ObjectiveTo summarize the research progress of KRAS mutation in pancreatic tumorigenesis and therapy.MethodThe research progress of KRAS mutation in pancreatic tumorigenesis and therapy were summarized by reading the domestic and international literatures published in recent years.ResultsPancreatic cancer had the title of " king of cancer”. More than 90% of pancreatic cancer patients had KRAS mutation. KRAS had a complex relationship with pancreatic cancer through downstream signaling pathways, including Raf (rapidly accelerated fibrosarcoma)-mitogen-activated protein kinase kinase (MEK)-extracellular signal-regulated kinase (ERK), phosphatidylinositol-4, 5-bisphosphate 3-kinase (PI3K)-protein kinase B (AKT), and RalGDS-Ral. Although basic research on pancreatic cancer was deepening, there was still a lack of effective molecular targeted drugs.ConclusionsKRASgene plays an important role in the occurrence of pancreatic cancer. The treatment associated with KRAS mutation provides a more effective prognostic possibility for pancreatic cancer patients.
Acute pancreatitis (AP) is a common clinical emergency of the abdomen with increasing incidence and lack of effective treatment. Traditional Chinese medicine, as a treasure of the Chinese people, has been used in the treatment of AP for decades with favorable therapeutic effects. Currently, clinical trials and experimental studies have shown that traditional Chinese medicine has the effects of inhibiting pancreatic enzyme activity, anti-inflammation, promoting gastrointestinal dynamics, as well as delaying the progress of AP, improving clinical symptoms, reducing related complications, and reducing the mortality rate. Therefore, traditional Chinese medicine has considerable clinic value in treating AP. Based on the related research progress and clinical practice of our team, the authors summarized the targets and mechanism of traditional Chinese medicine in treating AP.
Objective To summarize functions and mechanisms of fibroblast activation protein (FAP) and its application in targeted therapy. Method Literatures about FAP in recent years were collected to make a review. Results Thereis an important relationship between the FAP and the dipeptidyl peptidase-Ⅳ. FAP has a serine protease activity and is an important immunosuppressive component in the tumor microenvironment. FAP participate in the pathological process of the neoplastic and the non-neoplastic diseases. In the targeted therapy, the enzyme inhibitors, antibodies, vaccines, and prodrugs of FAP had been extensively studied. Conclusion FAP have various functions and participates in pathological process of many diseases, and it is of great significance to research of tumor targeted therapy.
Obesity is a chronic metabolic disease driven by multiple factors such as genetic susceptibility, environmental factors, and neuroendocrine system disorders. In recent years, the prevalence of obesity in China has been increasing year by year, and a series of obesity-induced diseases are a serious threat to public health. Glucagon-like peptide-1 receptor agonists, as a representative of the new weight loss drugs, have shown a therapeutic effect close to that of weight-loss metabolic surgery in clinical trials by targeting central appetite and metabolism and other synergistic effects, but they still face key problems such as significant differences in individual efficacy, limited evidence of the safety of long-term treatment, and regaining body weight after discontinuation of the drug. The mechanism of action and clinical evidence of several obesity drugs approved and listed in China are summarized, and the progress and challenges of obesity drug therapy in China in combination with recent advances in the development of multi-target agents internationally are discussed, with a view to providing a scientific basis for the clinical drug management of obesity and providing ideas for the research and development of obesity drugs in China as well as for the clinical transformation.
