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1.
Zhonghua Xue Ye Xue Za Zhi ; 45(4): 345-350, 2024 Apr 14.
Artículo en Chino | MEDLINE | ID: mdl-38951061

RESUMEN

Objective: This study investigated the efficacy and safety of denosumab (DENOS) versus zoledronic acid (ZOL) in the bone disease treatment of newly diagnosed multiple myeloma. Methods: The clinical data of 80 patients with myeloma bone disease (MBD) at the Fifth Medical Center of PLA General Hospital between March 1, 2021 and June 30, 2023 were retrospectively reviewed. Eighteen patients with severe renal impairment (SRI, endogenous creatinine clearance rate<30 ml/min) were treated with DENOS, and 62 non-SRI patients were divided into DENOS (30 patients) and ZOL group (32 patients) . Results: Hypocalcemia was observed in 26 (33%) patients, and 22 patients developed hypocalcemia during the first treatment course. The incidence of hypocalcemia in the non-SRI patients of DENOS group was higher than that in the ZOL group [20% (6/30) vs 13% (4/32), P=0.028]. The incidence of hypocalcemia in SRI was 89% (16/18). Multivariate logistic regression analysis revealed that endogenous creatinine clearance rate<30 ml/min was significantly associated with hypocalcemia after DENOS administration (P<0.001). After 1 month of antiresorptive (AR) drug application, the decrease in the serum ß-C-terminal cross-linked carboxy-telopeptide of collagen type I concentrations of SRI and non-SRI patients in the DENOS group were significantly higher than that in the ZOL group (68% vs 59% vs 27%, P<0.001). The increase in serum procollagen type Ⅰ N-terminal propeptide concentrations of patients with or without SRI in the DENOS group were significantly higher than that in the ZOL group (34% vs 20% vs 11%, P<0.05). The level of intact parathyroid hormone in each group increased after AR drug treatment. None of the patients developed osteonecrosis of the jaw and renal adverse events, and no statistically significant differences in the overall response rate, complete remission and stringent complete remission rates were found among the groups (P>0.05), and the median PFS and OS time were not reached (P>0.05) . Conclusions: In the treatment of MBD, DENOS minimizes nephrotoxicity and has strong AR effect. Hypocalcemia is a common adverse event but is usually mild or moderate and manageable.


Asunto(s)
Conservadores de la Densidad Ósea , Enfermedades Óseas , Denosumab , Hipocalcemia , Mieloma Múltiple , Ácido Zoledrónico , Humanos , Ácido Zoledrónico/administración & dosificación , Denosumab/efectos adversos , Denosumab/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Enfermedades Óseas/etiología , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/efectos adversos , Hipocalcemia/inducido químicamente , Hipocalcemia/etiología , Masculino , Femenino , Resultado del Tratamiento , Persona de Mediana Edad , Anciano
3.
Zhonghua Xue Ye Xue Za Zhi ; 44(12): 1016-1021, 2023 Dec 14.
Artículo en Chino | MEDLINE | ID: mdl-38503525

RESUMEN

Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.


Asunto(s)
Anticuerpos Monoclonales , Trasplante de Células Madre Hematopoyéticas , Mieloma Múltiple , Neumonía , Masculino , Femenino , Humanos , Persona de Mediana Edad , Anciano , Mieloma Múltiple/tratamiento farmacológico , Estudios Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante Autólogo , Neumonía/etiología , Dexametasona , Bortezomib/uso terapéutico
4.
Zhonghua Xue Ye Xue Za Zhi ; 41(2): 117-122, 2020 Feb 14.
Artículo en Chino | MEDLINE | ID: mdl-32135627

