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1.
Ann Hematol ; 103(3): 999-1005, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38285081

RESUMEN

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that is highly aggressive with a poor prognosis. There is no standard treatment for BPDCN. Although conventional chemotherapies are usually sensitive in the initial therapy, relapse and drug resistance are inevitable within a short duration. Targeted therapies have enlightened new prospects for the treatment of BPDCN, especially for those in a frail state and intolerable to standard chemotherapies or hematopoietic stem cell transplantation. Here, we report an 82-year-old man diagnosed with cutaneous-limited BPDCN. Considering the old age and limited involvement of the tumor, we reduced the dosage of venetoclax. His skin lesions subsided significantly after 1 cycle of azacytidine (100 mg d1-7) combined with reduced doses of venetoclax (200 mg d1-14). The reduction in the dose of venetoclax avoided severe myelosuppression while achieving satisfactory outcomes. The patient received 2 cycles of therapy with no skin lesions re-occurred for 7 months before relapsing.


Asunto(s)
Compuestos Bicíclicos Heterocíclicos con Puentes , Neoplasias Hematológicas , Trastornos Mieloproliferativos , Neoplasias Cutáneas , Sulfonamidas , Masculino , Humanos , Anciano de 80 o más Años , Azacitidina/uso terapéutico , Células Dendríticas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Cutáneas/patología , Neoplasias Hematológicas/terapia , Trastornos Mieloproliferativos/patología
2.
Clin Microbiol Infect ; 30(1): 107-113, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37271194

RESUMEN

OBJECTIVES: To evaluate the diagnostic performance and clinical impact of metagenomic next-generation sequencing (mNGS) of plasma microbial cell-free DNA (mcfDNA) in febrile neutropenia (FN). METHODS: In a 1-year, multicentre, prospective study, we enrolled 442 adult patients with acute leukaemia with FN and investigated the usefulness of mNGS of plasma mcfDNA for identification of infectious pathogens. The results of mNGS were available to clinicians in real time. The performance of mNGS testing was evaluated in comparison with blood culture (BC) and a composite standard that incorporated standard microbiological testing and clinical adjudication. RESULTS: In comparison with BC, the positive and negative agreements of mNGS were 81.91% (77 of 94) and 60.92% (212 of 348), respectively. By clinical adjudication, mNGS results were categorized by infectious diseases specialists as definite (n = 76), probable (n = 116), possible (n = 26), unlikely (n = 7), and false negative (n = 5). In 225 mNGS-positive cases, 81 patients (36%) underwent antimicrobials adjustment, resulting in positive impact on 79 patients and negative impact on two patients (antibiotics overuse). Further analysis indicated that mNGS was less affected by prior antibiotics exposure than BC. DISCUSSION: Our results indicate that mNGS of plasma mcfDNA increased the detection of clinically significant pathogens and enabled early optimization of antimicrobial therapy in patients with acute leukaemia with FN.


Asunto(s)
Ácidos Nucleicos Libres de Células , Neutropenia Febril , Leucemia Mieloide Aguda , Adulto , Humanos , Estudios Prospectivos , Leucemia Mieloide Aguda/complicaciones , Secuenciación de Nucleótidos de Alto Rendimiento , Antibacterianos , Metagenómica , Neutropenia Febril/diagnóstico , Sensibilidad y Especificidad
3.
Cancer Med ; 12(24): 21742-21750, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38059559

