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1.
Chinese Journal of Gastrointestinal Surgery ; (12): 459-466, 2023.
Article in Chinese | WPRIM | ID: wpr-986814

ABSTRACT

Objective: To explore the clinicopathological features, treatment strategy and to analysis of prognosis-related risk factors of gastric neuroendocrine neoplasms(G-NEN). Methods: In this study, a retrospective observational study method was used to collect the clinicopathological data of patients diagnosed with G-NEN by pathological examination in the First Medical Center of PLA General Hospital from January 2000 to December 2021. The basic information of the patients, tumor pathological characteristics, and treatment methods were entered, and the treatment information and survival data after discharge were followed up and recorded. The Kaplan-Meier method was used to construct survival curves, and the log-rank test to analyze the differences in survival between groups. Cox Regression model analysis of risk factors affecting the prognosis of G-NEN patients. Results: Among the 501 cases confirmed as G-NEN, 355 were male and 146 were female, and their median age was 59 years. The cohort comprised 130 patients (25.9%) of neuroendocrine tumor (NET) G1, 54 (10.8%) of NET G2, 225 (42.9%) of neuroendocrine carcinoma (NEC), and 102 cases (20.4%) of mixed neuroendocrine-non-neuroendocrine(MiNEN). Patients NET G1 and NET G2 were mainly treated by endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR). The main treatment for patients with NEC/MiNEN was the same as that for gastric malignancies, namely radical gastrectomy+lymph node dissection supplemented with postoperative chemotherapy. There were significant differences in sex, age, maximum tumor diameter, tumor morphology, tumor numbers, tumor location, depth of invasion, lymph node metastasis, distant metastasis, TNM staging and expression of immunohistological markers Syn and CgA among NET, NEC, and MiNEN patients (all P<0.05). Further for NET subgroup analysis, there were significant differences between NET G1 and NET G2 in the maximum tumor diameter, tumor shape and depth of invasion(all P<0.05). 490 patients (490/501, 97.8%) were followed up with a median of 31.2 months. 163 patients had a death during follow-up (NET G1 2, NET G2 1, NEC 114, MiNEN 46). For NET G1, NET G2, NEC and MiNEN patients,the 1-year overall survival rates were 100%, 100%, 80.1% and 86.2%, respectively; the 3-year survival rates were 98.9%, 100%, 43.5% and 55.1%, respectively. The differences were statistically significant (P<0.001). Univariate analysis showed that gender, age, smoking history, alcohol history, tumor pathological grade, tumor morphology, tumor location, tumor size, lymph node metastasis, distant metastasis, and TNM stage were associated with the prognosis of G-NEN patients (all P<0.05). Multivariate analysis showed that age ≥60 years, pathological grade of NEC and MiNEN, distant metastasis, and TNM stage III-IV were independent factors influencing the survival of G-NEN patients (all P<0.05). 63 cases were stage IV at initial diagnosis. 32 of these were treated with surgery and 31 with palliative chemotherapy. Stage IV subgroup analysis showed that the 1-year survival rates were 68.1% and 46.2% in the surgical treatment and palliative chemotherapy groups, respectively, and the 3-year survival rates were 20.9% and 10.3%, respectively; the differences were statistically significant (P=0.016). Conclusions: G-NEN is a heterogeneous group of tumors. Different pathological grades of G-NEN have different clinicopathological features and prognosis. Factors such as age ≥ 60 years old, pathological grade of NEC/MiNEN, distant metastasis, stage III, IV mostly indicate poor prognosis of patients. Therefore, we should improve the ability of early diagnosis and treatment, and pay more attention to patients with advanced age and NEC/MiNEN. Although this study concluded that surgery improves the prognosis of advanced patients more than palliative chemotherapy, the value of surgical treatment for patients with stage IV G-NEN remains controversial.


