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1.
Cancer Res Treat ; 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32019282

RESUMO

Myeloproliferative neoplasms (MPNs) are classified as chronic myeloid leukemia (CML) and Philadelphia chromosome-negative MPN. In MPN cases, the presence of a BCR-ABL1 translocation with a coexisting mutation is exceptionally rare. Herein, we report the first documented patient with CML harboring CALR mutation in Korea. A 33-year-old woman was referred to our hospital in February 2015 with splenomegaly, leukocytosis, and thrombocytosis. She was diagnosed with CML and started receiving nilotinib. In October 2015, a major molecular response was observed, but thrombocytosis persisted. A repeat bone marrow (BM) examination revealed no specific findings. However, as thrombocytosis worsened, we changed nilotinib to dasatinib. In May 2019, owing to persistent thrombocytosis, we repeated the BM examination and found CALR mutation (15.97%) on the MPN-next generation sequencing (NGS) test. We then retrospectively performed repeat MPN-NGS testing using the BM aspirate sample obtained in 2015 and found CALR mutation (10.64%).

2.
Ann Hematol ; 99(2): 255-264, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897676

RESUMO

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin's lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1-46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Doença de Hodgkin , Proteínas de Neoplasias/sangue , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteína C-Reativa/metabolismo , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Doença de Hodgkin/sangue , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/mortalidade , Humanos , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Recidiva , Taxa de Sobrevida , Fatores de Tempo , Fator de Necrose Tumoral alfa/sangue , Fator A de Crescimento do Endotélio Vascular/sangue
3.
Front Neurosci ; 13: 1200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780886

RESUMO

We evaluated whether blind subjects have advantages in auditory spectral resolution, temporal resolution, and speech perception in noise compared with sighted subjects. We also compared psychoacoustic performance between early blind (EB) subjects and late blind (LB) subjects. Nineteen EB subjects, 16 LB subjects, and 20 sighted individuals were enrolled. All subjects were right-handed with normal and symmetric hearing thresholds and without cognitive impairments. Three psychoacoustic measurements of the subjects' right ears were performed via an inserted earphone to determine spectral-ripple discrimination (SRD), temporal modulation detection (TMD), and speech recognition threshold (SRT) in noisy conditions. Acoustic change complex (ACC) responses were recorded during passive listening to standard ripple-inverted ripple stimuli. EB subjects exhibited better SRD than did LB (p = 0.020) and sighted (p = 0.003) subjects. TMD was better in EB (p < 0.001) and LB (p = 0.007) subjects compared with sighted subjects. SRD was positively correlated with the duration of blindness (r = 0.386, p = 0.024). Acoustic change complex data for ripple noise change at the Cz and Fz electrodes showed trends toward significant correlations with the behavioral results. In conclusion, compared with sighted subjects, EB subjects showed advantages in terms of auditory spectral and temporal resolution, while LB subjects showed an advantage in temporal resolution exclusively. These findings suggest that it might take longer for auditory spectral resolution to functionally enhance following visual deprivation compared to temporal resolution. Alternatively, a critical period of very young age may be required for auditory spectral resolution to improve following visual deprivation.

4.
Cancer Commun (Lond) ; 39(1): 58, 2019 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619290

RESUMO

BACKGROUND: The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III-IV CD20-positive MZL who had responded to first-line R-CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R-CVP warrants further investigation. METHODS: Prior to rituximab-maintenance therapy, patients received 6-8 cycles of first-line R-CVP therapy for stage III-IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1-5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R-CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. RESULTS: 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R-CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R-CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). CONCLUSION: Rituximab-maintenance therapy following first-line R-CVP demonstrated good PFS in patients with stage III-IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095.

5.
Acta Haematol ; : 1-12, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390612

RESUMO

OBJECTIVE: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). METHODS: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. RESULTS: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. CONCLUSION: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs.