RESUMEN

Objective: To explore the efficacy and prognostic factors of hematopoietic stem cell transplantation (HSCT) for the treatment of patients with anaplastic large cell lymphoma (ALCL) . Methods: The clinical records of 33 ALCL patients after HSCT were collected and analyzed retrospectively to evaluate the rates of overall survival (OS) and recurrence after autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT) and the factors influencing prognosis. Results: The median-age of this cohort of 33 ALCL cases at diagnosis was 31 (12-57) years old with a male/female ratio of 23/10, 24 cases (72.7%) were ALK(+) and 9 ones (27.3%) ALK(-). Of them, 25 patients (19 ALK(+) and 6 ALK(-)) underwent auto-HSCT and 8 cases (5 ALK(+) and 3ALK(-)) allo-HSCT with a median follow-up of 18.7 (4.0-150.0) months. Disease states before HSCT were as follows: only 6 patients achieved CR status and received auto-HSCT, 16 patients achieved PR (14 cases by auto-HSCT and 2 ones allo-HSCT) , the rest 11 cases were refractory/relapse (5 cases by auto-HSCT and 6 ones allo-HSCT) . There were 7 cases died of disease progression (5 after auto-HSCT and 2 allo-HSCT) and 5 cases treatment-related mortality (TRM) (2 after auto-HSCT and 3 allo-HSCT) , TRM of two groups were 8.0% and 37.5%, respectively. Both the median progression-free survival (PFS) and OS were 15 months after auto-HSCT, the median PFS and OS after allo-HSCT were 3.7 (1.0-90.0) and 4.6 (1.0-90.0) months, respectively. There was no statistically significant difference in terms of survival curves between the two groups (OS and PFS, P=0.247 and P=0.317) . The 2-year OS rates in auto-HSCT and allo-HSCT groups were 72% and 50%, respectively. The 5-year OS rates in auto-HSCT and allo-HSCT groups were 36% and 25%, respectively. Conclusion: ALCL treated by chemotherapy produced high rates of overall and complete responses. Chemotherapy followed by auto-HSCT remained to be good choice for patients with poor prognostic factors. High-risk patients should be considered more beneficial from allo-HSCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Anaplásico de Células Grandes , Adolescente , Adulto , Niño , Femenino , Humanos , Linfoma Anaplásico de Células Grandes/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
5.
Zhonghua Xue Ye Xue Za Zhi ; 41(1): 10-15, 2020 Jan 14.
Artículo en Chino | MEDLINE | ID: mdl-32023748

RESUMEN

Objective: To analyze the frequency and composition of risk-related cytogenetic abnormalities (CAs) in patients with newly-diagnosed multiple myeloma (NDMM) . Methods: The frequency and composition of risk-related CAs from a cohort of 1 015 Chinese patients with NDMM were determined by interphase fluorescence in situ hybridization (iFISH) , individually or in combination. Results: Of the cohort of 1 015 Chinese patients with NDMM, the frequencies of IgH arrangement, del (13q) /13q14, 1q gain and del (17p) were 54.0%, 46.4%, 46.1% (35.8% and 12. 7% for 3 or more than 3 copies) and 9.9%, respectively. Among 454 patients who had the baseline information for all risk-related CAs [except t (14;20) , which was not covered by the FISH panels performed routinely at all five centers], the frequencies of t (4;14) , t (11;14) or t (14;20) were 14.1%, 11.2% and 4.8%, respectively; of them, 44.3% patients carried 2 or more CAs (28.0%, 13.4% and 2.9% for 2, 3 or ≥4 CAs) ; 83.3%, 95.0% or 68.6% patients with 1q gain, del (17p) or IgH rearrangement had 1 or more additional CA (s) , with del (13q) /13q14 as the most frequently accompanied CA; 57.7% patients carried at least 1 HRCA; the incidences of double-hit (DH) MM (DHMM) (=2 HRCAs) and triple-hit (TH) (THMM) (≥3 HRCAs) were 14.3% and 2.9%, respectively. Conclusions: Our results provided an up-to-date profile of CAs in Chinese NDMM patients, which revealed that approximately 58% patients might carry at least 1 HRCA, and 17% could experience so-called DHMM or THMM who presumably had the worst outcome.


