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1.
J Cell Mol Med ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636169

RESUMO

In chemotherapy for childhood acute lymphoblastic leukaemia (ALL), maintenance therapy consisting of oral daily mercaptopurine and weekly methotrexate is important. NUDT15 variant genotype is reportedly highly associated with severe myelosuppression during maintenance therapy, particularly in Asian and Hispanic populations. It has also been demonstrated that acquired somatic mutations of the NT5C2 and PRPS1 genes, which are involved in thiopurine metabolism, are detectable in a portion of relapsed childhood ALL. To directly confirm the significance of the NUDT15 variant genotype and NT5C2 and PRPS1 mutations in thiopurine sensitivity of leukaemia cells in the intrinsic genes, we investigated 84 B-cell precursor-ALL (BCP-ALL) cell lines. Three and 14 cell lines had homozygous and heterozygous variant diplotypes of the NUDT15 gene, respectively, while 4 and 2 cell lines that were exclusively established from the samples at relapse had the NT5C2 and PRPS1 mutations, respectively. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with DNA-incorporated thioguanine levels after exposure to thioguanine at therapeutic concentration. Considering the continuous exposure during the maintenance therapy, we evaluated in vitro mercaptopurine sensitivity after 7-day exposure. Mercaptopurine concentrations lethal to 50% of the leukaemia cells were comparable to therapeutic serum concentration of mercaptopurine. Both NUDT15 variant genotype and NT5C2 and PRPS1 mutations were significantly associated with mercaptopurine sensitivity in 83 BCP-ALL and 23 T-ALL cell lines. The present study provides direct evidence to support the general principle showing that both inherited genotype and somatically acquired mutation are crucially implicated in the drug sensitivity of leukaemia cells.

2.
Int J Hematol ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34591292

RESUMO

Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that occurs most often in adolescents and young adults and is rare in children. Because of the aggressive clinical course, resistance to conventional chemotherapy and poor prognosis of HSTCL, an effective treatment has not been established. We report the case of a 3-year-old girl with HSTCL presenting with trilineage myelodysplasia. Although the HSTCL was refractory to conventional chemotherapy, remission was achieved with salvage chemotherapy that included fludarabine and cytarabine, which were shown to be effective in the drug sensitivity assay. After undergoing umbilical cord blood transplantation with a conditioning regimen consisting of etoposide, cyclophosphamide and total body irradiation, the patient has remained in complete remission for 8 years. Single-nucleotide polymorphism array analysis revealed heterozygous deletions of PAX5 (9p), ETV6 (12p) and homozygous deletions of CDKN2A (9p). Exome analysis showed a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. To improve the poor prognosis of HSTCL, the chemotherapeutic regimen can be selected for each patient on the basis of drug sensitivity and molecular genetic characteristics.

3.
Bull Tokyo Dent Coll ; 62(3): 181-192, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34393142

RESUMO

Aggressive periodontitis mostly affects young people, causing rapid destruction of periodontal tissue and loss of supporting alveolar bone. The destruction of periodontal tissue induces pathological tooth movement, resulting in various types of malocclusion such as crowding or spacing in the dentition. This report describes orthodontic treatment for malocclusion due to generalized aggressive periodontitis. The patient was a 31-year-old woman who presented with the chief complaint of displacement in the anterior teeth. An oral examination revealed pathological tooth mobility throughout the entire oral cavity due to severe loss of periodontal support. Many gaps in the displaced maxillary anterior teeth and crowding in the mandibular anterior teeth were also observed. The goal of subsequent treatment was to achieve ideal overjet and overbite by aligning the teeth and closing the spaces via non-extraction orthodontic treatment with stripping. The periodontal disease was managed by a periodontist who provided guidance on oral hygiene and periodontal disease control throughout the course of orthodontic treatment. Appropriate occlusion and a good oral environment were achieved. The condition of the periodontal tissue stabilized during and after orthodontic treatment, and favourable occlusal stability was observed at the 2-year follow-up examination.