RESUMEN

BACKGROUND: The malignancy of cholangiocarcinoma is highly pronounced, and it exhibits a propensity for recurrence and metastasis even in the presence of standard chemotherapy. The efficacy of adjuvant chemotherapy combined with immunotherapy in patients with resected cholangiocarcinoma needs to be substantiated. METHODS: Data from 101 patients with cholangiocarcinoma treated at the Sun Yat-sen University Cancer Center between 2015 and 2020 were studied. RESULTS: After propensity score matching, there were no significant differences in baseline characteristics between patients in the combined adjuvant chemotherapy and immunotherapy group (AC + IM group) and the adjuvant chemotherapy alone group (AC group) (all p > 0.05). The AC + IM group demonstrated a statistically significant improvement in relapse-free survival (RFS) compared to the AC group (p = 0.032). Likewise, the AC + IM group exhibited a significantly superior overall survival (OS) outcome when compared to the AC group (p = 0.044). Multivariate Cox analysis unveiled perineural invasion (p = 0.041), lymph node metastasis (p = 0.006), and postoperative immunotherapy (p = 0.008) as independent prognostic factors exerting a significant impact on the OS of patients. In the cohort of patients with perineural invasion, the AC + IM group exhibited significantly improved OS compared to the AC group (p = 0.0077). Similarly, within the subset of patients with lymph node metastasis, the AC + IM group exhibited a significantly superior OS outcome when compared to the AC group (p = 0.023). CONCLUSION: Combining postoperative adjuvant chemotherapy with immunotherapy extends the RFS and OS of patients with cholangiocarcinoma following radical resection.


Asunto(s)
Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Metástasis Linfática , Estudios Retrospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/patología , Quimioterapia Adyuvante , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/patología
4.
J Transl Med ; 21(1): 911, 2023 12 14.
Artículo en Inglés | MEDLINE | ID: mdl-38098005

RESUMEN

OBJECTIVE: Pancreatic cancer is an aggressive malignancy with high mortality, and cancer cell stemness and related drug resistance are considered important contributors to its poor prognosis. The objective of this study was to identify regulatory targets associated with the maintenance of pancreatic cancer stemness. MATERIALS AND METHODS: Pancreatic tumor samples were collected from patients at Sun Yat-sen University Cancer Center, followed by immunofluorescence analysis. Pancreatic cancer cell lines with Interleukin-20 receptor subunit beta (IL20RB) overexpression and knockdown were established, and clonal formation, spheroid formation and side population cell analysis were conducted. The effects of IL20RB knockdown on the tumor-forming ability of pancreatic cancer cells and chemotherapy resistance in vivo were explored. RESULTS: IL20RB expression was significantly upregulated in pancreatic cancer tissues, and was correlated with unfavorable prognosis. The IL20RB receptor promotes stemness and chemoresistance in both in vitro and in vivo models of pancreatic cancer. Mechanistically, IL20RB enhances the stemness and chemoresistance of pancreatic cancer by promoting STAT3 phosphorylation, an effect that can be counteracted by a STAT3 phosphorylation inhibitors. Additionally, Interleukin-19 derived from the microenvironment is identified as the primary ligand for IL20RB in mediating these effects. CONCLUSION: Our findings demonstrate that IL20RB plays a crucial role in promoting stemness in pancreatic cancer. This discovery provides a potential therapeutic target for this lethal disease.


Asunto(s)
Resistencia a Antineoplásicos , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Transducción de Señal , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Pronóstico , Células Madre Neoplásicas/patología , Microambiente Tumoral
5.
World J Microbiol Biotechnol ; 40(2): 54, 2023 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-38147274

RESUMEN

Daqu is of great significance to the brewing process of Baijiu, and there are variations in the light-flavor Baijiu Daqu in different regions. However, few studies have been conducted on light-flavor Daqu from the north and south regions of China. In this study, the physicochemical indices, volatile flavor components, and microbial community structure of two types of Daqu from the north and south regions of China were comparatively analyzed. The study findings reveal that Daqu originating from the southern region of China (HB) exhibits superior moisture content, acidity, starch content, and saccharification power. In contrast, Daqu from the northern region of China (SX) displays higher fermentation, esterification, and liquefaction power. The analysis of the microbial community structure revealed that HB was dominated by Bacillus, Kroppenstedtia, Saccharomycopsis, and Thermoascus, while SX was dominated by Bacillus, Prevotella, and Saccharomycopsis. The analysis detected a total of 47 volatile components in both HB Daqu and SX Daqu. The volatile components of pyrazine were significantly more abundant in HB Daqu than in SX Daqu, while alcohol compounds were more prominent in SX Daqu than in HB Daqu. In addition, the RDA analysis established a correlation between dominant microorganisms and volatile components. Cyanobacteria, Fusobacteriota, Ascomycota, Blastocladiomycota, Basidiomycota, and Mucormyce exhibited positive correlations with a significant proportion of the key volatile compounds. This study establishes a scientific foundation for improving the quality of light-flavor Daqu liquor in different regions of China.