Subject(s)
Humans , Male , Female , Middle Aged , Stomach Neoplasms/pathology , Lymphatic Metastasis , Prognosis , Neuroendocrine Tumors/pathology , Carcinoma, Neuroendocrine/therapy , Neoplasm Staging , Retrospective Studies
2.
Journal of Southern Medical University ; (12): 183-190, 2023.
Article in Chinese | WPRIM | ID: wpr-971513

ABSTRACT

OBJECTIVE@#To develop and validate a nomogram for predicting outcomes of patients with gastric neuroendocrine neoplasms (G-NENs).@*METHODS@#We retrospectively collected the clinical data from 490 patients with the diagnosis of G-NEN at our medical center from 2000 to 2021. Log-rank test was used to analyze the overall survival (OS) of the patients. The independent risk factors affecting the prognosis of G-NEN were identified by Cox regression analysis to construct the prognostic nomogram, whose performance was evaluated using the C-index, receiver-operating characteristic (ROC) curve, area under the ROC curve (AUC), calibration curve, DCA, and AUDC.@*RESULTS@#Among the 490 G-NEN patients (mean age of 58.6±10.92 years, including 346 male and 144 female patients), 130 (26.5%) had NET G1, 54 (11.0%) had NET G2, 206 (42.0%) had NEC, and 100 (20.5%) had MiNEN. None of the patients had NET G3. The numbers of patients in stage Ⅰ-Ⅳ were 222 (45.3%), 75 (15.3%), 130 (26.5%), and 63 (12.9%), respectively. Univariate and multivariate analyses identified age, pathological grade, tumor location, depth of invasion, lymph node metastasis, distant metastasis, and F-NLR as independent risk factors affecting the survival of the patients (P < 0.05). The C-index of the prognostic nomogram was 0.829 (95% CI: 0.800-0.858), and its AUC for predicting 1-, 3- and 5-year OS were 0.883, 0.895 and 0.944, respectively. The calibration curve confirmed a good consistency between the model prediction results and the actual observations. For predicting 1-year, 3-year and 5-year OS, the TNM staging system and the nomogram had AUC of 0.033 vs 0.0218, 0.191 vs 0.148, and 0.248 vs 0.197, respectively, suggesting higher net benefit and better clinical utility of the nomogram.@*CONCLUSION@#The prognostic nomogram established in this study has good predictive performance and clinical value to facilitate prognostic evaluation of individual patients with G-NEN.


Subject(s)
Humans , Male , Female , Middle Aged , Aged , Nomograms , Retrospective Studies , Prognosis , Neoplasm Staging , Stomach Neoplasms/pathology
3.
Chinese Journal of Gastrointestinal Surgery ; (12): 440-446, 2022.
Article in Chinese | WPRIM | ID: wpr-936100

