ABSTRACT
Objective: To investigate the diagnostic performance of MRI Liver Imaging Reporting and Data System version 2018 in high-risk hepatocellular carcinoma (HCC) patients with intrahepatic parenchymal substantial lesions ≤3.0 cm. Methods: A retrospective analysis was conducted in hospitals between September 2014 to April 2020. 131 pathologically confirmed non-HCC cases with lesions ≤3.0 cm in diameter were randomly matched with 131 cases with lesions ≤3.0 cm in diameter and divided into benign (56 cases), other hepatic malignant tumor (OM, 75 cases), and HCC group (131 cases) in a 1:1 ratio. MRI features of the lesions were analyzed and classified according to LI-RADS v2018 criteria (tie-break rule was applied to lesions with both HCC and LR-M features). Taking the pathological results as the gold standard, the sensitivity and specificity of the LI-RADS v2018 classification criteria and the more stringent LR-5 criteria (with three main signs of HCC at the same time) were calculated for HCC, OM or benign lesions diagnosis. Mann -Whitney U test was used to compare the classification results. Results: The number of cases classified as LR-M, LR-1, LR-2, LR-3, LR-4, and LR-5 in HCC group after applying the tie-break rule were 14, 0, 0, 12, 28, and 77, respectively. There were 40, 0, 0, 4, 17, 14 and 8, 5, 1, 26, 13, 3 cases in benign and OM group, respectively. There were 41 (41/77), 4 (4/14) and 1 (1/3) lesion case in the HCC, OM and benign group, respectively, that met the more stringent LR-5 criteria. The sensitivity of LR-4 combined with LR-5 (LR-4/5) criteria, LR-5 criteria and more stringent LR-5 criteria for HCC diagnosis were 80.2% (105/131), 58.8% (77/131) and 31.3% (41/131), respectively, and the specificity were 64.1% (84/131), 87.0% (114/131) and 96.2% (126/131), respectively. The sensitivity and specificity of LR-M were 53.3% (40/75) and 88.2% (165/187), respectively. The sensitivity and specificity using LR-1 combined with LR-2 (LR-1/2) criteria for the diagnosis of benign liver lesions were 10.7% (6/56) and 100% (206/206), respectively. Conclusions: LR-1/2, LR-5, and LR-M criteria have high diagnostic specificity for intrahepatic lesions with a diameter of ≤3.0 cm. Lesions classified as LR-3 are more likely to be benign. The specificity of LR-4/5 criteria is low, while the more stringent LR-5 criteria has a high specificity for HCC diagnosis.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Retrospective Studies , Magnetic Resonance Imaging/methods , Sensitivity and Specificity , Contrast MediaABSTRACT
Objective: To explore the effects of K-ras gene on the expressions of oncogenes and cancer suppressor genes in human bronchial epithelial (HBE) cells which were exposed to PM(2.5). Methods: According to the mRNA sequence of K-ras gene provided by GenBank in September 2019, interference sequences were designed and synthesized, and the recombinant lentiviral vector was transfected into HBE cell to construct the K-ras gene-silenced cells. HBE cells and K-ras gene-silenced cells were exposed to 10 µg/ml, 50 µg/ml PM(2.5) suspension and 10 µmol/L Cr(6+). Real-time fluorescent quantitative PCR was used to detect the mRNA expression levels of c-myc, c-fos, N-ras, cyclin-D1, p16 and p53 genes, the expression levels of p53 and c-myc proteins were detected by Western blot. Results: In K-ras silenced cell group, K-ras mRNA expression level decreased (80.5%±3.6%) and K-ras protein level decreased (58.9%±4.7%) when compared with the control group (P<0.01) . Compared with the correspoding cell control group without exposure, the mRNA expression levels of c-myc, c-fos, N-ras and cyclin-D1 genes in HBE cell group exposed to different concentrations of PM(2.5), K-ras silenced cell group exposed to different concentrations of PM(2.5), HBE cell group exposed to 10 µmol/L Cr(6+) and K-ras silenced cell group exposed to 10 µmol/L Cr(6+) were increased, the mRNA expressions of p16 and p53 genes were decreased (P<0.01) . Compared with HBE cell group exposed to 10 µg/ml PM(2.5), the mRNA expressions of c-myc, c-fos and p16 genes in K-ras silenced cells exposed to 10 µg/ml PM(2.5) were decreased, and the p53 mRNA level was increased (P<0.01) . Compared with HBE cell group exposed to 50 µg/ml PM(2.5), the mRNA expression levels of c-fos, N-ras, cyclin-D1, p16 and p53 genes in K-ras silenced cell group exposed to 50 µg/ml PM(2.5) were decreased (P<0.01) . Compared with the HBE cell group without exposure, c-myc protein increased and p53 protein decreased in HBE cells exposed to 50 µg/ml PM(2.5) (P<0.05) . Compared with the K-ras silenced cell group without exposure, c-myc protein increased in K-ras silenced cells exposed to 50 µg/ml PM(2.5) (P<0.05) . Conclusion: PM(2.5) can increase the expression levels of oncogenes in HBE cells, and K-ras gene silencing can inhibit the expression levels of oncogenes in HBE cells treated with PM(2.5).
