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1.
BMC Cancer ; 22(1): 250, 2022 Mar 07.
Article in English | MEDLINE | ID: mdl-35255858

ABSTRACT

BACKGROUND: This study aims to investigate thrombospondin 2 (TSP2) expression levels in gastric cancer (GC) and determine the relationship between TSP2 and clinical characteristics and prognosis. METHODS: The online database Gene Expression Profile Interactive Analysis (GEPIA) was used to analyse TSP2 mRNA expression levels in GC. The Kaplan-Meier plotter prognostic analysis tool was used to evaluate the influence of TSP2 expression on clinical prognosis in GC patients. TSP2 expression levels were analysed in paraffin-embedded GC samples and adjacent normal tissues by immunohistochemistry. The relationship between the clinicopathological characteristics and prognosis of GC patients was assessed. Transwell experiments were used to evaluate the effect of TSP2 on HGC27 and AGS cell invasion and migration. The EdU experiment was used to detect the effect of transfection of TSP2 on cell proliferation, and the flow cytometry experiment was used to detect the effect of TSP2 on cell apoptosis and the cell growth cycle. Western blotting (Wb) technology was used to detect MMP, E-cadherin, N-cadherin, Vimentin, Snail, AKT, PI3K, and VEGF protein expression in HGC27 cells. RESULTS: Compared with normal tissues, TSP2 mRNA expression in GC was significantly upregulated and was closely related to the clinical stage of GC. High TSP2 expression significantly affected the OS, FP and PPS of patients with GC. Among these patients, TSP2 expression levels did not affect the prognosis of patients with GC in the N0 subgroup but significantly affected the prognosis of patients with GC in the N (1 + 2 + 3) subgroup. TSP2 protein expression levels were significantly higher in GC tissue compared with normal tissues (P < 0.01). The overall survival (OS) and relapse-free survival (RFS) of patients with high TSP2 expression were lower than those of patients with low TSP2 expression. Cells transfected with the TSP2-silencing sequence exhibited increased apoptosis and inhibition of proliferation, migration and invasion. AKT and PI3K expression in cells was significantly downregulated (P < 0.01). AKT, PI3K and VEGF expression in cells transfected with the TSP2 silencing sequence was significantly reduced. Proliferation, migration, invasion ability, and TSP2 expression levels significantly correlated with mismatch repair genes, such as PMS2, MSH6, MSH2, and MLH1 (P < 0.05). CONCLUSION: TSP2 expression is significantly increased in GC. TSP2 expression is closely related to metastasis and the mismatch repair process in GC patients and affects GC patient prognosis. The mechanism may involve regulating gastric cancer cell proliferation and migration by modulating the VEGF/PI3K/AKT signalling pathway. TSP2 is a potential marker and therapeutic target for the prognosis of GC patients.


Subject(s)
DNA Mismatch Repair/genetics , Stomach Neoplasms/genetics , Thrombospondins/metabolism , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic/genetics , Humans , Immunohistochemistry , Neoplasm Metastasis/genetics , Prognosis , Signal Transduction/genetics , Survival Rate
2.
Dis Markers ; 2021: 8686307, 2021.
Article in English | MEDLINE | ID: mdl-34745388

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third most common tumor worldwide. Aberrant N6-methyladenosine (m6A) modification can influence the progress of the CRC. Additionally, long noncoding RNA (lncRNA) plays a critical role in CRC and has a close relationship with m6A modification. However, the prognostic potential of m6A-related lncRNAs in CRC patients still remains to be clarified. METHODS: We use "limma" R package, "glmnet" R package, and "survival" R package to screen m6A-related-lncRNAs with prognostic potential. Then, we comprehensively analysed and integrated the related lncRNAs in different TNM stages from TCGA database using the LASSO Cox regression. Meanwhile, the relationship between functional enrichment of m6A-related lncRNAs and immune microenvironment in CRC was also investigated using the TCGA database. A prognostic model was constructed and validated to determine the association between m6A-related lncRNAs in different TNM stages and the prognosis of CRC. RESULT: We demonstrated that three related m6A lncRNAs in different TNM stages were associated with the prognosis of CRC patients. Patients from the TCGA database were classified into the low-risk and the high-risk groups based on the expression of these lncRNAs. The patients in the low-risk group had longer overall survival than the patients in the high-risk group (P < 0.001). We further constructed and validated a prognostic nomogram based on these genes with a C-index of 0.80. The receiver operating characteristic curves confirmed the predictive capacity of the model. Meanwhile, we also found that the low-risk group has the correlation with the dendritic cell (DC). Finally, we discovered the relationship between the m6A regulators and the three lncRNAs. CONCLUSION: The prognostic model based on three m6A-related lncRNAs exhibits superior predictive performance, providing a novel prognostic model for the clinical evaluation of CRC patients.


