Advance of Cellular Immunotherapy in Clinical and Translational Medicine of Lung Cancer Hot!
Lung cancer is one of the most common cancers and ranks the first in the mortality worldwide. The core of immunotherapy, especially cellular immunotherapy, is to activate the T cell-mediated tumor-killing effect in patients with tumors, so as to increase their anti-tumor effect. Surgery and radio- and chemotherapy cannot radically eliminate cancerous cells, but immunotherapy is an important supplementary method in killing tumor stem cells and non-proliferating cells. Cellular immunotherapy contains dendritic cells (DC), cytokine-induced killer (CIK), DC-CIK, natural killer T cells (NKT) and γδ T cells, which provides new techniques for the comprehensive treatment of lung cancer. Using CIK combined with DC, radiochemotherapy, radiofrequency ablation and monomers of Chinese medicine to induce CIK cells that directionally migrate to cancerous nest can increase tumor-killing ability and immunoregulatory ability of CIK cells, reduce adverse and toxic reactions and increase patients’ quality of life, and NKT cell and γδ T cell therapies have also been gradually perfected and promoted in clinical translation. This study mainly introduced the clinical translation of DC vaccines, CIK cells and DC-CIK treatment for lung cancer, hoping to provide new pathways and reference for the clinical treatment of lung cancer.
Diagnosis and Treatment of Chronic Hepatitis B and Liver Cirrhosis in View of Translational Medicine: A 10-Year Retrospective Survey
Diagnosis and Treatment of Chronic Hepatitis B and Liver Cirrhosis in View of Translational Medicine: A 10-Year Retrospective Survey
Objective: To retrospectively analyze the epidemics and clinical characters of inpatients and outpatients due to chronic hepatitis B (CHB) and liver cirrhosis, hoping to provide references for the prevention and treatment of CHB and liver cirrhosis.
Methods: Data were retrospectively analyzed, such as the number of inpatients and outpatients within 10 years, mortality, morbidity of liver failure, classification of CHB and liver cirrhosis, and the number of patients receiving anti-viral therapy.
Results: The data showed that the number of inpatients and outpatients within 10 years was increased by >2 folds; the number of patients with CHB was increased by >4 folds; the mortality of hospitalized patients decreased though it showed an increasing tendency; the number of patients with liver failure was reduced by 1/9 than that 10 years ago due to anti-viral therapy; the number of patients receiving anti-viral therapy with nucleoside drugs increased annually; in the patients with liver cirrhosis, patients without anti-viral therapy and those with anti-viral therapy accounted for 77.3% and 22.6%, respectively; from 2007 to 2013, the number of patients died of CHB hepatitis and liver cirrhosis after CHB was 1 585, in whom patients without anti-viral therapy and those with anti-viral therapy accounted for 63% and 37 %, respectively.
Conclusion: The morbidity of CHB and liver cirrhosis shows an increasing tendency annually, and anti-viral therapy can significantly reduce the morbidity of liver failure, inhibit the rate of liver cirrhosis, and reduce the mortality of CHB and cirrhosis.
Evaluation on the Use of Afatinib Alone or Combined with Other Drugs in Clinical Trials Hot!
Afatinib, an oral tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER-2) and HER4, has been approved in treating patients with EGFR-mutation positive non-small cell lung cancer (NSCLC). Additionally, it also has efficacy in other tumors. Currently, the recommended dose of afatinib is 40 mg once daily, but in clinical trials, the other doses are also used. This article mainly summarized the usage of afatinib alone or combined with other drugs in clinical trials, hoping to provide a better treatment reference for its clinical application.
Advance of Therapeutic Methods for Malignant Pleural Effusion
Malignant pleural effusion (MPE) is a condition caused by primary malignant tumors in the pleura or other malignant tumors metastasis to the pleura. It is also one of common serious complications of middle-late malignant tumor, which has severe impact on the quality of life, even threatening the life of the patients. The selection of treatments for MPE depends on many factors, including the symptoms, performance status, primary tumor types, response to systemic therapy, and degree of lung recruitment maneuvers (LRM) after drainage of pleural effusion. Generally, the treatment methods include thoracentesis, indwelling pleural catheter, pleurodesis, intrapleural injection of drugs, chemotherapy, radiotherapy, anti-angiogenesis therapy, surgery, and thermotherapy. With the in-depth study on pathogenesis of MPE, the treatments of MPE have continuous improvements. This study mainly reviewed the treatment methods for MPE so as to provide the basis for clinical practice in the future.