Asunto(s)
Bacillus , Microbiota , China , Esterificación , Etanol
6.
Eur J Med Res ; 28(1): 606, 2023 Dec 19.
Artículo en Inglés | MEDLINE | ID: mdl-38115156

RESUMEN

OBJECTIVE: In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. MATERIALS AND METHODS: Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. RESULTS: 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). CONCLUSIONS: The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.


Asunto(s)
Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Puntaje de Propensión , Análisis de Supervivencia , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/patología , Quimioterapia Adyuvante , Estadificación de Neoplasias
7.
Appl Microbiol Biotechnol ; 107(4): 1453-1463, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36703009

RESUMEN

Caproic acid is an important fatty acid with diverse applications. In this study, the biomass growth and metabolites of Lacrimispora celerecrescens JSJ-1 were investigated under different carbon sources (ethanol, starch, sucrose, and glucose), with a focus on the effect of the coexistence of glucose and ethanol on the synthesis of caproic acid. The results showed that starch, glucose, and sucrose all contributed to the biomass of L. celerecrescens JSJ-1. Under the three carbon sources, L. celerecrescens JSJ-1 produced acetic acid, butyric acid, lactic acid, ethanol, and butanol, but caproic acid was not produced. Ethanol was the optimal substrate for the production of caproic acid. When glucose and ethanol coexisted, the generation time of caproic acid was delayed compared with that in ethanol sodium acetate medium (ES medium). This was because glucose was preferentially consumed over ethanol. Lactic acid was generated as a result of glucose consumption, which led to a significant decrease in pH from 6.45 to 4.68. The low pH (< 5) inhibited the synthesis of caproic acid. Then, the strain's usage of lactic acid and the reaction between CaCO3 and lactic acid caused the pH to increase. L. celerecrescens JSJ-1 did not start producing caproic acid using ethanol and acetic acid until the pH increased to 5.8. This research enriches the knowledge regarding the metabolism of L. celerecrescens JSJ-1 and provides guidelines for the industrial production of caproic acid by using L. celerecrescences JSJ-1. KEY POINTS: • Ethanol is the optimal substrate for the synthesis of caproic acid by Lacrimispora celerecrescens JSJ-1. • Lacrimispora celerecrescens JSJ-1 produced lactic acid rapidly when it used glucose, causing a sharp drop in pH. • pH is a crucial factor affecting the synthesis of caproic acid from ethanol by Lacrimispora celerecrescens JSJ-1.


Asunto(s)
Ácido Acético , Etanol , Ácido Acético/metabolismo , Etanol/metabolismo , Glucosa/metabolismo , Clostridium/metabolismo , Ácido Butírico/metabolismo , Fermentación , Carbono/metabolismo , Ácido Láctico/metabolismo , Sacarosa/metabolismo
8.
Biomater Adv ; 139: 213031, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35882122

RESUMEN

Inhibiting thrombus formation and intimal hyperplasia is essential for orthotopic tissue-engineered vascular grafts. The matching mechanical properties of autologous blood vessels and inhibition of platelet aggregation are considered as two points to improve the success rate of transplantation. The poly(ε-caprolactone)/collagen/heparin composite vascular graft (PCLHC) with three-dimensional network structure were constructed by electrospinning, which can mimic natural vascular biomechanics and enhance the viability of cells viability in vitro. The hybrid collagen matrix network nanofibers formed by electrospinning exhibited uniform and smooth morphology. The results of mechanical experiments showed that PCLHC had similar mechanical properties to natural blood vessels. And the addition of heparin enhanced the anticoagulation of PCLHC. Simultaneous three-component hybrid nanofibers showed a potentially reliable ability to promote the proliferation of human umbilical vein endothelial cells (HUVECs). In summary, all the results showed that the three-dimensional network structure of PCLHC presented the potential to heal injured vessels.


