Double-negative T cells: a promising avenue of adoptive cell therapy in transplant oncology / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Tumor recurrence is one of the major life-threatening complications after liver transplantation for liver cancer. In addition to the common mechanisms underlying tumor recurrence, another unavoidable problem is that the immunosuppressive therapeutic regimen after transplantation could promote tumor recurrence and metastasis. Transplant oncology is an emerging field that addresses oncological challenges in transplantation. In this context, a comprehensive therapeutic management approach is required to balance the anti-tumor treatment and immunosuppressive status of recipients. Double-negative T cells (DNTs) are a cluster of heterogeneous cells mainly consisting of two subsets stratified by T cell receptor (TCR) type. Among them, TCRαβ+ DNTs are considered to induce immune suppression in immune-mediated diseases, while TCRγδ+ DNTs are widely recognized as tumor killers. As a composite cell therapy, healthy donor-derived DNTs can be propagated to therapeutic numbers in vitro and applied for the treatment of several malignancies without impairing normal tissues or being rejected by the host. In this work, we summarized the biological characteristics and functions of DNTs in oncology, immunology, and transplantation. Based on the multiple roles of DNTs, we propose that a new balance could be achieved in liver transplant oncology using them as an off-the-shelf adoptive cell therapy (ACT).

Taurine as a Drug for Protection of Liver and Kidney against Toxicity of Dinitrotoluene on Male Rats (Applicable Study)

Technical grade dinitrotoluene (tg-DNT) [CH3C6H3 (NO2)2] nitroaromatic agents which are manufactured in theindustries and applied in both commercial and military in all over the world and Egypt. DNT causes malfunctions inkidneys, heart, liver, testes and mammary glands in animals and human beings, which may be considered as carcinogenic inexperimental animals and human. Moreover, taurine, a free β-amino acid with remarkable antioxidant activity, hasimportant beneficial effects on the human body; hepatoprotection, nephroprotection, cardiovascular protection,hypoglycemic impact and hypolipidemicaction. Currently, taurine level in the serum is used as early marker of breast,endometrial and colon cancers. The current research was aimed to explore the potential impacts of the antioxidantproperties of taurine as a protecting material on tg-DNT induced toxicity in the liver and kidney in male rats. 100apparently healthy male rats in 4 groups were included; the first is Frank control group, mouth feeding via gavage withdistilled water; the other groups were administered as following, taurine alone, tg-DNT alone (toxic group), taurine + tgDNT (protective group) in the second, third and fourth groups, respectively. In these groups, blood biochemistry and taurineconcentrations in serum were measured for all animals. Furthermore, histopathological examination studies for liver andkidney were done for all groups. The results showed that, the protective group has marked improvement in most biochemicalparameters than the toxic group. Histological studies revealed a significant marked disturbance in the histopathologicalarchitectures of the kidney and liver in all toxic rats. However, marked improvements in histological architectures wereobserved in protective group. The results support the ameliorative effect of taurine as a protective agent against tg-DNTtoxicity in experimental rats.

Immunotherapy of pancreatic cancer and the application of DNT cell in the therapy of pancreatic cancer / 国际外科学杂志

Pancreatic cancer is a kind of malignant tumor with a high degree of malignancy and a very poor prognosis.The onset is occult,early metastasis is easy,and progression is rapid.Despite clinically increasing the resection rate of pancreatic cancer,the survival time after surgery is not significantly prolonged.Pancreatic cancer is not sensitive to radiotherapy and chemotherapy,so there is no effective treatment.Adoptive immunotherapy is an important auxiliary method for the treatment of malignant tumors and refers to killing the malignant tumor cells in patients by injecting effective immune cells into the patient without damaging the patient's own immune system.The DNT cells discovered in recent years,namely TCR +,CD3 +,CD4-,and CD8-T cells,are T-cell subpopulations with unique immunomodulatory functions,and their expression of Fas/FasL,TNF/TNFR,and MHCI,etc.They have an important role in anti-tumor,immune regulation,immunosuppression,etc.