ABSTRACT

Objective: To explore the feasibility and preliminary technical experience of the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after total laparoscopic proximal gastrectomy (TLPG) in the treatment of adenocarcinoma of esophagogastric junction (AEG). Methods: A descriptive case series study method was used. Clinical data of 12 AEG patients who underwent the double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG from January 2021 to June 2021 at the Department of General Surgery, First Medical Center, PLA General Hospital were retrospectively analyzed. Among the 12 patients, the median tumor diameter was 2.0 (1.5-2.9) cm, and the pathological stage was T1-3N0-3aM0. All the patients routinely underwent TLPG and D2 lymph node dissection with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: (1) Double-tract reconstruction combined with π-shaped esophagojejunal anastomosis: mesentery 25 cm away from the Trevor ligament was treated, and an incision of about 1 cm was made on the mesenteric border of the intestinal wall and the right wall of the esophagus, two arms of the linear cutting closure were inserted, and esophagojejunal side-to-side anastomosis was performed. A linear stapler was used to cut off the lower edge of the anastomosis and close the common opening to complete the esophagojejunal π-shaped anastomosis. (2) Side-to-side gastrojejunostomy anastomosis: an incision of about 1 cm was made at the jejunum to mesenteric border and at the greater curvature of the remnant stomach 15 cm from the esophagojejunostomy, and a linear stapler was inserted to complete the gastrojejunostomy side-to-side anastomosis. (3) Side-to-side jejunojejunal anastomosis: an incision of about 1 cm was made at the proximal and distal jejunum to the mesangial border 40 cm from the esophagojejunostomy, and two arms of the linear stapler were inserted respectively to complete the side-to-side jejunojejunal anastomosis. A midline incision about 4-6 cm in the upper abdomen was conducted to take out the specimen, and an abdominal drainage tube was placed, then layer-by-layer abdominal closure was performed.@*INDICATIONS@#(1) adenocarcinoma of esophagogastric junction (Seiwert type II-III) was diagnosed by endoscopy and pathological examination; (2) ability to preserve at least 1/2 of the distal stomach after R0 resection of proximal stomach was evaluated preoperatively.@*CONTRAINDICATIONS@#(1) evaluation indicated distant metastasis of tumor or invasion of other organs; (2) short abdominal esophagus or existence of diaphragmatic hiatal hernia was assessed during the operation; (3) mesentery was too short or the tension was too high; (4) existence of severe comorbidities before surgery; (5) only palliative surgery was required in preoperative evaluation; (6) poor nutritional status.@*MAIN OUTCOME MEASURES@#operation time, intraoperative blood loss, postoperative complications, time to first flatus and time to start liquid diet, postoperative hospital stay, operation cost, etc. Continuous variables that conformed to normal distribution were presented as mean ± standard deviation, and those that did not conform to normal distribution were presented as median (Q1,Q3). Results: All the patients successfully completed TLPG with double-tract reconstruction combined with π-shaped esophagojejunal anastomosis, and postoperative pathology showed that no cancer cells were found on the upper incision margin. The operation time was (247.9±62.4) minutes, the median intraoperative blood loss was 100.0 (62.5, 100.0) ml, no intraoperative blood transfusion was required, the incision length was (4.9±1.0) cm, and the operation cost was (55.5±0.7) thousand yuan. The median time to start liquid diet was 1.0 (1.0, 2.0) days, and the mean time to flatus was (3.1±0.9) days. All the patients were discharged uneventfully. Only 1 patient developed postoperative paralytic ileus and infectious pneumonia with Clavien-Dindo classification of grade II. The patient recovered after conservative treatment. There was no surgery-related death. The postoperative hospital stay was (8.3±2.1) days. Conclusion: The double-tract reconstruction combined with π-shaped esophagojejunal anastomosis after TLPG is safe and feasible, which can minimize surgical trauma and accelerate postoperative recovery.


Subject(s)
Humans , Adenocarcinoma/surgery , Anastomosis, Surgical/methods , Blood Loss, Surgical , Esophagogastric Junction/surgery , Flatulence , Gastrectomy/methods , Laparoscopy , Retrospective Studies , Stomach Neoplasms/surgery
4.
Chinese Journal of Gastrointestinal Surgery ; (12): 157-165, 2022.
Article in Chinese | WPRIM | ID: wpr-936059