Asunto(s)
Nanofibras , Andamios del Tejido , Colágeno/farmacología , Heparina/química , Células Endoteliales de la Vena Umbilical Humana , Humanos , Nanofibras/uso terapéutico , Poliésteres/farmacología , Andamios del Tejido/química
9.
Front Surg ; 8: 642468, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336913

RESUMEN

Background: Gastric carcinoma (GC), which contains signet ring cell (SRC) components are frequently observed in postoperative pathological assessment. This study aims to study the prognostic significance of SRC components in GC patients. Methods: From 2003 to 2017, surgically resected primary GC patients were retrospectively reviewed. All enrolled patients were divided into three groups according to the proportion of SRC. The overall survival (OS) and disease-free survival (DFS) of GC patients with different tumor stages were analyzed. Results: Patients with SRC or mixed-SRC were more associated with female, younger age, middle or lower third of the stomach, larger tumor, higher pN stage, and more lymphovascular invasion. For GC patients in stage I, multivariate survival analysis showed that age >60, SRC components >50%, and pT stage were independent prognostic factors for OS (all p < 0.05). The 5-year OS of patients with SRC were higher than that of patients with pure adenocarcinoma (p = 0.021). For GC patients in stage II/III, multivariate survival analysis showed that age >60, SRC proportion, surgical types, Borrmann's type, pT stage, pN stage, and lymphovascular invasion were independent prognostic factors for OS (all p < 0.05). The 5-year OS/DFS of patients with SRC were lower than that of patients with pure adenocarcinoma (p < 0.001). Conclusions: SRC seemed to be a favorable prognostic factor in GC patients in stage I. However, for GC patients in stage II/III, the SRC components were associated with poor prognosis, independent of other clinicopathological factors.

10.
Life Sci Alliance ; 4(1)2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33234677

RESUMEN

The anemia of inflammation is related in part to abnormal erythropoiesis in bone marrow. G-CSF regulates granulopoiesis and is increased during systemic inflammation. Here, we have showed that high levels of G-CSF are associated with repression of bone marrow erythropoiesis and expansion of splenic erythropoiesis in Escherichia coli-infected mice and lipopolysaccharide-treated mice. Under lipopolysaccharide-induced systemic inflammatory conditions in mice, G-CSF neutralization with antibody alleviated the blockage of bone marrow erythropoiesis, prevented the enhancement of splenic erythropoiesis, ameliorated splenomegaly, and reduced the brittleness of spleen. We further demonstrated that after lipopolysaccharide treatment, TLR4-knockout mice display low levels of G-CSF, healthy bone marrow erythropoiesis, almost no stress erythropoiesis in the spleen, and normal size and toughness of spleen. In addition, we found HIF-mediated erythropoietin production is essential for splenic erythropoiesis in the setting of G-CSF-induced suppression of bone marrow erythropoiesis. Our findings identify G-CSF as a critical mediator of inflammation-associated erythropoiesis dysfunction in bone marrow and offer insight into the mechanism of G-CSF-induced splenic erythropoiesis. We provide experimentally significant dimension to the biology of G-CSF.