ObjectiveTo investigate the effect of dexamethasone on mammalian target of rapamycin (mTOR) expression of astrocytes in hippocampus of rats with sepsis associated encephalopathy (SAE). MethodsTotally, 90 cases of 30-day-old male Wistar rats were randomly divided into sham-operation group (n=10) and cecal ligation and puncture (CLP) group (n=80). Models of rats with sepsis were established by CLP. At 12 hours after CLP, if rats appeared lower neurobehavioral scores, abnormal electroencephalogram (EEG) and somatosensory evoked potential (SEP), they were diagnosed with SAE. And then, they were randomly divided into non-treated group and dexamethasone group. Rats in the dexamethasone group were injected with dexamethasone (1 mg/kg) via tail vein every other day for a total of 3 times. The same dose of saline was used in the non-treated group. The neurobehavioral score was measured, SEP and EEG were examined in the age of 40 days, and then the rats were killed and the hippocampus was taken. Expressions of mTOR protein were measured by Western blot. The glial fibrillary acidic protein (GFAP) and mTOR were detected by immunofluorescence assay, and the number of positive cells was calculated by image analysis system software. ResultsSix of 80 CLP rats died in 12 hours after operation, and 28 of 74 rats were diagnosed as SAE because they appeared lower neurobehavioral scores, abnormal EEG and SEP at 12 hours after CLP. The incidence of SAE was 37.84% (28/74). In the age of 40 days, compared with non-treated group, neurobehavioral score of rats in the dexamethasone group was low, the amount of alpha waves in EEG reduced, delta waves increased, the amplitude of P1 waves in SEP was decreased, and the latencies of P1 and N1 waves were prolonged (P＜0.05). GFAP immunofluorescence staining showed astrocytic body and processes were small in the sham operation group. However, astrocytes in the non-treated group had large body and hypertrophic processes, and compared with the sham operation group, the number of these cells increased significantly (P＜0.05). Astrocytic body and processes were small in the dexamethasone group compared with the non-treated group, and the number of cells also decreased (P＜0.05). The mTOR positive astrocytes in the non-treated group were more than those in the sham operation group (P＜0.05). But mTOR positive astrocytes in the dexamethasone group were fewer than those in the non-treated group (P＜0.05). ConclusionsAstrocytes are activated in the hippocampus of rats with SAE. They show features of reactive hyperplasia, and the expression of mTOR is up-regulated, while dexamethasone can inhibit effects on these.
Liposome is an ideal drug carrier with many advantages such as excellent biocompatibility, non-immunogenicity, and easy functionalization, and has been used for the clinical treatment of many diseases including tumors. For the treatment of tumors, liposome has some passive targeting capability, but the passive targeting effect alone is very limited in improving the drug enrichment in tumor tissues, and active targeting is an effective strategy to improve the drug enrichment. Therefore, active targeting liposome drug-carriers have been extensively studied for decades. In this paper, we review the research progresses on active targeting liposome drug-carriers based on the specific binding of the carriers to the surface of tumor cells, and summarize the opportunities, challenges and future prospects in this field.
ObjectiveTo investigate the value of integrin αvβ3 targeted microPET/CT imaging with 68Ga-NODAGA-RGD2 as radiotracer for the detection of osteosarcoma and theranostics of osteosarcoma lung metastasis.MethodsThe 68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 were prepared via one-step method and their stability and integrin αvβ3 binding specificity were investigated in vitro. Forty-one nude mice were injected with human MG63 osteosarcoma to established the animal model bearing subcutaneous osteosarcoma (n=21), osteosarcoma in tibia (n=5), and osteosarcoma pulmonary metastatic (n=15). The microPET-CT imaging was carried out in 3 animal models at 1 hour after tail vein injection of 68Ga-NODAGA-RGD2. Biodistribution study of 68Ga-NODAGA-RGD2 was performed in animal model bearing subcutaneous osteosarcoma at 10, 60, and 120 minutes. The animal model bearing pulmonary metastatic osteosarcoma was injected with 177Lu-NODAGA-RGD2 at 7 weeks after model establishment to observe the therapeutic effect of pulmonary metastatic osteosarcoma. Histological and immunohistochemistry examinations were also done to confirm the establishment of animal model and integrin β3 expression in animal models bearing subcutaneous osteosarcoma and bearing pulmonary metastatic osteosarcoma.Results68Ga-NODAGA-RGD2 and 177Lu-NODAGA-RGD2 had good stability in vitro with the 50% inhibitory concentration value of (5.0±1.1) and (6.5±0.8) nmol/L, respectively. The radiochemical purity of 68Ga-NODAGA-RGD2 at 1, 4, and 8 hours was 98.5%±0.3%, 98.3%±0.5%, and 97.9%±0.4%; while the radiochemical purity of 177Lu-NODAGA-RGD2 at 1, 7, and 14 days was 99.3%±0.7%, 98.7%±1.2%, and 96.0%±2.8%. 68Ga-NODAGA-RGD2 microPET-CT showed that the accumulation of 68Ga-NODAGA-RGD2 in animal models bearing subcutaneous osteosarcoma and osteosarcoma in tibia and in lung metastasis as small as 1-2 mm in diameter of animal model bearing pulmonary metastatic osteosarcoma. Biodistribution study of 68Ga-NODAGA-RGD2 in animal model bearing subcutaneous osteosarcoma revealed rapid clearance from blood with tumor peak uptake of (3.85±0.84) %ID/g at 120 minutes. The distribution of 177Lu-NODAGA-RGD2 in lung metastasis was similar with 68Ga-NODAGA-RGD2. The number and size of osteosarcoma metastasis decreased at 2 weeks after 177Lu-NODAGA-RGD2 administration and integrin targeting specificity was confirmed by pathology examination.Conclusion68Ga-NODAGA-RGD2 was potential for positive imaging and early detection of osteosarcoma and metastasis. Targeted radiotherapy with 177Lu-NODAGA-RGD2 was one potential alternative for osteosarcoma lung metastasis.
