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1.
ESMO Open ; 8(5): 101629, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37660406

RESUMO

BACKGROUND: We aimed to investigate the efficacy of locoregional radiotherapy (LRRT) in patients with de novo metastatic nasopharyngeal carcinoma (dmNPC) receiving chemotherapy combined with anti-programmed cell death receptor-1 monoclonal antibodies (anti-PD-1 mAbs) as first-line treatment and identify optimal candidates for LRRT. MATERIALS AND METHODS: We enrolled patients with dmNPC receiving platinum-based palliative chemotherapy and anti-PD-1 mAbs followed or not followed by LRRT from four centers. The endpoints were progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). We used the inverse probability of treatment weighting (IPTW) to balance the baseline characteristics of the LRRT and non-LRRT groups to minimize selection bias before comparative analyses. Multivariate analyses were carried out using the Cox proportional hazards model. RESULTS: We included 163 patients with dmNPC (median follow-up: 22 months). The median PFS was 20 months, and the ORR was 92.0%; the median OS was not achieved. After IPTW adjustments, patients who received LRRT had a significant survival benefit over those not receiving LRRT (median PFS: 28 versus 15 months, P < 0.001). The Epstein-Barr virus DNA (EBV DNA) level after four to six cycles of anti-PD-1 mAbs [weighted hazard ratio (HR): 2.19, 95% confidence interval (CI) 1.22-3.92, P = 0.008] and LRRT (weighted HR: 0.58, 95% CI 0.34-0.99, P = 0.04) were independent prognostic factors. Patients with undetectable EBV DNA levels after four to six cycles of anti-PD-1 mAbs (early EBV DNA clearance) benefitted from LRRT (HR: 0.41, 95% CI 0.22-0.79, P = 0.008), whereas those with detectable levels did not (HR: 1.30, 95% CI 0.59-2.87, P = 0.51). CONCLUSIONS: Palliative chemotherapy combined with anti-PD-1 mAbs followed by LRRT was associated with improved PFS in patients with dmNPC, especially for patients with early EBV DNA clearance.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/patologia , Infecções por Vírus Epstein-Barr/terapia , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/radioterapia , Prognóstico , Herpesvirus Humano 4/genética , Quimiorradioterapia , DNA
2.
Zhonghua Zhong Liu Za Zhi ; 45(2): 170-174, 2023 Feb 23.
Artigo em Chinês | MEDLINE | ID: mdl-36781239

RESUMO

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Anticorpos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/cirurgia , Cisplatino , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Terapia Neoadjuvante , Receptor de Morte Celular Programada 1/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
5.
Artigo em Chinês | MEDLINE | ID: mdl-31623040

RESUMO

Objective:To explore the signal pathway that mediates the effect of 2-methoxyestradiol(2ME2) on human laryngeal papilloma cell line, in terms of cell proliferation and neovascularization. Method:HIF-1α expression of human laryngeal papilloma cell line(Hs840. T) was interfered using siRNA, and the cells were then processed by 2ME2 in two concentrations. RT-PCR and ELISA were performed to detect the difference of HIF-1α in cells with normal or lower HIF-1α mRNA level, with ELISA test of excretory VEGF level and CCK8 test of cell viability. Result:The IC50of 2ME2 in Hs840. T was 0.309 µmol/L in terms of the inhibition effect of cell proliferation(P<0.01). Baseline level of intracellular HIF-1α was detectable, and procession of Hs840. T cells by 2ME2 of 0.4 µmol/L inhibited the transcription and expression of HIF-1α by(76.8±2.0)% and(68.6±3.5)% [vs blank group(100.0±2.7)% and(100.0±6.9)%, P<0.01]. VEGF excretion decreased to(50.8±2.1) and(28.1±4.0)% [vs blank group(100.0±3.1)%, P<0.01]after procession by 2ME2 of 0.2 µmol/L and 0.4 µmol/L. After the successful interference of HIF-1α by siRNA, the inhibition effect on cell proliferation by 2ME2 of 0.4 µmol/L decreased to(51.5±3.8)% [vs control group(65.7±1.7)%, P<0.01]. siRNA interference of HIF-1α lead to a decrease of HIF-α mRNA and protein level to(16.3±0.9)% and(7.4±0.8)% [vs cells not interfered(76.8±2.0)% vs(68.6±3.5)%, P<0.01]. Secretory VEGF dropped to(41.0±2.9)% [vs cells not interfered(28.1±4.0)%, P<0.05]. Conclusion:2ME2 has a significant inhibitory effect on human laryngeal cell line. The inhibition of cell proliferation was mediated by a lower level of HIF-1α and therefore lower VEGF. 2ME2 might serve as a novel potential therapy for patients of recurrent respiratory papillomatosis.