Asunto(s)
Médula Ósea/metabolismo , Eritropoyesis/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Factor Estimulante de Colonias de Granulocitos/metabolismo , Transducción de Señal/efectos de los fármacos , Bazo/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/metabolismo , Animales , Médula Ósea/efectos de los fármacos , Eritropoyesis/genética , Eritropoyetina/biosíntesis , Escherichia coli , Infecciones por Escherichia coli/metabolismo , Infecciones por Escherichia coli/microbiología , Inyecciones Subcutáneas , Lipopolisacáridos/efectos adversos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Transducción de Señal/genética , Bazo/efectos de los fármacos , Síndrome de Respuesta Inflamatoria Sistémica/inducido químicamente , Receptor Toll-Like 4/deficiencia , Receptor Toll-Like 4/genética
11.
Cancer Med ; 8(1): 182-189, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30575310

RESUMEN

The tumor immune infiltrate, as recently evaluated with the immunoscore methodology, has been reported to be related to colorectal cancer (CRC) progression. Nevertheless, results varied from different studies. A meta-analysis was conducted to solve this problem. We collected data from included studies to evaluate the prognostic role of immunoscore in CRC patients on overall survival (OS) and disease-free survival (DFS). MEDLINE, EMBASE, and Cochrane libraries were searched through 30 June 2018. Hazard ratio (HR) with 95% confidence intervals (95% CI) was pooled using a random-effects model for OS and a fixed-effects model for DFS. Finally, eight studies (involving 4689 CRC cases) were identified as eligible publications. The results of the meta-analysis showed that low immunoscore was significantly correlated with poor OS (HR = 1.74, 95% CI: 1.43-2.13) and DFS (HR = 1.82, 95% CI: 1.64-2.03). The findings from most subgroup analyses were consistent with those from the overall analysis. The immunoscore could be a useful prognostic marker in patients with CRC. It is necessary to evaluate immunological markers in international multicenter studies.


Asunto(s)
Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/mortalidad , Humanos , Pronóstico , Análisis de Supervivencia
12.
Oncotarget ; 9(8): 8081-8088, 2018 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-29487716

RESUMEN

Human papillomavirus (HPV) DNA and p16 expression have been identified to be related to the progression of anal squamous cell carcinoma (ASCC). However, the prognostic relevance of combined detection, particularly HPV-/p16+ and HPV+/p16- signatures, is unknown. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Data were collected from studies comparing overall survival (OS) and disease-free survival (DFS) / disease-specific survival (DSS) / relapse-free survival (RFS) / progression-free survival (PFS) in ASCC patients with HPV and p16 status. The electronic databases of MEDLINE and EMBASE were searched from their inception till 31 May 2017. Study-specific risk estimates were pooled using a fixed-effects model for OS and DFS/DSS/RFS/PFS. Four studies involving a total of 398 ASCC cases were included in this meta-analysis. The pooled results showed that HPV+/p16+ cancers were significantly associated with improved OS (HR = 0.30, 95% CI: 0.17-0.51) and DFS/DSS/RFS/PFS (HR = 0.23, 95% CI: 0.14-0.36). However, patients with HPV-/p16+ or HPV+/p16- do not have a comparably good prognosis compared with HPV+/p16+ patients. The meta-analysis indicated that concomitant detection of HPV-DNA and p16 expression may be of prognostic or therapeutic utility in the evaluation of factors contributing to ASCC. Testing tumor specimens for HPV-DNA and p16 expression might indirectly affect treatment decisions.