Subject(s)
Genes, ras , Oncogenes , Epithelial Cells , Genes, ras/genetics , Humans , Particulate Matter/toxicity , Proto-Oncogene Proteins c-fos/geneticsABSTRACT
Objective: To investigate the immunity markers related to nosocomial infection in children with sepsis. Methods: A retrospective study including 155 cases diagnosed as sepsis from September 2015 to June 2020 in children's intensive care unit (PICU) of Shanghai Children's Medical Center was conducted. According to the presence of nosocomial infection occurred in PICU, septic children were divided into two groups: no nosocomial infection and nosocomial infection group. The differences about helper T-cells 1 and 2 cytokines, T cells subgroup absolute count, the proportion of CD14+ human leukocyte antigen DR (CD14+HLA-DR), the proportion of regulatory T cells, pediatric risk of mortality â ¢ (PRISM-â ¢), the treatment and outcome between the two groups were compared. Through propensity score matching (PSM), the disease severity and treatment of the two groups were matched to analyze the differences between the above indicators. Chi-square test or U test was used for comparison between groups. Receiver operating characteristic (ROC) curve was used to predict the occurrence of nosocomial infection. Results: There were 104 cases in no nosocomial infection group and 51 cases in nosocomial infection group. The first PICU-acquired infections occurred at (12±7) days after PICU admission. The most common PICU-acquired infections were pneumonia (26 cases, 51.0%) and bloodstream infections (15 cases, 29.4%). PRISM-â ¢ of nosocomial infection group was significantly higher than that in no nosocomial infection group (8 (0-31) vs. 4 (0-17), Z=3 913.00, P<0.01).The proportion of using vasoactive drugs and invasive mechanical ventilation of nosocomial infection group was significantly higher (35.3% (18/51) vs. 10.6% (11/104), χ²=13.77, P<0.01; 86.3% (44/51) vs. 38.5% (40/104), χ²=31.51, P<0.01).The PICU length of stay of nosocomial infection group was significantly longer (20 (3-94) vs.7 (2-41) days, Z=4 585.50, P<0.01). The mortality of the nosocomial infection group was significantly higher than that of the group without nosocomial infection (29.4% (15/51) vs. 6.7% (7/104), χ²=14.45, P<0.01). Interleukin-6 and interleukin-10 of the nosocomial infection group were significantly higher than that in no nosocomial infection group (37.83 (2.23-7 209.99) vs. 13.45 (0.80~50 580.64) ng/L, Z=3 390.50, P=0.01; 10.42 (1.11-6 052.21) vs.4.10 (0.16-409.28) ng/L, Z=3 212.00, P=0.03). CD4+/CD8+ and the percentage of CD14+HLA-DR were significantly lower in the nosocomial infection group compared with the no nosocomial infection group (1.16 (0.44-4.96) vs. 1.61 (0.15-6.37), Z=1 955.00, P=0.01; 0.48 (0.08-0.99) vs. 0.67 (0.09-0.98), Z=1 915.50, P<0.01). After PSM, the percentage of CD14+HLA-DR of nosocomial infection group was significantly lower than that in no nosocomial infection group (0.44 (0.08-0.99) vs. 0.64 (0.09-0.98), Z=758.00, P=0.02). The ROC curve analysis of the percentage of CD14+HLA-DR in predicting nosocomial infection showed that the area under the curve was 0.642, the cut-off value was 0.39, and the 95%CI was 0.528-0.755. Conclusion: The level of the percentage of CD14+HLA-DR maybe is related to the occurrence of nosocomial infection in children with sepsis.