Advances of MicroRNAs in Translational Medicine and Immunotherapy of Renal Tumors
microRNA (miRNA) is an important molecular component for cells under normal and pathological status，and plays an important role in oncobiology, including the improvement of tumor growth, invasion, angiogenesis and immunoescape by inhibiting the expression of gene miRNAs. Translational medicine can accelerate the industrialization process of transforming scientific research into engineering application, and its application in medicine may lead to the fast shortening of distance between basic research and clinical practice. According to the study of miRNAs in translational medicine, it is discovered that the pathological subtypes of relative diseases can be identified and patients’ survival time and prognosis can be predicted through the expression profiles of miRNAs in tumors, that the invasive examinations can be reduced to realize the diagnosis of tumors by detecting tumor-associated miRNA biomarkers, and that miRNAs can be used for the clinical treatment of tumors. Renal cell carcinoma (RCC) is a common tumor in urinary system, and application of some specific miRNAs as a biomarker for the complementary diagnosis and treatment as well as evaluation of prognosis has become a hot topic in modern medicine. This study mainly analyzed and summarized the latest development in miRNAs and tumor studies, hoping to provide a theoretical basis for the diagnosis and prognosis of renal cancer.
Biological Characteristics of Caspase-14 and Its Expression in Neoplastic Diseases in the View of Translational Medicine Hot!
Caspase-14, a member of caspase family, only exists in mammals. As the most divergent member in the family of mammalian caspases, caspase-14 displays a variety of unique characteristics. It is expressed in a limited number of tissues and has the shortest amino acid sequence within the caspase protein family. At present, it has been found that caspase-14 is functionally different from the inflammatory reaction group of typical caspase family members. It exerts a certain effect in the promotion of final differentiation of epidermal cells and hydration of stratum corneum so as to maintain the steady state of skin barrier. In recent years, caspase-14 expression has been discovered in neoplastic diseases. Translational medicine integrates experimental research results and clinical guidance into the optimal implementation criteria for promoting the prediction, prevention and treatment of diseases. Via human genomics and molecular biology, translational medicine offers a possibility of screening molecular markers so that it can be used to diagnose the neoplastic diseases. In this article, the biological characteristics and substrates of caspase-14 as well as its expression in embryonic period and neoplastic diseases were reviewed.
Effect of hTERT Gene Expression on Proliferation and Apoptosis of Cervical Cancer Caski Cells by Lentivirus-Mediated Small Interfering RNA
Objective: To explore the feasibility of lentivirus-mediated small interfering RNA (siRNA) silencing the human telomerase reverse transcriptase (hTERT) and its influence on the proliferation and apoptosis of cervical cancer Caski cells.
Methods: The cervical cancer Caski cells were transfected by lentivirus expression vectors anti-hTERT-TV and NC-LV which had been constructed in advance. There were three groups in the experiment, namely blank group (NC group), negative control group (NC-LV group) and interference group (anti-hTERT-LV group). The expression level of hTERT mRNA was determined by real-time fluorescent quantitative polymerase chain reaction (PCR), while the cell cycle and apoptosis were detected by flow cytometry.
Results: The relative expression level of hTERT mRNA in anti-hTERT-LV group was significantly lower than those in NC group and NC-LV group (P<0.001). The proportion of cells in G1 phase in anti-hTERT-LV group was significantly higher than those in NC group and NC-LV group (P<0.001), while that in S phase was significantly lower than those in NC group and NC-LV group (P<0.001). The number of cell clones in anti-hTERT-LV group was significantly lower than those in NC group and NC-LV group (P<0.001), but there was no statistical significance between NC-LV group and NC group (P>0.05).
Conclusion: The lentivirus-mediated siRNA can induce silencing hTERT gene, effectively suppress its expression, promote the cell apoptosis and inhibit the proliferation of cervical cancer Caski cells.
Effect of Target Controlled Infusion of Remifentanil Combined with Sufentanil on Stress Reaction and Postoperative Pain of Elderly Patients in Perioperative Period
Objective: To explore the effect of target controlled infusion (TCI) of remifentanil combined with sufentanil on the stress reaction and postoperative pain of elderly patients in perioperative period.
