ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC). MethodsThe related literatures about the therapeutic targets of PC were reviewed. ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes. ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
Objective To study the effect of Huaier granule on the recurrence and metastasis of hepatocellular carcinoma (HCC) and immune rejection in the postoperative patients with liver transplantation for HCC. Methods Twenty-eight patients of liver transplantation for HCC who had taken Huaier granule orally for more than 6 months from September 2001 to March 2007 in West China Hospital were included as treatment group, and other 56 patients of liver transplantation for HCC who didn’t take any Huaier granule in the same time were included as the control group according to the same stage of TNM, degree of tumor differentiation (Edmondson grading) respectively with the treatment group. The method of retrospective cohort study was used to compare the incidence of immune rejection and the 6-month, 1-year, and 2-year recurrence and metastasis of HCC, disease free survival rate, and survival rate between two groups after 2 years’ follow-up beginning from the date of surgery. Results The 6-month, 1-year, and 2-year tumor recurrence and metastasis incidences in treatment group were 14.3%, 32.1%, and 39.3% respectively, which were 23.2%, 32.1%, and 50.0% respectively in control group, and the 2-year tumor recurrence and metastasis incidence of the treatment group was lower than that of the control group. The 6-month, 1-year, and 2-year disease free survival rates in treatment group were 85.7%, 67.5%, and 60.0% respectively, which were 76.7%, 67.6%, and 49.3% respectively in control group, and the 2-year disease free survival rate of treatment group was higher than that of the control group. The 6-month, 1-year, 2-year survival rates in treatment group were 92.9%, 78.6%, and 67.9% respectively, which were 89.3%, 75.0%, and 62.5% respectively in control group. But the 2-year tumor recurrence and metastasis incidence (P=0.353), 2-year disease free survival curve (P=0.386), and 2-year survival curve (P=0.620) were not significantly different between two groups. The incidence of immune rejection was 14.29% in the treatment group and 16.07% in the control group, which was not significantly different between the two groups (P=0.831). Conclusions Huaier granule can increase the 2-year tumor-free survival rate and restrain the recurrence and metastasis of HCC, and does not increase the incidence of immune rejection. Huaier granule as a treatment of HCC in patients with liver transplantation is safe and effective.
ObjectiveTo analyze the efficacy and safety of immunotherapy and bevacizumab combined with chemotherapy (BIC), bevacizumab combined with chemotherapy (BC), chemotherapy (CT), immunotherapy combined with chemotherapy (IC), bevacizumab combined with immunotherapy (BI), bevacizumab (B) in the first-line treatment of advanced wild-type non-squamous non-small cell lung cancer. MethodsThe PubMed, Embase, Cochrane Library and Web of Science databases were searched to collect phase Ⅱ/Ⅲ randomized controlled trials (RCTs) related to the objectives of the study from January 2010 to December 1, 2022. After two investigators independently screened the literatures, extracted the data and evaluated the risk of bias of the included studies, a reticular meta-analysis was performed using R 3.6.1 software. ResultsA total of 11 RCTs were finally included, including 5 329 patients and six treatment combinations. Meta-analysis results showed that BIC was superior to CT for progression-free survival (PFS) (HR=0.34, 95% CI 0.18 to 0.69), but BIC did not show a significant advantage over the other groups for overall survival (OS). Bayesian ranking results showed that the BIC group had the greatest probability in terms of OS, PFS, and ORR. Among all programmed death ligand 1 (PD-L1) expressing subgroups, there was no significant difference in OS between BIC, BC, IC, CT, BI, and B. Compared with CT, IC was significantly improved in OS (HR=0.68, 95%CI 0.52 to 0.92), PFS (HR=0.58, 95%CI 0.45 to 0.75), and ORR (HR=0.47, 95%CI 0.33 to 0.66). ConclusionIn the first-line treatment of wild-type advanced non-squamous NSCLC, immunotherapy and bevacizumab combined with chemotherapy may improve the efficacy in the short term, but do not change the long-term survival time. Immunotherapy combined with chemotherapy can significantly improve the survival time and prognosis of patients compared with chemotherapy alone. Due to the limited quantity and quality of the included studies, more high-quality studies are needed to verify the above conclusion.
In recent years, the incidence of primary liver cancer has been increasing, among which hepatocellular carcinoma (HCC) being the most common subtype. The treatment of early HCC is mainly surgery, but most patients are not diagnosed until the late stage of the disease. The treatment methods and effects are very limited and the prognosis is very poor. Although targeted therapy has prolonged the overall survival of patients with HCC, the overall efficacy is unsatisfactory. The emergence of immunotherapy has brought new therapeutic prospects for HCC. Immune checkpoint inhibitors, among which programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte associated antigen-4 are the representative immunological checkpoints, have attracted more attention. This article will introduce the application of immune checkpoint inhibitors in the treatment of advanced HCC, in order to provide a theoretical basis for the use of immune checkpoint inhibitors in the treatment of advanced HCC.