Subject(s)
Cross Infection , Sepsis , Child , China/epidemiology , Humans , Prognosis , ROC Curve , Retrospective StudiesABSTRACT
Objective: To study the effect of p38 mitogen-activated protein kinase (MAPK) gene silencing on expression of apoptotic genes and oncogenes in hepatocytes treated with PM(2.5). Methods: From June to September 2019, according to the p38MAPK gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, ligated into PLVX-shRNA2-puro after annealing, and the recombinant lentiviral vector was transfected into L02 hepatocytes. The p38MAPK silencing cells were identified by real-time fluorescent quantitative PCR and western blotting. The normal L02 cells and p38MAPK silencing cells were treated with 50 µg/mL PM(2.5) water soluble solution, 10 µmol/L positive control Cr(6+), and a blank control group was set up, the treatment time was 24 h. The mRNA levels of oncogenes (c-fos, c-myc, k-ras) , tumor suppressor gene (p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by Western blotting. Results: The expression levels of p38MAPK mRNA and protein in p38MAPK gene silencing cells were significantly lower than those in L02 hepatocytes (P<0.05) , and the p38MAPK gene silencing cell line was successfully constructed. Compared with the blank control group, the expression levels of the oncogenes c-fos, c-myc, k-ras and the apoptosis genes Caspase-3, Caspase-8 and Caspase-9 increased, the expression level of tumor suppressor gene p53 decreased in the L02 hepatocyte group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Compared with the L02 hepatocytes group treated with PM(2.5) water soluble matter, the expression levels of the oncogenes c-fos, c-myc, k-ras and apoptosis genes Caspase-3, Caspase-8 and Caspase-9 decreased, the expression level of tumor suppressor gene p53 increased in the p38MAPK gene silencing cells group treated with PM(2.5) water soluble matter, and the differences were statistically significant (P<0.05) . Conclusion: PM(2.5) has effects on the expression of oncogenes, tumor suppressor genes and apoptotic genes in L02 hepatocytes, while p38MAPK gene silencing can inhibit the effects of PM(2.5) on L02 hepatocytes.
Subject(s)
Hepatocytes , Oncogenes , Apoptosis , Gene Silencing , Humans , Particulate MatterABSTRACT
OBJECTIVE: A model to predict the overall survival (OS) of pancreatic adenocarcinoma (PAC) is required in consideration of its inferior prognosis. PATIENTS AND METHODS: The patients diagnosed with pancreatic cancer between 1975 and 2016 in the Surveillance, Epidemiology, and End Results (SEER) database was used as raw data. A training cohort and a verification cohort were used for internal validation and external validation, respectively. The nomogram model was constructed to predict the OS. RESULTS: A total of 5,805 patients with PAC from 2010-2015 were analyzed. Most patients were over 65 years old (61.8%), white (81.2%), in stage IIA, IIB (49.0%), and IV (32.4%), less than 50 mm in diameter (80.2%). PAC patients with wide involvement range, no metastasis, and infiltration range more than 300 accounted for 58.2%, 67.6%, 78.2%, respectively. The vast majority of the PAC patients (90.9%) did not receive primary site surgery. Most of the PAC patients (68.1%) received chemotherapy and only 25.8% of PAC patients received radiotherapy. The overall mean survival time, overall median survival time and overall survival rate were 15.1 months, 10.0 months, and 16.7%, respectively. CONCLUSIONS: Our nomogram that based on age, chemotherapy, grade, Radiation sequence with surgery, Radiation recode, RX Summ-Surg Prim at Site (surgery that removes and/or destroys primary tumor performed as part of the first course of therapy), size, and stage was of well prediction ability.