13.
Blood ; 128(6): 852-61, 2016 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-27281793

RESUMEN

Elevated expression of the activating Fcγ receptor (FcγR) I and FcγRIIa together with decreased expression of the inhibitory FcγRIIb are involved in the pathogenesis of primary immune thrombocytopenia (ITP). Thrombopoietin receptor agonists (TPO-RAs) have been used clinically for the management of ITP; however, little is known about the effect of TPO-RAs on FcγR modulation in ITP. In this prospective study, we measured the alteration in monocyte FcγR expression from 21 corticosteroid-resistant/relapsed patients with chronic ITP receiving eltrombopag therapy. Results showed that the mRNA and protein levels of FcγRIIb were significantly elevated after 6-week eltrombopag treatment. Concurrently, FcγRI and IIa levels decreased remarkably, whereas FcγRIII expression did not change. In vitro phagocytosis assays indicated that a shift in the balance of FcγR toward inhibitory FcγRIIb on monocytes was accompanied with a considerable decrease in monocyte/macrophage phagocytic capacity. The response to eltrombopag therapy in patients with ITP was associated with FcγR phenotype and functional changes of monocytes/macrophages. Moreover, the plasma transforming growth factor-ß1 (TGF-ß1) concentrations increased significantly in eltrombopag responders. Modulation of monocyte FcγR balance by TPO-RAs was also found in a murine model of ITP established by transferring splenocytes from immunized CD61 knockout mice into CD61(+) severe combined immunodeficient mice. Romiplostim administration in ITP mice significantly upregulated inhibitory FcγRII expression and downregulated activating FcγRI expression. These findings showed that recovery of platelet counts after TPO-RA treatment in ITP is associated with the restoration of FcγR balance toward the inhibitory FcγRIIb on monocytes, and suggested that thrombopoietic agents have a profound effect on immune modulation in ITP. This study is registered at ClinicalTrials.gov as #NCT01864512.


Asunto(s)
Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Monocitos/efectos de los fármacos , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Receptores de IgG/análisis , Receptores de Trombopoyetina/agonistas , Adulto , Anciano de 80 o más Años , Benzoatos/efectos adversos , Femenino , Humanos , Hidrazinas/efectos adversos , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Fagocitosis/efectos de los fármacos , Estudios Prospectivos , Púrpura Trombocitopénica Idiopática/inmunología , Pirazoles/efectos adversos , Receptores de IgG/inmunología , Factor de Crecimiento Transformador beta1/sangre , Adulto Joven
14.
Drug Deliv ; 23(4): 1374-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26208133

RESUMEN

PURPOSE: Lymph cancers are heterogeneous malignancies of the hematopoietic and lymphoid tissues. Doxorubicin (DOX) and vincristine (VCR) are commonly used anti-cancer chemotherapeutic drugs, but their clinical uses are associated with dose-limiting systemic toxicity. METHODS: In the present study, DOX and VCR were encapsulated into nanostructured lipid carriers (NLCs) and used them to treat B-cell lymphoma cells through the targeted delivery of DOX and VCR to lymph cancer animal model. RESULTS: DOX and VCR encapsulated NLCs (DOX/VCR NLCs) demonstrated controlled drug release under physiological conditions. In addition, DOX/VCR NLCs exhibited the highest cytotoxicity and synergistic effect of two drugs in B-cell lymphoma cells and the best anti-tumor effect in vivo. CONCLUSION: DOX/VCR NLCs were proved to be more efficacious than the equivalent dose of free DOX and single drug (DOX or VCR) formulation in vitro and in vivo, and significantly reduced the drug-associated systemic toxicity.


Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Lípidos/química , Linfa/química , Linfa/efectos de los fármacos , Nanoestructuras/química , Vincristina/farmacología , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/farmacología , Antineoplásicos/farmacocinética , Línea Celular Tumoral , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacocinética , Portadores de Fármacos , Liberación de Fármacos , Resistencia a Múltiples Medicamentos , Humanos , Vincristina/química , Vincristina/metabolismo , Vincristina/farmacocinética
15.
Int J Infect Dis ; 37: 97-103, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25931196