Subject(s)
Adenosine/analogs & derivatives , Biomarkers, Tumor/genetics , Colorectal Neoplasms/genetics , RNA, Long Noncoding/genetics , Tumor Microenvironment/immunology , Adenosine/metabolism , Biomarkers, Tumor/metabolism , Cell Movement , Colorectal Neoplasms/immunology , Colorectal Neoplasms/pathology , Dendritic Cells/immunology , Dendritic Cells/physiology , Humans , Lymphocytes, Tumor-Infiltrating/immunology , Prognosis , RNA Processing, Post-Transcriptional , RNA, Long Noncoding/metabolism
3.
Front Pharmacol ; 12: 687399, 2021.
Article in English | MEDLINE | ID: mdl-34163367

ABSTRACT

Immunotherapy of malignant tumor is a verified and crucial anti-tumor strategy to help patients with cancer for prolonging prognostic survival. It is a novel anticancer tactics that activates the immune system to discern and damage cancer cells, thereby prevent them from proliferating. However, immunotherapy still faces many challenges in view of clinical efficacy and safety issues. Various nanomaterials, especially gold nanoparticles (AuNPs), have been developed not only for anticancer treatment but also for delivering antitumor drugs or combining other treatment strategies. Recently, some studies have focused on AuNPs for enhancing cancer immunotherapy. In this review, we summarized how AuNPs applicated as immune agents, drug carriers or combinations with other immunotherapies for anticancer treatment. AuNPs can not only act as immune regulators but also deliver immune drugs for cancer. Therefore, AuNPs are candidates for enhancing the efficiency and safety of cancer immunotherapy.

4.
Int J Biol Sci ; 17(7): 1757-1768, 2021.
Article in English | MEDLINE | ID: mdl-33994860

ABSTRACT

Background: Long noncoding RNA KCNQ1 opposite strand/antisense transcript 1 (lncRNA KCNQ1OT1) is abnormally expressed in various solid tumors. The purpose of this study was to explore the prognostic value and potential functional role of lncRNA KCNQ1OT1 across cancers. Methods: We performed a meta-analysis of published literature to evaluate the prognostic value of lncRNA KCNQ1OT1 across cancers. Verification, functional analysis, and genomic variation analysis were performed using the GEPIA, TIMER, and LnCeVar databases. According to the immune cell infiltration level, we established a prognostic model of lncRNA KCNQ1OT1 expression using public datasets of TIMER. We used quantitative real-time polymerase chain reaction (RT-qPCR) and western blot to detect the expression levels of lncRNA KCNQ1OT1 and the CD155 protein in colorectal cancer (CRC) tissues and cell lines. Then, a lncRNA KCNQ1OT1-knockdown cell line was cocultured to explore the role of lncRNA KCNQ1OT1 and CD155 in the T cell response by flow cytometric analysis. Results: Our results showed that the high expression of lncRNA KCNQ1OT1 was significantly related to poor overall survival across cancers, especially CRC. Interestingly, we found that COAD patients with high lncRNA KCNQ1OT1 expression and high CD8+ T cell infiltration levels had a worse prognosis than those with low lncRNA KCNQ1OT1 expression and high CD8+ T cell infiltration levels. Moreover, lncRNA KCNQ1OT1 and CD155 showed significantly higher expression in CRC tissue than in normal tissue, and lncRNA KCNQ1OT1 expression was positively correlated with CD155 expression in CRC. Finally, knockdown of lncRNA KCNQ1OT1 reduced CD155 expression in HCT116 and SW620 cells and enhanced the immune response in coculture with CD8+ T cells. Conclusions: High lncRNA KCNQ1OT1 expression is significantly correlated with poor prognosis of CRC patients and mediates the CD8+ T cell response in CRC. These findings indicate that lncRNA KCNQ1OT1 is a prognostic biomarker and potential immune therapeutic target for enhancing the CD8+ T cell response in CRC.