Asunto(s)
Mieloma Múltiple , Aberraciones Cromosómicas , Análisis Citogenético , Humanos , Hibridación Fluorescente in Situ , Pronóstico , Estudios Retrospectivos
6.
Zhonghua Yi Xue Za Zhi ; 99(48): 3786-3791, 2019 Dec 24.
Artículo en Chino | MEDLINE | ID: mdl-31874515

RESUMEN

Objective: To evaluate the clinical outcomes in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) who had undergone allogeneic hematological stem cell transplantation (allo-HSCT). Methods: From June 2007 to June 2017, the clinical data of PTCL patients who underwent HSCT from eight hospitals were assessed retrospectively. Results: There were 23 patients diagnosed as relapsed or refractory PTCL with chemoresistance who underwent allo-HSCT. Among these patients, 18 were identified as progressive disease (PD) status and 5 patients as stable disease (SD) status before allo-HSCT. Seventeen patients received allo-HSCT from matched sibling donor (MSD),2 patients from matched unrelated donor and 4 patients from related haplo-identical donor (HD). After a median follow-up of 29 months, 21 patients survived longer than 28 days after allo-HSCT. Hematopoietic reconstitution was achieved in 20 of the 21 patients. The median time of myeloid and platelet engraftment were+13 (9-22) d and+16(10-38) d, respectively. The 100-d treatment-related mortality rate was 13.1%. Acute GVHD occurred in 11(47.8%) patients at a median time of 22(6-82) d after transplantation. Grade Ⅱ~Ⅳ aGVHD occurred in 6 patients. Chronic GVHD occurred in 10 patients at a median of 7.9 (3.5-27) months. After a median follow-up of 29 months, 13 patients died after HSCT. Four of them died of complications associated with allo-HSCT, and other 9 patients died of the primary lymphoma. The 3-years cumulative overall survival (OS) and progress-free survival (PFS) were 43.03% (95%CI: 29.79-69.16) and 39.13% (95%CI: 23.50-65.14), respectively. No significant difference was found in the 3-year PFS between patients with PD status and SD status before allo-HSCT (P=0.133). Conclusion: Allo-HSCT can be a promising treatment for relapsed or refractory PTCL with chemoresistance.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Resistencia a Antineoplásicos , Humanos , Linfoma de Células T Periférico/tratamiento farmacológico , Recurrencia Local de Neoplasia , Estudios Retrospectivos
7.
Environ Pollut ; 246: 668-677, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30611943

RESUMEN

The aim of this study was to chemically characterize the fine particulate matter (PM2.5) at a subtropical forest in East Asia under the influences of anthropogenic and biogenic sources and a complex topographic setting. Four seasonal campaigns were conducted at the Xitou Experimental Forest in central Taiwan from the winter of 2013 to the autumn of 2014. The results indicated that the ambient levels and chemical features of PM2.5 exhibited pronounced seasonal variations. Non-sea-salt sulfate (nss-SO42-) constituted the major component of PM2.5, followed by ammonium (NH4+) and nitrate (NO3-) during winter, summer and autumn. However, it was revealed that the mass fraction of NO3- increased to be comparable with that of nss-SO42- in springtime. The mass contribution of secondary organic carbon (SOC) to PM2.5 peaked in summer (13.2%), inferring the importance of enhanced photo-oxidation reactions in SOC formation. Diurnal variations of O3 and SO2 coincided with each other, suggesting the transport of aged pollutants from distant sources, whereas CO and NOx were shown to be under the influences of both local and regional sources. Notably high sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were observed, which were 0.93 ±â€¯0.05 and 0.39 ±â€¯0.20, respectively. Precursor gases (i.e. SO2 and NOx) could be converted to sulfate and nitrate during the transport by the uphill winds. Furthermore, due to the high relative humidity at Xitou, enhanced aqueous-phase and/or heterogeneous reactions could further contribute to the formation of sulfate and nitrate at the site. This study demonstrated the significant transport of urban pollutants to a subtropical forest by the mountain-valley circulations as well as the long-range transport from regional sources, whereas the implications of which for regional climate change necessitated further investigation.