Assuntos
2-Metoxiestradiol/metabolismo , Linhagem Celular Tumoral , Estradiol , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neoplasias Laríngeas , Papiloma , Fator A de Crescimento do Endotélio Vascular/metabolismo
6.
Sci Rep ; 9(1): 7490, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31097727

RESUMO

We report a new diluted ferromagnetic semiconductor Li1+y(Cd,Mn)P, wherein carrier is doped via excess Li while spin is doped by isovalence substitution of Mn2+ into Cd2+. The extended Cd 4d-orbitals lead to more itinerant characters of Li1+y(Cd,Mn)P than that of analogous Li1+y(Zn,Mn)P. A higher Curie temperature of 45 K than that for Li1+y(Zn,Mn)P is obtained in Li1+y(Cd,Mn)P polycrystalline samples by Arrott plot technique. The p-type carriers are determined by Hall effect measurements. The first principle calculations and X-ray diffraction measurements indicate that occupation of excess Li is at Cd sites rather than the interstitial site. Consequently holes are doped by excess Li substitution. More interestingly Li1+y(Cd,Mn)P shows a very low coercive field (<100 Oe) and giant negative magnetoresistance (~80%) in ferromagnetic state that will benefit potential spintronics applications.

7.
Appl Opt ; 57(30): 9022-9031, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30461890

RESUMO

Intense multi-peak red fluorescence and effective near-infrared (NIR) ultra-broadband emission have been observed in Pr3+ doped ion-exchangeable aluminum germanate (NMAG) glasses. The maximum emission cross section for P03→F23 red emission is up to 100.58×10-21 cm2, and the NIR emission corresponding to D21→G41 transition possesses a full-width at half-maximum (FWHM) of 210 nm. Although the obvious cross-relaxation (CR) process at high concentration causes a decrease of the quantum efficiency, the CR broadens the spectral FWHM effectively from another perspective. The admirable red fluorescence trace and the NIR single-mode transmission confirm that Pr3+ doped NMAG glass planar waveguides can support the generation of visible fluorescence and the amplification of infrared signal. For a waveguide channel ion-exchanged in molten KNO3 for 2 h, the single-mode field diameters at 1.55 µm are identified to be 10.4 µm in the horizontal direction and 6.5 µm in the vertical direction, implying an acceptable overlap with a standard single-mode fiber. Effective red fluorescence and broad NIR emission demonstrate that Pr3+ doped NMAG glasses are a promising substrate in developing irradiative luminescence sources and ultra-broadband waveguide amplifiers, especially operating at the entire S-, C-, and L- bands.

8.
J Biol Regul Homeost Agents ; 31(4): 1073-1079, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29254317

RESUMO

Colon cancer is a common malignant tumor with particularly high morbidity and mortality. The aim of this study was to compare the effect of quick rehabilitation nursing and routine nursing in postoperative recovery of patients with colon cancer after laparoscopic surgery. Two hundred forty patients with colon cancer were classified into four random groups (A, B, C and D, with 60 patients in each group). All patients underwent surgery to remove the colon tumor by laparoscopy under general anesthesia. Patients in groups A and B received quick rehabilitation nursing for post-surgery recovery. In group C patients, local anesthesia associated with quick rehabilitation nursing for post-surgery recovery was used. Group D was used as control group and the patients were treated based on routine nursing. Time to get out of bed, first bowel movement time and the average time of hospitalisation in group A was lower than group D (p less than 0.05), postoperative leukocyte level as well as the occurrence rate of nausea and vomiting, ankylenteron and pelvic adhesion was decreased in group A compared to group D (p less than 0.05), but the postoperative albumin and total protein level was higher than group D (p less than 0.05). The serum level of C-Reactive Protein (CRP) and interleukin 6 (IL-6) in group A was decreased compared to group D several days after surgery (p less than 0.05); group B had 4 cases of intestinal obstruction after surgery that could be cured through conservative treatment, while group D had 10 cases of intestinal obstruction, 8 of which could be cured through conservative treatment and two needed surgery (p less than 0.05); VAS for pain degree of group C in active state was clearly lower at 1h, 5h, 7h, 15h, 30h and 42h after surgery, and side effects of postoperative analgesia were clearly reduced. Time to get out of bed was obviously decreased, while there was no evident effect on postoperative dosage, chronic pain and complications. Adopting quick rehabilitation nursing can effectively reduce occurrence of complications and postoperative pain, speed up the recovery of gastrointestinal function, shorten the length of stay, and improve patients’ satisfaction.


