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In the last decades, researchers have been focusing on cancer cells looking for novel targets, however, tumours grow in a host environment that either contribute to or inhibit tumour expansion and metastatization. Several efforts have been focused on cancer microenvironment for diagnostic and therapeutic purposes. Nuclear medicine can contribute to understand the complexity and role of tumour microenvironment by imaging several of its components (chemokine receptors, immune cells, stromal antigens, vascular factors, etc). In a tumour, each microenvironment component offers many potential targets for several drugs or radiopharmaceuticals. Cancer may be studied using different strategies from different viewpoints: imaging tumour markers or differentiating markers for diagnostic purposes in order to plan personalized therapies (receptor agonists or superagonists); imaging tumour stroma and vascularization to monitor cell adhesion, metastases, angiogenesis and hypoxia; imaging the host response of cancer cells to monitor efficacy of immunotherapeutic strategies
En las últimas décadas los investigadores han centrado su atención en la observación de las células cancerosas, en búsqueda de nuevos sitios blanco. Sin embargo, el crecimiento del tumor se produce en un entorno que, o inhibe, o contribuye a la expansión del tumor y su metástasis. Varios esfuerzos han estado enfocados al estudio del microentorno del cáncer, con propósitos diagnósticos o terapéuticos. La Medicina Nuclear puede contribuir a la comprensión de la complejidad y del papel que juega el microentorno del tumor, mediante la obtención de las imágenes de varios de sus componentes (receptores de quimioquinas, células inmunes, antígenos del estroma, factores vasculares, etc.). En un tumor, cada componente del microentorno ofrece muchos blancos potenciales para varias drogas o radiofármacos. El cáncer puede ser estudiado mediante diferentes estrategias y enfoques: mediante la imagen de marcadores tumorales, o la diferenciación de estos, con propósitos diagnósticos a fin de planificar terapias personalizadas (receptores agonistas o superagonistas); mediante la imagen del estroma del tumor y la vascularización, para monitorear la adhesión celular, la metástasis, la angiogénesis y la hipoxia; mediante la imagen de la respuesta del huésped de las células cancerosas, con el objetivo de monitorear la eficacia de las estrategias inmunoterapéuticas
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Objective To investigate the clinical significance of the expression of lymphocytes and cytokines in patients with laryngeal tuberculosis.Methods 96 cases of laryngeal tuberculosis were selected as the research objects.Of which 42 cases of infiltrating type,31 cases of ulcer type,mass type in 23 cases,the other 50 cases of healthy persons were selected as the healthy control group,all the research objects,extracting the morning fasting venous peripheral blood for detection of T lymphocyte subsets and cytokines were detected,and the results were compared.Results Invasive laryngeal tuberculosis CD3+ index (63.10 ± 5.33) ％ (t =1.922),CD4+ (40.32 ± 5.06) ％ (t =1.758),CD8+ (24.41 ± 4.59) ％ (t =1.710),compared with the control group,CD4+,CD3+ index significantly reduced,CD8+ index increased significantly,the differences had statistical significance (t =1.922,1.758,1.710,all P ＜ 0.05),and the ulcer type and mass type results compared with invasive had significant difference(all P ＜0.05).In the analysis of laryngeal tuberculosis pathological types,reduced the mass type CD3+,CD4+ T index and CD8+ index of lymphocyte increased obviously the most significant;all laryngeal tuberculosis in patients with IL-4,IL-10 and TNF-alpha significantly increased compared with the control group,while the IFN-gamma was significantly reduced,and the mass in the type of change was the most significant,the differences had statistical significance(all P ＜ 0.05).Conclusion The use of lymphocytes and cytokines detection can improve the laryngeal tuberculosis patients with the clinical diagnosis rate,with the detection results of different degree and different pathological types of laryngeal tuberculosis patients,can be used for preliminary assessment of laryngeal tuberculosis disease and pathological type,the choice of treatment modality for patients with guidance value,with in-depth clinical study and promotion application of value.