Practice and prospect of the green channel management for stroke patients in a hospital / 中华医院管理杂志

The hospital took the lead in the area to carry out stroke process improvement, including the accountability practice of the president, micro-videos for illness condition description, standardized language communication, CT-room thrombolysis, and interdisciplinary seamless corporation among others. The timespan from admission to thrombolysis ( door to needle time, DNT) has shortened significantly, scoring the median time of 25 minutes and the shortest of 8 minutes. The hospital is also the first in the area to initiate the program to bypass the emergency department and the thrombolytic treatment on the ambulance. Such bypass program keeps the DNT of emergency patients within 15 minutes.

Role of TRAIL pathway and NKG2D pathway in double negative T cell cell anti-tumor / 国际外科学杂志

Double negative T cell is a rare type of cells that regulates immune responses in a way that is unique.In the process of adoptive immunotherapy,it gradually becomes a hot spot,because of its obvious anti-tumor effect.However,the mechanism by which DNT cell kills tumor cell is not clear.Tumor necrosis factor-related apoptosis-inducing ligand(TRAIL) and natural-killer group 2,member D (NKG2D) pathway is a more important part of its killing mechanism,and NKG2D receptor can also regulate the production of soluble TRAIL,making the two channels to establish a certain link.In this paper,the effect of Double negative T cell and the mechanism of TRAIL and NKG2D pathway in DNT cell's anticancer were described.

A Case Report on Percutaneous Coronary Intervention in Chronic Total Occlusion by Retrograde Visualization.

As bilateral approach is paramount in chronic total occlusions with retrograde flow, the use of two radial arteries,two femoral arteries or combination technique using one radial and one femoral artery will probably be increasingly reported in the near future. After puncture of opposite groin, a diagnostic 6 Fr catheter is used to intubate the ostium of the contralateral artery. By visualizing the distal vessel in multiple projections, contralateral injections help to direct the progression of the wire in the occluded segment towards the distal true lumen. and confirm the intraluminal position of the wire after the occluded segment. We are reporting a case with chronic total occlusion where we used bilateral femoral access and simultaneous contrast injection to visualize retrograde flow in LAD while opening CTO through ante-grade pathway.

Analysis of correlation between NKG2D receptor pathway and the mechanism of DNT cell' killing effect / 国际外科学杂志

NKG2D is an activating receptor expressed on various immune cells' surfaces.Currently,eight ligands have been found,they can be divided into two kinds:MHC Ⅰ related protein and ULBP molecules.NKG2D receptors and their respective ligands differentially exist in normal and cancerous tissues.So far,many researchers have found that a lot of immune cells' anti-tumor mechanism is mediated by NKG2D receptor and it can't be replaced in the resistance to the development of carcinoma.adoptive immunotherapy is a new method of treating cancer that propose to find tumor-specific cytotoxicity immune cells and enlarge the amount of it,then injected into human body to resist tumor.Recently,many researchers have found that DNT cells (CD4-CD8-T 细胞)have the function of anti-tumor;sadly its mechanisms are unclear.After the summary of NKG2D receptor-mediated pathway of destruction,this paper try to analyze its relevance to DNT cells' killing effect,on the purpose of finding the Killing mechanism of DNT cells that may existed.

Advances in double negative T cells in tumor immunotherapy / 国际外科学杂志

Double negative T cells,namely DNT cells,are specific regulatory cells with TCR+ CD3 + CD4-CD8-in cell phenotype,divide into αβ T cell and γδ T cell,play a very important role in regulating immunoreaction.Previous research restricted to the treatment of autoimmune disease and organ transplantation immunity.Recently dnt cells adoptive immunotherapy,as a new anti-tumor method,gradually come into public view.This review mainly focuses on the source of DNT cells,their anti-tumor effect,as well as the possible mechanism.

