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Previously, we have generated EGFRvIII-targeting CAR-T cells and brought hope for treating advanced breast cancer. However, EGFRvIII-targeting CAR-T cells were defined limited anti-tumor efficacy, which might be due to reduced accumulation, persistence of therapeutic T cells in tumor site of breast cancer. CXCLs were highly expressed in tumor environment of breast cancer and CXCR2 is the main receptor for CXCLs. Here, CXCR2 could significantly improve the trafficking and tumor specific accumulation of CAR-T cells both in vivo and in vitro. However, the anti-tumor effect of CXCR2 CAR-T cells were weaken which might be results of the apoptosis of T cells. Cytokines could stimulate Tcell proliferation, such as interleukin (IL)-15 and IL-18. Then, we generated CXCR2 CAR with synthetic IL-15 or IL-18 production. Co-expressing IL-15 or IL-18 could significantly suppress the exhaustion and apoptosis of T cells and enhanced the anti-tumor activity of CXCR2 CAR-T cells in vivo. Further, coexpression IL-15 or IL-18 in CXCR2 CAR-T cells did not cause toxicity. These findings provide a potential therapy strategy of co-expression IL-15 or IL-18 in CXCR2 CAR-T cells for the treatment of advancing breast cancer in the future.
Subject(s)
Breast Neoplasms , Interleukin-18 , Humans , Female , Interleukin-18/genetics , Breast Neoplasms/drug therapy , Interleukin-15/genetics , Interleukin-15/therapeutic use , T-Lymphocytes/pathologyABSTRACT
Objective@#To investigate the clinical efficacy of arthroscopic irrigation combined with surgical debridement in the treatment of shoulder infection after arthroscopic rotator cuff repair.@*Methods@#Data of 4 post-operative infected patients [(male 3 cases, female 1 case; 55 years (51-61 years)] after arthroscopic rotator cuff repair who underwent arthroscopic irrigation combined with surgical debridement from January 2016 to June 2019 were retrospectively analyzed. Less than 1 month after surgery, swelling, pain in the surgical area occurred and all patients had fever, abscess and sinus. Hematology and radiology were conducted immediately after admission. Antibiotic treatment was applied, and adjusted according to the culture results timely. All patients underwent arthroscopic irrigation combined with surgical debridement. Antibiotics continued accordingly after the operation. Blood routine, erythrocyte sedimentation rate, C-reactive protein, X-ray, etc. were rechecked regularly to evaluate the symptomatic relief of the infection and prognosis. Visual analogue scale (VAS) and American Shoulder and Elbow Surgeons (ASES) score were used to evaluate shoulder function during the pre-operative and post-operative follow-up period.@*Results@#The surgery was successfully completed in all 4 patients. One was treated with VSD for vacuum suction and the wound was closed one week later. The results of microbial culture showed that 2 cases were Mycobacterium tuberculosis positive, 1 case Pseudomonas aeruginosa positive, and 1 case was Staphylococcus aureus positive. After treatment, the shoulder sinuses of all patients were healed, without swelling, pain, etc. The follow-up time was 3, 4, 32, and 33 months, respectively. There was no recurrence of infection until the latest follow-up. The joint mobility and scores were better than the situation of preoperative. The VAS score and ASES score of 2 patients with early debridement (< 1 month duration of infected symptoms) were respectively improved significantly from 5 and 40, 6 and 23 before operation to 1 and 80, 1 and 73 respectively at the latest follow up. The VAS score and ASES score of other 2 patients (> 6 months duration of infected symptoms) were respectively improved from 6 and 28, 6 and 32 to 1 and 62, 2 and 65 respectively. All patients were satisfied with the results.@*Conclusion@#Early arthroscopic irrigation combined with surgical debridement is an effective method to treat the post-operative infections after arthroscopic rotator cuff repair.
ABSTRACT
Objective To investigate the clinical efficacy of arthroscopic irrigation combined with surgical debridement in the treatment of shoulder infection after arthroscopic rotator cuff repair.Methods Data of 4 post-operative infected patients [(male 3 cases,female 1 case;55 years (51-61 years)] after arthroscopic rotator cuff repair who underwent arthroscopic irrigation combined with surgical debridement from January 2016 to June 2019 were retrospectively analyzed.Less than 1 month after surgery,swelling,pain in the surgical area occurred and all patients had fever,abscess and sinus.Hematology and radiology were conducted immediately after admission.Antibiotic treatment was applied,and adjusted according to the culture results timely.All patients underwent arthroscopic irrigation combined with surgical debridement.Antibiotics continued accordingly after the operation.Blood routine,erythrocyte sedimentation rate,C-reactive protein,X-ray,etc.were rechecked regularly to evaluate the symptomatic relief of the infection and prognosis.Visual analogue scale (VAS) and American Shoulder and Elbow Surgeons (ASES) score were used to evaluate shoulder function during the pre-operative and post-operative follow-up period.Results The surgery was successfully completed in all 4 patients.One was treated with VSD for vacuum suction and the wound was closed one week later.The results of microbial culture showed that 2 cases were Mycobacterium tuberculosis positive,1 case Pseudomonas aeruginosa positive,and 1 case was Staphylococcus aureus positive.After treatment,the shoulder sinuses of all patients were healed,without swelling,pain,etc.The follow-up time was 3,4,32,and 33 months,respectively.There was no recurrence of infection until the latest follow-up.The joint mobility and scores were better than the situation of preoperative.The VAS score and ASES score of 2 patients with early debridement (＜ 1 month duration of infected symptoms) were respectively improved significantly from 5 and 40,6 and 23 before operation to 1 and 80,1 and 73 respectively at the latest follow up.The VAS score and ASES score of other 2 patients (＞ 6 months duration of infected symptoms) were respectively improved from 6 and 28,6 and 32 to 1 and 62,2 and 65 respectively.All patients were satisfied with the results.Conclusion Early arthroscopic irrigation combined with surgical debridement is an effective method to treat the post-operative infections after arthroscopic rotator cuff repair.
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The association of the polymorphisms of interleukin (IL)-1?, IL-4, IL-6, tumor necrosis factor-? (TNF-?) gene with Hashimoto′s thyroiditis (HT) in Shandong population of China was investigated. The results showed that the frequency of the t allele in the promoter region of IL-4 at position -590 in HT group was significantly lower than that in control group (0.060 vs 0.155, P
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Objective:To observe the efficacy of microcapsules to prolong islet xenografts survival in mice.Methods:Human fetal pancreatic islets were isolated from the embryo which was obtained from legal abortion(gestational age 16～24 weeks) with collagenase and enclosed in semipermeable alginate BaCl 2 capsules.Diabetic BALB/ C mice induced with streptozotocin were divided into 3 groups.Each group had 7 mice.Then transplantation was performed.Results:Transplantation of 1000?100 encapsulated fetal islets into the peritoneal cavities of 7 BALB/ C mice restord normalglycemia for 78.4?21.27 days without immunosuppression.The second group of 7 diabetic mice received an equal number of uncultured pancreatic fragments.These unprotected xenografts were functional for only 7.43?3.42 days,but high mortality occured.There was significant differences between the two groups(P