Subject(s)
CD8-Positive T-Lymphocytes/pathology , Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , Apoptosis , CD8-Positive T-Lymphocytes/metabolism , Cell Movement , Cell Proliferation , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Humans , Potassium Channels, Voltage-Gated/biosynthesis , Potassium Channels, Voltage-Gated/genetics , Tumor Cells, Cultured
5.
Int J Med Sci ; 18(11): 2327-2338, 2021.
Article in English | MEDLINE | ID: mdl-33967609

ABSTRACT

Background: An increasing number of studies had shown that tertiary lymphoid structure (TLS) plays an important role in tumor progression. However, the prognostic role of TLS in various tumors remains controversial. This meta-analysis aims to investigate the clinicopathological and prognostic values of TLS in solid tumors. Methods: A systematic search was conducted in PubMed, EMBASE and Cochrane Library undated to November 2, 2020. Odds ratios of clinical parameters, hazard ratio (HR) of overall survival (OS), relapse-free survival (RFS), disease-free survival (DFS) and relapse rate were calculated in order to evaluate the relationship between TLS expression and clinicopathological or prognostic values in different tumors. Result: 27 eligible studies including 6647 patients with different types of tumors were analyzed. High TLS expression was associated with a longer OS (HR = 0.66, 95% CI: 0.50 - 0.86, P = 0.002) and RFS (HR = 0.61, 95% CI: 0.47 - 0.79, P = 0.0001). Moreover, high TLS levels in tumor were associated with a low risk of recurrence (HR = 0.43, 95% CI: 0.32 - 0.57, P < 0.0001). However, there was no relationship between TLS expression and DFS. Meanwhile, high TLS expression was associated with smaller tumor size (P < 0.00001) and higher tumor infiltrating lymphocytes (TILs). Furthermore, the subgroup analysis showed high TLS expression that may be associated with a lower clinical grading and N stage in breast cancer and colorectal cancer. Conclusion: High TLS expression is associated with the longer OS and RFS in solid tumors, and a lower risk of cancer relapse. Meanwhile, high TLS expression is also associated with a smaller tumor size, higher infiltration of TILs, lower clinical grading and N stage in the tumor. Therefore, high TLS expression in the tumor is a favorable prognostic biomarker for solid tumor patients.


Subject(s)
Neoplasm Recurrence, Local/epidemiology , Neoplasms/mortality , Tertiary Lymphoid Structures/immunology , Disease-Free Survival , Humans , Neoplasm Grading , Neoplasm Recurrence, Local/immunology , Neoplasms/diagnosis , Neoplasms/immunology , Neoplasms/therapy , Prognosis , Tertiary Lymphoid Structures/pathology , Tumor Burden
6.
Transl Cancer Res ; 10(2): 681-693, 2021 Feb.
Article in English | MEDLINE | ID: mdl-35116401

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer globally. In the treatment of CRC, surgical resection is commonly adopted, and neoadjuvant chemotherapy or immunotherapy is mainly administered for patients with advanced disease. However, despite the developments in the field of cancer treatment, the mortality rate of CRC has remained high. Therefore, novel treatments for CRC need to be explored. Astragalus membranaceus, commonly known in China as Huangqi (HQ), a traditional Chinese medicine, has been reported to be a potential antitumorigenic agent. This study aimed to investigate the mechanisms of action of HQ. METHODS: Active ingredients and putative targets of HQ were obtained through a comprehensive search of the Traditional Chinese Medicine Systems Pharmacology database. CRC-related targets were retrieved from the GeneCards database and then overlapping targets were acquired. After visualization of the compound-disease network and protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the overlapping genes were performed. Additionally, HCT116 cells were treated with the active components of HQ at a 20-µM concentration. Cell Counting Kit-8 was used to detect cell activity, and real-time quantitative polymerase chain reaction was carried out to detect the expression of genes downstream of the interleukin (IL)-17 signaling pathway. RESULTS: A PPI network comprising 177 nodes and 318 edges was obtained. The GO analysis of the overlapping genes showed enrichment in response to lipopolysaccharide and oxidative process. For the KEGG analysis, the AGE-RAGE signaling pathway and inflammation-related pathways, such as the IL-17 and tumor necrosis factor (TNF) signaling pathways, were enriched. The in vitro experiments showed that HQ promoted the apoptosis of CRC cells by inhibiting the expression of the CCL2, CXCL8, CXCL10, and PTGS2 genes. CONCLUSIONS: This study systematically revealed the multitarget mechanism of HQ in CRC through a network pharmacology approach. We verified that HQ promotes CRC cell death via the IL-17 signaling pathway. This finding provides indications for further mechanistic studies and the development of HQ as a potential treatment for CRC patients.