The drug-target protein interaction prediction can be used for the discovery of new drug effects. Recent studies often focus on the prediction of an independent matrix filling algorithm, which apply a single algorithm to predict the drug-target protein interaction. The single-model matrix-filling algorithms have low accuracy, so it is difficult to obtain satisfactory results in the prediction of drug-target protein interaction. AdaBoost algorithm is a strong multiple classifier combination framework, which is proved by the past researches in classification applications. The drug-target interaction prediction is a matrix filling problem. Therefore, we need to adjust the matrix filling problem to a classification problem before predicting the interaction among drug-target protein. We make full use of the AdaBoost algorithm framework to integrate several weak classifiers to improve performance and make accurate prediction of drug-target protein interaction. Experimental results based on the metric datasets show that our algorithm outperforms the other state-of-the-art approaches and classical methods in accuracy. Our algorithm can overcome the limitations of the single algorithm based on machine learning method, exploit the hidden factors better and improve the accuracy of prediction effectively.
Objective To explore the application value of time of flight magnetic resonance angiography (TOF-MRA) in target bypass surgery for moyamoya disease. Methods The data of patients with moyamoya disease in Affiliated Drum Tower Hospital, Medical College, Nanjing University between May 1 and August 30, 2020 were retrospectively analyzed. Patients were divided into navigation group and control group according to whether navigation technology was used during operation. All patients completed TOF-MRA evaluation before operation, and all patients completed surgical treatment. One week after operation, TOF-MRA was reviewed to evaluate the patency of anastomotic stoma. The intraoperative and postoperative conditions of the two groups were compared. Results Finally, 48 patients with moyamoya disease were included. 22 patients who used intraoperative navigation were included in the navigation group, and 26 patients with moyamoya disease who did not use intraoperative navigation in the same period were included in the control group. There was no significant difference between the two groups in gender, age, Suzuki stage before operation, proportion of posterior circulation involvement, proportion of bleeding type, proportion of hypertension and proportion of diabetes (P>0.05). The operation duration [(3.3±0.4) vs. (3.6±0.6) h] and postoperative hospital stay [(7.3±1.9) vs. (8.8±2.7) d] in the navigation group were shorter than those in the control group (P<0.05). There was no significant difference between the two groups in the proportion of patients who completed bypass surgery, the proportion of middle meningeal artery retained, the postoperative patency rate, the proportion of temporary dysfunction, and the proportion of serious complications (P>0.05). Conclusion TOF-MRA sequence combined with navigation technology can effectively guide the surgical scheme design and postoperative evaluation of moyamoya disease.
This study aims to compare the prostate cancer detection rate between magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) cognitive fusion targeted biopsy and systematic biopsy. A total of 614 patients who underwent transrectal prostate biopsy during 2016-2018 with multiparametric magnetic resonance imaging (mpMRI) were included. All patients with a PI-RADS V2 score ≥ 3 accepted both targeted biopsy and systematic biopsy, and those with a PI-RADS V2 score ≤ 2 only accepted systematic biopsy. Overall prostate cancer detection rate between the two biopsies was compared. MRI-TRUS cognitive fusion targeted biopsy identified 342 cases (75.7%) of prostate cancer while systematic biopsy identified 358 cases (79.2%). There was no significant difference in the detection rate between the two groups (χ2 = 1.621, P = 0.203). Targeted biopsy had significant fewer biopsy cores compared with systematic biopsy, reducing (9.3 ± 0.11) cores (P < 0.001) in average. Targeted biopsy had about 10.8% (P < 0.001) more tumor tissues in positive cores compared with systematic biopsy. The results show that both MRI-TRUS cognitive fusion targeted biopsy and systematic biopsy have good detection rate on prostate cancer. Cognitive targeted biopsy may reduce biopsy cores and provide more tumor tissues in positive cores.