Asunto(s)
Contaminantes Atmosféricos/análisis , Altitud , Monitoreo del Ambiente/métodos , Bosques , Material Particulado/análisis , Estaciones del Año , Taiwán , Clima Tropical , Viento
8.
Zhonghua Xue Ye Xue Za Zhi ; 40(7): 573-577, 2019 Jul 14.
Artículo en Chino | MEDLINE | ID: mdl-32397020

RESUMEN

Objective: To evaluate clinical outcomes of autologous (auto-HSCT) and allogeneic hematopoietic stem cell transplantation (allo-HSCT) for angioimmunoblastic T-cell lymphoma (AITL) . Methods: From June 2007 to June 2017, clinical data of AITL patients who underwent HSCT in eight hospitals were assessed retrospectively. Results: Of 19 patients, 13 male and 6 female with a median age of 50 (32-60) years old, 12 auto-HSCT and 7 allo-HSCT recipients were enrolled in this study, all donors were HLA-identical siblings. Two of allo-HSCT recipients were relapsed auto-HSCT ones. There were 5 patients (5/12) in complete response (CR) status and 7 (7/12) in partial remission (PR) status before transplantation in auto-HSCT group, and 2 (2/7) in PR status and 3 (3/7) in progression disease (PD) status before transplantation in allo-HSCT group. The median follow-up for the surviving patients was 46.5 months (range, 1-100 months) for the whole series, two patients lost in auto-HSCT group. Three patients developed acute graft-versus-host disease (aGVHD) and 5 chronic graft-versus-host disease (cGVHD) after allo-HSCT. Three patients died of primary disease and 1bleeding in auto-HSCT group. One patient died of primary disease and 2 transplantation-related mortality in allo-HSCT group. The 3-year cumulative overall survival (OS) were 56% (95%CI 32%-100%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.979) . The 3-year cumulative progression-free survival (PFS) were 34% (95%CI 14%-85%) and 57% (95%CI 30%-100%) for auto-HSCT and allo-HSCT, respectively (P=0.451) . Conclusion: Both auto-HSCT and allo-HSCT were optimal choices for AITL. In clinical practice, which HSCT was better for AITL patients should be based on comprehensive factors including sensitivity to chemotherapy, risk stratification and disease status at transplantation.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T/terapia , Adulto , Femenino , Enfermedad Injerto contra Huésped , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento
9.
Zhonghua Xue Ye Xue Za Zhi ; 39(9): 729-733, 2018 Sep 14.
Artículo en Chino | MEDLINE | ID: mdl-30369182

RESUMEN

Objective: To evaluate clinical outcomes of autologous and allogeneic peripheral blood stem cell transplantation (PBSCT) for aggressive peripheral T-cell lymphoma (PTCL). Methods: From June 2007 to June 2017, clinical data of PTCL patients who underwent PBSCT were assessed retrospectively. Results: Among 41 patients, 30 was male, 11 female, and median age was 38(13-57) years old. Seventeen patients with autologous PBSCT (auto-PBSCT) and 24 patients with allogeneic PBSCT (allo-PBSCT) were enrolled in this study. Eight patients (8/17, 47.1%) in auto-PBSCT group were ALK positive anaplastic large cell lymphoma (ALCL), 7 patients (7/24, 29.2%) with NK/T cell lymphoma and 9 patients (9/24, 37.5%) with PTCL-unspecified (PTCL-U) in allo-PBSCT group (P=0.035). There were 58.8% patients (10/17) in complete response (CR) status and 11.8% (2/17) in progression disease (PD) status before transplantation in auto-PBSCT group, and 8.3% (2/24) in CR status and 45.8% (11/24) in PD status before transplantation in allo-PBSCT group (P=0.026). The 2-years cumulative overall survival (OS) were (64.0±10.8)% and (53.5±9.7)% for auto-PBSCT and allo-PBSCT respectively (P=0.543). The 2-years cumulative disease-free survival (DFS) were (57.1±12.4)% and (53.5±10.6)% for auto-PBSCT and allo-PBSCT respectively (P=0.701). In patients with dead outcomes after PBSCT, 83.3% (5/6) of death cause was relapse in auto-PBSCT and 41.7% (5/12) of death cause was relapse in allo-PBSCT. Conclusion: Both auto-PBSCT and allo-PBSCT were effective for PTCL. Allo-PBSCT maybe was better than auto-PBSCT for high-risk PTCL with poor prognosis.