6.
Leuk Lymphoma ; 60(13): 3251-3257, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31170847

RESUMO

This trial was designed to investigate the efficacy and toxicity of bendamustine, carboplatin, and dexamethasone (BCD) for relapsed or refractory peripheral T-cell lymphomas (PTCLs), which would be expected to exhibit more promising clinical outcomes compared with bendamustine therapy alone. After treatments with BCD, eight patients exhibited a complete response (CR; 29%) and seven exhibited a partial response (PR; 25%). The overall response rate (ORR) was 54%. Five patients proceeded to ASCT and three patients finally achieved CR. The median progression-free survival (PFS) was 4.4 months (2.8-6.0, 95% CI). For a total of 85 cycles of BCD, grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in 17.6, 38.8, and 16.5% of cycles, respectively. Only one patient experienced febrile neutropenia. BCD was a considerable salvage regimen for relapsed or refractory PTCLs with acceptable toxicity; AITL or ASCT eligible patients were more effective to BCD.ClinicalTrials.gov Identifier:NCT02424045.

7.
Cancer Res Treat ; 51(4): 1302-1312, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30764603

RESUMO

PURPOSE: Primary effusion lymphoma (PEL) is a type of body cavity-based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. Materials and Methods: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. RESULTS: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. CONCLUSION: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.


Assuntos
Antígenos Virais/metabolismo , Infecções por HIV/epidemiologia , Herpesvirus Humano 8/isolamento & purificação , Linfoma de Efusão Primária/epidemiologia , Proteínas Nucleares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD20/metabolismo , Feminino , Infecções por HIV/metabolismo , Herpesvirus Humano 8/metabolismo , Humanos , Antígeno Ki-1/metabolismo , Linfoma de Efusão Primária/metabolismo , Linfoma de Efusão Primária/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Análise de Sobrevida
8.
Anticancer Res ; 39(1): 127-133, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30591449

RESUMO

AIM: Cytotoxic chemotherapy-based treatment of multiple myeloma (MM) is not curative, and the disease eventually recurs. This is partially because although currently available anti-MM strategies are effective in targeting the bulk of tumor cells, they do not target the tumor-initiating subpopulation of cancer stem cells. This study investigated the prevalence and biological functions of side population (SP) cells in MM cell lines including RPMI8226, ARH77, MM.1R and IM 9. MATERIALS AND METHODS: Flow cytometry-based Hoechst 33342 staining was used to evaluate the existence of SP cells. In addition, the ability of SP cells to regenerate the original population was determined. RESULTS: The frequency of SP cells was heterogeneous. Most cell lines (ARH77, IM9, and MM.1R) contained fewer than 1% SP cells; however, RPMI8226 contained approximately 10% SP cells. Sorted SP cells showed a higher proliferative ability and clonogenicity than the MP in the RPMI8226 myeloma cell line. The activity of ATP-binding cassette subfamily G member 2 (ABCG2), which is associated with high rates of proliferation, was higher in SP cells. However, the expression of specific surface markers such as cluster of differentiation (CD)138, CD34, CD38, CD19, CD20, and CD27 did not differ between SP and MP cells. Bortezomib was the only agent that significantly affected proliferation of both SP and MP cells. CONCLUSION: Our studies demonstrated that the SP fraction of myeloma cells possessed clonogenic tumor-initiating potential and revealed new mechanisms of action for bortezomib on SP cells.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Bortezomib/farmacologia , Mieloma Múltiplo/tratamento farmacológico , Proteínas de Neoplasias/genética , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Citometria de Fluxo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/patologia , Células da Side Population/efeitos dos fármacos , Células da Side Population/patologia
9.
Sci Rep ; 9(1): 20302, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31889144

RESUMO

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29-80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0-33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6-24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7-1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4-9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.

10.
Blood Res ; 53(3): 227-232, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30310790

RESUMO

Background: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. Methods: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. Results: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P<0.001). Even when VTE included SVT, the result was similar (P<0.001). Conclusion: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.