7.
J Immunol Res ; 2016: 2697860, 2016.
Article in English | MEDLINE | ID: mdl-28058265

ABSTRACT

It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR) that has received widespread attention, the early acute T-cell-mediated rejection (TCMR) may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%), which was similar to that in the first transplant patients (4.4%). However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P < 0.001). Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.


Subject(s)
Antibodies/immunology , Graft Rejection/immunology , Kidney Transplantation/methods , Reoperation/statistics & numerical data , T-Lymphocytes/immunology , Adult , Female , Graft Survival , Humans , Immunization , Kidney/surgery , Kidney Failure, Chronic/surgery , Male , Middle Aged , Retrospective Studies
8.
Clin Transpl ; : 231-4, 2014.
Article in English | MEDLINE | ID: mdl-26281150

ABSTRACT

Kidney tubular damage caused by ischemia-reperfusion injury is considered the major cause of delayed graft function (DGF) after renal transplantation. It is not clear whether early generated de novo donor specific antibodies (DSA) play a role in DGF. Here, we report 2 cases of renal transplant with DGF, which seems to be associated with de novo DSA. When the early produced de novo DSA are not potent enough to mediate acute rejection, they may cause mild intra-graft injury, which has a significant impact on the degree of DGF and its recovery. Antibody-targeted therapy seems to be beneficial to the recovery of patients with DGF.


Subject(s)
Delayed Graft Function/immunology , HLA Antigens/immunology , Histocompatibility , Isoantibodies/blood , Kidney Transplantation/adverse effects , Adult , Biomarkers/blood , Delayed Graft Function/blood , Delayed Graft Function/diagnosis , Delayed Graft Function/physiopathology , Delayed Graft Function/therapy , Desensitization, Immunologic/methods , Drug Therapy, Combination , Female , Humans , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/methods , Living Donors , Middle Aged , Recovery of Function , Renal Dialysis , Time Factors , Treatment Outcome
9.
Zhonghua Yi Xue Za Zhi ; 94(42): 3284-8, 2014 Nov 18.
Article in Chinese | MEDLINE | ID: mdl-25622624

ABSTRACT

OBJECTIVE: To explore the generation pattern and clinical relevance of de novo HLA-DQ antibodies in renal transplantation. METHODS: A total of 175 primary renal transplant recipients without pre-transplant HLA antibodies were recruited from January 2012 to December 2013. The average follow-up period was 10 (6-18) years. They were divided into control group (n = 94) with normal renal graft function (serum creatinine <120 µmol/L); dysfunction group (n = 54) with continued serum creatinine >150 µmol/L over 6 months; and graft loss group (n = 27) with resumed hemodialysis. The sera were collected and screened for de novo HLA antibodies by flow PRA or Luminex mixed beads. And HLA-A, -B, -DR and -DQ specific antibodies were identified by HLA single antigen beads. RESULTS: Positive de novo HLA antibodies were detected in 48% (26/54) of patients from dysfunction group and in 52% (14/27) from graft loss group, but only in 17% (16/94) from control group (P < 0.01). The frequency of de novo DQ antibodies among patients with any positive HLA antibody was the highest in all three groups (14/16, 24/26 and 14/14). Additionally, the average mean peak fluorescence intensity of DQ antibodies was almost the highest when compared to other antibodies. Moreover, when those with positive HLA antibodies in each group were analyzed, 10/16 in control group were detected to have DQ antibodies alone. However, 17/26 of patients in dysfunction group and 14/14 in graft loss group were detected to have DQ antibodies plus HLA-DR and/or -A, -B antibodies. It indicated that the combined presence of DQ-and non-DQ- antibodies was associated with chronic renal graft failure. CONCLUSIONS: The presence of de novo HLA-DQ antibodies is frequent after renal transplantation. And it is associated with chronic graft failure when co-displaying with other HLA antibodies. The screening and detection of HLA-DQ antibodies after kidney transplantation may aid early warning of donor antigen-specific activation of immune system and subsequent graft dysfunction. Thus it serves as an indication for early treatment.