Assuntos
Periodontite Agressiva , Má Oclusão Classe II de Angle , Má Oclusão , Adolescente , Adulto , Periodontite Agressiva/terapia , Oclusão Dentária , Feminino , Humanos , Má Oclusão/terapia , Técnicas de Movimentação Dentária
4.
Artigo em Inglês | MEDLINE | ID: mdl-34455570

RESUMO

BACKGROUND: Plerixafor was approved in Japan in 2016 for peripheral blood stem cell (PBSC) mobilization in autologous stem cell transplantation (A-SCT). OBJECTIVE: Our objective was to evaluate the safety and effectiveness of plerixafor in Japanese patients undergoing A-SCT for various indications in real-world practice. PATIENTS AND METHODS: This post-marketing surveillance study included Japanese patients initiating PBSC mobilization with plerixafor for A-SCT. Safety assessments included the incidence of adverse events (AEs) including serious AEs, adverse drug reactions (ADRs), and laboratory variables. Effectiveness assessments were the proportion of patients with the target CD34+ cell yield (≥2 × 106 cells/kg) ≤4 days after plerixafor administration and the number of days required to reach the target CD34+ cell yield. RESULTS: In total, 785 patients were registered, and the safety and effectiveness analysis sets comprised 764 and 717 patients, respectively. ADRs occurred in 12.2% of patients, with gastrointestinal disorders (5.5%), laboratory investigations (4.5%), and blood and lymphatic system disorders (3.0%) being the most common. A total of 71.1% of patients had the target CD34+ cell yield within ≤4 days of treatment, with a mean (standard deviation) of 1.3 (0.7) days to reach the target CD34+ cell yield. Over 80% of patients with a baseline CD34+ cell count >2 cells/µL had a target CD34+ cell yield within ≤4 days of treatment. CONCLUSIONS: This large post-marketing surveillance study provided real-world evidence detailing the safety and effectiveness of plerixafor for PBSC mobilization in Japanese patients undergoing A-SCT. Importantly, no new safety concerns were identified, and the safety profile of plerixafor was consistent with the established profile of this drug.

6.
Blood Adv ; 5(14): 2925-2934, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34309636

RESUMO

The phase 2, open-label study (DIALOG) of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) met its coprimary end points, showing sustained nilotinib efficacy in patients with newly diagnosed (ND) or imatinib/dasatinib resistant/intolerant (R/I) CML. This update assessed growth and safety profiles in patients who had completed ≥48, 28-day treatment cycles of nilotinib 230 mg/m2 twice daily, or previously discontinued the study. Height was assessed regularly and reported using standard deviation scores (SDSs) based on World Health Organization growth charts. All data were summarized descriptively (cutoff, 6 March 2019). Overall, 33 patients in the R/I cohort and 25 patients in the ND cohort received nilotinib. Each cohort showed a negative slope in height SDS over the course of the study, indicating attenuated growth rates during nilotinib treatment: overall median change from baseline in height SDS after 48 cycles was -0.54 SDS (range, - 1.6 to 0.4) and -0.91 SDS (-1.4 to -0.1) in R/I and ND cohorts, respectively. Patients in the R/I cohort were shorter at baseline than those in the ND cohort, and remained so throughout the study. The most common all-cause adverse events were increased blood bilirubin (53.4%), headache (46.6%), pyrexia (37.9%), and increased alanine transferase (36.2%). Apart from the impact on growth, the safety profile of nilotinib was generally consistent with previous reports. This study was registered on www.clinicaltrials.gov at #NCT01844765.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Pirimidinas , Criança , Transtornos do Crescimento , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Pirimidinas/efeitos adversos
7.
Blood ; 2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110416

RESUMO

CRLF2-rearranged (CRLF2r) acute lymphoblastic leukemia (ALL) comprises over half of Philadelphia chromosome-like (Ph-like) ALL, is associated with poor outcome in children and adults. Overexpression of CRLF2 results in activation of JAK-STAT and parallel signaling pathways in experimental models, but existing small molecule inhibitors of Janus kinases show variable and limited efficacy. Here we evaluated the efficacy of proteolysis-targeting chimeras (PROTACs) directed against Janus kinases. Solving the structure of type I JAK inhibitors ruxolitinib and baricitinib bound to the JAK2 tyrosine kinase domain enabled the rational design and optimization of multiple series of cereblon (CRBN)-directed JAK PROTACs utilizing derivatives of JAK inhibitors, linkers and CRBN-specific molecular glues. The resulting JAK PROTACs were evaluated for target degradation, and activity tested in a panel of leukemia/lymphoma cell lines and xenograft models of kinase-driven ALL. Multiple PROTACs were developed that degraded Janus kinases and potently killed CRLF2--rearranged cell lines, the most active of which also degraded the known CRBN neosubstrate GSPT1, and suppressed proliferation of CRLF2-rearranged ALL in vivo. While dual JAK/GSPT1-degrading PROTACs were most potent, development and evaluation of multiple PROTACs in an extended panel of xenografts identified a potent JAK2-degrading GSPT1-sparing PROTAC that demonstrated efficacy in the majority of the kinase-driven xenografts which were otherwise unresponsive to type I JAK inhibitors. Together, these data show the potential of JAK-directed protein degradation as a therapeutic approach in JAK-STAT-driven ALL, and highlight the interplay of Janus kinase and GSPT1 degradation activity in this context.