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Pré-eclâmpsia é uma síndrome sistêmica caracterizada por intenso estado inflamatório e antiangiogênico. A fisiopatologia da pré-clâmpsia envolve alterações no processo de invasão trofoblástica, com consequente inadequado suprimento sanguíneo uterino e estresse oxidativo do tecido placentário. As alterações placentárias decorrentes desse processo levam à maior produção de sFlt-1, um receptor solúvel para as moléculas de VEGF e PlGF. O sFlt-1 impede com que VEGF e PlGF realizem suas funções na homeostase endotelial, culminando com disfunção dessas células. De uma maneira geral, os processos inflamatórios, de disfunção endotelial e estresse oxidativo estão interligados e agem de maneira sinérgica. Trabalhos recentes têm demonstrado que elevações nas concentrações séricas de sFlt-1 ocorrem 5 a 6 semanas antes das manifestações clínicas da pré-eclâmpsia. Concomitantemente, observa-se queda nas concentrações séricas de PlGF. Sendo assim, as dosagens séricas de sFlt-1 e PlGF têm sido sugeridas para o diagnóstico precoce de pré-eclâmpsia. Ademais, os conhecimentos adquiridos a respeito dos fatores antiangiogênicos proporcionam ainda a possibilidade de novas linhas de pesquisa sobre possíveis terapias para a pré-eclâmpsia. Neste artigo, foram revisados os aspectos inflamatórios e antiangiogênicos envolvidos na fisiopatologia da pré-eclâmpsia. Por fim, foram correlacionados esses aspectos com o risco elevado para doenças cardiovasculares apresentado por essas pacientes ao longo de suas vidas.
Preeclampsia is a systemic syndrome characterized by inflammatory and antiangiogenic states. The pathogenesis of preeclampsia involves deficient trophoblast invasion that is responsible for altered uterine blood flow and placental oxidative stress. The damaged placenta produces higher concentrations of sFlt-1, a soluble receptor for VEGF and PlGF that is released in the maternal circulation and is involved in endothelial dysfunction. Actually, all processes involved in inflammation, endothelial dysfunction and oxidative stress are strongly correlated and act in a synergistic way. Recent data have shown that an increase in serum concentrations of sFlt-1 initiates 5 to 6 weeks before the clinical manifestations of preeclampsia and these alterations correlate with a decrease in serum concentrations of PlGF. Therefore, both sFlt-1 and PlGF have been suggested to be useful for an early-diagnosis of preeclampsia. The knowledge about the role of antiangiogenic factors in the pathogenesis of preeclampsia has raised the possibility of a therapy involving these factors.In this article we revisited the pathogenesis of preeclampsia addressing its antiangiogenic and inflammatory states.In conclusion, we correlated these alterations with the higher risk for cardiovascular diseases presented by these women in future life.
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Femenino , Humanos , Recién Nacido , Embarazo , Endotelio Vascular/fisiopatología , Inflamación/complicaciones , Estrés Oxidativo , Preeclampsia/etiología , Resultado del EmbarazoRESUMEN
Objective To determine the incidence, clinical manifestation and part of lymphokines which represent the balance of Th1 and Th2 in the role of the immunologic mechanisms for IRIS(immune restoration inflammatory syndromes)in patients initiating HAART(Highly Active Antiretroviral Therapy).Methods A prospective study of all patients initiating HAART was performed. A period of six months tracking initiating HAART was performed. The incidence of IRIS, time of occurrence and clinical disease spectrum were recorded. The main T lymphokines including IL-2, INF-γ, IL-4, IL-10 which on behalf of the balance of Th1 and Th2 were detected. To explore the immunopathologic mechanisms for IRIS, the levels of T lymphokines at pre-HAART, initiating HAART for 1 month, 3months and 6 months were compared in IRIS group and non-IRIS group, healthy group. Results A total of 212 patients were enrolled in this study. 59 patients were diagnosed as IRIS at a median of 21 days after HAART initiation (QR 19 days).The main disease spectrum included tuberculosis, herpes virus infections, pneumocystis jirovecii pneumonia. No matter in the IRIS group or non-IRIS group, the main lymphokines baseline of IL-2, INF-γ reduced and IL-4, IL-10 increased before HAART compared to healthy group (P ＜ 0. 05), which had the tendency to restore balance relations initiating HAART. The lymphokines levels had significant difference between baseline and 6 months initiating HAART (P ＜ 0. 05). The changed levels of lymphokines between IRIS group and non-IRIS group before HAART had significant difference compared to healthy group. IL-2, INF-γ increased level[(11.68 ± 2. 89) pg/ml vs (8.52 ±2.26) pg/ml; (22. 19 ± 6. 22) pg/ml vs (18.34 ±5. 35) pg/ml] and IL-10 decreased level [(19. 21 ± 4. 03) pg/ml vs (23. 19 ± 5.92) pg/ml] had significant difference between IRIS group and non-IRIS group initiating HAART I month(P ＜0. 05). Conclusions The incidence of IRIS during 6 months initiating HAART in HIV/AIDS was 27. 8%, IRIS usually occurred in 1 month initiating HAART. The most common disease spectrum was infectious disease, including tuberculosis and herpes virus infection. Lymphokine of Th1 and Th2 existed unbalance in IRIS group and non-IRIS group before HAART. The unbalance tendency in IRIS group was more obvious. All lymphokines had the trend to recover balance. IL-2, INF-γ significantly increased and IL-10 significantly decreased, which might involve the occurrence of the IRIS.