Assuntos
Neoplasias do Colo/reabilitação , Obstrução Intestinal/diagnóstico , Laparoscopia/reabilitação , Dor Pós-Operatória/prevenção & controle , Náusea e Vômito Pós-Operatórios/prevenção & controle , Enfermagem em Reabilitação/métodos , Adulto , Idoso , Albuminúria/sangue , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Anestesia Geral/métodos , Anestesia Local/métodos , Proteína C-Reativa/metabolismo , Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Feminino , Humanos , Interleucina-6/sangue , Obstrução Intestinal/sangue , Obstrução Intestinal/patologia , Obstrução Intestinal/cirurgia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/sangue , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/fisiopatologia , Satisfação do Paciente/estatística & dados numéricos , Náusea e Vômito Pós-Operatórios/sangue , Náusea e Vômito Pós-Operatórios/diagnóstico , Náusea e Vômito Pós-Operatórios/fisiopatologia , Período Pós-Operatório , Estudos Prospectivos
9.
Br J Dermatol ; 176(5): 1247-1258, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27718503

RESUMO

BACKGROUND: Cutaneous malignant melanoma arises from transformed melanocytes de novo or from congenital or acquired melanocytic naevi. We have recently reported that T-type Ca2+ channels (TT-Cs) are upregulated in human melanoma and play an important role in cell proliferation. OBJECTIVES: To describe for the first time in formalin-fixed paraffin-embedded tissue the immunoexpression of TT-Cs in biopsies of normal skin, acquired melanocytic naevi and melanoma, in order to evaluate their role in melanomagenesis and/or tumour progression, their utility as prognostic markers and their possible use in targeted therapies. METHODS: Tissue samples from normal skin, melanocytic naevi and melanoma were subjected to immunohistochemistry for two TT-Cs (Cav3.1, Cav3.2); markers of proliferation (Ki67), the cell cycle (cyclin D1), hypoxia (Glut1), vascularization (CD31) and autophagy (LC3); BRAF V600E mutation (VE1) and phosphatase and tensin homologue (PTEN). Immunostaining was evaluated by histoscore. In silico analysis was used to assess the prognostic value of TT-C overexpression. RESULTS: TT-C immunoexpression increased gradually from normal skin to common naevi, dysplastic naevi and melanoma samples, but with differences in the distribution of both isoforms. Particularly, Cav3.2 expression was significantly higher in metastatic melanoma than in primary melanoma. Statistical correlation showed a linear interaction between PTEN loss/BRAF V600E/Cav3.1/LC3/ Ki67/cyclin D1/Cav3.2/Glut1. Disease-free survival (DFS) and overall survival correlated inversely with overexpression of Cav3.2. DFS also correlated inversely with overexpression of Cav3.1. CONCLUSIONS: TT-C immunoexpression on melanocytic neoplasms is consistent with our previous in vitro studies and appears to be related to tumour progression. TT-C upregulation can be considered as a prognostic marker using The Cancer Genome Atlas database. The high expression of Cav3.2 in metastatic melanoma encourages the investigation of the use of TT-C blockers in targeted therapies.


Assuntos
Biomarcadores Tumorais/metabolismo , Canais de Cálcio Tipo T/metabolismo , Melanoma/diagnóstico , Nevo Pigmentado/diagnóstico , Neoplasias Cutâneas/diagnóstico , Proliferação de Células/fisiologia , Progressão da Doença , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Melanoma/mortalidade , Recidiva Local de Neoplasia/etiologia , Nevo Pigmentado/mortalidade , Prognóstico , Neoplasias Cutâneas/mortalidade , Regulação para Cima
10.
Neoplasma ; 64(1): 40-47, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27881003