Subject(s)
Kidney Transplantation , Antibodies , HLA-DQ Antigens , HLA-DR Antigens , Humans , Kidney Diseases , Renal Dialysis , Tissue Donors
10.
Front Med ; 5(1): 80-5, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21681679

ABSTRACT

Highly sensitized patients experience an increased number of rejection episodes and have poorer graft survival rates; hence, sensitization is a significant barrier to both access to and the success of organ transplantation. This study reports our experience in kidney transplantation in highly sensitized patients. Fourteen patients with sensitization or high levels of panelreactive antibodies (PRA) were studied. All patients were desensitized with pre-transplant intravenous immunoglobulin (IVIG)/plasmapheresis (PP) with or without rituximab and thymoglobulin induction therapy, combined with a Prograf/MMF/Pred immunosuppressive regimen. Of 14 patients, 10 showed good graft functions without acute rejection (AR) episodes. Acute cellular rejection in two patients was reversed by methylprednisolone. Two patients underwent antibody-mediated rejection; one was treated with PP/IVIG successfully, whereas the other lost graft functions due to the de novo production of donor-specific antibodies (DSA). Graft functions were stable, and there were no AR episodes in other patients. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful live-donor kidney transplantation in sensitized recipients.


Subject(s)
Desensitization, Immunologic/methods , Graft Rejection/immunology , Graft Survival/immunology , Kidney Transplantation/immunology , Adult , Anti-Inflammatory Agents/administration & dosage , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Female , Graft Rejection/drug therapy , Graft Rejection/therapy , Graft Survival/drug effects , Humans , Immunoglobulins, Intravenous/administration & dosage , Immunologic Factors/administration & dosage , Immunosuppressive Agents/administration & dosage , Kidney Transplantation/methods , Male , Methylprednisolone/administration & dosage , Mycophenolic Acid/administration & dosage , Mycophenolic Acid/analogs & derivatives , Plasmapheresis , Retrospective Studies , Rituximab , Tacrolimus/administration & dosage
11.
Zhonghua Yi Xue Za Zhi ; 91(8): 520-3, 2011 Mar 01.
Article in Chinese | MEDLINE | ID: mdl-21418851

ABSTRACT

OBJECTIVE: To summarize the histopathological features of posttransplant complications for renal allografts and evaluate the biopsy values. METHODS: Between January 1997 and May 2010, a total of 1712 percutaneous renal allograft biopsies were performed in 1500 kidney transplants and diagnostic procedures for staining, classification and staging had been performed according to the Banff 1997 and 2005 Schema. RESULTS: There were 213 (14.2%) cases of acute T cell-mediated rejection post transplantation in 1500 kidney transplants. Meanwhile there were 36 (2.4%) cases of acute antibody-mediated rejection. Chronic T cell-mediated rejection and chronic antibody-mediated rejection were 251 (16.7%) cases and 45 (3.0%) cases, respectively. Acute CNI-nephrotoxicity and chronic CNI-nephrotoxicity were 106 (7.1%)cases and 251 (16.7%) cases, respectively. Relapsed or new nephropathy were 6 (0.4%) cases. Chronic CNI-nephrotoxicity is the most common cause of allograft dysfunction in the long survival recipients. CONCLUSION: Percutaneous renal allograft biopsy is valuable for the diagnosis of various posttransplantation complications.