11.
Biol Blood Marrow Transplant ; 24(12): 2471-2478, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30064012

RESUMO

Natural killer (NK)/T cell lymphoid malignancy comprises extranodal NK/T cell lymphoma (ENKTL) and aggressive NK cell leukemia (ANKL), and the outcomes for advanced or relapsed/refractory ENKTL and ANKL remain poor. Allogeneic stem cell transplantation (SCT) can be used as a frontline consolidation treatment to prevent the relapse of advanced disease or as salvage treatment after chemotherapy for relapsed sensitive disease. We retrospectively analyzed 36 patients (ENKTL, n = 26; ANKL, n = 10) who underwent upfront (n = 19) and salvage allogeneic SCT (n = 17) at 6 hospitals. Patients received myeloablative (n = 25) or reduced-intensity (n =11) conditioning regimens depending on the institute's policy. The median age at the time of allogeneic SCT was 37 years (range, 17 to 62), and more patients with ANKL (8/10) received upfront allogeneic SCT than ENKTL patients (11/26). Disease status before allogeneic SCT, conditioning regimen, and donor source did not differ between upfront and salvage allogeneic SCT groups. Febrile neutropenia (n = 20) and acute graft-versus-host disease (n = 16) were common adverse events. The median overall survival (OS) and progression-free survival (PFS) after allogeneic SCT were 11.8 months and 10.0 months, respectively. Twelve patients died from disease relapse and 12 from nondisease-related causes. Ten deaths occurred within 100 days after allogeneic SCT (10/24); these were mostly related to disease relapse (n = 8). The OS after allogeneic SCT did not differ between ENKTL and ANKL (P = .550) or between upfront and salvage SCT (P = .862). Complete chimerism was significantly associated with better PFS (P < .001). No significant differences in PFS were observed based on the conditioning regimen or source of stem cells (P > .05). Allogeneic SCT may be beneficial for patients with ENKTL and ANKL given that some patients were able to maintain their remission after allogeneic SCT. However, allogeneic SCT should only be performed in highly selected patients because the risks of disease relapse and nondisease-related mortality remain high.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Linfoide/terapia , Células T Matadoras Naturais/metabolismo , Terapia de Salvação/métodos , Transplante Homólogo/métodos , Adolescente , Adulto , Feminino , Humanos , Leucemia Linfoide/patologia , Masculino , Pessoa de Meia-Idade , Células T Matadoras Naturais/patologia , Adulto Jovem
12.
Ann Hematol ; 97(10): 1851-1857, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29947974

RESUMO

Both-side synchronous involvement has been reported to account for 7-24% of ocular adnexal marginal zone lymphoma (OAML). We conducted a retrospective analysis to identify the clinical features and treatment outcomes of synchronous bilateral OAML (SB-OAML) by treatment modality. We analyzed patients with a histologic diagnosis of SB-OAML, excluding metachronous bilateral involved OAML. We enrolled a total of 95 patients for this analysis, 36 males and 59 females; the median patient age was 42 years (range 16-77 years). Eleven (11.6%) patients had been treated with chemotherapy or chemo-immunotherapy (eight R-CVP, two CVP, and one R-CHOP). The median number of treatments was 6 (range 6-8); there were 9 complete responses (CRs; 81.8%) and 2 partial responses (PRs; 18.2%). Nearly all patients (88.4%) received radiotherapy in both eyes, and the median radiation dose was 27 Gy (range 20-40 Gy) to each eye; 68 CRs (80.9%) and 14 PRs (16.7%) were achieved. Ten-year progression-free survival (PFS) and overall survival (OS) rates were 79.8 and 91.1%, respectively. Radiotherapy continued to be an independent prognostic marker, with the hazard of progression (P = 0.036). Eleven patients (13.1%) had surgery for cataract treatment during follow-up, and patients who received low-dose radiation (< 30.3 Gy) experienced fewer cataract operations. SB-OAML was predominantly observed in young females, and they had good response and prognosis regardless of treatment modalities. Low-dose radiotherapy to both eyes showed a tendency of longer PFS than did chemotherapy and could decrease cataract operations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Oculares/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Neoplasias Primárias Múltiplas/tratamento farmacológico , Adolescente , Adulto , Idoso , Catarata/etiologia , Terapia Combinada , Gerenciamento Clínico , Intervalo Livre de Doença , Neoplasias Oculares/diagnóstico por imagem , Neoplasias Oculares/radioterapia , Feminino , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/mortalidade , Linfoma de Zona Marginal Tipo Células B/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/diagnóstico por imagem , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/radioterapia , Curva ROC , Radioterapia/efeitos adversos , República da Coreia/epidemiologia , Estudos Retrospectivos , Terapia de Salvação , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
13.
Ann Coloproctol ; 34(2): 88-93, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29742856

