Seguimentos , Humanos , Lactente , Masculino , Meduloblastoma/epidemiologia , Meduloblastoma/mortalidade , Meduloblastoma/terapia , Prognóstico , Falha de Tratamento
15.
Cancer Lett ; 375(1): 39-46, 2016 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-26945966

RESUMO

The purpose of this study is to report the first nationwide protocol (Wuhan Protocol) developed by Chinese Children's Cancer Group and the results of multidisciplinary effort in treating hepatoblastoma. In this study, we reported the final analysis, which includes 153 hepatoblastoma patients in 13 hospitals from January 2006 to December 2013. The 6-year overall survival and event-free survival rates were 83.3 ± 3.1% and 71.0 ± 3.7%, respectively, in this cohort. The univariate analysis revealed that female (P = 0.027), under 5 years of age (P = 0.039), complete surgical resection (P = 0.000), no metastases (P = 0.000), and delayed surgery following neoadjuvant chemotherapy (P = 0.000) had better prognosis. In multivariate analysis, male, 5 years of age or above, stage PRETEXT III or IV, and incomplete surgical resection were among the some adverse factors contributing to poor prognosis. The preliminary results from this study showed that patients who underwent treatment following Wuhan Protocol had similar OS and EFS rates compared to those in developed countries. However, the protocol remains to be further optimized in standardizing surgical resection (including liver transplantation), refining risk stratification and risk-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hepatoblastoma/terapia , Neoplasias Hepáticas/terapia , Quimioterapia Adjuvante , Criança , Pré-Escolar , China , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Hepatoblastoma/mortalidade , Hepatoblastoma/secundário , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Análise Multivariada , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Distribuição por Sexo , Resultado do Tratamento , Vincristina/administração & dosagem
16.
Zhonghua Yi Xue Za Zhi ; 83(21): 1863-6, 2003 Nov 10.
Artigo em Zh | MEDLINE | ID: mdl-14642067

RESUMO

OBJECTIVES: To study the frequency distribution patterns of the genetic polymorphisms for glutathione S-transferase Pi (GST-Pi) in children with acute leukemia, and explore the possible relationship of GST-Pi gene mutation to the vulnerability of children with leukemia and the chemotherapeutic response. METHOD: Direct DNA sequencing was applied to detect the genotype polymorphism in 85 healthy children as the control group and 120 children with acute leukemia. The distribution difference of the genotypes between them was analyzed. RESULTS: Gene mutation rate of GST-Pi exon5 was 47.5% in children with acute leukemia, significantly higher than that of 31.8% in the control group (OR = 1.944, 95% CI 1.088-3.473), and this polymorphism distribution pattern was similar to that reported abroad. The mutation rate was much higher in ALL group than in others groups and was not significantly between the AML children and the control group. The overall mutation rate of B-lineage ALL (60.3%) was markedly higher than that of T-ALL (47.1%), but the homozygous mutation rate of the latter group (17.6%) was much higher than that of the former group (3.4%) (P < 0.05). The average survival time of the children with wild type exon5 was 24 months, longer than that of the mutation group (17.6 months), however with no statistical difference (P > 0.05). The genotype of exon5 had no effect on the survival time of AML children. No Ala(114)Val variant genotype of GST-Pi exon6 reported in literatures was found in this study, but two new mutant genotypes were discovered. A/G hybridity at 99 loci of exon6 was found in one healthy child and such hybrid genotype did not result in amino acid alteration. G-->T/G bases hybridity at 103 loci of exon6 occurred in two children with leukemia, leading to GAC of Asp (aspartic acid) replaced by TAC of Try (tyrosine) at 147 loci of the protein peptide chain, producing Asp(147) Try hybrid mutation with a genotypic frequency of 1.7%. CONCLUSION: The gene mutation of GST-Pi exon5 is one of the potential vulnerable factors in leukemogenesis of the Chinese children and the genetic polymorphism of exon6 in Chinese is greatly different from that in other races. The role of the newly discovered variant genotype Asp(147) Try in leukemogenesis remains to be further studied.


