Abstract: Immunotherapy is regarded as the most significant method for cancer treatment in recent years. Chimeric antigen receptor T cells (CAR-T) technology, one form of target immunotherapy, has made a great breakthrough in hematological malignancies treatment and also a few progress in solid tumor treatment. This article reviews the history and mechanism of CAR-T, as well as the advantages and limitations of CAR-T in clinical cancer treatment. Then the review mainly discussed the clinical trial progress of CAR-T cell therapy in solid tumor treatment. A primary obstacle of CAR-T therapy is the heterogeneity in solid tumors. With an increasing number of solid tumor surface antigens being discovered, different varieties of CARs have been designed to treat solid tumors and have made some progress in clinical trial. In the end, this review puts forward a possible development direction of CAR-T.
Abstract: Pre-transfusion tests include ABO/RhD blood typing, irregular antibody screening and cross-matching test, which are pivotal for safe and effective clinical transfusion. The best pre-transfusion test technology should be selected to ensure the safety of the clinical transfusion, use blood resources effectively, improve the transfusion’s effect, and achieve a precision transfusion. Here we reviewed the progress of main techniques and applications of pre-transfusion tests in recent years. aiming to give clinicians a systematic understanding of current pre-transfusion test techniques in clinical transfusion treatment.
Abstract: Few systematic investigations have assessed the correlations between red blood cell (RBC) antibodies and human leukocyte antigen (HLA)-DRB1 alleles in the Chinese population. In this case-control study, we investigated whether specific HLA-DRB1 alleles were associated with RBC alloimmunization by calculating the odds ratios for the frequencies of HLA alleles associated with alloimmunization to different RBC antigens. Three hundred and eight patients harboring RBC alloantibodies were analyzed as the case group, and the frequencies of the HLA-DRB1and HLA-DQB1 alleles in control individuals were analyzed by collecting data from the China Marrow Donor Program (including more than 1.6 million healthy people). HLA alleles were genotyped by single specific primer-polymerase chain reaction. The development of anti-C was associated with DRB1*07, DQB1*06, and DQB1*08; anti-C,e was associated with DRB1*07 and DQB1*06; and anti-E and anti-M were associated with DQB1. Other associations were identified between anti-E and DRB1*09 and between anti-Lea and DRB1*01. Thus, our findings confirmed that HLA-DRB1 and DQB1 restriction played an important role in the generation of RBC alloantibodies in Chinese individuals.
Abstract: T cell modified by chimeric antigen receptor (CAR) is considered one of the most promising tumor therapies for its almost magic effect in the treatment of hematologic malignancies. Encouraged by breakthroughs in this area, we produced Trop-2-redirected chimeric antigen receptor-modified T (Trop-2 CAR-T) cells and tested their function on ovarian cancer cells in vitro molecular cloning. Gene recombination technology was introduced to construct the Trop-2 CAR vector. The expression of Trop-2 CAR on 293T cells was tested by western blot. The effect of Trop-2 CAR-T cells on the proliferation of ovarian cancer cells was evaluated by CCK-8 assay. We found that Trop-2 CAR-T cells prominently inhibited the growth of ovarian cancer cells with Trop-2 antigen expression (P<0.05), moreover, high levels of IFN-γ and IL-2 were detected in supernatant by ELISA (P<0.01). These results suggest that Trop-2 CAR-T cells have the potential to be a clinical treatment for patients with Trop-2 positive ovarian cancer.
Abstract: The aim of the study was to examine the sero-prevalence and frequency of red blood cell (RBC) alloantibodies (RAAbs) and to investigate the risk factors for producing RAAbs among the Han and Uyghurs in Xinjiang. The RBC antibody screening test and identification were conducted for 45,163 Han and 70,633 Uyghurs admitted to the First Affiliated Hospital of Xinjiang Medical University from October 2010 to December 2014. RBC alloantibodies against the Rh antigens were the most frequent, including anti-E(21.7% in the Han, 21.6% in Uyghurs) and anti-D(18.5% in the Han, 18.2% in Uyghurs). Notably, the sero-prevalence of anti-K and anti-Fya was also high in Xinjiang. Transfusion and pregnancy were risk factors among both the Han and Uyghurs; furthermore, Uyghurs had a higher sero-prevalence of RBC antibodies compared to that of Han because of a higher incidence of these risk factors. We concluded that RBC alloantibodies against the Rh factor showed the highest frequency, and antibodies against Asian-related high-frequency antigens, including Fya and low-frequency antigens, such as K were notably high in Xinjiang.