RESUMO

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

14.
Oncotarget ; 9(4): 4961-4968, 2018 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-29435155

RESUMO

This study was performed to assess if a recently recommended genomic classification is predictive in patients with normal-karyotype (NK) acute myeloid leukemia (AML). A total of 393 patients were included. Analysis of genetic mutations was performed using targeted resequencing with an Illumina Hiseq 2000. We identified driver mutations across 40 genes, with one or more driver mutations identified in 95.7% of patients. The molecular subclassification was as follows: 34.6% patients (n = 136) with AML with the NPM1 mutation, 10.7% (n = 42) with AML with mutated chromatin or RNA-splicing genes or both, 1.5% (n = 6) with AML with TP53 mutations, 13.5% (n = 53) with AML with biallelic CEBPA mutations, 2.0% (n = 8) with AML with IDH2-R172 mutations and no other class-defining lesion, 29.5% (n = 116) with AML with driver mutations but no detected class-defining lesion, 4.3% (n = 17) with AML with no detected driver mutation, and 3.8% (n = 15) patients with AML who met the criteria for ≥2 genomic subgroups. The 5-year overall survival and relapse rate of subgroup in AML with mutated chromatin, RNA-splicing genes, or both was 11.6% (95% CI = 1.4-21.8%) and 71.4% (95% CI = 45.7-86.5%), respectively. This study suggests that the recently recommended genomic classification is an appropriate and replicable categorization system in the NK AML population. The subgroup of AML with mutated chromatin, RNA-splicing genes, or both showed extremely poor survival in NK-AML; thus, a novel approach is needed to improve their prognosis.

15.
Sci Rep ; 8(1): 800, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29335454

RESUMO

The objective of this study was to examine the relationship between spectrotemporal modulation (STM) sensitivity and the ability to perceive music. Ten normal-nearing (NH) listeners, ten hearing aid (HA) users with moderate hearing loss, and ten cochlear Implant (CI) users participated in this study. Three different types of psychoacoustic tests including spectral modulation detection (SMD), temporal modulation detection (TMD), and STM were administered. Performances on these psychoacoustic tests were compared to music perception abilities. In addition, psychoacoustic mechanisms involved in the improvement of music perception through HA were evaluated. Music perception abilities in unaided and aided conditions were measured for HA users. After that, HA benefit for music perception was correlated with aided psychoacoustic performance. STM detection study showed that a combination of spectral and temporal modulation cues were more strongly correlated with music perception abilities than spectral or temporal modulation cues measured separately. No correlation was found between music perception performance and SMD threshold or TMD threshold in each group. Also, HA benefits for melody and timbre identification were significantly correlated with a combination of spectral and temporal envelope cues though HA.


Assuntos
Percepção Auditiva , Perda Auditiva/patologia , Estimulação Acústica , Adulto , Implante Coclear , Implantes Cocleares , Feminino , Humanos , Masculino , Música , Psicoacústica , Adulto Jovem
16.
Int J Speech Lang Pathol ; 20(2): 238-246, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28000516

