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Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized. We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome. A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58â±â17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03-8.48; Pâ=â0.04) and age (OR 4.80; 95% CI 1.84-12.53; Pâ=â0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82-13.18; Pâ=â0.002) and DM (OR 3.07; 95% CI 0.98-9.59; Pâ=â0.05) were independent risk factors for unfavorable prognosis. Glomerulonephritis related to staphylococcal infection has different features than typical postinfectious glomerulonephritis. The diagnosis of glomerulonephritis related to staphylococcal infection relies on immunofluorescence and electron microscopy findings. Age and DM are independent risk factors of poor prognosis for glomerulonephritis related to staphylococcal infection.
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Glomerulonefrite/etiologia , Glomerulonefrite/fisiopatologia , Infecções Estafilocócicas/complicações , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Diabetes Mellitus/epidemiologia , Feminino , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/epidemiologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Prognóstico , Adulto JovemRESUMO
The increasing recognition of the properties of marrow stromal cells has spawned a major switch in our perception of their nature and the potential therapeutic applications that have been envisioned and implemented. Yet, several aspects of bone marrow stromal cell biology remain in question. This report describes the ability of recombinant human macrophage colony-stimulating factor (rhM-CSF) to maintain proliferation and differentiation of bone marrow stromal cells ex vivo. Our results demonstrated that M-CSF was essential for proliferation and differentiation of bone marrow-derived stromal cells and exerted its effects in a dose-dependent manner. The number of colony-forming unit (CFU) fibroblasts increased by 25% after incubation with rhM-CSF. In vitro expanded bone marrow stromal cells were easy to passage and differentiated to adipocyte and chondroblast cells under appropriate culture conditions. Furthermore, these expanded stromal cells to support CD34+ hematopoietic stem cells, as demonstrated by their ability to form CFU-Mix, burst-forming units-erythroid, and CFU-granulocyte macrophage colonies after 3 weeks of culture. The homing efficiency of in vitro expanded or fresh isolated bone marrow-derived stromal cells, which were labeled with carboxy fluorescein diacetate succinimidyl ester, to bone marrow was also investigated. Homing assays demonstrated that freshly isolated CD45+-depleted bone marrow cells were able to home to bone marrow in a dose-dependent manner, although some cells were found in the spleen, liver, and lung. However, their ability to home was dramatically reduced with culture time and was completely lost after five to seven passages in vitro. Animal studies showed that freshly isolated or rhM-CSF-induced bone marrow stromal cells promoted hematopoietic reconstitution in lethally irradiated mice. The ability to easily expand human stromal cells, which support survival and proliferation of CD34+ cells, has many important clinical applications for hematopoietic disorders.
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Medula Óssea/fisiologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/fisiologia , Células Estromais/fisiologia , Adipócitos/fisiologia , Animais , Antígenos CD34/metabolismo , Movimento Celular/fisiologia , Terapia Baseada em Transplante de Células e Tecidos , Células Cultivadas , Condrócitos/fisiologia , Técnicas de Cocultura , Células Precursoras Eritroides/fisiologia , Raios gama , Células Precursoras de Granulócitos/fisiologia , Doenças Hematológicas/terapia , Hematopoese/fisiologia , Hematopoese/efeitos da radiação , Humanos , Antígenos Comuns de Leucócito/metabolismo , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Recombinantes , Células Estromais/citologia , Células Estromais/transplante , Transplante HeterólogoRESUMO
Objective:To investigate the expression of PD-L1 in peripheral blood with gastric cancer patients and its clinical significance.Methods:Peripheral blood samples were collected from 44 gastric cancer patients (before and after the surgery) and 18 healthy subjects.The expression of PD-1 and PD-L1 on CD3+CD4+T,CD3+CD8+T cells and CD14+monocytes was detected by flow cy-tometry.Results:The expression of PD-L1 on CD14+monocytes of the gastric cancer patients was significantly higher than that of the healthy control[(29.2±16.7)% vs (17.5±9.7)%,P=0.007 3],while there was no statistical difference on CD4+T cells and CD8+T cells[(11.1±6.4)% vs(9.8±5.6)%,P=0.453 2;(13.9±12.0)% vs(12.0±7.1)%,P=0.558 9].The expression of PD-L1 on CD4+T cells and CD8+T cells in patients with gastric cancer was significantly higher than that before surgery[(15.8 ± 8.2)% vs (11.1±6.4)%,P=0.001 5;(22.5±13.3)% vs(13.9±12.0)%,P=0.000 2].However,no significant change was found on CD14+mononuclear cells[(33.8±17.3)% vs (29.2±16.7)%,P=0.082 8].There was no significant difference in the expression of PD-1 on CD4+T and CD8+T cells before and after surgery[(25.6 ±9.9)% vs (26.9 ±8.9)%,P=0.505 5;(26.5 ±14.6)% vs (29.9 ± 10.4)%,P=0.118 7].Conclusion:PD-L1 can be used as an effective marker to monitor the immune function and prognosis of patients with primary gastric cancer.