Asunto(s)
Linfoma de Células T Periférico , Trasplante de Células Madre de Sangre Periférica , Adolescente , Adulto , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Linfoma de Células T Periférico/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estudios Retrospectivos , Trasplante Autólogo , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
10.
Zhonghua Xue Ye Xue Za Zhi ; 39(6): 460-464, 2018 Jun 14.
Artículo en Chino | MEDLINE | ID: mdl-30032560

RESUMEN

Objective: To evaluate the impact of KIT D816 mutation on the salvage therapy in relapsed acute myeloid leukemia (AML) with t(8;21) translocation. Method: The characteristics of the first relapsed AML with t(8;21) translocation from 10 hospitals were retrospectively collected, complete remission (CR(2)) rate after one course salvage chemotherapy and the relationship between KIT mutation and CR(2) rate was analyzed. Results: 68 cases were enrolled in this study, and 30 cases (44.1%) achieved CR(2). All patients received KIT mutation detection, and KIT D816 mutation was identified in 26 cases. The KIT D816 positive group had significantly lower CR(2) compared with non-KIT D816 group (23.1% vs 57.1%, χ(2)=7.559, P=0.006), and patients with longer CR(1) duration achieved significantly higher CR(2) than those with CR(1) duration less than 12 months (74.1% vs 31.9%, χ(2)=9.192, P=0.002). KIT D816 mutation was tightly related to shorter CR(1) duration. No significant difference of 2 years post relapse survival was observed between KIT D816 mutation and non-KIT D816 mutation group. Conclusion: KIT D816 mutation at diagnosis was an adverse factor on the salvage therapy in relapsed AML with t(8;21) translocation, significantly related to shorter CR1 duration, and can be used for prediction of salvage therapy response. KIT D816 mutation could guide the decision-making of salvage therapy in relapsed AML with t(8;21) translocation.


Asunto(s)
Leucemia Mieloide Aguda/terapia , Terapia Recuperativa , Protocolos de Quimioterapia Combinada Antineoplásica , Citarabina , Humanos , Pronóstico , Estudios Retrospectivos
11.
Oncogene ; 36(15): 2095-2104, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27721403

RESUMEN

The accumulation of myeloid-derived suppressor cells (MDSCs) has been observed in solid tumors and is correlated with tumor progression; however, the underlying mechanism is still poorly understood. In this study, we identified a mechanism by which tumor cells induce MDSC accumulation and expansion in the bladder cancer (BC) microenvironment via CXCL2/MIF-CXCR2 signaling. Elevated expression of CXCL2 and MIF and an increased number of CD33+ MDSCs were detected in BC tissues, and these increases were significantly associated with advanced disease stage and poor patient prognosis (P<0.01). A positive association was observed between CXCL2 or MIF expression and the number of tumor-infiltrating CD33+ MDSCs (P<0.01). Subsequently, we demonstrated that CD45+CD33+CD11b+HLA-DR- MDSCs from fresh BC tissues displayed high levels of suppressive molecules, including Arg1, iNOS, ROS, PDL-1 and P-STAT3, and stronger suppression of T-cell proliferation. Interestingly, these CD45+CD33+CD11b+HLA-DR- MDSCs exhibited increased CXCR2 expression compared with that in peripheral blood from BC patients or healthy controls (P<0.05). Chemotaxis assay revealed that bladder cancer cell line J82 induced MDSC migration via CXCL2/MIF-CXCR2 signaling in vitro. Mechanistic studies demonstrated that J82-induced MDSC trafficking and CXCR2 expression were associated with increased phosphorylation of p38, ERK and p65. Conversely, inhibition of the phosphorylation of p38, ERK or p65 decreased J82-induced MDSC trafficking and CXCR2 expression. CXCL2/MIF-stimulated activation of the mitogen-activated protein kinase and nuclear factor kappa B pathways in MDSCs was MyD88 dependent. Overall, our results identify the CXCL2/MIF-CXCR2 axis as an important mediator in MDSC recruitment and as predictors and potential therapeutic targets in BC patients.