9.
Jpn J Clin Oncol ; 51(8): 1204-1211, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34021341

RESUMO

BACKGROUND: Palonosetron has demonstrated non-inferiority to ondansetron for prevention of chemotherapy-induced nausea and vomiting in pediatric patients in the United States and Europe. We conducted a single-arm registration study to evaluate the efficacy, safety and pharmacokinetics of palonosetron in pediatric patients in Japan. METHODS: Key inclusion criteria were age of 28 days to 18 years and malignant disease for which initial highly emetogenic chemotherapy or moderately emetogenic chemotherapy was planned. Patients received palonosetron at 20 µg/kg over at least 30 s intravenously before the start of highly emetogenic chemotherapy or moderately emetogenic chemotherapy and received dexamethasone on Days 1-3. The primary endpoint was the proportion of patients achieving a complete response in the overall phase (0-120 h) in Course 1, and its threshold was set at 30%. RESULTS: From December 2016 to June 2019, 60 patients were enrolled, and 58 received at least one dose of palonosetron. The proportion of patients achieving a complete response during the overall phase was 58.6% (95% confidence interval, 44.9%-71.4%), showing the primary endpoint was met (P < 0.0001). Treatment-related adverse events occurred in two patients (3.4%). Regarding the pharmacokinetics of palonosetron, neither the plasma concentration immediately after administration nor the area under the plasma concentration-time curve from time 0 to infinity differed significantly among the age groups. CONCLUSION: We demonstrated the efficacy of palonosetron in pediatric patients receiving highly emetogenic chemotherapy or moderately emetogenic chemotherapy and confirmed the appropriateness of the 20 µg/kg dose, regardless of age, considering the safety and pharmacokinetic profiles. TRIAL REGISTRATION: JapicCTI-163305, registered 6 June 2016.

10.
Bone Marrow Transplant ; 56(9): 2173-2182, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33911201

RESUMO

In high-risk neuroblastoma, the presence of an MYCN gain/amplification (MYCN-GA) is not always a risk factor of cancer-specific death. We herein examined the effect modification of high-dose chemotherapy with autologous hematopoietic stem cell rescue (HDC-autoSCR) in terms of the interaction between MYCN status and remission status (complete remission or very good partial remission [CR/VGPR] vs. partial remission or less [≤PR]). The present study recruited patient data from 1992 to 2017 in the Japan Society of Hematopoietic Cell Transplantation's national registry. The MYCN status was known in 586 of 950 patients with a single course of HDC-autoSCR. Cumulative hazard curves for neuroblastoma-specific death showed that a subgroup with MYCN-GA and ≤PR had a significantly poorer prognosis than three other subgroups, namely, the MYCN-NGA/ ≤ PR, MYCN-NGA/CR/VGPR, and MYCN-GA/CR/VGPR subgroups even after adjusting for non-infants and stage IV disease (hazard ratio: 2.79; 95% confidence interval: 1.91-4.09; P < 0.001). The interaction between MYCN-GA and ≤PR was significant (pinteraction = 0.006). Hence, the patients with MYCN-GA with non-remission status at HDC-autoSCR had a significantly poorer prognosis than the other subgroups, suggesting that HDC-autoSCR may be effective in patients with CR/VGPR regardless of MYCN gene status and in patients with MYCN-NGA regardless of remission status.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neuroblastoma , Protocolos de Quimioterapia Combinada Antineoplásica , Intervalo Livre de Doença , Humanos , Lactente , Japão , Proteína Proto-Oncogênica N-Myc/genética , Proteína Proto-Oncogênica N-Myc/uso terapêutico , Neuroblastoma/tratamento farmacológico , Neuroblastoma/terapia , Prognóstico
11.
Bull Tokyo Dent Coll ; 62(1): 27-39, 2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33583878