Tumor neuroepitelial disembrioplásico: presentación de caso y revisión de la literatura / Dysembryoplastic Neuroepithelial Tumor (DNT): Case Presentation and Literature Review

El tumor neuroepitelial disembrioplásico (DNT) fue descrito por primera vezpor Daumas-Duport, en 1988, e incorporado a la clasificación de tumores de laOrganización Mundial de la Salud, desde 1993, como parte del grupo de tumoresneurogliales. El artículo describe un caso típico, dada su presentación clínica, hallazgosimaginólógicos e histológicos, con adecuada evolución postoperatoria. Se haceuna revisión de la literatura del DNT, describiendo su epidemiología, presentaciónclínica, hallazgos imaginólógicos e histológicos, posibilidades de tratamiento actualy pronóstico...

Dysembryoplastic neuroepithelial tumors (DNT)were first described by Daumas-Duport in 1988and incorporated into the new World Health Organizationclassification of brain tumours as partof the group of glioneuronal tumours in 1993. Wedescribe a typical case due to its clinical presentation,image and hystologic findings, with goodpostoperative course. A review of the literatureof DNT is made, describing its epidemiology,clinical presentation, image and histological findings,current treatment options and prognosis...

MRI Features of Dysembryoplastic Neuroepithelial Tumor / 实用放射学杂志

Objective To investigate MRI features of dysembryoplastic neuroepithelial tumor(DNT).Methods The MR images of ten cases with surgically and pathologically proved DNT were retrospectively reviewed.Results MR imaging showed cystic component with mural nodule in 6,mainly cystic component with septa in 3.The solid components of the tumors were long T_1 and long T_2 signal intensity,the cystic components were even longer T_1 and T_2 signal intensity which resembled the signal of cerebrospinal fluid.Mild enhancement could be found at the intra-tumoral solid nodule or septations after injection of constrast medium but the cystic component did not show any enhancement.No peri-tumoral edema and mass effect were found in most cases.Conclusion DNTs are of some special features on the MR images,the diagnosis can be exactly done before operation if MRI features in combination with clinical data of the patients.

DNT cells isolated and identified in the peripheral blood and its content detection / 国际外科学杂志

Objective The immune magnetic separation(MACS)method of DNT cells was set up and their content Was detected in peripheral blood of healthy man.Methods DNT cells were separated from the peripheral blood.Trypan blue staining and flow cytometry were used to detect their activity and purity,and flow cytometry Was used to detect their content in normal human peripheral blood.Results DNT cell activi ty using MACS sorting was＞97%,the purity Was 82.77%;DNT cells accounted for(6.25±2.61)% (n=45)in the TCRαβ+T cells.Conclusion MACS Can quickly sort out high purity DNT cells,and do not affect the vitality of cells.DNT cells accounted for(6.25±2.61)%in the TCRCD3+T cells.

Effect of DNT cells on tumor cells / 国际外科学杂志

DNT cells(CD4-CD8-double-negative T cells)ale newly discovered immune cells,whose surface ex press neither CD4 nor CD8 molecules.In recent years,the prognosis and survival quality of tumour patient have been greatly improved through cell immunotherapy.Immunocyte can kill the tumour directly Or through immunoregu lation.The study of DNT cells(double-nnegative T cell)on cancer cells will be of vital significance.

Role of CD4 CD8 double-negetive T cells in tumor / 国际外科学杂志

In recent years,the prognosis and survival quality of tumour patient would be improved greatly through cell immunotherapy,which becomes the priority scientific research.Immunoeytes can kill the tumour cell directly or through immunoregulation.CD4CD8 double-negative T cells is a newly found subset of T cells whose SUlface express neither CD4 nor CD8.This article mainly introduces the advancement of one subet of DNT cell,DN Tregs,in tumor.