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<p><b>OBJECTIVE</b>To evaluate the therapeutic effects of combined administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF), recombinant human thrombopoietin (rhTPO) and recombinant human interleukin-2 (rhIL-2) on radiation-induced severe haemopoietic acute radiation sickness (ARS) in rhesus monkeys, so as to provide experimental evidences for the effective clinical treatment.</p><p><b>METHODS</b>Seventeen rhesus monkeys were exposed to 7.0 Gy (60)Co γ-ray total body irradiation (TBI) to establish severe haemopoietic ARS model, and were randomly divided into supportive care group, rhG-CSF+rhTPO treatment group and rhG-CSF+rhTPO+rhIL-2 treatment group. Survival time, general signs such as bleeding and infections, and peripheral blood cell counts in each group were monitored. Bone marrow cells were cultivated to examine the colony formation ability. The histomorphology changes of bone marrow were observed at 45 d post irradiation.</p><p><b>RESULTS</b>After 7.0 Gy (60)Co γ-ray TBI, monkeys of supportive care group underwent tarry stool and emesis, then died in 12~18 d. The overall survival rate in this group was 16.7%. Gastrointestinal reactions of monkeys in two combined-cytokines treatment groups were inapparent. Combined-cytokines treatment induced 100% survival. Complete blood cells declined sharply after irradiation in each group, but two combined-cytokines treatment schemes could elevate the nadir of all blood cells, shorten the duration of pancytopenia and accelerate the recovery of hemogram. Compared with rhG-CSF+ rhTPO treatment, rhG-CSF+ rhTPO+ rhIL-2 treatment could increase the counts of lymphocytes and monocytes. The colony-formation rate of haemopoietic stem/progenitor cells in bone marrow dropped markedly at 2 d after irradiation. Combined-cytokines treatment promoted the ability of colony formation on day 29. Hematopoietic cells mostly disappeared in bone marrow of animals in supportive care group, but hematopoietic functions were recovered after cytokines were administrated.</p><p><b>CONCLUSION</b>rhG-CSF+ rhTPO and rhG-CSF+ rhTPO+ rhIL-2 treatment can significantly promote hematopoiesis recovery, improve the quantity of life, simplify the supportive therapy, and enhance the survival rate of rhesus monkeys with severe haemopoietic ARS induced by 7.0 Gy (60)Co γ-ray exposure. Especially the application of rhIL-2 can accelerate the recovery of lymphocytes and monocytes and restore the immunological function. Thus, combination of rhG-CSF, rhTPO and rhIL-2 on the basis of supportive care is an efficient strategy to treat severe haemopoietic ARS.</p>
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Animais , Humanos , Medula Óssea , Patologia , Células da Medula Óssea , Patologia , Raios gama , Fator Estimulador de Colônias de Granulócitos , Farmacologia , Hematopoese , Células-Tronco Hematopoéticas , Biologia Celular , Interleucina-2 , Farmacologia , Macaca mulatta , Lesões por Radiação , Tratamento Farmacológico , Distribuição Aleatória , Proteínas Recombinantes , Usos Terapêuticos , Trombopoetina , Farmacologia , Irradiação Corporal TotalRESUMO
<p><b>BACKGROUND</b>B7-H3 has been widely studied in the context of tumor progression in recent years, and behaves as a tumor cell marker in a variety of tumors including colorectal carcinoma. The mechanism of B7-H3 in tumor progression is complicated and not clear yet. Studies have revealed that B7 family molecules are expressed on infiltrated lymphocytes as well as tumor cells in tumor microenvironment, which indicates that different expression pattern may lead to different clinical outcomes.</p><p><b>METHODS</b>The expression of B7-H3 was detected in tissues of 98 colorectal carcinoma patients by using immunohistochemistry. Then the expression of B7-H3 on CD3(+) T lymphocytes isolated from fresh cancer tissues of 12 colorectal carcinoma patients was analyzed by flow cytometry assay. The relationship between the expression of B7-H3 on CD3(+) T lymphocytes and patients' clinical pathological parameters was demonstrated with statistical analysis.