Subject(s)
Adenocarcinoma/pathology , Nomograms , Pancreatic Neoplasms/pathology , SEER Program , Adenocarcinoma/therapy , Aged , Female , Humans , Male , Pancreatic Neoplasms/therapy , Survival Rate , Pancreatic NeoplasmsABSTRACT
Objective: To construct the c-myc gene silenced hepatocytes, study the effect of c-myc gene silence on expression of oncogenes and apoptosis genes in hepatocytes treated with PM2.5. Methods: According to the c-myc gene mRNA sequence provided by GenBank, three interfering sequences were designed and synthesized, the recombinant lentiviral vector was transfected into L02 hepatocytes. The real-time quantitative PCR and western blotting were used to identify the effect of c-myc gene silencing. L02 cells and c-myc gene silenced cells were used as experimental subjects. The normal L02 cells and c-myc silenced cells were treated with 50 µg/ml PM(2.5) water soluble solution, 10 µM positive control Cr(6+) and a blank control, the treatment period was 24 h. The mRNA levels of oncogenes (c-myc, c-fos, k-ras, p53) and apoptotic genes (Caspase-3, Caspase-8, Caspase-9) were detected by real-time PCR. The protein levels of oncogenes and apoptotic genes were detected by western blotting. Results: The mRNA level and protein level of c-myc decreased by 81% and 70% in c-myc silenced cells when compared with the normal L02 hepatocytes, the above results indicate that c-myc gene silenced cells were successfully constructed. After c-myc silenced cells were treated with PM2.5 water soluble solution, The mRNA levels of c-myc, c-fos, and k-ras decreased by 84.1%, 45.4%, and 54.6% (P<0.05) , p53 increased by 192.9% (P<0.05) , and the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 24.4%, 36.1%, 60.9% (P<0.05) . In the Cr(6+) positive control group, the expression of c-myc, c-fos, and k-ras decreased by 72.1%, 82.2%, and 54.0% (P<0.05) , p53 increased by 250.0% (P<0.05) , the expression of Caspase-3, Caspase-8, and Caspase-9 decreased by 34.6%, 36.0%, 68.9% (P<0.05) , respectively, when compared with the normal L02 hepatocytes (P<0.05) . Western blotting results showed that the protein levels of c-myc and c-fos increased, p53 decreased after PM(2.5) exposure; the protein levels of Caspase-3, Caspase-8, Caspase-9 increased after PM(2.5) exposure (P<0.05) . When in comparison with the c-myc silenced group, the protein levels of c-myc and c-fos decreased, p53 protein increased in PM(2).5 exposed group (P<0.05) . Conclusion: c-myc gene silenced cells were successfully constructed in this paper. PM(2.5) could promote the expression of oncogenes and apoptotic genes in L02 cells, and c-myc gene silencing can inhibit the expression of oncogenes and apoptotic genes after PM(2.5) treatment in L02 cells.