RESUMEN

OBJECTIVES: Febrile neutropenia (FN) is a common but lethal complication of chemotherapy in hematological malignance. The aim of this study was to identify the prognostic risk factors for antibiotic treatment outcome in PN patients, and provide the optimal choice for the initial empirical antibiotic treatment. METHODS: 227 consecutive FN hematologic malignancies from four hospitals in Northeast China were enrolled. The outcome of antibiotic therapy was investigated until 14 days after the onset of FN. The factors affecting antibiotic therapy outcome were evaluated using Univariate analysis and Multivariate logistic regression analysis. RESULTS: Among all patients, 27 patients did not achieve favorable outcome either clinically or bacteriologically. It was shown that the risk factors for poor FN therapy outcome were associated with prolonged duration of neutropenia over 9 days during FN (P=0.019), slow neutrophil recovery (P=0.039), respiratory infection (P=0.005), and that initial monotherapy with drugs recommended by the guidelines indicated better outcome (P=0.009). Additionally, patients with multi-bacterial infection, as well as further ANC decrease after fever, had a poor prognosis. CONCLUSIONS: Our results indicate that early application of antibiotics and prevention of respiratory infection as well as good clinical care are able to improve clinical outcomes from empirical antibiotic treatment in FN patients with hematological malignances.


Asunto(s)
Antibacterianos/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Neoplasias Hematológicas/complicaciones , Adolescente , Adulto , Anciano , Neutropenia Febril Inducida por Quimioterapia/microbiología , China , Femenino , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven
16.
Blood ; 125(10): 1541-7, 2015 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-25575541

RESUMEN

This study aimed to compare the efficacy and safety of rituximab (RTX) plus recombinant human thrombopoietin (rhTPO) with RTX alone in patients with immune thrombocytopenia (ITP) who had failed to respond to corticosteroids or relapsed. Recruited patients were randomized at a ratio of 2:1 into 2 groups: the combination group (RTX + rhTPO, n = 77) and the monotherapy group (RTX, n = 38). Overall response was achieved in 79.2% of patients in the combination group vs 71.1% in the monotherapy group (P = .36), and the complete response (CR) rate was 45.4% in the combination group compared with 23.7% in the monotherapy group (P = .026). The combination group had significantly shorter time to response (TTR; median and range, 7 and 4-28 days) compared with the monotherapy group (28 and 4-90 days) (P < .01). There was no difference between these 2 groups in terms of the long-term response (P = .12). Our findings demonstrated that the combination of RTX and rhTPO significantly increased the CR rate and shortened TTR compared with RTX monotherapy in the treatment of corticosteroid-resistant or relapsed ITP but failed to show a beneficial effect on the long-lasting response. This study is registered at www.clinicaltrials.gov as #NCT01525836.


Asunto(s)
Anticuerpos Monoclonales de Origen Murino/administración & dosificación , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Púrpura Trombocitopénica Idiopática/terapia , Trombopoyetina/administración & dosificación , Adolescente , Corticoesteroides/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales de Origen Murino/efectos adversos , Autoanticuerpos/sangre , Niño , Terapia Combinada , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Púrpura Trombocitopénica Idiopática/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Recurrencia , Rituximab , Trombopoyetina/efectos adversos , Resultado del Tratamiento , Adulto Joven
18.
Ann Hematol ; 91(10): 1623-31, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22526360

RESUMEN

Indoleamine 2,3-dioxygenase (IDO) expression in dendritic cells (DCs) can induce or maintain peripheral immune tolerance. Impaired IDO-mediated tryptophan catabolism has been observed in autoimmune diseases. In order to investigate the effects of IDO-mediated tryptophan catabolism and IDO-expressing DCs in immune thrombocytopenia, the concentrations of kynurenine were detected by high-pressure liquid chromatography. The expressions of IDO were analyzed by flow cytometry and western blot analysis. The effects of IDO(+) DCs stimulated with CTLA-4-Ig on T cells proliferation and activation, lymphocyte apoptosis, and Tregs were measured by flow cytometry. We found that the expression of IDO in DCs of immune thrombocytopenia (ITP) patients was significantly decreased. CTLA-4-Ig significantly increased the expression of functional IDO in DCs of ITP patients. IDO(+) DCs stimulated with CTLA-4-Ig suppressed T cells proliferation and activation, promoted lymphocyte apoptosis, and increased the percentage of Tregs. These results suggest that decreased IDO expression in DCs may play a critical role in ITP. CTLA-4-Ig successfully corrected the disorder of IDO expression in ITP. IDO(+) DCs stimulated with CTLA-4-Ig inhibited immune responses by an IDO-dependent mechanism. Increasing the expression and activity of IDO in DCs might be a promising therapeutic approach for ITP.


