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With a deepened understanding of the pathophysiology and pathogenesis of thoracic malignancies, the treatment has been transited from traditional treatment on the basis of surgery, radiotherapy, and chemotherapy to individualized and precise targeted therapy and immunotherapy. As an antitumor immunotherapy, chimeric antigen receptor gene-modified T (CAR-T) cells have been approved by the FDA for the treatment of hematological malignancies in five CAR-T products. They have also achieved good therapeutic effects in solid tumors. However, significant challenges remain in the clinical application of CAR-T cell immunotherapy in thoracic malignancies. In this review, the latest research progress of CAR-T cell immunotherapy in the treatment of thoracic malignancies were summarized, including the basic characteristics of CAR-T cells, the popular target antigens, and the existing problems and challenges, to provide new ideas and strategies for clinical immunotherapy of thoracic malignancies.
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Objective:Clinical research is widely carried out in medical institutions, and there are differences in the use of research and conventional medical funds. This paper aimed to analyze the compliance issues of insurance fund in clinical research and explore the management strategies in the institutions conducting clinical trials or research.Methods:By consulting the literature, questionnaire, and work practice, this paper analyzed the current situation and existing problems of the compliance of the medical insurance fund in domestic clinical trials, proposed targeted management measures for the use of funds, and standardizes the corresponding workflow.Results:This paper summarized three payment methods of research-related funds and analyzed the main problems at present, including the definition of trial requirements, the payment of combined drugs specified in the protocol, the particularity of medical device trials, the payment of adverse events in clinical trial, the insurance of post-marketing research and clinical trial. According to the regulatory requirements and work practices, the corresponding management countermeasures were sorted out, including that the project funds and insurance audit should be carried out inside the medical institution. Clinical research, medical insurance management departments, ethics committees, and other departments should collaborate on establishing and improving a compliance management system. The research team should strengthen the management of adverse events, strengthen the publicity and education of the participants, and make good use of the sharing platform.Conclusions:The research institution should establish standardized and feasible processes, the research team should strengthen the management, and the use of the sharing platform is conducive to ensuring the compliance of the medical insurance fund and protecting the interests of the participants.
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Objective:To explore the influence of bromodomain-containing protein 4 (BRD4) inhibitor on wild-type Kras differentiated thyroid carcinoma (DTC) and its mechanism.Methods:The DTC cell line Kras WT TPC-1 was selected and the mutant Kras G12D TPC-1 cells were constructed. CCK-8 assay was used to detect the effect of BRD4 inhibitor JQ-1 on the proliferation activity of Kras WT TPC-1 cells. Kras WT TPC-1 cells were treated with 0.2 μmol/L JQ-1 (JQ-1 group), and a negative control group (NC group) was set. Transwell invasion assay and flow cytometry were used to detect the effect of JQ-1 on the invasion and apoptosis of Kras WT TPC-1 cells. The effect of JQ-1 on the expressions of BRD4, miR-106b-5p and P21, and the effect of P21 inhibitor UC2288 on the expressions of P21 and BRD4 were detected. Kras WT TPC-1 cells were divided into JQ-1+ NC-OE group, JQ-1+ p21-OE group (overexpression of p21) and JQ-1+ p21-OE+ miR-106b-5p mimic group (overexpression of p21 and miR-106b-5 at the same time), and the proliferation, invasion and apoptosis of cells in each group were detected. TPC-1 cells were divided into Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, and the cell proliferation, invasion and apoptosis of each group were detected. Results:JQ-1 inhibited the proliferation activity of Kras WT TPC-1 cells in a dose-dependent and time-dependent manner. In the NC group and JQ-1 group, the numbers of cell invasion were 124.67±9.61 and 82.67±8.02, and the apoptosis rates were (5.91±0.34)% and (10.33±1.10)%, respectively, with statistically significant differences ( t=5.812, P=0.004; t=6.653, P=0.003). JQ-1 significantly inhibited the expressions of BRD4 and miR-106b-5p, and promoted the