Subject(s)
Genes, myc , Oncogenes , Apoptosis , Genes, myc/genetics , Hepatocytes , Humans , Proto-Oncogene Proteins c-fosABSTRACT
Objective: To investigate the sedation weaning strategies in critically ill patients with mechanical ventilation in pediatric intensive care unit (PICU) and to explore the effect of different sedative weaning patterns on withdrawal syndrome. Methods: A single-center prospective cohort study was conducted from April 1, 2016 to April 30, 2017. One hundred and twelve patients who required mechanical ventilation and benzodiazepines and (or) opioids for at least 5 consecutive days in PICU of Shanghai Children's Medical Center were enrolled. Twenty patients (17.9%) had an intermittent weaning pattern, defined as a 50% or greater increase in daily benzodiazepine and (or) opioid dose after the start of weaning, and the remaining 92 cases (82.1%) had a steady weaning pattern. The demographic and clinical features, duration and dose of sedative and analgesics, and the incidence of withdrawal syndrome were evaluated. Mann-Whitney U test was used for comparison about clinical features between different weaning pattern groups and children with withdrawal syndrome or not. Logistic regression was used to explore the risk factors of withdrawal syndrome. Results: Among the 112 patients, 46 (41.1%) had withdrawal syndrome. The patients with the intermittent weaning pattern had a high score of pediatric risk of mortality â ¢ (PRISM-â ¢) (10.0 (3.5, 12.0) vs. 6.0 (2.0, 10.0), U=654.50, P=0.043) and were prone to re-intubation (35.0% (7/20) vs. 7.6% (7/92), P=0.003). The patients with withdrawal syndrome had longer duration of sedation (19.5 (16.8, 24.3) vs. 10.0 (7.0, 17.3) days, U=743.50, P<0.01), higher incidence of intermittent weaning pattern (32.6% (15/46) vs. 7.6% (5/66),χ(2)=11.58, P=0.001), longer PICU hospitalization (19.0 (15.8, 25.3) vs. 12.0 (8.8, 17.0) days, U=755.00, P<0.01) and higher cost (89 (57,109) vs. 53 (32, 79) thousand yuan, U=804.00, P<0.01). Logistic regression showed that intermittent weaning pattern (odds ratio (OR)=4.85, 95% confidence interval (CI) 1.39-16.91, P=0.013), perioperative period of liver transplantation (OR=6.97, 95%CI 1.25-39.04, P=0.027) and a cumulative dose of midazolam ≥ 34.7 mg/kg (OR=8.12, 95%CI 3.09-21.37, P<0.01) were risk factors of withdrawal syndrome. Conclusions: Withdrawal syndrome is more likely to occur in children who are intermittently weaned from sedation. Steady weaning strategy may help prevent iatrogenic withdrawal syndrome.
Subject(s)
Hypnotics and Sedatives/administration & dosage , Intensive Care Units, Pediatric , Respiration, Artificial , Substance Withdrawal Syndrome/etiology , Ventilator Weaning/methods , Analgesics, Opioid , Child , China , Humans , Prospective StudiesABSTRACT
OBJECTIVE: To investigate the types and distribution of musculoskeletal ultrasonographic changes of the symptomatic joints, their correlations with clinical manifestations in systemic lupus erythematosus (SLE) patients, as well as the differences of ultrasonographic changes from Rhupus syndrome [SLE overlapping with rheumatoid arthritis (RA)] patients. METHODS: In the study, 114 SLE patients who complained of arthralgia or arthritis from May 2014 to August 2017 and 15 Rhupus syndrome patients were recruited for ultrasound evaluation. Ultrasound scans of the symptomatic joint areas were completed. The correlation between ultrasonographic changes and clinical characteristics was analyzed. Additionally, ultrasound changes of bilateral wrists and hands of the SLE patients were compared with those of the Rhupus syndrome patients. RESULTS: In a total of the 114 SLE patients with 1 866 joints scanned, synovial hyperplasia, tenosynovitis, erosion, and osteophytes were all observed. Synovial hyperplasia was more often observed in wrists in 33.3% (23/69) patients, knees in 28.6% (12/42) patients, and ankles in 25.0% (7/28) patients. Tenosynovitis and erosion were most commonly found in shoulders in 35.0% (7/20) and 65.0% (13/20) patients. Osteophytes were more common in proximal interphalangeal (PIP) joints, elbows and knees. Among 69 patients with 22 joints (bilateral wrists and hands) scanned, 57 (82.6%) of them had ultrasonographic changes. Synovial hyperplasia was observed in 36.2% of the patients and erosion in 14.5% of the patients. The agreement between synovial hyperplasia and swollen joints in PIP was fair (κ=0.633, P<0.01), however poor in wrists between synovial hyperplasia and swollen/tender joints (κ=0.089, P=0.584). 18.4% patients with synovial hyperplasia had no tenderness or swollen clinically, while 15.8% patients with tenderness or swollen had no synovial hyperplasia on ultrasound. No correlation was found between ultrasonographic changes with the SLE disease activity index. Both synovial hyperplasia and erosion were more common in the Rhupus syndrome patients (73.3% vs. 36.2%, P=0.08; 66.7% vs. 14.5%, P=0.03) with significantly higher grey scale scores (7.4±6.4 vs. 1.6±4.1, P=0.04) than in the SLE patients. CONCLUSION: Variety of changes could be observed by ultrasound in different joint areas of SLE patients. The ultrasonographic changes and clinical manifestations did not always correspond to each other. Synovial hyperplasia and erosion was more common in Rhupus syndrome patients.