</p><p><b>RESULTS</b>Patients with more CD3(+) T cell infiltration survived much longer than patients with less CD3(+) T cell infiltration (P < 0.05); B7-H3 was highly expressed by infiltrating CD3(+) T lymphocytes in colorectal carcinoma tissues. The expression of B7-H3 was found to be significantly related with lymph node metastasis status (P < 0.05), but not with the patient's gender, age, tumor size, differentiation degree, depth of tumor invasion, Dukes' stage, distant metastasis and whether or not mucinous adenocarcinoma was present (P > 0.05). Moreover, the survival time of patients with low expression of B7-H3 was obviously longer than those of high B7-H3 expression patients, but the seven-year survival rate showed no difference between the high and low B7-H3 expression patients (P > 0.05).</p><p><b>CONCLUSION</b>The negative costimulatory molecule B7-H3 on infiltrating CD3(+) T lymphocytes in colorectal carcinoma bears importance in the clinical pathological progress and prognosis of colorectal carcinoma.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antígenos B7 , Complexo CD3 , Neoplasias Colorretais , Alergia e Imunologia , Mortalidade , Patologia , Citometria de Fluxo , Imuno-Histoquímica , Linfócitos do Interstício Tumoral , Alergia e Imunologia , Taxa de Sobrevida , Linfócitos T , Alergia e ImunologiaRESUMO
<p><b>OBJECTIVE</b>To analyze the expression of co-stimulatory molecules PD-1/PD-L1 in peripheral blood mononuclear cells in lung cancer patients, and to explore its biological significance.</p><p><b>METHODS</b>One hundred and thirty-three lung cancer patients, 25 lung infection patients and 23 healthy donors were enrolled in this study. 100 µl of whole blood from these subjects were collected. Multi-color immunofluorescence staining and flow cytometry were used to detect PD-1/PD-L1 expression. The results were statistically analyzed.</p><p><b>RESULTS</b>The expression level of CD3⁺CD8⁺ T cells in the lung cancer patients was (38.83 ± 1.74)%, significantly lower than that in the control group [(43.25 ± 3.35)%, P < 0.05]. CD8⁺CD28⁺ T cell subset in the peripheral blood of lung cancer patients was (17.73 ± 1.21)% significantly lower than that of the healthy donors [(27.96 ± 2.72)%, P < 0.01]. The CD8⁺CD28⁻ T cell subset was (21.19 ± 1.92)% in the lung cancer patients, significantly higher than that of the healthy control group [(15.18 ± 2.93)%, P < 0.05]. The expression level of PD-1 on the surface of CD8⁺CD28⁺ T cells was (10.67 ± 1.12)% in the group of lung cancer patients, significantly higher than that of the control group [(5.32 ± 1.58)%, P < 0.01]. It was also found that the expression of PD-1 on CD8⁺CD28⁻ T cells was up-regulated in the group of lung cancer patients (7.46 ± 1.25)%, significantly higher than that of the healthy control group [(2.68+1.07)%, P < 0.01]. The expression level of PD-L1 on CD68⁺ cells in the lung cancer patients was (16.03 ± 2.06)%, significantly higher than that of the healthy control group [(9.32 ± 2.00)%, P < 0.05].</p><p><b>CONCLUSION</b>Up-regulation of PD-1/PD-L1 on peripheral blood cells in lung cancer patients negatively regulates the lymphocytes, inhibits the immune response for killing tumor cells, and promotes tumor development and immune escape.</p>
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Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adenocarcinoma , Sangue , Patologia , Antígeno B7-H1 , Metabolismo , Antígenos CD28 , Metabolismo , Complexo CD3 , Metabolismo , Antígenos CD8 , Metabolismo , Carcinoma de Células Grandes , Sangue , Patologia , Carcinoma de Células Escamosas , Sangue , Patologia , Estudos de Casos e Controles , Neoplasias Pulmonares , Sangue , Patologia , Receptor de Morte Celular Programada 1 , Metabolismo , Carcinoma de Pequenas Células do Pulmão , Sangue , Patologia , Linfócitos T , Alergia e Imunologia , Metabolismo , Regulação para CimaRESUMO
Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.