Abstract: The aim of this study was to identify the specific RhD alleles that are risk factors for stimulating allo-anti-D and develop a precise strategy for blood transfusion. To confirm the D phenotype, red blood cells suspended in saline should react to serological anti-D from three manufacturers. An antibody screen test, a saline phase test and a micro-column test were conducted to identify allo-anti-D and other allo-antibodies. RhD alleles were genotyped by PCR using sequence-specific primers. Seven hundred subjects who were either pregnant or had undergone transfusion were enrolled in our study; however, 28 samples were excluded because their RhD alleles were normal, as revealed by tests using genotyping kits. A total of 498 cases (74.1%) were RhD-null (lacking exons 1–10 of RhD), 336 were DEL RhD 1227A (20.2%), and 38 were RHD-CE (2-9) -D (5.6%). There were 136 cases (20.2%) with allo-anti-D among the 672 cases, with an allo-anti-D prevalence of 126 cases (25.3%) in 498 cases that were RhD-null, followed by 10 cases (26.3%) among 38 cases with RHD-CE (2-9) -D, and none in 366 cases with RhD1227A. RhD genetic polymorphism was observed in RhD-negative individuals. We concluded that RhD-null and partial D are risk factors for alloimmunization to the D antigen and should be transfused with Rh-negative blood. RHD1227A recipients can be transfused with RhD-positive blood. Pregnant women with the d/d and D-CE(2-9)-D alleles require appropriate anti-D prophylaxis and RhD1227A may induce a higher tolerance.
Abstract: Aberrant expression of microRNA-34a (miR-34a) has been reported to be involved in the tumorigenesis and progression of various classes of malignancies. However, its role in colorectal cancer (CRC) has not been completely clarified. In the current study, we have investigated the clinical significance of miR-34a. MiR-34a expression in forty-three cases of colorectal cancer tissues decreased significantly compared to that in the adjacent non-tumorous colorectal tissues (P<0.05), as detected by real-time quantitative RT-PCR (qRT-PCR). Significantly, the expression of miR-34a was correlated with infiltration depth and clinical TNM stage (P <0.05). The miR-34a however had no correlation with other features, such as age, gender, site, tumor sizes, lymph node metastasis, serous membrane infiltration ( all P> 0.05). MiR-34a is a tumor suppressor miRNA that plays a vital role in the oncogenesis and progression of colorectal cancer. This study suggests that miR-34a may be a new tumor marker or prognostic factor in colorectal cancer. The strategies to increase miR-34a level might be a critical targeted therapy for CRC in the future.
Abstract: Xinjiang represents one of the richest minorities’ areas in China. This high ethnic diversity reflects in the blood groups and immune status and has a consequent impact on blood transfusions. To evaluate the risks of cross-minority transfusion in Xinjiang, we investigated the frequencies of erythrocytic Rh and K antigens among 1,073 Uyghurs and 213 Kazaks. We further reviewed the literature on the frequency of erythrocytic antigens to develop a simulation model for calculating the risk of patients in Xinjiang exposed to mismatched erythrocytic antigens. The frequencies of RhE, RhC, and K phenotypes were as follows: C antigen, 52.3% in Uyghurs and 56.8% in Kazaks; c antigen, 47.7% in Uyghurs and 43.2% in Kazaks; E antigen, 25.5% in Uyghurs and 27.2% in Kazaks; e antigen, 74.5% in Uyghurs and 72.8% in Kazaks; K antigen, 1.8% in Uyghurs and 1.8% in Kazaks. The population-adjusted cumulative match rate demonstrated that 53.3%, 51.4%, 50.6%, and 53.7% of the Uyghur, Kazak, Han, and Hui populations were recipients, respectively, although the recipients were transfused with an unknown Rh blood type. We concluded that the risks of cross-minority transfusion in Xinjiang are insignificant. The best strategy appears to be K and Rh-matched transfusions in this region due to the much higher frequency of the K antigen compared to other areas in China.