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Objective To provide immunological evidence for clinical transfer of chemical extracted acellular nerve allografL Methods One hundred and twenty-eight BALB/C mice were randomly divided into 4 groups of equal size according to their different treatments:negative contrast group(NC),fresh autograft group(AG),fresh allogeneic nerve group(FN)and chemical extracted aceflular allogeneic nerve group(CEN).Then we implanted various kinds of nerve grafts into the thigh muscle of BALB/C mice in corresponding groups.At 3,7,14,28 days postoperatively,8 mice from each group were killed each time to harvest their spleens,from which T lymphocytes were collected.Theu monoclonal antibodies(CD3,CD4 CD8 CD25,IL-2,IFN-γ, TNF-α)were added into the suspension.Then fluorescence.activated cell sorting(FACS)was used to determine the positive rates of cells combined with the above monoclonal antibodies. Results There were no statistically significant differences between CEN group,NC group,and AG group,but indexes of FN group were significantly higher than those of the other 3 groups at corresponding time points. Conclusion There is no obvious immune reiection of chemical extracted acellular nerve allograft when compared with fresh nerve autograft.
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Objective To assess the effect of recombinant human leukemia inhibitory factor (rhLIF) on mouse embryo development in vitro Methods Mice were randomly divided to three groups, one in vivo control (group Ⅰ) and two in vitro (group Ⅱ and Ⅲ) Mice were sacrificed at 116 120 hours (group Ⅰ) and 44-48 hours (group Ⅱ and Ⅲ) subsequent human chorionic gonadotropin (hCG) injection Two cell embryos (group Ⅱ and Ⅲ) and blastocysts (group Ⅰ) were obtained Embryos in group Ⅱwere cocultured with human tubal fluid (HTF) + 10% human serum and in group Ⅲ with HTF + 10% human serum+rhLIF (1 000 U/ml) The number of embryo in different stage was recorded and compared Results Embryo in four, eight cell and morula was noted in group Ⅱ and Ⅲ, 87 7% versus 91 2% and 75 0% versus 85 4% respectively There was no significant difference. However, further embryo development to the blastocyst, expanded blastocyst, and hatching blastocyst in group Ⅱ (48 1%, 32 1% and 18 4%) was lower than that in group Ⅲ (82 3%, 59 7% and 36 3%) There was no difference between blastocyst in group Ⅰ and group Ⅲ (86 0% vs 82 3%). Conclusion RhLIF does not provide obvious stimulation in early mouse embryo, however, rhLIF can promote the growth, differentiation, and hatching of preimplantion blastocyst
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AIM: To investigate the biological characteristics of cytokine-induced killer (CIK) cells in vitro METHODS: The non-adhere peripheral blood monoclear cells from healthy donors were induced into CIK cells in the presence of IFN-?, IL-1?, IL-2 and anti-CD3 antibody. LAK (lymphokine activated killer) cells were prepared as a control. The cellular phenotype were detected by FCM and immunocytochemistry and the cytotoxicity was measured by LDH release assay. RESULTS: After 2 weeks of induction, the proliferation rate of CIK cells reached a peak and the proportion of CD3 + population was above 95%, and then the cells growth entered to plateau phase at week 3. The proportion of CD3 +CD56 + NKT subset cells was 16 5% on day 15 and it had no obvious variety between 2 and 4 weeks. Correspondingly, LAK cells grew slowly and had lower proliferation rate compared with the CIK cells ( P
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Objective To explore the clinical significance of changes of umbilical artery and amniotic fluid vascular endothelial growth factor (VEGF) level in newborn infants with asphyxia. Methods The VEGF levels in umbilical artery and amniotic fluid were detected by ELSIA in 67 newborn infants with asphyxia (asphyxia group) and 44 normal term newborn infants (control group). Results The VEGF level of umbilical artery ( 674?150) ng/L and amniotic fluid (225?78) ng/L in asphyxia groups were significantly higher than that of umbilical artery (129?30) ng/L and amniotic fluid (57?4) ng/L in control group ( P
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Objective To investigate the role of angiogenesis and expression of vascular endothelial growth factor (VEGF) in the pathophysiology of adenomyosis of the uterus. Methods The study included 32 patients with histologically proven adenomyosis and 30 patients with asymptomatic leiomyoma of the uterus. Immunohistochemical staining was used to detect VEGF expression in different parts of the uterus. A computerized morphometric study on the VEGF expression was performed. Results The VEGF H-Score of glandular cells in the endometrium of adenomyosis uterus [proliferative phase (9.6?1.4), secretory phase (11.7?1.6)] was much higher than that of leiomyoma uterus [proliferative phase (8.3?1.7),secretory phase (10.2?1.5)] (P0.05). The VEGF H-Score of myometrium around the ectopic lesions [proliferative phase (9.5?1.3), secretory phase (8.7?1.3)] was higher than that of normal myometrium [proliferative phase (4.8?1.9), secretory phase (4.5?1.4)] (P
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Objective To evaluate the function of vascular endothelial growth factor (VEGF) and other clinical indexes to forcast ovarian hyperstimulation syndrome (OHSS). Method Collecting the serum and follicular fluid (FF) of 42 cases in the in vitro fertilization and embryo transfer (IVF-ET) cycles and then analysis the relationship of the clinical and detected indexes between the OHSS (10 cases) and the non-OHSS (32 cases). Results The concentration of VEGF in FF?E 2 on the day of human chorionic gonadotropin (hCG) injection, basal luteinizing hormone (LH) and the number of ovum retried much higher in the OHSS than in the non-OHSS. Conclusions The concentration of VEGF in FF of OHSS cases is higher than that of controls, supporting the role of VEGF as a mediator of OHSS. Therefore VEGF in FF is a forcast index of OHSS.