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Humanos , Antineoplásicos , Usos Terapêuticos , Apoptose , Proteínas Reguladoras de Apoptose , Metabolismo , Autofagia , Leucemia Mieloide Aguda , Tratamento Farmacológico , Metabolismo , Patologia , Leucemia Promielocítica Aguda , Tratamento Farmacológico , Metabolismo , Patologia , Terapia de Alvo Molecular , Proteínas de Fusão Oncogênica , Metabolismo , Tretinoína , Usos TerapêuticosRESUMO
<p><b>BACKGROUND</b>Molecular testing is more precise compared to serology and has been widely used in genotyping blood group antigens. Single nucleotide polymorphisms (SNPs) of blood group antigens can be determined by the polymerase chain reaction with sequence specific priming (PCR-SSP) assay. Commercial high-throughput platforms can be expensive and are not approved in China. The genotype frequencies of Kidd, Kell, Duffy, Scianna, and RhCE blood group antigens in Jiangsu province were unknown. The aim of this study is sought to detect the genotype frequencies of Kidd, Kell, Duffy, Scianna, and RhCE antigens in Jiangsu Chinese Han using molecular methods with laboratory developed tests.</p><p><b>METHODS</b>DNA was extracted from EDTA-anticoagulated blood samples of 146 voluntary blood donors collected randomly within one month. Standard serologic assay for red blood cell antigens were also performed except the Scianna blood group antigens. PCR-SSP was designed to work under one PCR program to identify the following SNPs: JK1/JK2, KEL1/KEL2, FYA/FYB, SC1/SC2, C/c and E/e.</p><p><b>RESULTS</b>Serologic antigen results were identical to the phenotypes that were predicted from genotyping results. The allele frequencies for Jk*01 and Jk*02 were 0.51 and 0.49, respectively; for Fy*A and Fy*B 0.94 and 0.06; for RHCE*C and RHCE*c 0.68 and 0.32; and for RHCE*E and RHCE*e 0.28 and 0.72. Among 146 blood donors, all were KEL*02/KEL*02 and SC*01/SC*01, indicating allele frequencies for KEL*02 and SC*01 close to 1.00.</p><p><b>CONCLUSIONS</b>The use of PCR-SSP working under the same condition for testing multiple antigens at the same time is practical. This approach can be effective and cost-efficient for small-scale laboratories and in developing counties. These molecular tests can be also used for identifying rare blood types.</p>
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Humanos , Antígenos de Grupos Sanguíneos , Genética , Butirofilinas , China , Etnologia , Sistema do Grupo Sanguíneo Duffy , Genética , Frequência do Gene , Genótipo , Sistema do Grupo Sanguíneo de Kell , Genética , Sistema do Grupo Sanguíneo Kidd , Genética , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Sistema do Grupo Sanguíneo Rh-Hr , GenéticaRESUMO
This study was to explore the expression of two subtype molecules of CD133 and its relationship with clinical prognostic factors in childhood with B linage acute lymphoblastic leukemia (B-ALL) at initial diagnosis and the 33rd day of induction chemotherapy. Expression of CD133-1 and CD133-2 in 48 cases of B-ALL and 25 cases at initial diagnosis and the 33rd day of treatment was detected by flow cytometry. Minimal residual disease (MRD) of B-ALL at 33rd day was evaluated by flow cytometry. The results indicated that the expression of CD133-1 was positive in 18 cases (37.5%), and expression of CD133-2 in 30 cases (62.5%) was positive from 48 cases with newly diagnosed ALL (P < 0.05). At 33rd day of treatment, expression of CD133-1 in 2 cases (8.0%) from 25 cases was positive, and expression of CD133-2 in 23 cases (92.0%) was positive (P < 0.05). After induction chemotherapy in B-ALL, the expression of CD133-1 decreased significantly, but still higher than that in the normal control group. Compared to expression of CD133-1, expression of CD133-2 decreased slowly. It is concluded that there is no relations among expression of CD133 and sex, age, white blood cell count, percentage of bone marrow blast cells, FAB subtype, cytogenetics, leukemia fusion gene, risk stratification and complete remission rate in childhood B-ALL. The positive expression rates and levels of CD133-2 are higher than those of CD133-1 in B-ALL. There is no statistical correlation between expression of CD133 and CD34 in B-ALL. The expression of CD133-2 is significantly related to the level of MRD.