expression of P21 in Kras WT TPC-1 cells. UC2288 significantly inhibited P21 expression, but had no significant effect on BRD4 expression. In the JQ-1+ NC-OE group, JQ-1+ p21-OE group and JQ-1+ p21-OE+ miR-106b-5p mimic group, the proliferation activities at 24 h of Kras WT TPC-1 cells was 0.46±0.03, 0.35±0.04 and 0.44±0.03 ( F=8.720, P=0.017), and the proliferation activity of JQ-1+ p21-OE group was significantly lower than that of the JQ-1+ NC-OE group ( P<0.05). The numbers of cell invasion in the three groups were 83.00±9.17, 56.67±6.03 and 79.67±10.07 ( F=8.347, P=0.018), and the number of cell invasion in the JQ-1+ p21-OE group was significantly lower than that in the JQ-1+ NC-OE group ( P=0.009). The apoptosis rates of the three groups were (10.00±0.49)%, (15.39±1.14)% and (10.32±0.80)% ( F=37.764, P<0.001), and the apoptosis rate of the JQ-1+ p21-OE group was significantly higher than that in the JQ-1+ NC-OE group ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between JQ-1+ p21-OE+ miR-106b-5p mimic group and JQ-1+ NC-OE group (all P>0.05). In Kras WT group, Kras WT+ JQ-1 group, Kras G12D group and Kras G12D+ JQ-1 group, the cell proliferation activities at 24 h were 0.50±0.05, 0.39±0.04, 0.68±0.08 and 0.64±0.05 ( F=17.776, P<0.001). Compared with the Kras WT group, cell proliferation activity in the Kras WT+ JQ-1 group was significantly decreased, while that in the Kras G12D group was significantly increased (both P<0.05). The numbers of cell invasion in the four groups were 129.33±11.50, 86.00±9.54, 161.67±13.01 and 146.33±13.20 ( F=22.598, P<0.001). Compared with the Kras WT group, the number of cell invasion in the Kras WT+ JQ-1 group was significantly decreased ( P=0.002), and that in the Kras G12D group was significantly increased ( P=0.010). The apoptosis rates in the four groups were (6.17±0.50)%, (10.42±0.73)%, (3.43±0.47)% and (3.41±0.32)% ( F=119.170, P<0.001). Compared with the Kras WT group, the apoptosis rate in the Kras WT+ JQ-1 group was significantly increased ( P<0.001), and that in the Kras G12D group was significantly decreased ( P<0.001). There were no significant differences in cell proliferation activity, invasion number and apoptosis rate between Kras G12D+ JQ-1 group and Kras G12D group (all P>0.05). Conclusion:BRD4 inhibitor can specifically inhibit the development of wild-type Kras DTC via regulating the molecular axis of BRD4/miR-106b-5p/P21, but has no significant effect on the proliferation, invasion and apoptosis of mutant Kras DTC tumor cells.
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OBJECTIVE:To observe clinical efficacy and safety of Kangfuxin liquid in the treatment of radioactive dermatitis of nasopharyngeal carcinoma patients. METHODS:A total of 73 nasopharyngeal carcinoma patients with radioactive dermatitis in the Third Affiliated Hospital of Kunming Medical University during Feb. 2016 to Feb. 2017 were divided into control group (36 cases) and observation group (37 cases) according to random number table. Both groups received routine treatment as Methylrosanilinium chloride solution,Compound cod liver oil and zinc oxide ointment for external use. Observation group was additionally given gauze soaked with Kangfuxin liquid on affected area,3 times a day on the basis of routine treatment. Both groups were treated for 4 weeks. Clinical efficacies of 2 groups were compared,and RTOG classification and dermatitis area were compared before and after treatment. The occurrence of ADR was recorded. RESULTS:There was statistical significance in the total response rate between observation group (94.6％) and control group (97.2％)(P<0.05). Before and after treatment,there were no RTOG Ⅳ patients in 2 groups. Before treatment,there was no statistical significance in the proportion of RTOG 0-Ⅲpatients or dermatitis area between 2 groups (P>0.05). After treatment,RTOG classification of observation group was improved significantly, the proportion of grade 0 patients was significantly higher than control group, that of gradeⅠpatients was significantly lower than control group,with statistical significance(P<0.05). There was no statistical significance in the proportion of RTOG 0-Ⅲpatients of control group before and after treatment(P>0.05). Two,four weeks after treatment,dermatitis areas of 2 groups were decreased significantly;dermatitis area 4 weeks after treatment was significantly smaller than 2 weeks after treatment;observation group was significantly smaller than control group,with statistical significance(P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:Additional use of Kangfuxin liquid in the treatment of radioactive dermatitis of nasopharyngeal carcinoma patients can effectively relieve symptoms and reduce dermatitis area with good safety.