Asunto(s)
Células Dendríticas/enzimología , Células Dendríticas/inmunología , Regulación hacia Abajo/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/antagonistas & inhibidores , Indolamina-Pirrol 2,3,-Dioxigenasa/biosíntesis , Trombocitopenia/enzimología , Trombocitopenia/inmunología , Adolescente , Adulto , Proliferación Celular , Células Cultivadas , Femenino , Regulación Enzimológica de la Expresión Génica , Humanos , Tolerancia Inmunológica/genética , Masculino , Persona de Mediana Edad , Linfocitos T/inmunología , Linfocitos T/patología , Trombocitopenia/patología , Adulto Joven
19.
Cell Biochem Biophys ; 62(2): 361-4, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21938557

RESUMEN

We sought to evaluate in this study the significance of cytokeratin (CK)-19 and CK-20 in determining the peritoneal micrometastasis of gastric carcinoma and also determine the factors related with the occurrence of peritoneal micrometastasis. For this purpose, 152 patients with gastric cancer were enrolled in the study and transverse mesocolon biopsies were undertaken intraoperatively. The CK19 and CK20 immunohistochemical staining were performed on the tissue samples, and the results were compared with those of H&E staining and peritoneal lavage cytology (PLC). Our data show that the positivity rates of CK19 and CK20 in transverse mesocolon were 48.6 and 61.2%, respectively, which were significantly higher (P < 0.05) than that (10.0%) of PLC. Besides, the positivity rate increased with the depth of tumor invasion. Based on these data, we concluded that CK19 and CK20 expressions could be adopted to determine the peritoneal micrometastasis for accurate clinical staging of the patients. These data provide reliable guideline for postoperative treatment and prognosis of gastric carcinoma.


Asunto(s)
Carcinoma/patología , Colon Transverso/metabolismo , Regulación Neoplásica de la Expresión Génica , Queratina-19/metabolismo , Queratina-20/metabolismo , Neoplasias Gástricas/patología , Adulto , Anciano , Carcinoma/mortalidad , Carcinoma/cirugía , Colon Transverso/patología , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Micrometástasis de Neoplasia/patología , Lavado Peritoneal , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/cirugía
20.
Dev Change ; 42(4): 947-65, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22164881

RESUMEN

China's economic reforms over the past three decades have dramatically changed the mechanisms for allocating goods and labour in both market and non-market spheres. This article examines the social and economic trends that intensify the pressure on the care economy, and on women in particular in playing their dual roles as care givers and income earners in post-reform China. The analysis sheds light on three critical but neglected issues. How does the reform process reshape the institutional arrangements of care for children and elders? How does the changing care economy affect women's choices between paid work and unpaid care responsibilities? And what are the implications of women's work­family conflicts for the well-being of women and their families? The authors call for a gendered approach to both social and labour market policies, with investments in support of social reproduction services so as to ease the pressures on women.


Asunto(s)
Cuidadores , Familia , Factores Socioeconómicos , Salud de la Mujer , Mujeres Trabajadoras , Cuidadores/economía , Cuidadores/educación , Cuidadores/historia , Cuidadores/psicología , China/etnología , Familia/etnología , Familia/historia , Familia/psicología , Historia del Siglo XX , Historia del Siglo XXI , Renta/historia , Factores Socioeconómicos/historia , Salud de la Mujer/etnología , Salud de la Mujer/historia , Derechos de la Mujer/economía , Derechos de la Mujer/educación , Derechos de la Mujer/historia , Derechos de la Mujer/legislación & jurisprudencia , Mujeres Trabajadoras/educación , Mujeres Trabajadoras/historia , Mujeres Trabajadoras/legislación & jurisprudencia , Mujeres Trabajadoras/psicología
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