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Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Antígeno AC133 , Doença Aguda , Antígenos CD , Alergia e Imunologia , Metabolismo , Regulação Leucêmica da Expressão Gênica , Glicoproteínas , Alergia e Imunologia , Metabolismo , Leucemia de Células B , Alergia e Imunologia , Metabolismo , Neoplasia Residual , Peptídeos , Alergia e Imunologia , MetabolismoRESUMO
<p><b>OBJECTIVE</b>Elderly patients with obstructive sleep apnea/hypopnea syndrome (OSAHS) has a higher risk of cardiovascular and cerebrovascular disease. However, changes of homocysteine (Hcy) as markers of cardiovascular and cerebrovascular disease associated with OSAHS and their mechanism have not been elucidated so far. This study aims to investigate the changes of both serum Hey and oxidative stress and their possible links with OSAHS in elderly patients.</p><p><b>METHODS</b>Based on polysomnogram (PSG) and age, 83 patients with OSAHS were recruited and divided into elderly-OSAHS (n=32) and non-elderly OSAHS groups (n=51). Fifty two subjects without OSAHS were divided into elderly control (n=29) and non-elderly control groups (n=23). A total of 135 subjects were included in the present study. All subjects were recorded for PSG variables and the contents of homocysteine (Hcy), malonaldehyde (MDA), and glutathione (GSH) which were detected after sleep. Serum homocysteine was measured by cyclophorase. MDA and GSH were measured by spectrophotometer.</p><p><b>RESULTS</b>(1) The serum levels of Hcy showed significant difference among the four groups (P < 0.05). The concentrations of Hey in elderly OSAHS patients were higher than in other groups, while those in the elderly control group were higher than in the non-elderly control; the concentrations in the non-elderly OSAHS group were higher than in the non-elderly control. (2) The concentrations of MDA and GSH changed at an equal pace with Hey in the four groups. (3) Multielement linearity regression analysis indicated a statistically significant relationship between Hcy concentration and age, MDA, GSH, and apnea hypopnea index (AHI).</p><p><b>CONCLUSIONS</b>(1) The concentrations of Hey and oxidative stress have increased with advancing age. (2) The concentrations of Hey and oxidative stress have further increased in the elderly patients with OSAHS. (3) Oxidative stress might cause high-level serum Hey in the elderly patients with OSAHS.</p>
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Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Homocisteína , Sangue , Estresse Oxidativo , Fisiologia , Síndromes da Apneia do Sono , SangueRESUMO
<p><b>OBJECTIVE</b>To investigate liver and kidney lesions in HBV-GN patients and relationship between them and provide evidences to make early diagnosis of HBV-GN.</p><p><b>METHODS</b>Reviewing the clinicopathological and laboratory indexes of 205 patients with HBV-GN diagnosed by renal biopsy in our hospital from September 1995 to November 2008.</p><p><b>RESULTS</b>HBV-GN account for 5.6% of all renal biopsies at the same time. Among them, 157 (76.5%) patients were male,123 (60%) was 19-45 years-old. 95 (46%) patients break out with kidney disease. HBsAg, HBeAg, HBcAg were the most common HBV makers. 102 (49.8%) patients present nephrotic syndrome, 18 (8.8%) suffered kidney dysfunction; 18 patients with hepatic cirrhosis. Patients with or without liver disfunction got no different in clinic manifestation and renal pathology. With the rising of the content of HBV-DNA in surum, the urinary protein increases. Renal data shows that membranous nephropathy(MN) was the most frequent type (60.5%).</p><p><b>CONCLUSION</b>The peak incidence of HBV-GN is in the twentieth to forth decade of life. There was a 3:1 predominance of males. Nephrotic syndrome was the most common clinic manifestation and membranous nephropathy was the most common pathology. 10% persent patisnts had loss of renal function at the time of renal biopsy. The HBV copies in serum correlated with the albuminuria. HBV-GN patients had desynchroneity lesions in kidney and liver. As the high rate of HBV infection in China, It needs to prevent the kidney damage in HBV infectious people and to elevate early diagnosis and therapy.</p>
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Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , DNA Viral , Sangue , Glomerulonefrite , Patologia , Virologia , Hepatite B , Patologia , Vírus da Hepatite B , GenéticaRESUMO
Objective To investigate the expression of GOLPH3 in the tumor tissues of patients with gliomas and evaluate its clinical significance. Methods Seventy-six patients with brain gliomas (13 with grade Ⅰ, 27 grade Ⅱ, 25 grade Ⅲ and 11 with glioblastoma) performed surgical excision in our hospitals from July 2008 to December 2009 were chosen and 9 cases of normal brain tissues from patients performed decompression operation resulting from cerebral hernia were selected as the controls in our experiment. RT-PCR and Western-blotting were used to detect the mRNA and protein expressions of GOLPH3. Results The results investigated by RT-PCR and Western-blotting were consistent,revealing that the mRNA and protein expression rate of GOLPH3 in glioma tissues was not significantly different between different grades of tumors (P>0.05), but their expression value was obviously significant between different grades of tumors and increased in a grade-dependent manner (P<0.05). And minimal mRNA and protein expressions of GOLPH3 were found in the tissues of controls. The up-regulative protein expression of GOLPH3 was positively correlated to the malignancy-grade of the gliomas (r,=0.961, P=0.000). Conclusion The mRNA and protein expressions of GOLPH3 are noted with positive correlation to the pathological grades of the gliomas, indicating th at GOLPH3 may play an important role in the generation and development of gliomas.