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Tripartite motif-containing 14 (TRIM14) is a member of tripartite motif family.Regulating innate immune response and affecting cell differentiation are the main physiological functions of TRIM14.It is reported TRIM14 expresses in various tumors such as non-small cell lung cancer,breast cancer,hepatocellular carcinoma,osteosarcoma and oral squamous cell carcinoma.The proliferation,invasion,metastasis,drug resistance of malignant tumors and the prognosis of patients with cancer can be affected via different mechanisms of TRIM14.
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Objectives 99mTc-methoxyisobutylisonitrile (MIBI) SPECT imaging technology was used to observe the condition of tumor cell in-taking imaging agent in the C57BL/6J mice Lewis lung cancer model before and after using Ginsenoside Rg3 (short for Rg3).We aimd so as to discuss the feasibility of using this method to evaluate tumor multidrug resistance (MDR) status.Methods Mice Lewis lung cancer models were randomly divided into Rg3 group and the control group.After applying Rg3,semi-quantitative analysis was made on 99mTc-MIBI SPECT imaging and region of interest (ROI) to observe the multidrug resistance state of tumor and then the results were compared with the detection results of flow cytometry.Results The tumor intake ratio (T/N) difference between the control group and the Rg3 group in imaging,imaging before applying Rg3 and imaging after applying Rg3 were separately 15,60 and 120 min.The differences were statistical significant (P ＜ 0.01).The eliminate indexes (WR) of the control group and Rg3 group were positively related to P-gp protein expression positive cells detected by flow cytometry (P ＜ 0.05).Conclusions 99mTc-MIBI imaging is negatively related to P-glycoprotein (P-gp) expression in mice Lewis lung cancer cells,which can clearly show the multidrug resistance state of tumors and dynamically monitor the effect of Rg3 on multidrug resistance reversion of mice Lewis lung cancer.
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Eight mouse hybridoma cell lines which stably secreted monoclonal antibodies ( McAbs ) against human prostate-specific antigen-α1-antichymotrypsin complex ( PSA-ACT ) were obtained through hybridoma technique. After purification, the immunological characters of 8 McAbs were identified and classified by epitopes analysis through indirect enzyme-linked immunosorbent assay ( ELISA) . A pair of McAbs was chosen from above 8 McAbs, based on which a highly sensitive, simple and rapid chemiluminescence enzyme immunoassay ( CLEIA) was developed for determination of PSA-ACT in human serums using the lumino-H2 O2 reaction catalyzed by horseradish peroxidase ( HRP) as the chemiluminescence system. Several experiment factors such as coating buffer, coating concentration, dilution ratio of PSA-ACT-HRP complex, incubation time, immunoreaction protocol and chemiluminescence reaction time were optimized. The results showed that the linear range of the proposed method for PSA-ACT determination was 0-40 ng/mL (R2=0. 9943), with the detection limit of 0. 53 ng/mL. The inter-assay relative standard deviations (RSDs) were 4. 6%-6. 6%, and intra-assay RSDs were 5 . 7%-8 . 0%. The recoveries of PSA-ACT at three spiked levels in serum samples were 95. 4%-104. 2%. The proposed method exhibited a cross-reactivity of 0. 6% with free-PSA. The proposed method is stable, sensitive, rapid and simple, and provides a foundation for the development of PSA-ACT CLEIA kit and shows great value in clinical auxiliary diagnosis of prostate cancer.