RESUMO

Hepatocellular carcinoma (HCC) is the third leading cause of cancer associated mortality. Accumulating evidence has shown that microRNAs (miRNAs) act as critical factors for tumor recurrence and metastasis. MiR-508-5p has been reported as a down-regulated miRNA in the primary gastric cancer tissues. However, the role of miR-508-5p on HCC has not been well elucidated. In this study, we observed that miR-508-5p was downregulated in HCC tissues when compared to the non-tumorous tissues. We then demonstrated that overexpression of miR-508-5p attenuated HepG2 cells proliferation and invasion and induced cell apoptosis in vitro. Furthermore, our further investigations revealed that mesoderm development candidate 1 (MESDC1) is a potential target of miR-508-5p, as well as miR-508-5p overexpression downregulated MESDC1 expression. Overexpression of MESDC1 promoted HepG2 cells migration, invasion and proliferation in vitro. In addition, miR-508-5p markedly suppressed the tumor growth in xenograft model, while MESDC1 promoted the tumor growth in xenograft model. This study provides new insight into molecular mechanisms that miR-508-5p acts as a tumor suppressor by targeting MESDC1 in HCC progression.


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Chaperonas Moleculares/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Genes Supressores de Tumor , Células Hep G2 , Humanos , Recidiva Local de Neoplasia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Appl Opt ; 54(19): 5976-82, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-26193141

RESUMO

Ho(3+)-doped and Ho(3+)/Yb(3+)-codoped multicomponent germanium tellurite (MGT) glasses with multifarious emission channels in the near-infrared wavelength region have been fabricated and characterized. Judd-Ofelt intensity parameters of Ho(3+)-doped MGT glasses are solved to be Ω2=5.32×10(-20) cm(2), Ω(4)=2.73×10(-20) cm(2), and Ω(6)=1.12×10(-20) cm(2), indicating a higher asymmetric and stronger covalent environment around Ho(3+) ions in MGT glasses. Efficient infrared fluorescences have been observed in MGT glasses, and spontaneous emission probabilities are derived to be 230.4, 79.9, and 138.3 s(-1) for the (5)I(6)→(5)I(8), ((5)F(4),(5)S(2))→(5)I(5), and (5)I(7)→(5)I(8) radiative transitions, respectively. In Ho(3+)/Yb(3+)-codoped MGT glasses, the maximum stimulated emission cross-section of 2.0 µm emission is calculated to be 4.93×10(-21) cm(2), and the corresponding gain cross-section is derived to be 3.62×10(-21) cm(2) when the excited state population fraction P reaches 0.8. Multifarious infrared emissions show that Ho(3+) in MGT glasses is a good candidate for optical amplifiers and optoelectronic devices.


Assuntos
Germânio/química , Hólmio/química , Raios Infravermelhos , Telúrio/química , Desenho de Equipamento , Fluorescência , Vidro , Temperatura Alta , Luminescência , Dispositivos Ópticos , Óptica e Fotônica , Probabilidade , Espectrofotometria/métodos , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Itérbio/química
12.
Opt Express ; 21(1): 1030-40, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23388997

RESUMO

Pr3+-doped medium-low phonon energy heavy metal germanium tellurite (NZPGT) glasses have been fabricated and the intense multi-peak red fluorescence emissions of Pr3+ are exhibited. Judd-Ofelt parameters Ω2 = 3.14 × 10(-20)cm(2), Ω4 = 10.67 × 10(-20)cm(2) and Ω6 = 3.95 × 10(-20)cm(2) indicate a high asymmetrical and covalent environment in the optical glasses. The spontaneous emission probabilities A(ij) corresponding to the 1D2→3H4, 3P0→3H6, and 3P0→3F2 transitions are derived to be 1859.6, 6270.1 and 17276.3s(-1), respectively, and the relevant stimulated emission cross-sections σ(em) are 5.20 × 10(-21), 14.14 × 10(-21) and 126.77 × 10(-21)cm(2), confirming that the effectiveness of the red luminescence in Pr3+-doped NZPGT glasses. Under the commercial blue LED excitation, the radiant flux and the quantum yield for the red fluorescence of Pr3+ are solved to be 219µW and 11.80%, respectively. 85.24% photons of the fluorescence in the visible region are demonstrated to be located in 600-720nm wavelength range, which matches the excitation band of the most photosensitizers (PS), holding great promise for photodynamic therapy (PDT) treatment and clinical trials.