Subject(s)
Kidney Transplantation/pathology , Kidney/pathology , Adolescent , Adult , Aged , Biopsy, Needle , Female , Graft Rejection/pathology , Humans , Middle Aged , Transplants , Young Adult
12.
Clin Transpl ; : 359-60, 2009.
Article in English | MEDLINE | ID: mdl-20524298

ABSTRACT

This is a case of one patient who was treated with a bortezomib-based desensitization regimen to treat sensitization obtained though a previous transplant lost to chronic rejection. This regimen successfully convert a positive crossmatch to negative, prevented both hyperacute and acute rejections out to 3-months post transplant, and was without any noticeable side effects. This account demonstrates that desensitization by bortezomib combined with plasmapheresis and low-dose IVIG is a possible way to transplant a highly sensitized patient.


Subject(s)
Boronic Acids/therapeutic use , Desensitization, Immunologic/methods , Kidney Neoplasms/immunology , Protease Inhibitors/therapeutic use , Pyrazines/therapeutic use , Adult , Bortezomib , Creatinine/blood , Graft Survival , Humans , Isoantibodies/blood , Living Donors , Lymphocytes/immunology , Male , Treatment Outcome
13.
Zhonghua Wai Ke Za Zhi ; 45(5): 326-30, 2007 Mar 01.
Article in Chinese | MEDLINE | ID: mdl-17535712

ABSTRACT

OBJECTIVE: To report the modified technique and the short-term results of simultaneous pancreas-kidney transplantation (SPK) with the enteric drainage (ED) of exocrine secretions. METHODS: From June 2000 to August 2006, thirty-eight patients with diabetes complicated with uremia underwent SPK. The pancreas graft was placed intraperitoneally with exocrine secretions drained into the proximal jejunum without Roux-en-Y procedure. The mean cold ischemic times of pancreas and kidney were (10 +/- 2.0) h and (7 +/- 2.0) h, respectively. Quadruple immunosuppressive therapy with antilymphocyte globulin or anti-CD25 monoclonal antibody, tacrolimus, mycophenolate mofetil and steroids was adopted except one patient. RESULTS: The 6-month survival rates of patients and grafts were both 97.4% after transplantation. All patients achieved insulin-free euglycemia at (7 +/- 6.9) d postoperative except one. For preoperative patients, mean fasting insulin and C-peptide values were (9 +/- 8.1) mU/L and (6 +/- 4.5) mU/L. After operation, fasting insulin and C-peptide values of patients were (12 +/- 5.8) mU/L and (6 +/- 4.7) mU/L, respectively, which peaked to an insulin level of (57 +/- 43.0) mU/L and a C-peptide level of (11 +/- 6.8) mU/L with stimulation. There were eight cases of delayed renal graft function. All other patients achieved immediate renal graft function. No graft losses occurred due to leakage or intra-abdominal infection. The most common surgical complications were wound infection (n = 12), enteric anastomostic hemorrhage (n = 5) and perirenal hemorrhage (n = 2). Three patients (7.9%) had been reoperated for the reasons of intra-abdominal hemorrhage and perirenal hemorrhage. CONCLUSIONS: SPK is an effective treatment option for selected patients with diabetes mellitus and approaching end-stage renal disease. Enteric exocrine drainage by direct side-to-side anastomosis (without Roux-en-Y) seems to be a simple and reliable technique.


Subject(s)
Drainage/methods , Jejunum/surgery , Kidney Transplantation/methods , Pancreas Transplantation/methods , Diabetes Mellitus/surgery , Female , Follow-Up Studies , Graft Rejection/prevention & control , Graft Survival , Humans , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Postoperative Complications/prevention & control , Treatment Outcome , Uremia/surgery
14.
Zhonghua Wai Ke Za Zhi ; 45(4): 254-7, 2007 Feb 15.
Article in Chinese | MEDLINE | ID: mdl-17502023

ABSTRACT

OBJECTIVE: To investigate the protective effects on allografts and the possible mechanism of adeno-associated heme-oxygenase-1 (AdHO-1) gene therapy against chronic rejection injury. METHODS: Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed. RESULTS: AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4(+) T cells. CONCLUSIONS: AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.