ObjectiveTo study the immunogenicity of human bone marrow mesenchymal stem cells (BMSCs) and the suppression ability to the proliferation of peripheral blood mononuclear cell (PBMC) during osteogenic, chondrogenic, and adipogenic differentiations. MethodsBMSCs were isolated from bone marrow of healthy donors and were induced to osteogenic, chondrogenic, and adipogenic differentiations for 7, 14, and 21 days. The expressions of human leukocyte antigen (HLA) class I and class II were detected by flow cytometry. PBMC were isolated from peripheral blood of healthy donors and were co-cultured with BMSCs at a ratio of 10∶1 for 5 days. The suppression ability of undifferentiated and differentiated BMSCs to proliferation of PBMC were detected by flow cytometry. ResultsThe HLA class I expression was observed but almost no expression of HLA class II was seen in undifferentiated BMSCs. There was no obviously change of the HLA class I and class II expressions during osteogenic and chondrogenic differentiations (P>0.05), and a low expression of HLA class II was kept. The HLA class I expression gradually increased at 14 and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 and 7 days (P<0.05);the HLA class II expression also gradually increased at 7, 14, and 21 days after adipogenic differentiation, showing significant differences when compared with the value at 0 day (P<0.05). There was no proliferation of PBMC without the stimulation of CD3 and CD28 microspheres and significant proliferation was observed when CD3 and CD28 microspheres were added, and undifferentiated BMSCs could significantly inhibit the proliferation of PBMC. There was no obvious change of the ability of BMSCs to inhibit the proliferation of PBMC during osteogenic and chondrogenic differentiations (P>0.05);and the ability of BMSCs to inhibit the proliferation of PBMC was gradually weakened at 7, 14, and 21 days after adipogenic differentiation, showing significant differences among different time points (P<0.05). ConclusionBMSCs maintain low immunogenicity and strong immune suppression ability during osteogenic and chondrogenic differentiations, which are suitable for allogenic tissue engineering repair and cell transplantation. However, increased immunogenicity and decreased immune suppression ability after adipogenic differentiation may not be suitable for allogenic tissue engineering repair and cell transplantation.
Objective To discuss the correlation between immune status and clinical characteristics in pulmonary cryptococcosis. Methods The clinical data of 32 non-AIDS patients with pulmonary cryptococcosis, diagnosed from August 2001 to October 2017 in Tianjin Medical University General Hospital, were retrospectively analyzed. The enrolled patients were divided into an immune-competent group with 13 cases and an immune-suppressed group with 19 cases. The clinical characteristics were compared between the two groups with different immune status. Results All 32 patients were treated for clinical symptoms. The main symptoms were cough, expectoration, fever, chest tightness, chest pain, and hemoptysis. There were no statistical differences between the two groups. The computed tomography of chest showed that there were 2 patients (6.3%) involving upper lung in the immune-competent group, and 5 patients (15.6%) in the immune-suppressed group. There were 9 patients (28.1%) involving lower lung in the immune-competent group, and 12 patients (37.5%) in the immune-suppressed group. There were 10 patients (31.3%) with nodular masses of lesions in the immune-competent group and none in the immune-suppressed group. There was 1 patient with infiltrating in the immune-competent group and 8 patients in the immune-suppressed group. There were 2 patients with mixed types of lesions in the immune-competent group and 11 patients in the immune-suppressed group. Five patients were complicated with cryptococcal meningitis, and 2 patients with eosinophilia. Conclusions The clinical characteristics of the patients with pulmonary cryptococcosis are not specific in difference immune status. The chest CT shows that the lesions of immune-competent patients are mainly nodular masses type, while lesions of immune-suppressed patients are mainly infiltrating shadow and mixed shadow. The treatment should be chose according to immune status.
Objective To summarize the role of costimulatory molecules in inducing immune tolerance of organ transplantation. Methods Domestic and international publications online involving costimulatory molecules and immune tolerance in recent years were collected and reviewed. Results The relationship between costimulatory pathways and transplantation immunity has already been clarified in recent years. The main costimulatory molecules alreadly found mainly include B7-CD28/CTLA4, CD40-CD154, 4-1BB/4-1BBL, and ICOS-B7h, etc. Costimulatory pathways com-inhibition or combining with other immunosuppression methods could obtain stable and long lasting immune tolerance. Conclusions With the development of immunology and molecular biology, costimulatory pathways of T lymphocyte activation will be further interpreted. Other new costimulatory molecules will be discovered in the future, which will afford theory evidence for inducing immune tolerance.