Subject(s)
Arthritis, Rheumatoid , Lupus Erythematosus, Systemic , Arthralgia , Humans , UltrasonographyABSTRACT
Objective: To investigate the safety, feasibility and operation key points of whole lung lavage in infants with pulmonary alveolar proteinosis. Methods: The clinical manifestations, genetic screening, therapeutic interventions and outcome of an infant with pulmonary alveolar proteinosis complicated with respiratory failure who received whole lung lavage in November 2018 in Shanghai Children's Medical Center Affiliated to Shanghai Jiaotong University School of Medicine were reported. Websites including PubMed, Springer Link, China National Knowledge Infrastructure (CNKI), Weipu Database, and Wanfang Database were searched using the key words of "whole lung lavage" "pediatric" and "pulmonary alveolar proteinosis" for articles published from their establishments to April 2019. Relevant literature was reviewed. Results: A 3-month-old boy had experienced cough, shortness of breath and cyanosis for 1 week prior to admission to pediatric intensive care unit. Physical examination showed hepatosplenomegaly. Complete blood cell count showed mild anemia (hemoglobin 96 g/L) and normal white blood cells. The patient had normal C-reactive protein and normal blood platelet. Biochemical panel showed hypoalbuminemia (31 g/L), mildly elevated glutamic oxaloacetic transaminase (115 U/L) and blood ammonia (165 µmol/L), extremely elevated lactate dehydrogenase (>6 600 U/L) and hyperferritinemia (>4 500 µg/L). Chest computed tomography (CT) revealed decreased transmittance of both lungs, patchy high density shadow and ground glass opacity. Genetic testing revealed a mutation of c.625+1G>A in SLC7A7. Schiff reaction (PAS staining) in bronchoalveolar lavage fluid was positive. The patient was diagnosed with severe pneumonia, respiratory failure, lysinuria urinary protein intolerance, and pulmonary alveolar proteinosis. The patient received sequential unilateral whole lung lavage in 2 days and was successfully weaned from ventilator. He was discharged home breathing room air. Eleven articles (11 in English and non in Chinese) were reviewed. Twenty-one patients were included. After whole lung lavage, 76% (16/21) of the patients had improvement in respiratory function. Conclusions: Whole lung lavage can effectively improve respiratory failure caused by pulmonary alveolar proteinosis in infant patients. The procedure is feasible and safe.
Subject(s)
Bronchoalveolar Lavage/methods , Lung/pathology , Pulmonary Alveolar Proteinosis/therapy , Amino Acid Transport System y+L , Child , China , Cough/etiology , Fusion Regulatory Protein 1, Light Chains , Humans , Infant , Male , Pulmonary Alveolar Proteinosis/diagnosis , Treatment OutcomeSubject(s)
Adaptor Proteins, Signal Transducing , Adaptor Proteins, Vesicular Transport , Hematopoietic Stem Cells/metabolism , Leukemia/metabolism , Proteins/metabolism , Antigens, CD34 , Humans , Phosphorylation , Shc Signaling Adaptor Proteins , Src Homology 2 Domain-Containing, Transforming Protein 1 , TyrosineABSTRACT
In recent years, tumor-infiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach: a. cold digestion with collagenase at 4 degrees C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-fold was greater than that with the original approach. Cytotoxicity against tumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL/IL2, LAK/IL2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.