Methods: Ninety-four patients receiving general anesthesia who underwent upper abdominal operation selectively were collected and randomly assigned into observation group (n=47) and control group (n=47). The patients in control group were given remifentanil 5 ng/mL for anesthesia induction and 4 ng/mL for anesthesia maintenance. Patient-controlled intravenous analgesia (PCIA) was conducted at the time of suture. The patients in observation group were given remifentanil and sufentanil 2 ng/mL for anesthesia induction and maintenance. PCIA was performed at the time of suture. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) of patients in two groups were compared respectively before anesthesia (T1), before intubation (T2), 1 min after intubation (T3), 1 min after laparotomy (T4) and 1 min after extubation (T5). The violent fluctuation times of intraoperative hemodynamics were closely observed. The levels of serum cortisol and glucose before operation, during operation, 12 h and 24 h after operation, visual analogue scale (VAS) scores and doses of analgesics at different postoperative time points were also recorded.
Results: Both SBP and DBP at different time points as well as HR at T3 and T4 were significantly lower in observation group than in control group, and the difference was shown statistically significance (P<0.05 or P<0.01). The violent fluctuation times of intraoperative hemodynamics were (2.7±1.2) in observation group and (3.9±1.7) in control group, and the difference was shown statistically significance (t=3.954, P<0.001). The levels of serum cortisol and glucose, VAS scores and doses of analgesics were all significantly lower in observation group than in control group at different postoperative time points, and there was statistical significance (P<0.05 or P<0.01).
Conclusion: For elderly patients in perioperative period, TCI of remifentanil combined with sufentanil can effectively attenuate the increase of blood pressure and HR, maintain the fluctuation times of hemodynamics and depth of anesthesia, and decrease the stress reaction and postoperative doses of analgesics.
Evaluation on the Clinical Efficacy of Dendritic Cell-Activated Cytokine-Induced Killer Cells Combined with Conventional Therapy in the Treatment of Malignant Tumors Hot!
Objective: To evaluate the clinical efficacy of dendritic cell-activated cytokine-induced killer (DC-CIK) cells combined with conventional therapy in the treatment of malignant tumors.
Methods: A total of 100 patients with malignant tumors were randomly divided into two groups. Treatment group received conventional therapy combined with DC-CIK while control group received conventional therapy alone. The short-term efficacy, adverse reactions and changes of lymphocyte subpopulation were all compared between two groups after treatment.
Results: The overall response rate (ORR) was higher in treatment group (86.00%) than in control group (54.00%), the difference was statistically significant (P<0.05). White blood cell count (WBC) reduced after treatment when compared with treatment before (P=0.001), but liver and kidney function had no obvious change in treatment group (P>0.05). WBC reduced markedly, but the level of alanine aminotransferase (ALT) increased obviously after treatment in control group (P<0.001). WBC was higher, but the level of ALT was lower in treatment group than in control group (P<0.001). However, there was no difference between two groups regarding serum creatinine (Scr) and blood urea nitrogen (BUN) (P>0.05). In treatment group, the levels of CD3+, CD3+CD4+, CD3+CD8+, and CD3+CD56+ increased (P<0.05), but the level of CD4+/CD8+ had no significant change (P>0.05). In control group, the levels of CD3+ and CD3+CD4+ reduced (P<0.05), while the levels of CD3+CD8+, CD3+CD56+ and CD4+/CD8+ had no significant change (P>0.05). The levels of CD3+, CD3+CD4+, CD3+CD8+ and CD3+CD56+ in treatment group were higher than those in control group (P<0.01), whereas CD4+/CD8+ was lower than that in control group (P<0.01).
Conclusion: DC-CIK combined with conventional therapy, safe and effective, is capable of promoting the recovery of leukocytes and liver and kidney function, and improving the cellular immune function, which may provide a new therapeutic regimen for patients with malignant tumors.
Effect of Gegen (Radix Puerariae) in Treatment of Osteoporosis in Ovariectomized Mice Hot!
Objective: To explore the effect of Gegen (Radix Puerariae) in the treatment of osteoporosis in ovariectomized mice.