A Primary Study of the Subgroups of T Lymphocytes in MHV-3 Induced Chronic Viral Hepatitis / 中国病毒学

To study the contribution of T cell subsets in the pathogenesis of Murine hepatitis virus Type3 (MHV-3) induced chronic viral hepatitis in C3H/Hej mice, ninety C3H/Hej mice were chosen to individually receive 10 plaque forming units (PFU) of MHV-3 intraperitoneally. The changes of virus titer and pathology in liver tissue were examined by standard plaque assay and by the hematoxylin/eosin (HE) staining method from 2 days post MHV-3 infection. The ratios of T cell subsets including CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4-CD8-, CD3+CD4+CD25+, CD3+CD4+CD25- and CD3+CD4-CD25+ T lymphocyte of total T lymphocytes in blood, spleen and liver were examined at 0, 2, 4, 6,8, 10, 12, 15, 20, 25, 30, 40 days post MHV-3 infection by flow cytosorting. We observed that the virus titer raised and showed persistent virus duplications and inflammatory changes in the livers of C3H/Hej mice from 2 days post MHV-3 infection. The double negative T cell (DN Treg cell) and CD4+CD25+ T cell ratios increased significantly from 2 days post MHV-3 infection in C3H/Hej mice, and CD3+CD4+CD8-, CD3+CD4-CD8+, CD3+CD4+CD25- and CD3+CD4-CD25+ T cell ratios decreased accordingly. In conclusion, the changes of virus titer and pathology in the livers of C3H/Hej mice post MHV-3 suggest their contribution to viral persistence. Further characterizations of DN Treg cells are that infection indicates that MHV-3 could induce the chronic inflammation in livers of C3H/Hej mice.The increase of the DN Treg cell and CD4+CD25+ T cell ratios in C3H/Hej mice post MHV-3 infection suggests that DN Treg cells and CD4+CD25+ T cells may both have important suppressive immunomodulation functions in the development of chronic viral hepatitis and have important roles in the virus persistent infection. Further characterizations of DNT cell and CD4+CD25+ T cell are under investigation.

A Case of Recurrent Dysembryoplastic Neuroepithelial Tumor in the Temporal Lobe / 대한간질학회지

A boy since 6 years of his age who have had complex partial seizure was referred to our Department in March 1998. The left anterior temporal lobectomy with the resection of the head and body of hippocampus and gross total tumor removal was also performed in April 1998. He has been seizure free and stable about 3 years postoperatively. In January 2001, he revisited us due to headache, nausea, and vomiting from one week before. MRI revealed recurrence of the tumor, and a partial removal of the tumor was performed. Nine months from the second operation, the tumor recurred again and the thrid operation was followed. The pathologic findings were dysembryoplastic neuroepithelial tumor (DNT) in all three cases and no evidences of anaplastic changes were found in two recurrent cases. In general, DNT is known to be a disease that rarely transforms into the malignant, postoperative adjuvant radio-or chemotherapy is unnecessary even after partial resection of the tumor. However, in our case, there were two episodes of recurrence after the total resection. Here, we report the first case of recurrent DNT even after the total resection within three years in our knowledge.

Coexistence of Neoplasia and Cortical Dysplasia Associated with Intractable Epilepsy: A Clinical Study of Seven Surgical Patients and Surgical Strategies

A tumor and cortical dysplasia may be the concomitant cause of the causes of intractable epilepsy, but a few studies have examined so far. From among 249 patients who underwent surgery for intractable epilepsy at Dongsan Epilepsy Center, those in whom neoplasia and cortical dysplasia coexisted were selected for this study, and were reviewed the clinical, electrophysiological, neuroimaging and pathological findings. In 17 of 25 lesionrelated epilepsy patients, tumors including dysembryoplastic neuroepithelial tumor(DNT)(n=6), ganglioglioma(n=5), gangliocytoma(n=1), low grade astrocytoma(n=2), oligodendroglioma(n=2), hypothalamic hamartoma(n=1) were verified. Of these 17 cases involving tumors, concomitant cortical dysplasia was observed in 7(DNT; 6, ganglioglioma; 1). All these patients underwent sophisticated presurgical evaluation and intraoperative acute recording(EcoG) for the identification of adjacent or remote epileptogenic areas as well as functional brain mapping by electrical stimulation or SSEP to verify the eloquent areas. In intractable epilepsy, the coexistence of cortical dysplasia and neoplasia is not common, though careful intraoperative evaluation of the tumor and surrounding tissue using electrocorticogram (EcoG) may lead to its pathological identification and excellent surgical results for these rare lesions.