RESUMO

PURPOSE: To examine the developmental course of labial and alveolar manner of articulation contrasts, and to determine how that course may be different for typically developing (TD) children with cochlear implants (CI). METHOD: Eight young adults, eight TD 5-8 year-old children, and seven 5-8 year-old children with CIs participated. Labial /ba/-/wa/ and alveolar /da/-/ja/ continua stimuli were presented, with each continuum consisting of nine synthetic stimuli varying in F2 and F3 transition duration. Participants were asked to label the stimuli as either a stop or glide, and responses were analysed for phonetic boundaries and slopes. RESULT: For the /ba/-/wa/ contrast, children with CIs required longer transition durations compared to TD children or adults to cross from one phoneme category to another. The children with CIs demonstrated less confidence in labelling the stimuli (i.e. less steep slopes) than the TD children or the adults. For the /da/-/ja/ contrast, the children with CIs showed less steep slope values than adults. CONCLUSION: These results suggest that there are differences in the way TD children and children with CIs develop and maintain phonetic categories, perhaps differences in phonetic representation or in linking acoustic and phonetic representations.


Assuntos
Implantes Cocleares , Percepção da Fala/fisiologia , Criança , Pré-Escolar , Feminino , Perda Auditiva Neurossensorial/cirurgia , Humanos , Masculino , Fonética , Adulto Jovem
17.
Oncotarget ; 8(54): 92171-92182, 2017 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-29190906

RESUMO

The National Comprehensive Cancer Network (NCCN)-International Prognostic Index (IPI) and GELTAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula Ósea)-IPI were developed to enable better risk prediction of patients with diffuse large B-cell lymphoma (DLBCL). The present study compared the effectiveness of risk prediction between IPI, NCCN-IPI, and GELTAMO-IPI in patients with DLBCL particularly in terms of determining high-risk patients. Among 439 patients who were enrolled to a prospective DLBCL cohort treated with R-CHOP immunochemotherapy, risk groups were classified according to the three IPIs and the prognostic significance of individual IPI factors and IPI models were analyzed and compared. All three IPI effectively separated the analyzed patients into four risk groups according to overall survival (OS). Estimated 5-year OS of patients classified as high-risk according to the IPI was 45.7%, suggesting that the IPI is limited in the selection of patients who are expected to have a poor outcome. In contrast, the 5-year OS of patients stratified as high-risk according to NCCN- and GELTAMO-IPI was 31.4% and 21.9%, respectively. The results indicate that NCCN- and GELTAMO-IPI are better than the IPI in predicting patients with poor prognosis, suggesting the superiority of enhanced, next-generation IPIs for DLBCL.

18.
Blood Res ; 52(3): 207-211, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29043236

RESUMO

BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.

20.
J Acoust Soc Am ; 141(1): 613, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28147578

RESUMO

Spectral resolution limits speech perception with a cochlear implant (CI) in post-lingually deaf adults. However, the development of spectral resolution in pre-lingually deaf implanted children is not well understood. Acoustic spectral resolution was measured as a function of age (school-age versus adult) in CI and normal-hearing (NH) participants using spectral ripple discrimination (SRD). A 3-alternative forced-choice task was used to obtain SRD thresholds at five ripple depths. Effects of age and hearing method on SRD and spectral modulation transfer function (SMTF) slope (reflecting frequency resolution) and x-intercept (reflecting across-channel intensity resolution) were examined. Correlations between SRD, SMTF parameters, age, and speech perception in noise were studied. Better SRD in NH than CI participants was observed at all depths. SRD thresholds and SMTF slope correlated with speech perception in CI users. When adjusted for floor performance, x-intercept did not correlate with SMTF slope or speech perception. Age and x-intercept correlations were positive and significant in NH but not CI children suggesting that across-channel intensity resolution matures during school-age in NH children. No evidence for maturation of spectral resolution beyond early school-age in pre-lingually deaf implanted CI users was found in the present study.


Assuntos
Envelhecimento/psicologia , Implante Coclear/instrumentação , Implantes Cocleares , Pessoas com Deficiência Auditiva/psicologia , Percepção da Fala , Estimulação Acústica , Adolescente , Fatores Etários , Idoso , Audiometria da Fala , Limiar Auditivo , Estudos de Casos e Controles , Criança , Feminino , Audição , Humanos , Masculino , Pessoa de Meia-Idade , Ruído/efeitos adversos , Mascaramento Perceptivo , Psicoacústica
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