Subject(s)
Genetic Therapy/methods , Graft Rejection/prevention & control , Heme Oxygenase-1/genetics , Adenoviridae/genetics , Animals , Blood Vessels/transplantation , CD4 Lymphocyte Count , Chronic Disease , Genetic Vectors , Graft Rejection/etiology , Graft Survival , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Macrophages/pathology , Male , Rats , Rats, Inbred Lew , Transfection , Transplantation, Homologous
15.
Zhonghua Nan Ke Xue ; 12(5): 405-7, 2006 May.
Article in Chinese | MEDLINE | ID: mdl-16755867

ABSTRACT

OBJECTIVE: To study the effects of different immunodepressants on the sperm parameters of kidney transplant recipients. METHODS: In 15 healthy fertile men and 37 kidney transplant recipients, ejaculates were aseptically obtained by masturbation. Thirty-seven patients were divided into two groups, 20 patients were treated with Prograf (FK506) combination with mycophenolate mofetil (MMF) and prednisone; 17 patients were treated with cyclosporine (CsA) combination with azathioprine with prednisone. The sperm viability, mobility parameters such as prorsad percentage motility, straight line velocity (VSL), curve line velocity (VCL), velocity of average path (VAP) and morph were estimated with a computer-assisted sperm analyzer (CASA) provided with a multiple-exposure photography system. RESULTS: There were no significant difference in sperm viability rate [(81.7 +/- 5.7)%, (79.4 +/- 6.8)% and (83.8 +/- 6.0)%], VCL [(24.1 +/- 8.6)%, (23.9 +/- 4.4)%, (24.8 +/- 4.2)% ] and VAP [(19.7 +/- 6.6)%, (18.6 +/- 2.9)%, (21.0 +/- 4.0)%] among groups of FK506, CsA and control, respectively (P > 0.05). The rate of anomaly [(67.8 +/- 5.7)%], the prorsad percentage motility [(46.4 +/- 8.1)%] and VSL [(15.4 +/- 4.6)%] in the group of FK506 were respectively significantly lower and higher than those in the group of CsA [(80.1 +/- 5.6%, (33.3 +/- 6.4)%, (10.2 +/- 2.4)%] (P < 0.05). CONCLUSION: The application of FK506 combined with MMF could help recover the mobility and morphology of the sperm in kidney transplantation recipients.


Subject(s)
Cyclosporine/pharmacology , Immunosuppressive Agents/pharmacology , Kidney Transplantation , Sperm Motility/drug effects , Tacrolimus/pharmacology , Adolescent , Adult , Case-Control Studies , Drug Therapy, Combination , Humans , Male , Mycophenolic Acid/analogs & derivatives , Mycophenolic Acid/pharmacology , Prednisone/pharmacology
16.
Chin Med J (Engl) ; 116(4): 573-6, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12875725

ABSTRACT

OBJECTIVES: To simplify the enteric drainage (ED) procedure and to decrease surgical and metabolic complications in simultaneous pancreas-kidney transplantation (SPK) patients. METHODS: Between June 2000 and June 2002, nine patients with insulin-dependent diabetes mellitus (IDDM) and uremia underwent simultaneous pancreas-kidney transplantation. The arterial inflow of the pancreas was based upon the right external iliac artery, while venous drainage was systemic via the external iliac vein. The allografts' exocrine secretions were drained into the proximal jejunum via a two-layer hand sewn, side-to-side donor duodenum to proximal small bowel anastomosis after reperfusion. No Roux-en-Y an astomosis of the jejunum was performed. The kidney graft was placed in the left iliac fossa. Quadruple immunosuppressive therapy with antilymphocyte globulin or anti-CD25 monoclonal antibody (Zenapax), tacrolimus, mycophenolate mofetil and steroids was standard treatment in all patients. RESULTS: This procedure was successfully applied in all 9 patients without complication referable to the technique. All patients had achieved euglycemia and excellent renal function, and stopped being dependent on an external insulin source. Fasting serum glucose fell from 9.5 preoperatively to 4.8 mmol/L and remained stable thereafter. At the time this paper was written, the grafts from eight patients were functioning well. CONCLUSIONS: Our primary experience suggests that SPK with ED without Roux-en-Y anastomosis represents a more physiologic milieu, and a viable alternation to replace the bladder (BD) as the primary route of drainage for exocrine secretions of the pancreas. It is a feasible and safer procedure.