RESUMO

Aggressive periodontitis during adolescence has a poor prognosis due to rapid alveolar bone resorption. Few studies have investigated long-term follow-up after surgical orthodontic treatment performed in conjunction with that for invasive periodontitis. Here, we report a case of mandibular prognathism accompanied by generalized aggressive periodontitis and crowding. A 31-year-old woman was referred to our department for treatment of masticatory dysfunction due to reverse overjet. The patient exhibited a class III molar relationship, protrusion of the ANB of -6.0°, and severe maxillary crowding. Initial periodontal examination revealed deep periodontal pockets and extensive inflammation. Mandibular prognathism accompanied by generalized aggressive periodontitis and crowding was diagnosed. Therefore, it was necessary to adopt an interdisciplinary approach involving surgical, orthodontic, and periodontal treatment. Prior to commencement of orthodontic treatment, plaque control, scaling, and root planing of all teeth were performed by a periodontist to suppress inflammation and reduce probing depth. During pre-surgical orthodontic treatment, the maxillary first premolars were extracted to reduce crowding of the maxillary incisors. To correct the mandibular prognathism, the mandible was repositioned by sagittal split ramus osteotomy. Proper occlusion of the incisors and maximum intercuspation were achieved by post-surgical orthodontic treatment. After completion of active orthodontic treatment, acceleration of inflammation was observed together with aggravated resorption of the alveolar bone surrounding the molars. However, reduction of probing depth and inflammation were observed after scaling and root planing. The surgical-orthodontic treatment time was 1 year and 11 months, which was followed by a 2-year retention period. There was no tooth loss due to periodontitis, and an overall satisfactory outcome was achieved.


Assuntos
Periodontite Agressiva , Má Oclusão Classe III de Angle , Má Oclusão , Prognatismo , Adulto , Feminino , Seguimentos , Humanos , Má Oclusão Classe III de Angle/cirurgia , Mandíbula , Prognatismo/cirurgia
13.
Bone Marrow Transplant ; 56(2): 357-367, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32782350

RESUMO

The number of individuals undergoing unrelated cord blood transplantation (UCBT) has increased in recent years; however, information on prognostic factors is limited. We retrospectively analyzed data from 475 children and adolescents receiving UCBT with myeloablative conditioning for acute lymphoblastic leukemia (ALL) in complete remission (CR), based on a nationwide registry. In the total patient cohort, 5-year leukemia-free survival (LFS) and overall survival (OS) rates after UCBT were 61.1% and 67.7%, respectively. UCBT at first CR and UCBT after 2007 were associated with good survival, while grade II-IV acute graft-versus-host disease (GVHD) was associated with low relapse rate but did not affect survival. Analysis according to human leukocyte antigen (HLA) disparity revealed that tacrolimus-based GVHD prophylaxis resulted in higher OS and lower relapse rate and nonrelapse mortality (NRM) than cyclosporine-based GVHD prophylaxis in patients transplanted with 6/6 and ≤4/6 HLA-matched umbilical cord blood. Furthermore, grade II-IV acute GVHD was associated with good LFS and low relapse rate, without high NRM, in patients receiving 5/6 HLA-matched UCBT. These data indicate that prognostic factors for ALL differ depending on HLA disparity in UCBT.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Retrospectivos , Condicionamento Pré-Transplante
14.
Blood ; 137(4): 471-484, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-32881995