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<p><b>OBJECTIVE</b>To compare the diagnostic value of ⁹⁹Tc(m)-MIBI SPECT/localizable CT and ¹⁸FDG-PET/CT in patients with indeterminate solitary pulmonary nodules (SPNs) and assess the feasibility of using ⁹⁹Tc(m)-MIBI SPECT/localizable CT as an alternative when ¹⁸FDG-PET/CT is not available.</p><p><b>METHODS</b>Thirty-nine patients with indeterminate SPNs were examined by ⁹⁹Tc(m)-MIBI SPECT/localizable CT, and another 46 patients by ¹⁸FDG-PET/CT. The findings of the two modalities were analyzed qualitatively and semiquantitatively to assess their efficacy for a definitive diagnosis of SNPs.</p><p><b>RESULTS</b>Of the 39 patients examined by ⁹⁹Tc(m)-MIBI SPECT/localizable CT, 13 were identified to have malignant SPNs and 26 had benign SPNs; the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of the examination were 92.31% (12/13), 88.46% (23/26), 89.74% (35/39), 80% (12/15) and 95.83% (23/24), respectively. Of the 46 patients receiving ¹⁸FDG-PET/CT examination, 29 malignant cases and 17 benign cases were identified with a diagnostic sensitivity, specificity, accuracy, PPV and NPV of 96.55% (28/29), 76.47% (13/17), 89.13% (41/46), 87.50% (28/32) and 92.86% (13/14), respectively. The two modalities showed no significant differences in the diagnostic sensitivity (χ² =0.356, P=0.55), specificity (χ² =1.084, P=0.298), accuracy (χ² = 0.008, P=0.927), PPV (χ² = 0.453, P=0.501) or NPV (χ² =0.157, P=0.692). The ROC curve showed that with the early uptake ratio (EUR) of ⁹⁹Tc(m)-MIBI ≥ 1.474 and ≥ 1.38 as the cutoff values, the sensitivity of ⁹⁹Tc(m)-MIBI SPECT/localizable CT was both 100% and the specificity both 76.90%; with the maximum standard uptake value (SUVmax) of ¹⁸FDG ≥ 2.40 as the cutoff value, the sensitivity of ¹⁸FDG-PET/CT was 96.60% and the specificity was 76.50%, showing no significant differences between the two modalities in the diagnostic efficacy.</p><p><b>CONCLUSION</b>⁹⁹Tc(m)-MIBI-SPECT/localizable CT may be a useful and practical modality for early diagnosis of SNPs for patients with a medium or low income in small and medium-sized cities.</p>
Subject(s)
Humans , Diagnosis, Differential , Fluorodeoxyglucose F18 , Lung Neoplasms , Diagnosis , Positron-Emission Tomography , ROC Curve , Radiopharmaceuticals , Sensitivity and Specificity , Solitary Pulmonary Nodule , Diagnosis , Technetium Tc 99m Sestamibi , Tomography, Emission-Computed, Single-Photon , Tomography, X-Ray ComputedABSTRACT
Objective To investigate the diagnosis of value 99mTc-MIBI SPECT and CT fusion imaging in the differential solitary pulmonary nodule ( SPN). Methods Thirty-nine patients with SPN underwent 99mTc-MIBI-SPECT and positioning CT fusion imaging, and the imaging results carried on the qualitative and semi-quantitative analysis. The diagnostic value of the imaging method for SPN was judged according to the results of the final diagnosis. Results Of 39 cases with SPN, 13 cases were malignant and 26 cases were benign. The diagnostic sensitivity, specificity, accuracy, negative predictive value and positive predictive value of 99mTc-MIBI-SPECT positioning CT fusion imaging qualitative analysis in benign and malignant SPN was 92.31%(12/13),88.46%(23/26),89.74%(35/39),80% (12/15) and 95.83% (23/24),respectively. Receiver operating characteristic (ROC) curve analysis showed:using 99mTc-MIBI early uptake ratio (EUR) ≥1.474 as the critical value for identification the benign and malignant SPN, the sensitivity and specificity was 100% and 76.90%, respectively;using 99mTc-MIBI delayed uptake ratio (DUR) ≥ 1.38 as the critical value, the sensitivity and specificity was 100%and 76.90%. Conclusion The method of 99mTc-MIBI-SPECT and positioning CT fusion imaging has a high clinical value in the differential diagnosis of SPN.