Methods: Fifty mice performed with bilateral ovariectomy for establishing models of osteoporosis were randomly divided into model group, estradiol group, and high-, middle- and low-dose Gegen groups, 10 cases for each group. Another 10 mice with sham operation were selected as control group. High-, middle- and low-dose Gegen groups were treated with different doses of Gegen, estradiol group with 17β-estradiol, model group and control group with distilled water for continuous lavage from postoperative 1 month for totally 3 months. The changes of body mass, the uterus mass, fine structure of bone, thighbone density and calcium content of groups were observed.
Results: Compared with control group, the different indicators of mice improved in a dose-dependent manner after lavage of Gegen. The above indicators in high- and middle-dose groups were similar to those in control group, and the therapeutic effect in high- and middle-dose groups was as good as or superior to that in estradiol group. However, uterus mass in Gegen-treated groups didn’t increase.
Conclusion: Gegen, which has anti-osteoporosis effect like estradiol and doesn’t stimulate uterus, is applicable for the prevention and treatment of climacteric osteoporosis.
Influence of Rosuvastatin on Blood Lipids, Inflammatory Factors, Oxidative Stress and Matrix Metalloproteinases in Patients with Chronic Heart Failure Hot!
Objective: To investigate the influence of rosuvastatin on the blood lipids, inflammatory factors, oxidative stress and matrix metalloproteinases (MMPs) in patients with chronic heart failure (CHF).
Methods: Totally 114 patients with CHF admitted to Yanan Hospital of TCM were collected from December, 2014 to December 2015, and randomly assigned into observation group (n=57) and control group (n=57). The patients in control group were given conventional treatment for CHF, while those in observation group orally took Rosuvastatin Calcium, 20 mg per time, qd.. The course of treatment was 3 months. The changes of cardiac function parameters, blood lipids-related indexes, inflammatory factors, oxidative stress and matrix metalloproteinases (MMPs) were all observed in two groups before and after treatment.
Results: After treatment, left ventricular ejection fraction (LVEF) and level of high-density lipoprotein cholesterol (HDL-C) increased notably, while left ventricular end systolic diameter (LVESD), left ventricular end-diastolic dimension (LVEDD) and levels of triglyceride (TG), total cholesterol (TC) as well as low-density lipoprotein cholesterol (LDL-C) decreased obviously in two groups, which changed more significantly in observation group than those in control group (P<0.05 or P<0.01). After treatment, the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP) decreased significantly in observation group, which were lower than those in control group conspicuously (P<0.01). There was no significant change in control group by comparison to the level of each inflammatory factor (P>0.05). The levels of MDA, MMP-2 and MMP-9 were lower, while the level of SOD was evidently higher in observation group than those in control group, and the differences were shown statistically significant (P<0.01).
Conclusion: Rosuvastatin is promising in the treatment of CHF. It can not only improve the cardiac function and regulate blood lipids, but also reduce the levels of inflammatory factors, MMP-2 and MMP-9, and relieve oxidative stress.
A Translational Study of Low-Dose Estrogen Replacement Therapy on Kupperman Score and Levels of Hormones in Patients with Perimenopausal Syndrome Hot!
Objective: To explore the influence of low-dose estrogen replacement therapy on the Kupperman score and levels of hormones in patients with perimenopausal syndrome (PMS).
Methods: A total of 100 patients with PMS were enrolled and randomly divided into two groups: observation group (n=50) and control group (n=66). Control group was given oral administration of Medroxyprogesterone Acetate, 4 mg/d, while observation group, based on which, was treated with oral Estradiol Valerate Tablets, 0.65 mg/d. After three-month treatment, the uterine volume, endometrial thickness, Kupperman score, levels of hormones as well as adverse reactions were compared between two groups.
Results: Kupperman score decreased significantly in two groups after treatment compared with treatment before (P<0.01), and was lower in observation group than in control group after treatment (P<0.01). After three-month treatment, the level of estrogen increased significantly compared with treatment before (P<0.01), and was higher in observation group than in control group (P<0.01). The levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) decreased significantly after treatment compared with treatment before (P<0.01), and both in observation group were lower than those in control group (P<0.01). There was no difference between two groups after treatment in terms of uterine volume, endometrial thickness and adverse reactions (P>0.05).
Conclusion: Low-dose estrogen replacement therapy is effective in promoting the normalization of hormone secretion in the body, in significantly improving the clinical symptoms, as well as in reducing the occurrence of adverse reactions of patients with PMS.