Asunto(s)
Quimiocina CXCL2/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Factores Inhibidores de la Migración de Macrófagos/metabolismo , Células Mieloides/patología , Receptores de Interleucina-8B/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Estudios de Casos y Controles , Línea Celular Tumoral , Quimiotaxis , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Lectina 3 Similar a Ig de Unión al Ácido Siálico/metabolismo , Transducción de Señal , Factor de Transcripción ReIA/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
12.
Bone Marrow Transplant ; 51(11): 1464-1469, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27322853

RESUMEN

Emerging data demonstrate promising results of related haploidentical allogeneic hematopoietic stem cell transplantation (haplo-HCT) for the treatment of hematologic malignancies. Data about G-CSF primed PBSC as reliable source of graft with myeloablative conditioning are lacking. We updated the outcomes in 130 adult patients with high-risk hematologic malignancies who received haplo-PBSC transplantation consecutively under busulfan-based conditioning. PBSC were freshly isolated and infused without ex vivo T-cell depletion into the recipients. Myeloid recovery was achieved in 99.2% patients with full donor chimerism. The cumulative incidence of acute grade 3-4 GvHD, overall and extensive chronic GvHD was 14.9%, 38.6% and 16.5%, respectively. The 3-year non-relapse mortality rate was 24.1%. Non-remission prior to transplant was associated with higher incidence of relapse (P=0.006), inferior overall survival (P=0.017) and leukemia-free survival (P=0.024). These data suggest that PBSC is a reliable graft source in haploidentical, unmanipulated transplant settings under myeloablative conditioning in patients with high-risk hematologic malignancies.


Asunto(s)
Neoplasias Hematológicas/terapia , Trasplante de Células Madre de Sangre Periférica/métodos , Trasplante Haploidéntico/métodos , Adolescente , Adulto , Busulfano/uso terapéutico , Niño , Quimerismo , Femenino , Enfermedad Injerto contra Huésped , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Agonistas Mieloablativos/uso terapéutico , Trasplante de Células Madre de Sangre Periférica/efectos adversos , Trasplante de Células Madre de Sangre Periférica/mortalidad , Medición de Riesgo , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Trasplante Haploidéntico/efectos adversos , Trasplante Haploidéntico/mortalidad , Resultado del Tratamiento , Adulto Joven
13.
Nucl Instrum Methods Phys Res A ; 829: 24-29, 2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-28706325

RESUMEN

X-ray crystallography is one of the main methods to determine atomic-resolution 3D images of the whole spectrum of molecules ranging from small inorganic clusters to large protein complexes consisting of hundred-thousands of atoms that constitute the macromolecular machinery of life. Life is not static, and unravelling the structure and dynamics of the most important reactions in chemistry and biology is essential to uncover their mechanism. Many of these reactions, including photosynthesis which drives our biosphere, are light induced and occur on ultrafast timescales. These have been studied with high time resolution primarily by optical spectroscopy, enabled by ultrafast laser technology, but they reduce the vast complexity of the process to a few reaction coordinates. In the AXSIS project at CFEL in Hamburg, funded by the European Research Council, we develop the new method of attosecond serial X-ray crystallography and spectroscopy, to give a full description of ultrafast processes atomically resolved in real space and on the electronic energy landscape, from co-measurement of X-ray and optical spectra, and X-ray diffraction. This technique will revolutionize our understanding of structure and function at the atomic and molecular level and thereby unravel fundamental processes in chemistry and biology like energy conversion processes. For that purpose, we develop a compact, fully coherent, THz-driven atto-second X-ray source based on coherent inverse Compton scattering off a free-electron crystal, to outrun radiation damage effects due to the necessary high X-ray irradiance required to acquire diffraction signals. This highly synergistic project starts from a completely clean slate rather than conforming to the specifications of a large free-electron laser (FEL) user facility, to optimize the entire instrumentation towards fundamental measurements of the mechanism of light absorption and excitation energy transfer. A multidisciplinary team formed by laser-, accelerator,- X-ray scientists as well as spectroscopists and biochemists optimizes X-ray pulse parameters, in tandem with sample delivery, crystal size, and advanced X-ray detectors. Ultimately, the new capability, attosecond serial X-ray crystallography and spectroscopy, will be applied to one of the most important problems in structural biology, which is to elucidate the dynamics of light reactions, electron transfer and protein structure in photosynthesis.