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0.05). While serum pregesterone, hCG levels in inevitable group were (33.1?19.6) nmol/L, (10.3?3.2) kU/L respectively. Compared with normal early pregnancy and threatened abortion group, the levels of serum pregesterone and hCG reduced significantly ( P
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A novel factor which augments the expression of major histocompatibility complex I (MHC augmenting factor or MHC-AF) antigens on tumor cell lines, has been isolated from the culture supernatants of human peripheral blood mononuclear cells activated by concanavalin-A. A mouse equivalent of this factor has also been isolated from the culture supernatants of mouse spleen cells activated by mitogens or in a mixed lymphocyte reaction. Mouse MHC-AF enhances the expression of class I MHC antigens on murine tumor cell lines (EL-4 and BW5147) but not on human tumor cell lines (K562 and HR-7). Human MHC-AF on the other hand enhances the MHC I expression on both human as well as murine cell lines. Interferon gamma (IFN-gamma), a cytokine also known to enhance the expression of MHC I antigens, acts in a highly species specific manner with mouse IFN-gamma augmenting the MHC I on murine tumor cell lines and human IFN-gamma augmenting the MHC I on human tumor cell lines only. These results indicate important differences in the cross species biological activities of MHC-AF and IFN-gamma, and provide additional evidence for MHC-AF being distinct from IFN-gamma.
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Animales , Humanos , Ratones , Línea Celular , Línea Celular Tumoral , Mano , Antígenos de Histocompatibilidad Clase I , Interferones , Prueba de Cultivo Mixto de Linfocitos , Linfocitos , Linfocinas , Complejo Mayor de Histocompatibilidad , Mitógenos , Especificidad de la Especie , BazoRESUMEN
Objective To study the relationship between type 1 and type 2 cytokines and human acute graft-versus-host disease (aGVHD).Methods In 20 patients undergoing allogeneic peripheral blood stem cell transplantation (allo-PBSCT), plasma concentrations of interleukin-18 (IL-18), interleukin-2R (IL-2R), tumor necrosis factor-a (TNF-?) and interleukin-10 (IL-10) were measured by using enzyme-linked immunosorbent assay (ELISA).Results All the patients achieved engraftment. Eight cases deve- loped grade Ⅰ-Ⅱ aGVHD and 3 cases developed Ⅲ-Ⅳ aGVHD. The concentrations of IL-18 and IL-2R in the patients with aGVHD were significantly higher than those without aGVHD. The levels of IL-18 were correlated with the severity of aGVHD; The levels of TNF-? showed no difference between the patients with or without aGVHD; The concentrations of IL-10 in the patients with aGVHD were significantly declined but in those without aGVHD were significantly increased.Conclusion Type 1 and type 2 cytokines play an important opposite role in development of aGVHD.
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Objective To investigate the mRNA expression of secondary lymphoid tissue chemokine (SLC) in human gastric carcinoma. Method The study was designed to investigate semi-quantitatively the expression of SLC mRNA in gastric carcinoma and metastatic lymph nodes by reverse transcription-polymerase chain reaction.Result The expression of SLC mRNA in the gastric cancer tissues was markedly reduced compared with that in adjacent noncancer tissues. The average tumor/normal (T/N) ratio determined by RT-PCR was 0.43?0.08 in 29 patients.Metastatic lymph node/normal ratio was 0.63?0.07.Negative lymph node/normal ratio was 1.19?0.11. As a control,the mean G3PDH T/N ratio was 1.16?0.06,there was no correlation between SLC mRNA expression and clinicopathological characteristics in gastric cancer.ConclusionSLC mRNA expression is suppressed in the gastric tumours. SLC may play an important role in the early stage of carcinogenesis.