Objective To explore the association between plasma IgG and acute exacerbation (AE) or death risk in patients with chronic obstructive pulmonary disease (COPD). Methods A total of 262 COPD patients treated in our hospital from February 2018 to February 2020 were recruited in our study. All patients were divided into AE≥2 group and AE≤1 group according to AE frequency during follow-up of 1 year. Basic data and laboratory data such as IgG, IgA and IgM of two groups were comparatively analyzed. Univariate analysis and COX regression were performed to analyze the related factors of frequency of AE≥2 times in 1 year. Depicting restricted cubic spline was performed to analyze the relation between IgG and AE by R software. All patients were also divided into high IgG group, low IgG group, high IgA group and low IgA group based on median of patients’ baseline plasma IgG and IgA level, depicting survival curve by Kaplan-Meier to analyse differences between the groups with different IgG or IgA level in the risk of AE and death respectively. ResultsFinally, there were 14 patients lost to follow-up and 248 cases were included (AE≤1 group contained 154 cases, AE≥2 group contained 94 cases) until February 28, 2021. Age and COPD Assessment Test (CAT) scores in the AE≥2 group were higher than those in the AE≤1 group; Albumin, IgG and IgA level in the AE≥2 group were lower than those in the AE≤1 group; Neutrophil to lymphocyte ratio (NLR) in the AE≥2 group was higher than that in the AE≤1 group (all P<0.05). There were 99 and 114 cases of AE in the high IgG and low IgG groups respectively within 1 year. Kaplan Meier survival analysis showed that risk of AE in the high IgG group and high IgA group were lower than that in the low IgG group and the low IgA group (log rank χ2=23.791, 67.153, both P=0.000). Risk of death in the high IgG group was lower than that in the low IgG group (log rank χ2=6.214, P=0.013), there was no statistically difference in the risk of death in the high IgA group compared to the low IgA group (log rank χ2=2.400, P=0.121). Multivariate Cox regression analysis showed that CAT score (HR=1.096, P=0.001) and NLR (HR=2.061, P=0.000) were independent risk factors of frequency of AE≥2 times in 1 year for COPD patients, albumin (HR=0.921, P=0.006) and IgG (HR=0.572, P=0.000）were the independent protective factors. Restricted cubic spline analysis showed that combining the COX regression model, after adjusting for IgA, albumin, NLR and other variables, there was non-linear relationship between IgG level and AE (P=0.000).Conclusion Plasma IgG level is related to AE in COPD patients, and may become a reliable predictor of acute exacerbation risk in the future.
Objective To evaluate the host immune reaction against adenovirus mediated human bone morphogenetic protein 2 (Adv-hBMP-2) gene therapy in repairof tibial defects. Methods Twelve goats were made 2.1 cm segmental defects in he tibial diaphysis and divided into 2 groups. AdvhBMP2 transfected marrow mesenchymal stem cells(MSCs) and untransfected MSCs were implanted into the defect sites of transfected group(n=7) and untransfected group (n=5), respectively. The defect repair was observed by X-ray films after 4, 8, 16 and 24 weeks of transplantation and cellular and humoral immune reactions to adenovirus were assayed before implantation and after implantation. Results More bony callus was found in the bone defects of transfected group. The healing rates were 6/7 in transfected group and 2/5 in untransfected group, respectively at 24 weeks after implantation. The mixed culture of lymphocytes and MSCs showed that the lymphocytes stimulation indexes (SI) increased 14 days after implantation, and there was significant difference between the transfected group (4.213±1.278) and the untransfected group(－0.310±0.147，Plt;0.05); SI decreased after 28 days, but there was no significant difference between the transfected group (2.544±0.957) and the untransfected group (3.104±0.644，Pgt;0.05). After 14, 28, 49, and 120 days of treatment, the titer values of neutralizing antibody against Adv-hBMP-2 (log0.1) were 2.359±0226, 2.297±0.200, 2.214±0.215 and 2.297±0.210 in transfected group, and -0.175±0.335, -0.419±0.171, 0±0.171 and 0.874±0.524 in untransfected group, being significant differences betweentwo groups(Plt;0.05). Conclusion Adenovirus mediated BMP-2gene therapy can cause cellular and humoral immune reactions against adenovirus, which can eliminate the influence of adenoviral genes and proteins within a certain period.
The studies of immunohistochemistry, histochemisu3r and electron microscopy in 50 patients with retinoblastoma were carried out. Our results show that retinoblastoma origin from primitive retinal neuronal cells that can differentiate into nmture neuron (including retinal photoreeeptor) and glial cells.The glial component in the retinoblastoma is mainly reactive glial proliferation.There is a good prognosis in the patients with retinoblastoma in which there are a lot of differiation areas and glial proliferation. （Chin J Ocul Fundus Dis,1993,9:193-197）