Subject(s)
Antineoplastic Agents/therapeutic use , Immunotherapy, Adoptive , Liver Neoplasms/therapy , Lung Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Colonic Neoplasms/pathology , Colonic Neoplasms/therapy , Cytotoxicity, Immunologic , Drug Screening Assays, Antitumor , Humans , Liver Neoplasms/pathology , Lung Neoplasms/pathologyABSTRACT
To get a long-term culture of tumor-infiltrating lymphocytes (TILs) is very difficult. The authors have investigated some suitable enzymes, their digestive conditions such as time and temperature, which may influence the viability and cytotoxicity of TILs. The results showed that collagenase II and IV could keep viability of TILs much longer than those treated with trypsin or hyaluronidase. The digestion with collagenase II or IV at 4 degrees C for 24 hours was much less damage to viability of TILs than those treated at 37 degrees C for one hour. The TILs, which digested at 4 degrees C for 24 hours, still had cytotoxicity against autologous tumor cells as long as sixty to seventy-five days.
Subject(s)
Collagenases/pharmacology , Lymphocytes, Tumor-Infiltrating/drug effects , Cytotoxicity, Immunologic , Humans , Hyaluronoglucosaminidase/pharmacology , Leukocyte Count , Lymphocytes, Tumor-Infiltrating/immunology , Trypsin/pharmacologySubject(s)
Angina Pectoris/physiopathology , Electrocardiography , Adult , Aged , Exercise Test , Female , Humans , Male , Middle AgedABSTRACT
The effects of the epimeric glycyrrhizic acids (GA), 18 alpha-form and 18 beta-form, on D-galactosamine (Gal)-induced acute liver injury and fulminating hepatic failure (FHF) in rats were studied. In rats of acute liver injury, extensive liver parenchymal cell damage was observed by the elevation of alanine aminotransferase (ALT) activity and confirmed by significant histopathological changes 24 and 48 h after ip Gal 450 mg.kg-1. Moreover, marked elevation in the liver putrescine levels occurred along with that of serum ALT. The spermidine and spermine levels did not alter significantly. GA 18 alpha-form 300 mg.kg-1 ip suppressed the elevation of serum ALT and liver putrescine levels, and improved all the histopathologic features. On the other hand, GA 18 beta-form 300 mg.kg-1, which exhibited inhibitory effects 24 h after ip Gal, showed no action 48 h after ip Gal. The ALT levels in the serum from GA 18 alpha-form, 18 beta-form, vs control groups after 24 h were 70 +/- 24 (P < 0.01) and 78 +/- 42 (P < 0.01) vs 155 +/- 57, and after 48 h were 74 +/- 25 (P < 0.01) and 258 +/- 99 (P > 0.05) vs 293 +/- 110. The putrescine contents (nmol.g-1) in the liver from GA 18 alpha-form, 18 beta-form, vs control after 24 h were 34 +/- 9 (P < 0.01) and 51 +/- 12 (P < 0.01) vs 139 +/- 29, and after 48 h were 16 +/- 3 (P < 0.01) and 150 +/- 11 (P > 0.05) vs 156 +/- 23.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Glycyrrhetinic Acid/analogs & derivatives , Alanine Transaminase/blood , Animals , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Galactosamine , Glycyrrhetinic Acid/therapeutic use , Glycyrrhizic Acid , Liver Failure/drug therapy , Liver Failure/pathology , Male , Putrescine/metabolism , Rats , Rats, Wistar , Stereoisomerism , Structure-Activity RelationshipABSTRACT
11 endocrine cell types immunoreactive for either 5-hydroxytryptamine (5-HT), somatostatin, gastrin, cholecystokinin (CCK), gastric inhibitory peptide (GIP), motilin, secretin, neurotensin, pancreatic glucagon, enteroglucagon or bovine pancreatic polypeptide (BPP) were found in gastrointestinal tract of 2 species of insectivorous bats. 5 of these 11 types of endocrine cells were located in the stomach and all 11 types of endocrine cells were found in the intestine. However, the distribution and relative frequency of each immunoreactive endocrine cell varied among the cell types and between the 2 species of bats examined. In Brunner's glands, gastrin- and 5-HT-immunoreactive cells were detected very rarely in Pipistrellus and only occasionally in Plecotus. The present results obtained from the insectivorous bats were compared with those of the sanguivorous vampire bats.