RESUMO

Blinatumomab, a bispecific antibody that directs CD3+ T cells to CD19+ tumor cells, shows variable efficacy in B-progenitor acute lymphoblastic leukemia (B-ALL). To determine tumor-intrinsic and -extrinsic determinants of response, we studied 44 adults with relapsed or refractory B-ALL (including 2 minimal residual disease positive) treated with blinatumomab using bulk tumor and single-cell sequencing. The overall response rate in patients with hematological disease was 55%, with a high response rate in those with CRLF2-rearranged Philadelphia chromosome-like ALL (12 [75%] of 16). Pretreatment samples of responders exhibited a tumor-intrinsic transcriptomic signature of heightened immune response. Multiple mechanisms resulted in loss of CD19 expression, including CD19 mutations, CD19-mutant allele-specific expression, low CD19 RNA expression, and mutations in CD19 signaling complex member CD81. Patients with low hypodiploid ALL were prone to CD19- relapse resulting from aneuploidy-mediated loss of the nonmutated CD19 allele. Increased expression of a CD19 isoform with intraexonic splicing of exon 2, CD19 ex2part, at baseline or during therapy was associated with treatment failure. These analyses demonstrate both tumor-intrinsic and -extrinsic factors influence blinatumomab response. We show that CD19 mutations are commonly detected in CD19- relapse during blinatumomab treatment. Identification of the CD19 ex2part splice variant represents a new biomarker predictive of blinatumomab therapy failure.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígenos CD19/genética , Antígenos de Neoplasias/genética , Antineoplásicos Imunológicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Terapia de Salvação , Subpopulações de Linfócitos T/efeitos dos fármacos , Adolescente , Adulto , Idoso , Sequência de Aminoácidos , Aneuploidia , Anticorpos Biespecíficos/imunologia , Anticorpos Biespecíficos/farmacologia , Antígenos CD19/biossíntese , Antígenos CD19/imunologia , Antígenos de Neoplasias/biossíntese , Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/farmacologia , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Citotoxicidade Imunológica/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Recidiva , Estudos Retrospectivos , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Análise de Célula Única , Subpopulações de Linfócitos T/imunologia , Adulto Jovem
15.
Int J Hematol ; 113(1): 134-144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32949371

RESUMO

We retrospectively analyzed nationwide records of 163 Fanconi anemia (FA) patients [aplastic anemia (AA), n = 118; myelodysplastic syndrome (MDS), n = 30; acute leukemia, n = 15] who underwent first allogeneic hematopoietic stem cell transplantation (HSCT) between 1987 and 2015 in Japan. An alternative donor was used in 119 (73%) patients, and 160 (98%) patients received a non-T-cell-depleted graft. With an 8.7-year median follow-up, 5-year overall survival (OS) was 81%. The 5-year OS was significantly higher in AA patients than in MDS and acute leukemia patients (89%, 71%, and 44%, respectively). In the MDS/leukemia group, factors associated with poor outcome in univariate analysis were older age at HSCT (≥ 18 years), conditioning regimen without anti-thymocyte or lymphocyte globulin, and grade II-IV acute graft-versus-host disease. After 1 year, of 137 survivors, 15 developed subsequent malignancies, of whom 12 were diagnosed with head and neck (HN)/esophageal cancer. An irradiation regimen and older age were associated with the risk of HN/esophageal cancer. Five of seven deaths were attributed to subsequent malignancies more than 5 years after HSCT. On the basis of the risk factors for HSCT in MDS/leukemia patients and subsequent malignancies, a more effective HSCT approach is required.


Assuntos
Anemia de Fanconi/terapia , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Neoplasias Esofágicas/etiologia , Anemia de Fanconi/complicações , Anemia de Fanconi/mortalidade , Feminino , Seguimentos , Neoplasias de Cabeça e Pescoço/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Lactente , Japão , Leucemia/etiologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/etiologia , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
16.
Br J Haematol ; 193(1): 176-180, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32337716

RESUMO

The variability in myelosuppression after chemotherapy for acute myeloid leukaemia (AML) can affect its prognosis; however, the underlying mechanism remains controversial. In the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 study, we showed that prolonged neutropenia was associated with high overall survival (P = 0·011) and low frequency of relapse (P = 0·042) in patients without granulocyte-colony stimulating factor (G-CSF) who completed the indicated treatment protocol. Our data indicate that predisposition to prolonged neutropenia after chemotherapy is correlated with a better outcome of AML treatment. Our results promote the usage of individualised drug dosing strategies to improve the therapeutic outcome in AML patients.

17.
Intern Med ; 60(9): 1427-1432, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33250459

RESUMO

A 77-year-old man was treated with a DPP-4 inhibitor for type 2 diabetes. Hypoglycemia occurred frequently, and an examination revealed a tumor with a maximum diameter of 140 mm in both lobes of the liver. Western immunoblotting detected a high-molecular-weight form of insulin-like growth factor-II, and non-islet cell tumor hypoglycemia was diagnosed. Although prednisolone 40 mg was started, hypoglycemia continued to occur frequently. Surgical tumor removal was not indicated, so lenvatinib was initiated. Hypoglycemia improved quickly, and the tumor shrank until it had partially disappeared. His condition continued to improve, and he was discharged.