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<p><b>OBJECTIVE</b>To detect the frequencies of KIR2DS4 alleles in Chinese Han population and to study the impact of KR2DS4 alleles on clinical outcomes of HLA identical unrelated allo-HSCT.</p><p><b>METHODS</b>A Sequence-Based Testing (SBT) and TOPO TA cloning system for identifying and distinguishing alleles of the KIR2DS4 gene were established. A total of 150 Chinese-Han individuals, including 75 leukemia patients who received allo-HSCT and their HLA high-resolution typing identical unrelated donors (URD) were entered this study. The patients underwent transplantation for CML (n = 24), AML (n = 19), ALL (n = 29) and other malignancies (n = 3).</p><p><b>RESULTS</b>The majority (139) of the 150 samples (92.7%) were positive for KIR2DS4. Sequencing of the whole length coding region of this gene identified four of the 12 known KIR2DS4 alleles, KIR2DS4*00101, *003, *004, and *007. 2DS4*00101 was the most frequent, being found in 109 of the 139 individuals (78.4%). The ratio of deleted to non-deleted versions of KIR2DS4 was approximately 1:2. Three novel KIR2DS4 alleles were identified. Transplantations from KIR haplotype B/x donors showed significantly higher overall survival rates than those from KIR haplotype A/A donors [RR 3.1 (95%CI 1.1 - 8.6), P = 0.007]. There was a lower overall survival rates in recipients when their donors carried two 2DS4 full-length allele (2DS4*001) than those carried less (0 or 1) 2DS4*001 allele (P = 0.031). In the haplotype A/A group, a higher risk of acute GVHD (aGVHD) [RR 9.0 (95%CI 1.2 - 66.9), P = 0.01], especially grade III-IV aGVHD (P = 0.006), was seen when the donor was homozygous for the full-length KIR2DS4*00101 allele.</p><p><b>CONCLUSION</b>The development and application of the described SBT 2DS4 allele typing method highlights the diverse nature of the KIR gene family and displays the existence of KIR polymorphism that remains uncharacterized. Our findings suggest that KIR typing for 2DS4 be beneficial for selecting suitable donors.</p>
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Humanos , Alelos , Doença Enxerto-Hospedeiro , Genética , Haplótipos , Transplante de Células-Tronco Hematopoéticas , Receptores KIR , GenéticaRESUMO
<p><b>BACKGROUND</b>The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown.</p><p><b>METHODS</b>The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients (aged > or = 60 years) with primary non-small cell lung cancer (NSCLC) were analyzed by real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR). In addition, twenty young patients (aged < 60 years) with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls.</p><p><b>RESULTS</b>CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis (TNM) stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types.</p><p><b>CONCLUSIONS</b>The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.</p>
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Idoso , Humanos , Antígenos CD28 , Genética , Carcinoma Pulmonar de Células não Pequenas , Genética , Leucócitos Mononucleares , Metabolismo , Modelos Logísticos , Neoplasias Pulmonares , Genética , Reação em Cadeia da Polimerase , Receptor fas , GenéticaRESUMO
<p><b>OBJECTIVE</b>To investigate the influence of co-stimulatory molecules B7-H4 expression on prognosis of gastric cancer patients treated by cytokine-induced killer cells (CIK cells) adoptive immunotherapy.</p><p><b>METHODS</b>Clinical data of 156 cases of gastric cancer patients were retrospectively analyzed. Patients were divided into chemotherapy group(n=81) and chemotherapy combined with CIK cell therapy group(n=75). B7-H4 expression was detected in the surgical specimens of gastric cancer patients by immunohistochemistry assay. Disease-free survival was compared between the chemotherapy group and the CIK group at different expression levels of B7-H4.</p><p><b>RESULTS</b>The difference was not statistically significant in all clinical and pathological data between the chemotherapy group and the CIK treatment group (P>0.05). The postoperative median tumor-free survival in two groups was 18.0 and 45.0 months, respectively, and the difference was statistically significant (chi(2)=11.631, P=0.001). The postoperative median survival time was 27.0 and 49.0 months, respectively, and the difference was statistically significant (chi(2)=10.907, P=0.001). In 86 patients with low B7-H4 expression, the median tumor-free survival time was 32.0 and 62.0 months, respectively, and the difference was statistically significant (chi(2)=4.663,P=0.03). In 70 patients with high B7-H4 expression, the median tumor-free survival time was 11.0 and 18.0 months, respectively, and the difference was statistically significant (chi(2)=11.971, P=0.001).</p><p><b>CONCLUSION</b>The median tumor-free survival time of patients with gastric cancer may be further improved by chemotherapy combined with CIK cell therapy, regardless of the level of B7-H4 expression.</p>
Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica , Usos Terapêuticos , Antígeno B7-1 , Metabolismo , Células Matadoras Induzidas por Citocinas , Intervalo Livre de Doença , Imunoterapia Adotiva , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas , Diagnóstico , Metabolismo , Terapêutica , Inibidor 1 da Ativação de Células T com Domínio V-SetRESUMO
Objective To compare the clinical effects of microneurosurgery by supraorbital key-hole or endonasal transsphenoidal approaches in the treatment of pituitary adenoma and investigate their complications. Methods We retrospectively analyzed the data of 87 patients with pituitary adenoma of which the anteroposterior diameter was less than 3 cm. These patients, admitted to our hospital from May, 2006 to June, 2008, were operated in an endoscope-assisted microsurgical manner via a supraorbital key-hole approach (n=42) or an endonasal transsphenoidal approach (n=45). The efficacy of these two approaches was compared and their complications were observed. Results The excision rate of the pituitary adenoma developing on or around the sella turcica operated through the supraorbital key-hole approach was significantly higher than that through the endonasal transsphenoidal approach(P< 0.05); while that of microadenoma or adenoma developing towards the sphenoid sinus operated through the supraorbital keyhole approach was statistically lower than that through the endonasal transsphenoidal approach (P<0.05). No obvious differences on the improvement of endocrine secretion, visual acuity and field was noted in these two approaches (P>0.05). The incidence rate of epistaxis and unilateral dysosphresia in the supraorbital key-hole approach was significantly lower as compared with that in the endonasal transsphenoidal approach (P<0.05). Conclusion Rarely having such complications as dysosphresia, epistaxis and sphenoiditis, neuroendoscopic surgery through supraorbital key-hole approach is the best way of treating the pituitary adenoma developing on or around the sella turcica and worth to promote in clinic.
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<p><b>OBJECTIVE</b>To analyze the cloning result of CD40 mutant from RPMI8226 cells, a multiple myeloma (MM) cell line, and study the change of the expressions of costimulatory molecules and the apoptosis of RPMI8226 cells after activated with CD40.</p><p><b>METHODS</b>CD40 gene mutant in RPMI8226 cell was detected by RT-PCR and DNA sequencing. The cell lines were cultured with sCD40L, L929/CD40L, soluble 5C11 (an anti-CD40 mAb) plate-bound 5C11 and their respective controls. Their growth curves, change of phenotypes and cell cycles were detected. The signalosome of CD40 on RPMI8226 cells were analyzed with laser scanning confocal microscope.</p><p><b>RESULTS</b>There was a single base substitution (TCA-->TTA) in the open reading frame of CD40 from RPMI8226 cells, resulting in the conversion of a amino acid (Ser124Leu). Only plate-bound antibody could inhibit RPMI8226 cell proliferation [(2.5 +/- 0.6) x 10(5) vs (7.8 +/- 1.2) x 10(5), P <0.05] and cause G1 arrested [(58.0 +/- 3.6)% vs (42.0 +/- 2.3)%, P <0.05]. muCD40 was translocated to CD40 signalosome while CD40 activated.</p><p><b>CONCLUSION</b>The mutated CD40 in RPMI8226 cell might decrease its affinity to CD40L, leading to the disorder of CD40 signal.</p>
Assuntos
Humanos , Anticorpos Monoclonais , Farmacologia , Antígenos CD40 , Genética , Alergia e Imunologia , Ligante de CD40 , Genética , Farmacologia , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Análise Mutacional de DNA , Mieloma Múltiplo , Genética , Patologia , Mutação , Fenótipo , TransgenesRESUMO