13.
Opt Express ; 20(2): 879-89, 2012 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-22274434

RESUMO

In Sm(3+)-doped K(+)-Na(+) ion-exchanged aluminum germanate (NMAG) glass channel waveguide, a clear and compact red amplified spontaneous emission (ASE) trace is observed under the excitation of a 488nm Ar(+) laser. 78% photons of ASE fluorescence in visible region are demonstrated to be located in 600-730nm wavelength range. High-directivity and high-brightness ASE fluorescence of Sm(3+)-doped NMAG glass channel waveguide, which matches the excitation band of most photosensitizers (PS) currently used in photodynamic therapy (PDT) or clinical trials, has promising potential application as an excitation light source for PDT treatment.


Assuntos
Germânio/química , Lasers de Gás , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Neoplasias/cirurgia , Fotoquimioterapia/instrumentação , Samário/química , Desenho de Equipamento , Vidro/química , Humanos , Lasers Semicondutores , Modelos Teóricos , Fármacos Fotossensibilizantes/uso terapêutico , Terapia Ultravioleta/instrumentação
14.
Bone Marrow Transplant ; 45(2): 379-84, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19597415

RESUMO

Rapamycin (RAPA) is an immunosuppressive drug that prevents and treats graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplant (HCT). One possible mechanism for its efficacy is induction of tolerance, through increased number or enhanced survival of regulatory T cells. In our experiments, B10.D2 BM and splenocytes were injected into lethally irradiated BALB/cJ recipients. The mice received i.p. injections of either RAPA or vehicle control on days 1-28. There was a significant survival advantage in RAPA-treated mice. Evaluation of the skin biopsies showed a dense cellular infiltrate in RAPA-treated mice. Further characterization of these cells revealed a higher percentage of regulatory T cells characterized by FoxP3-positive cells in high-dose RAPA-treated mice as compared with controls on day 30. This effect appears to be dose dependent. When peripheral blood analysis for FoxP3-positive cells was performed, there was no significant difference observed in the RAPA-treated mice as compared with control mice. These data show a novel mechanism of rapamycin in GVHD, accumulation of regulatory T cells in the GVHD target tissue: the skin.


Assuntos
Fatores de Transcrição Forkhead/metabolismo , Doença Enxerto-Hospedeiro/tratamento farmacológico , Sirolimo/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Animais , Feminino , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Intestinos/imunologia , Fígado/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Pele/citologia , Pele/imunologia , Linfócitos T Reguladores/imunologia
15.
Cytotherapy ; 7(2): 126-33, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16040391

RESUMO

Allogeneic stem cell transplantation (alloSCT), especially in the mismatched setting, carries a high risk of life-threatening GvHD because of activation of donor T cells by Ag present on host cells. Removal of mature donor T cells can prevent GvHD but leads to delayed immune reconstitution, and an increased incidence of opportunistic infections and disease relapse. These findings demonstrate the vital role of donor T cells in providing graft-versus-tumor (GvT) and anti-pathogen effects as well as facilitating immune reconstitution. It has been well documented that GvHD can be separated from GvT effects, making it possible potentially to eliminate GvHD while preserving the immunotherapeutic benefits of donor T cells. Over the past decade, major attempts have been made to reduce GvHD incidence without loss of GvT effect, especially in the haplo-identical setting. Novel techniques to deplete host-reactive donor T cells selectively have been explored. This review focuses on the use of the photodynamic cell purging (PDP) process and of sorting memory T cells for the selective elimination of alloreactivity. Minimizing the threat of GvHD while maximizing the beneficial GvT effect would broaden the scope and effectiveness of alloSCT.


Assuntos
Memória Imunológica , Depleção Linfocítica/métodos , Transplante de Células-Tronco , Linfócitos T/transplante , Separação Celular/métodos , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia/imunologia , Efeito Enxerto vs Tumor/imunologia , Humanos , Memória Imunológica/imunologia , Fotoquimioterapia/métodos , Recuperação de Função Fisiológica/imunologia , Linfócitos T/imunologia , Transplante Homólogo
16.
Leuk Lymphoma ; 42(3): 253-65, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11699390