Subject(s)
Drainage/methods , Kidney Transplantation/methods , Pancreas Transplantation/methods , Adult , Amylases/blood , Female , Humans , Insulin/blood , Intestines , Male
17.
Zhonghua Yi Xue Za Zhi ; 82(22): 1514-7, 2002 Nov 25.
Article in Chinese | MEDLINE | ID: mdl-12609056

ABSTRACT

OBJECTIVE: To evaluate simultaneous kidney-pancreatic transplantation (SKPT) with bladder drainage and enteric drainage for its efficacy and safety. METHOD: SKPT was performed in 10 patients from Jan. 2000 to Feb. 2002. All patients had long-standing insulin-dependent diabetes mellitus and subsequent renal failure. Bladder drainage (BD) of exocrine secretion was used in the first 2 cases and enteric drainage (ED) in last 8 patients. In BD, a two-layer hand sewn duodenocystostomy was performed. In ED, a two-layered side-to-side anastomosis was fashioned between the donor duodenal segment and the recipient jejunum. No Roux-en-Y limb was used. Quadruple immunosuppressive therapy with antithymocyte globulin, tacrolimus, mycophenolate mofetil and steroids was standard treatment in all patients. The patients were treated with quadruple therapy, which included antilymphocyte globulin (ALG) or anti-CD25 monoclonal antibody (Zenapax) induction therapy, prednisone, Cyclosporine A/tacrolimus, and mycophenolat-mofetil (MMF). RESULTS: SPK was successfully applied to all cases without complication referable to the technique. All patients have achieved excellent renal function and euglycemia, and no further insulin treatment was needed between 1 and 5 days posttransplant. One patient with ED died due to sepsis and upper gastrointestinal hemorrhage 5 weeks after operation. The death occurred with functioning grafts. Until now no rejection episode and thrombosis were observed and all the grafts from nine patients are functioning well. The first 2 patients with BD underwent slight metabolic complications and microscopic hematuria with entire follow-up time. Two episodes of reflux graft pancreatitis followed by macroscopic hematuria occurred in one patient with BD. CONCLUSION: Compared with SPK with BD, ED without Roux-en-Y anastomosis might be a more physiological and prior procedure for type I diabetes mellitus with uremia.


Subject(s)
Kidney Transplantation , Pancreas Transplantation , Surgical Procedures, Operative/methods , Adult , Anastomosis, Surgical/methods , Cystostomy/methods , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/surgery , Drainage/methods , Duodenum/surgery , Female , Follow-Up Studies , Humans , Jejunum/surgery , Male , Middle Aged , Treatment Outcome , Uremia/complications , Uremia/surgery , Urinary Bladder/surgery
18.
Zhonghua Yi Xue Za Zhi ; 82(21): 1457-60, 2002 Nov 10.
Article in Chinese | MEDLINE | ID: mdl-12509905

ABSTRACT

OBJECTIVE: To study the effects of 3 different operational patterns of piggyback liver transplantation (PBLT) used to reconstruct backflow of hepatic veins. METHODS: Sixty-three operations of PBLT were performed on 59 patients with terminal hepatic diseases after three operational patterns: EEAT [the suprahepatic inferior vena cava (sup-H-IVC) of donor is anstomosed with the plasticized hepatic vein of recipient end-to-end, also called standard PBLT, SPBLT] in 17 cases, ESAT (the sup-H-IVC of donor is anastomosed with the sup-H-IVC of recipient end-to-side) in 12 cases, and SSAT [the retrohepatic IVC (RHIVC) of donor is anastomosed with the RHIVC of recipient side-to-side] in 32 cases, the latter two patterns being called ameliorative PBLT (APBLT) jointly. The effects were analyzed. RESULTS: Complications, such as backflow obstruction of hepatic vein and delayed recovery of liver function, were observed in the EEAT and ESAT groups, but not in the SSAT group. CONCLUSION: The SSAT pattern of PBLT is easy to perform and advantageous to avoid the technical maladies of the other 2 patterns and postoperative complications, and provides assurance of recovery after operation.


Subject(s)
Hepatic Veins/surgery , Liver Transplantation/methods , Adolescent , Adult , Alanine Transaminase/metabolism , Child , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/etiology , Humans , Liver/blood supply , Liver/pathology , Liver/surgery , Liver Diseases/surgery , Male , Middle Aged , Postoperative Complications , Survival Rate , Treatment Outcome , Vascular Surgical Procedures/methods , Vascular Surgical Procedures/mortality
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