Assuntos
Carcinoma Hepatocelular , Diabetes Mellitus Tipo 2 , Hipoglicemia , Neoplasias Hepáticas , Idoso , Carcinoma Hepatocelular/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hipoglicemia/induzido quimicamente , Fator de Crescimento Insulin-Like II , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Compostos de Fenilureia , Quinolinas
18.
Pediatr Blood Cancer ; 68(1): e28736, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991072

RESUMO

BACKGROUND: The prognosis of children with acute myeloid leukemia (AML) has improved with the efficacy of hematopoietic cell transplantation (HCT) as a second-line therapy and improvements in supportive care following anthracycline- and cytarabine-based chemotherapy; however, the outcomes of children with relapsed AML still remain unsatisfactory. PROCEDURE: In order to identify prognostic factors and improve their prognosis, we analyzed 111 patients who relapsed after treatment with the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) AML-05 protocol and who were registered in the retrospective JPLSG AML-05R study. RESULTS: The 5-year overall survival rate was 36.1%. The major determinant of survival was duration from the diagnosis to relapse. The mean duration in the nonsurviving group (10.1 ± 4.1 months) was shorter than that in the surviving group (16.3 ± 8.3 months) (P < .01). Moreover, achieving a second complete remission (CR2) prior to HCT was associated with a good prognosis (P < .01). Etoposide, cytarabine, and mitoxantrone (ECM)- or fludarabine, cytarabine, and granulocyte colony-stimulating factor (FLAG)-based regimens were therefore recommended for reinduction therapy (P < .01). A genetic analysis also revealed the prognostic significance of FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication as a poor prognostic marker (P = .04) and core binding factor-AML, t(8;21), and inv(16) as good prognostic markers (P < .01). CONCLUSIONS: Achieving a CR2 prior to HCT is important in order to improve the prognosis of relapsed pediatric AML. Recent molecular targeted therapies, such as FLT3 inhibitors, may contribute to overcome their prognoses. Larger prospective investigations are necessary to establish individualized treatment strategies for patients with relapsed childhood AML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Recidiva Local de Neoplasia/mortalidade , Adolescente , Antraciclinas/administração & dosagem , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Terapia Combinada , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Masculino , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Homólogo , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
19.
PLoS Negl Trop Dis ; 14(11): e0008855, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33147214

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic novel coronavirus that has caused a worldwide outbreak. Here we describe a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay that uses a portable device for efficient detection of SARS-CoV-2. This RT-LAMP assay specifically detected SARS-CoV-2 without cross-reacting with the most closely related human coronavirus, SARS-CoV. Clinical evaluation of nasal swab samples from suspected SARS-CoV-2 pneumonia (COVID-19) patients showed that the assay could detect over 23.7 copies within 15 min with a 100% probability. Since the RT-LAMP assay can be performed with a portable battery-supported device, it is a rapid, simple, and sensitive diagnostic assay for COVID-19 that can be available at point-of-care. We also developed the RT-LAMP assay without the RNA extraction step-Direct RT-LAMP, which could detect more than 1.43 x 103 copies within 15 min with a 100% probability in clinical evaluation test. Although the Direct RT-LAMP assay was less sensitive than the standard RT-LAMP, the Direct RT-LAMP assay can be available as the rapid first screening of COVID-19 in poorly equipped areas, such as rural areas in developing countries.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Pneumonia Viral/diagnóstico , COVID-19 , Humanos , Pandemias , Sistemas Automatizados de Assistência Junto ao Leito , SARS-CoV-2 , Fatores de Tempo
20.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 936-939, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-33018138

RESUMO

Vibroarthrographic (VAG) signals are sounds or vibrations caused when a knee joint is flexed or stretched. VAG signal collection is noninvasive and can be performed using an accelerometer or microphone attached to the skin. However, the sensor attached to the skin will move with the soft tissue caused by flexion and extension, causing the baseline of the VAG signal to drift. We call these interferences soft tissue movement artifacts (STMAs). In this study, an algorithm is proposed to filter out STMAs. We compare the proposed method's results with noises collected by an accelerometer. The noise reduction effect is evaluated, revealing an 11.85% increase in the peak signal-to-noise ratio and a 28.18% increase in signal-to-noise ratio compared with the case in which STMA noise was not removed.Clinical Relevance-This study focuses on a proposed post-processing method that can remove soft tissue movement artifacts that cause baseline wander and could thus improve the accuracy of clinical applications of VAG signals.


Assuntos
Artefatos , Processamento de Sinais Assistido por Computador , Algoritmos , Articulação do Joelho , Movimento
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