RESUMO

Triptolide is a diterpenoid triepoxide purified from a Chinese herb Tripterygium Wilfordii Hook F (TWHF). TWHF has been used in traditional Chinese medicine for more than two thousand years. However, its potential value was recognized by the western medicine only after investigators observed the effectiveness of TWHF in the treatment of leprosy and rheumatoid arthritis. Triptolide has been identified as the major component responsible for the immunosuppressive and anti-inflammatory effects of TWHF. Triptolide inhibits both Ca(2+)-dependent and Ca(2+)-independent pathways and affects T cell activation through inhibition of interleukin-2 transcription at a site different from the target of cyclosporin A. Triptolide also has inhibitory effects on a variety of proinflammatory cytokines and mediators and on the expression of adhesion molecules by endothelial cells. Triptolide is effective for the treatment of a variety of autoimmune diseases and in prevention of allograft rejection and graft-versus-host disease in both animals and humans. Moreover, triptolide possesses antitumor and male anti-fertility effect. However, the toxicities of triptolide may be associated with renal, cardiac, hematopoietic and reproductive systems. Currently available data suggest that triptolide is a promising immunosuppressive and anti-inflammatory agent and should be explored further in autoimmune diseases and transplantation.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos Alquilantes/farmacologia , Diterpenos/farmacologia , Imunossupressores/farmacologia , Fenantrenos , Animais , Diterpenos/isolamento & purificação , Medicamentos de Ervas Chinesas , Compostos de Epóxi , Sobrevivência de Enxerto , Camundongos , Ratos , Transplante Homólogo/imunologia
17.
Thyroid ; 11(10): 973-6, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11716046

RESUMO

The technique of fine-needle aspiration (FNA) biopsy of the thyroid is important to evaluate malignancy in thyroid nodules. Eighty-five percent of thyroid FNA procedures lead to sufficient cellular material for diagnosis. With more cells aspirated, the chance of sufficiency for diagnosis increases. Large-bore needles lead to more cellular material being aspirated but bloodier specimens that may interfere with cytologic interpretation. Small-bore needles may result in too few cells for diagnosis. We conducted a randomized prospective study contrasting 21-gauge and 25-gauge needles in the evaluation of 50 consecutively enrolled nodules at our institution. In our investigation, 21-gauge needles more frequently provided superior biopsy specimens (50%) than did 25-gauge needles (18%). In the remaining specimens (32%), the 21-gauge and 25-gauge needles provided similar cellular material. The rate of sufficient samples was the same. We conclude that use of 21-gauge needles results in more cellular specimens but may not result in increased diagnostic accuracy.


Assuntos
Biópsia por Agulha/instrumentação , Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Centrifugação/métodos , Hemólise , Humanos , Estudos Prospectivos , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/diagnóstico
18.
Biol Blood Marrow Transplant ; 7(8): 454-66, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11569891

RESUMO

T-cell reconstitution following allogeneic stem cell transplantation may involve thymic education of donor-derived precursors or peripheral expansion of mature T cells transferred in the graft. T cell-receptor excision circles (sjTRECs) are generated within the thymus and identify new thymic emigrants and those that have not divided. We measured quantitative and qualitative immunologic reconstitution and sjTREC levels in adult and pediatric recipients of umbilical cord blood transplants (UCBTs). sjTRECs were detected at normal levels in all children, starting 12 months after transplantation. sjTRECs were not detected until 18 months after transplantation in adults, and then only at a 3-fold lower level than expected for age. We used complementarity-determining region 3 (CDR3) spectratyping to measure changes in T cell-receptor diversity occurring with restoration of thymic function. T-cell repertoires were skewed in adults and children at 12 to 18 months after transplantation but recovered to near-normal diversity at 2 to 3 years post-UCBT. T-cell repertoires appeared more diverse earlier in children (at 1 to 2 years post-UCBT) than in adults (at 3 to 4 years post-UCBT). We conclude that early T-cell recovery after UCBT occurs primarily through peripheral expansion of adoptively transferred donor T cells and results in skewing of the T-cell repertoire. The reappearance of sjTREC-containing cells after UCBT is associated with increasing numbers of phenotypicaly naive T cells, improved mitogen and recall antigen responses, and diversification of the T-cell repertoire. The delay in central T-cell recovery in adults relative to children may be due to differences in thymic function resulting from age-related atrophy, graft-versus-host disease, or the pharmacologic effects of prophylaxis and treatment of graft-versus-host disease.


Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Linfócitos T/citologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Regiões Determinantes de Complementaridade/análise , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/prevenção & controle , Neoplasias Hematológicas/terapia , Hematopoese , Humanos , Lactente , Ativação Linfocitária , Contagem de Linfócitos , Subpopulações de Linfócitos , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T/análise , Linfócitos T/imunologia , Fatores de Tempo , Transplante Homólogo
19.
Artigo em Inglês | MEDLINE | ID: mdl-11166670

RESUMO

The purpose of this study was to investigate if carotenoids could alleviate the adverse effects caused by aflatoxin with respect to growth performance and immune response. In two experiments, a total of 320 mule ducklings were assigned to 5 treatments, i.e. control, aflatoxin B(1) (AFB(1)) 200 ppb, AFB(1) +beta-carotene (BC) 200 ppm, AFB(1)+BC 400 ppm, and AFB(1)+astaxanthin (AS) 200 ppm. In experiment 1, the addition of beta-carotene or astaxanthin in the diet containing AFB(1) 200 ppb resulted in a significant decrease in average daily gain as compared with the control. AFB(1) 200 ppb alone and the addition of BC or AS on top of AFB(1) resulted in a significantly lower daily feed intake than for the control group. There were no significant differences in relative organ weights among treatment groups. Both treatments of BC 400 ppm and AS 200 ppm had significantly more macrophages harvested per duck than the control and AFB(1) 200 ppb treatments. However, there were no significant differences among treatments in percentages of phagocytotic macrophages and number of Candida albican phagocytized by phagocytotic macrophages. In experiment 2, blood biochemical parameters and antibody titers were evaluated. There were no significant differences among treatments in total bilirubin content and alkaline phosphatase activity in the serum or in antibody titers against fowl cholera. However, AFB(1) treatment had the highest activities of AST and ALT in the serum. The addition of BC 400 ppm on top of AFB(1) significantly reduced ALT activity as compared with the AFB(1) 200 ppb treatment. These results suggest that carotenoids could provide a slightly toxic alleviating effect on growth performance, enhance the chemotaxis ability of macrophages, and reduce ALT activity elevated by AFB(1).


Assuntos
Aflatoxina B1/toxicidade , Patos/fisiologia , Macrófagos/efeitos dos fármacos , Aumento de Peso/efeitos dos fármacos , beta Caroteno/análogos & derivados , beta Caroteno/farmacologia , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Ração Animal , Animais , Anticorpos Antibacterianos/sangue , Formação de Anticorpos/efeitos dos fármacos , Aspartato Aminotransferases/sangue , Bilirrubina/sangue , Biomarcadores/sangue , Candida albicans , Toxina da Cólera/imunologia , Ingestão de Energia/efeitos dos fármacos , Macrófagos/imunologia , Tamanho do Órgão/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Valores de Referência , Xantofilas
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 15(5): 299-302, 2001 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-11761858

RESUMO

OBJECTIVE: To report repair and reconstruction of massively damaged wound under unusual condition. METHODS: One hundred and forty-seven patients with deep tissue defects were admitted from January 1993 to December 2000, among them, 96 cases suffered from electrical injury, 18 cases with hot press injury, 18 cases with deep burns as a result of CO poisoning or epileptic seizure, 6 cases caused by chemical producing necrosis and wound infection, 3 cases with radiation injuries, 2 cases with chemical burn, 2 cases with explosive injury, 2 cases with frostbite. One hundred and seventy five wounds in 147 patients were repaired by transfer of local flap, forearm conversal island skin flap, pectoralis major myocutaneous flap, delto-pectoral skin flap, latissimus dorsi skin flap, gastroecnemius myocutaneous flap, anterior and posterior tibial artery island skin flap, and so on. The wound defect ranged from 1 cm x 1 cm to 20 cm x 28 cm, and the flaps were 1.5 cm x 2.0 cm to 22 cm x 30 cm. The necrotic tendon was replaced with acellular allogenic tendon simultaneously in 7 cases. RESULTS: One hundred and sixty-nine flaps were survival with first intention, while necrosis of the tip of flap occurred in 6 cases. The transplantation of acellular allogenic tendon in all cases were survival. The function and configuration in 28 cases were satisfactory after 4 months to 8 years follow-up. CONCLUSION: Various types of flaps are choosen according to the position, defect range and degree of wound, which is an ideal method to restore the function and to improve patients' living condition.


Assuntos
Queimaduras Químicas/cirurgia , Queimaduras por Corrente Elétrica/cirurgia , Procedimentos de Cirurgia Plástica , Lesões dos Tecidos Moles/cirurgia , Retalhos Cirúrgicos , Adolescente , Adulto , Criança , Feminino , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Pele
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