<p><b>OBJECTIVE</b>To study the therapeutic effect of agonistic CD40 monoclonal antibody combined with tumor specific cytotoxic T lymphocyte (CTL) on B lymphoma.</p><p><b>METHODS</b>Human B lymphoma cell line, Daudi cells, were cultured with CD40 mAb (5C11) for 24 and 48 hours, respectively. Annexin V/PI-binding assay was employed to analyze apoptosis, and FCM to analyze Fas (CD95) expression. Human peripheral monocyte-derived DC were loaded with apoptotic Daudi cells and stimulated by SC11 for further maturation. Tumor specific CTL were generated in vitro by co-culture of mature DC with autologous T lymphocytes. DNA fragmentations of Daudi cells treated with 5C11, CTL or 5C11 combined with CTL were determined by JAM assay. To establish the B lymphoma model, Daudi cells were subcutaneously injected into humanized SCID mice (hu-SCID). 1 or 3 weeks after tumor transfer. tumor-bearing mice were respectively treated with SC11, CTL, 5C11 combined with CTL by intraperitoneal injection. Tumor volume in differently treated mice was measured every week after therapy, and the survival of tumor-bearing mice was recorded.</p><p><b>RESULTS</b>5C11 significantly up-regulated FAS expression in Daudi cells, but had no significant effect on apoptosis rate of Daudi cells. Tumor-specific CTL could effectively kill Daudi cells. Fragmentation of Daudi cells co-cultured with CTL was remarkably enhanced by combination with SC11. Tumor growth in hu-SCID mice was apparently delayed by treatment with SC11, CTL, or SC11 combined with CTL. Moreover, minimal tumor burden mice got 30.0% or 70.0% complete remission (CR), respectively, when received CTL treatment or combination treatment of SC11 with CTL, and the lifespan of tumor bearing mice was also prolonged significantly.</p><p><b>CONCLUSION</b>SC11 may enhance the sensitivity of Daudi cells to apoptosis by up-regulation of Fas expression and promote cytotoxicity of CTL in vitro and therapeutic effect in vivo.</p>
Assuntos
Animais , Feminino , Humanos , Camundongos , Anticorpos Monoclonais , Alergia e Imunologia , Usos Terapêuticos , Apoptose , Alergia e Imunologia , Antígenos CD40 , Alergia e Imunologia , Linhagem Celular Tumoral , Técnicas de Cocultura , Citometria de Fluxo , Imunoterapia Adotiva , Métodos , Linfoma de Células B , Alergia e Imunologia , Patologia , Terapêutica , Camundongos SCID , Indução de Remissão , Análise de Sobrevida , Linfócitos T Citotóxicos , Biologia Celular , Alergia e Imunologia , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor fas , Alergia e ImunologiaRESUMO
The immunoregulatory effects of mescenchymal stem cell (MSC) and its application have become a hot research topic in recent years. This article reviews the up-to-dated research advances in the features and mechanisms of immune regulation of MSC and its application.
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Animais , Humanos , Subpopulações de Linfócitos , Alergia e Imunologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fisiologia , Linfócitos T Reguladores , Alergia e ImunologiaRESUMO
<p><b>BACKGROUND</b>Tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) is related to the aging of many organs, but few data are available on the change of TIMP-1 in liver aging. The purpose of this study was to investigate the expression and role of TIMP-1, matrix metalloproteinase-2 (MMP-2) and MMP-9 in the process of natural aging in the livers of normal and transgenic mice, and to detect the effects of TIMP-1 on oxidative level and anti-oxidative ability of the livers of transgenic young mice.</p><p><b>METHODS</b>Normal and transgenic mice were divided into 3 groups according to their age: 3-month-old group (n = 5), 12-month-old group (n = 5) and 24-month-old group (n = 5). Histopathological changes of the liver were observed after HE and Masson staining. The messenger RNA (mRNA) levels of TIMP-1, MMP-2 and MMP-9 were determined by semi-quantitative reverse transcriptional polymerase chain reaction; protein expression was measured by Western blot in the livers of normal and transgenic mice of various ages. Changes in levels of superoxide dismutase (SOD), monoamine oxidase (MAO), malondialdehyde (MDA) as well as oxidative and anti-oxidative ability were measured.</p><p><b>RESULTS</b>Histologically, more fatty degeneration and collagen deposition were found in the aging livers of transgenic mice than in those of the normal mice as their age of months increased. The mRNA and protein expressions of TIMP-1 were significantly high in the oldest animals. The histopathological changes, mRNA and protein expressions of TIMP-1 increased significantly in the liver of transgenic mice as compared with normal mice. The expression of MMP-2 and MMP-9 showed a minor change in the process of aging. Liver change and collagen deposition were not observed in young mice, but the activity of SOD decreased (P < 0.05), and the activity of MAO (P < 0.01) and the content of MDA increased in the liver of transgenic mice (P < 0.01).</p><p><b>CONCLUSIONS</b>The expression of TIMP-1 is significantly high in the liver of transgenic mouse in the process of aging, indicating that the oxidative level increases and the anti-oxidative ability decreases in the liver of transgenic mouse. TIMP-1 plays an important role in the process of liver aging.</p>