Abstract: In order to ensure an adequate and safe blood supply, the plateletpheresis donor deferral rate in family replacement donors and volunteer donors were analyzed in this study. The study was undertaken in Chongqing Blood Center, China. Nucleic acid testing (NAT) and ELISA were applied to assess the hepatitis B virus surface antigen (HBsAg), antibodies against hepatitis C virus (anti-HCV), human immunodeficiency virus (HIV) and Treponema palladium（TP）in plateletpheresis donors. From January 2015 to December 2016, a total of 17,342 plateletpheresis donors in Chongqing blood center were enrolled in this study. Among the 3,642 plateletpheresis donors, 21.00% were younger than 25, followed by 26–35 years group (41.19%), 36-45 years group (22.46%), 46-55 years group (13.97%) and 56-60 years group (1.38%). Replacement and voluntary donors contributed 5,305 (30.59%) and 12,037 (69.41%), respectively. Among all the plateletpheresis donors, 194 (1.12%) were deferred because of seropositive serology. Replacement and voluntary deferred donors comprised 109 (2.05%) and 85 (0.68%), respectively (P<0.05). Among the deferred donors, 194 (1.12%) were seropositive for HBsAg (0.44%), followed by anti-HCV (0.28%), TP (0.24%) and HIV (0.15%). Prevalence deferred females contributed 67 (1.60%), while males contributed 127 (0.97%) of the deferred cases, respectively (P<0.05). Deferral rate was highest among 46-55 years group (1.65%) followed by 36-45 years group (1.63%), The other groups were less than 1%. It is necessary to reduce family replacement donors and replace them with regular volunteer donors, and to improve blood donor retention strategies to boost the regular blood donors’ motivating. In addition to increasing and maintaining volunteer supply, it is desirable to keep the deferral rate at a low level, to ensure an adequate and safe blood supply.
Abstract: Multiple myeloma (MM) is an incurable disease with the second most frequent hematopoietic malignancy. In this study, we found that the expression of Aurora kinase A (AURKA) was significantly increased in patients with high-risk multiple myeloma, especially in proliferation subgroups. MLN8237, a small molecule AURKA inhibitor, inhibited MM cell proliferation by inducing cell apoptosis and injury. Thus, we speculate MLN8237 is a potential therapeutic agent for MM and AURKA may be a potential target for MM treatment.
Abstract: Adult patients with chronic active EB virus infection (CAEBV) are few; however the disease runs an aggressive course. The goal of this study was to investigate the clinical characteristics, treatment as well as prognosis of CAEBV in adults. The clinical data of eight adult patients with CAEBV of were analyzed retrospectively. There were five male and three female patients with a median age of 47 (25-67) years old. The main clinical manifestations were fever, lymphadenopathy, splenomegaly, liver damage, abnormal coagulation and cytopenia. Peripheral blood EB virus DNA titers were significantly higher in all patients (4.14×104—4.60×105copy/mL). Most patients received treatment with glucocorticoids, cyclosporine and chemotherapy containing etoposide (as recommended in the HLH-2004 program or the scheme of ECOP). One patient progressed to aggressive natural killer (NK) cell leukemia in 5 months after diagnosis. Another patient without fever or cytopenia is still living now, after receiving hormone therapy. The remaining 6 cases died with a median survival of 15 months. In conclusion, CAEBV in adults is a rare but serious disease, often with multiple system damage, from which the prognosis is very poor. Further research is necessary to improve the understanding of this disease.