Assuntos
Glutationa Transferase/genética , Isoenzimas/genética , Leucemia Mieloide Aguda/genética , Polimorfismo Genético , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Adulto , Criança , Pré-Escolar , Éxons , Feminino , Glutationa S-Transferase pi , Humanos , Lactente , Masculino , Mutação
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 22(3): 653-9, 2014 Jun.
Artigo em Zh | MEDLINE | ID: mdl-24989271

RESUMO

This study was aimed to investigate the mRNA and protein expression of CTGF, CYR61, VEGF-C and VEGFR-2 in bone marrow of patients with leukemia, and to analyze the role and clinical significance of these 4 factors in genesis and development of leukemia, infiltration and metastasis of leukemic cells. A total of 100 cases of newly diagnosed leukemia, 26 cases of acute leukemia in complete remission and 30 controls were enrolled in this study. The mononuclear cells of bone marrow were collected, the mRNA and protein expression levels of CTGF, CYR61, VEGF-C, VEGFR-2 in leukemia patients and controls were detected by real time PCR and Western blot, respectively. The results showed that the mRNA and protein expression levels of above mentioned 4 factors were significantly higher than those in control (P < 0.05), only CTGF mRNA expression in AL patients after complete remission showed statistical difference as compared with control (P < 0.05), but the expression of CTGF mRNA showed statistical significance in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF protein showed difference in different chromosome karyotypes of leukemia (P < 0.05). The expression levels of CYR61 and VEGF-C proteins showed statistical difference in different bone marrow hyperplasia of acute leukemia (P < 0.05). The expression level of CTGF, CYR61, VEGF-C mRNA and protein in CML group were higher than that in control group. The expression levels of CTGF and CYR61 protein were higher than that in control. The mRNA and protein expression levels of above-mentioned 4 factors in sex and infiltration lf leukemic cells did not show statistical significance(P < 0.05). In correlative analysis, the mRNA expressions of above mentioned 4 factors were positively correlated with bone marrow blast count(P < 0.05), the protein expression of CTGF, CYR61 and VEGF-C were positively correlated with bone marrow blast count. It is concluded that the CTGF, CYR61, VEGF-C and VEGFR-2 mRNA and protein play a role in acute leukemia. In acute leukemia (AML/ALL), the expression of above mentioned factor was high, but except VEGFR-2. Most of them were positively correlated with bone marrow blast count. Joint block of these angiogenesis-related factors is likely to play an important role in targeting treatment of leukemia.


Assuntos
Medula Óssea/metabolismo , Leucemia/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Proteína Rica em Cisteína 61/metabolismo , Feminino , Humanos , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , Fator C de Crescimento do Endotélio Vascular/metabolismo , Adulto Jovem
18.
Zhonghua Xue Ye Xue Za Zhi ; 34(7): 581-6, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-23906450

RESUMO

OBJECTIVE: To retrospectively analyze the clinical characteristics and the treatment outcomes of older children with acute lymphoblastic leukemia (ALL), and to evaluate the multicenter cooperation regimen (ALL-2005). METHODS: The clinical data of 103 newly diagnosed ALL children aged 10 to 18 years old from five hospitals were enrolled in this study. They were all received ALL-2005 protocol. The clinical characteristics, the event-free survival (EFS), the overall survival (OS) and the prognostic analysis were evaluated. RESULTS: (1) Of the 103 patients, 62 were boys and 41 girls, with a median age of 12.3 years old. According to immunophenotyping, 90 (87.4% ) of 103 patients were diagnosed as B-ALL and 13 (12.6%) as T-ALL. According to risk factor, 65 (63.1%) were in intermediate risk group (MR-ALL) and 38 (36.9%) in high risk group (HR-ALL). Central nervous system leukemia (CNSL) happened in 4 (3.9%) patients at diagnosis. Of the 89 patients received chromosome test, 58 (65.2%) obtained the test results, including 21(36.2%) with aberrational chromosomes and 37 (63.8%) with normal karyotype. Of 81 patients received molecular biological test, 16 (19.8%) were positive for fusion gene. (2) After induction therapy, 97 (94.2%) obtained complete remission (CR). Twenty-eight patients relapsed with a median time of 11.9 months (ranged 2.9-57.8 months), and 38 (36.9%) patients died during the treatment. As of September 30, 2012, the median follow-up was 47 months (ranged 0.4-92.6 months). The 5-year EFS and 5-year OS of ALL patients were (60.2 ± 4.8)% and(64.1 ± 4.7)%. The 5-year EFS of MR-ALL and HR-ALL were (73.8 ± 5.5)% and (31.6 ± 8.3)% (P<0.01), the 5-year OS of MR- ALL and HR-ALL were (78.5 ± 5.1)% and (35.9 ± 8.0)% (P<0.01), respectively. (3) Cox proportion hazard regression model analysis indicated that age of 14-18 years old and BCR- ABL translocation or t(9;22) were independent risk prognostic factor for 5-year EFS. CONCLUSION: The incidence and prognosis in older childhood ALL were related with age, risk and biological characteristics. BCR-ABL translocation or t(9;22) was the risk factor of prognosis. ALL- 2005 protocol was recommended as the regimen for older childhood ALL.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Criança , Intervalo Livre de Doença , Feminino , Humanos , Incidência , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Prognóstico , Fatores de Risco , Resultado do Tratamento
19.
Biosens Bioelectron ; 50: 318-24, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23876543