14.
Oncogene ; 26(57): 7904-8, 2007 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-17599053

RESUMEN

The signaling mechanisms responsible for BCR/ABL-induced regulation of Mcl-1 expression in chronic myelogenous leukemia (CML) cells remain unclear. In this study, we show that BCR/ABL could upregulate sphingosine kinase-1 (SPK1) expression via multiple signal pathways, including mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K) and Janus kinase 2 (JAK2), leading to increase cellular SPK1 activity in CML cells. Retrovirus-mediated overexpression of bcr-abl gene in NIH-3T3, Ba/F3 and HL-60 cells results in upregulation and increased cellular activity of SPK1, whereas treatment of CML cells with specific inhibitors of the BCR/ABL, PI3K, MAPK and JAK2 pathways decreases BCR/ABL-induced SPK1 expression and cellular activity. BCR/ABL also induces upregulation of Mcl-1 expression in CML cells. Inhibition of SPK1 by adenovirus-mediated transfer of small interfering RNA or N,N-dimethylsphingosine reduced expression of Mcl-1 in CML cells. Our data indicated that BCR/ABL induces SPK1 expression and increases its cellular activity, leading to upregulation of Mcl-1 in CML cells. SPK1 silencing enhances the STI571-induced apoptosis of CML cell lines. It is suggested that SPK1 may be a potential therapeutic target in CML.


Asunto(s)
Proteínas de Fusión bcr-abl/fisiología , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Proteínas de Neoplasias/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/fisiología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Animales , Benzamidas , Humanos , Mesilato de Imatinib , Janus Quinasa 2/fisiología , Células K562 , Ratones , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Células 3T3 NIH , Fosfatidilinositol 3-Quinasas/fisiología , Fosfotransferasas (Aceptor de Grupo Alcohol)/antagonistas & inhibidores , Piperazinas/farmacología , Pirimidinas/farmacología , ARN Interferente Pequeño/farmacología , Transducción de Señal , Regulación hacia Arriba
15.
Acupunct Electrother Res ; 17(2): 75-94, 1992.
Artículo en Inglés | MEDLINE | ID: mdl-1353653

RESUMEN

It is generally accepted that more than 10(-6) gauss order magnetism was not detected in normal human condition. However, we detected 10(-3) gauss (mGauss) order bio-magnetic field strength from the palm in special persons who emitted External Qi ("Chi" or "Ki"). This detection was possible by special arranged magnetic field detection system, consisted of a pair of 2 identical coils with 80,000 turns and a high sensitivity amplifier. Each of the coils were rolled 80,000 turns accurately, and were connected in series in opposite direction, actuating as a gradiometer. We measure bio-magnetic field strength in 37 subjects with this detection system. The only 3 subjects of them exhibited strong bio-magnetic field of 2 to 4 mGauss in frequency range of 4 to 10 Hz. This magnetic field strength was greater than that of normal human bio-magnetism by 1,000 times at least. A simultaneous measurement of bio-magnetic field strength and its corresponding bio-electric current was examined in one subject. During exhibiting such strong bio-magnetism, its corresponding electric current was not detectable. Therefore, the extra-ordinary large bio-magnetic field strength can not derive from internal body current alone, hence the origin of the large bio-magnetism is still unknown. We suppose that the extraordinary large bio-magnetic field strength might be originated from "Qi" energy in the oriental medicine or in the oriental traditional philosophy.


Asunto(s)
Campos Electromagnéticos , Mano/fisiología , Medicina Tradicional de Asia Oriental , Estudios de Evaluación como Asunto , Femenino , Humanos , Masculino
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