RESUMO

Single-walled carbon nanotubes (SWCNTs) and hemoglobin (Hb) modified carbon fiber ultramicroelectrode (CFUME) were employed to construct a direct electron transfer based in vivo H2O2 sensor. At the low working potential of -0.1 V, Hb/SWCNTs/CFUME showed a dynamic range up to 0.405 mM with a low detection limit of 4 µM (S/N=3) and a high sensitivity of 1.07 log(A) log(M)(-1) cm(-2). The apparent Michaelis-Menten constant (Km, app) was estimated to be as low as 1.35 mM. Due to the extremely small dimension and low working potential, Hb/SWCNTs/CFUME could give directly amperometric in vivo monitoring of H2O2 in aloe leaves with salt stress for 19.5h without the requirement of complex data processing and extra surface coatings to avoid interferences. The sharp increase of H2O2 level in aloe leaves with salt stress was clearly observed using Hb/SWCNTs/CFUME from 12.5 h, while in the aloe without salt stress, H2O2 level remained stable in the whole measurement. For further confirming the in vivo response of Hb/SWCNTs/CFUME, catalase (CAT) was injected into the spot adjacent to the sensor and caused rapid current decrease, which suggests the scavenging of H2O2. These results indicate that Hb/SWCNTs/CFUME can be a powerful tool for in vivo investigation of ROS.


Assuntos
Aloe/fisiologia , Técnicas Biossensoriais/instrumentação , Carbono/química , Peróxido de Hidrogênio/análise , Nanotubos de Carbono/química , Aloe/química , Fibra de Carbono , Hemoglobinas/química , Peróxido de Hidrogênio/metabolismo , Microeletrodos , Pressão Osmótica , Folhas de Planta/química , Folhas de Planta/fisiologia , Salinidade , Estresse Fisiológico
20.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 20(5): 1103-9, 2012 Oct.
Artigo em Zh | MEDLINE | ID: mdl-23114128

RESUMO

The purpose of this study was to establish a method for the monitoring of minimal residual disease (MRD) in bone marrow samples of the children with T acute lymphoid leukemia (T-ALL), and to evaluate its value in clinical application. The immuno-phenotype of the leukemic cells were detected by flow cytometry with two sets of 4-color combinations of antibodies against TdT/CD5/cCD3/HLA-DR(+)CD19(+)CD33 and CD34/CD5/cCD3/HLA-DR(+)CD19(+)CD33 in 32 cases of de novo T-ALL and were compared with the results in 10 normal controls. The antibody combination in regions of the two-parameter plots where the leukemic cells appeared were different from the normal cells was screened as the effective combination which was used to monitor MRD in the bone marrows of the T-ALL children after the inductive treatment. The results indicated that the respective effective frequencies of antibodies against TdT/CD5/cCD3/HLA-DR(+)CD19(+)CD33 and CD34/CD5/cCD3/HLA-DR(+)CD19(+)CD33 were 90.6% and 62.5%. 32 cases of childhood T-ALL were successively screened for antibodies combinations of interest and were identified in 100% (32/32) of these cases. After inductive treatment, the positive rate in 129 times of MRD monitoring was 19.4% (25/129) by flow cytometry and 5.43% (7/129) by FAB morphology. It is concluded that monitoring MRD in patients with T-ALL by flow cytometry with two 4 color combinations of fluorescent antibodies is an quick and effective method. The sensitivity of this method is high and it may be of important significance for the treatment and prognostic evaluation in childhood T-ALL.


Assuntos
Citometria de Fluxo/métodos , Neoplasia Residual/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Imunofenotipagem , Masculino , Neoplasia Residual/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia
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