ABSTRACT

Objective: To explore the differences of short-term outcomes and quality of life (QoL) for gastric cancer patients between totally laparoscopic total gastrectomy using an endoscopic linear stapler and laparoscopic-assisted total gastrectomy using a circular stapler. Methods: A retrospective cohort study was conducted. Clinicopathological data of patients with stage I to III gastric adenocarcinoma who underwent laparoscopic total gastrectomy from January 2017 to January 2020 were retrospectively collected. Those who were ≥80 years old, had serious complications that could affect the quality of life, underwent multi-organ resections, palliative surgery, emergency surgery due to gastrointestinal perforation, obstruction, bleeding, died or lost to follow-up within 1 year after surgery were excluded. A total of 130 patients were enrolled and divided into circular stapler group (CS group, 77 cases) and linear stapler group (LS group, 53 cases) according to the surgical method. The differences of age, gender, body mass index, number of comorbidities, history of abdominal surgery, ASA, tumor location, degree of differentiation, tumor length, tumor T stage, tumor N stage, tumor pathological stage and preoperative quality of life between the two groups were not statistically significant (all P>0.05). The observation indicators: (1) Surgery and postoperative conditions. (2) Postoperative complications: Any adverse conditions that require conservative treatment or surgical intervention after surgery were defined as postoperative complications, of which, complications occurring within 30 days after surgery were defined as early complications; complications occurring within 30 days to 1 year after surgery were defined as late complications. (3) Postoperative quality of life was assessed by the quality of life core scale (QLQ-C30) and gastric cancer specific module scale (QLQ-STO22). The higher the scores of functional scales and global health status, the better the corresponding quality of life. The higher the scores of symptoms scales, the worse the corresponding quality of life. Results: (1) Surgery and postoperative conditions: Compared with the CS group, the LS group presented less intraoperative blood loss [50.0 (50.0-100.0) ml vs. 100.0 (100.0-100.0) ml, Z=-3.111, P=0.002] and earlier time to flatus [(3.1±0.8) days vs. (3.5±1.1) days, t=-2.490, P=0.014]. However, there were no statistically significant differences between two groups of patients in terms of operation time, time to start a liquid diet and postoperative hospital stay (all P>0.05). (2) Postoperative complications: The early complication rates of the CS group and the LS group were 22.1% (17/77) and 18.9% (10/53), respectively, while the late complication rate were 18.2% (14/77) and 15.1% (8/53), respectively, whose differences were not statistically significant (all P>0.05). (3) Postoperative quality of life: After 1-year follow-up, 7 (5.4%) patients were lost, including 5 in CS group and 2 in LS group. One year after operation, the QLQ-C30 scale showed that the score of financial difficulty of the LS group was significantly higher than that of the CS group [33.3 (0 to 33.3) vs.0 (0 to 33.3), Z=-1.972, P=0.049] with statistically significant difference, and there were no statistically significant differences in the scores of other functional fields and symptom fields between the two groups (all P>0.05). The QLQ-STO22 scale showed that the scores of dysphagia [0 (0 to 5.6) vs. 0 (0 to 11.1), Z=-2.094, P=0.036] and eating restriction were significantly lower [0 (0 to 4.2) vs. 0 (0 to 8.3), Z=-2.011, P=0.044] in patients of the LS group than those of the CS group. There were no significant differences in scores of other symptoms between two groups (all P>0.05). Conclusions: Compared with the circular stapler, the esophagojejunostomy with linear stapler for gastric cancer patients can reduce intraoperative blood loss, shorten the time to flatus after operation, alleviate the symptoms of dysphagia and eating restriction but increase the economic burden to a certain degree.


Subject(s)
Aged, 80 and over , Humans , Gastrectomy/methods , Laparoscopy/methods , Quality of Life , Retrospective Studies , Stomach Neoplasms/pathology , Treatment Outcome
5.
Chinese Journal of Gastrointestinal Surgery ; (12): 40-47, 2022.
Article in Chinese | WPRIM | ID: wpr-936044

ABSTRACT

Objective: To explore the independent risk factors of lymph node metastasis (LNM) in early gastric cancer, and to use nomogram to construct a prediction model for above LNM. Methods: A retrospective cohort study was conducted. Inclusion criteria: (1) primary early gastric cancer as stage pT1 confirmed by postoperative pathology; (2) complete clinicopathological data. Exclusion criteria: (1) patients with advanced gastric cancer, stump gastric cancer or history of gastrectomy; (2) early gastric cancer patients confirmed by pathology after neoadjuvant chemotherapy; (3) other types of gastric tumors, such as lymphoma, neuroendocrine tumor, stromal tumor, etc.; (4) primary tumors of other organs with gastric metastasis. According to the above criteria, 1633 patients with early gastric cancer who underwent radical gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital First Medical Center from December 2005 to December 2020 were enrolled as training set, meanwhile 239 patients with early gastric cancer who underwent gastrectomy at the Department of General Surgery of the Chinese PLA General Hospital Fourth Medical Center from December 2015 to December 2020 were enrolled as external validation set. Risk factors of LNM in early gastric cancer were identified by using univariate and multivariate logistic regression analyses. A nomogram prediction model was established with significant factors screened by multivariate analysis. Area under the receiver operating characteristic curve (AUC) was used for assessing the predictive value of the model. Calibration curve was drawn for external validation. Results: Among 1633 patients in training set, the mean number of retrieved lymph nodes was 20 (13-28), and 209 patients (12.8%) had lymph node metastasis. Univariate analysis showed that gender, resection range, tumor location, tumor morphology, lymph node clearance, vascular invasion, lymphatic cancer thrombus, tumor length, tumor differentiation, microscopic presence of signet ring cells and depth of tumor invasion were associated with LNM (all P<0.05). Multivariate analysis revealed that females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa, and poor differentiation were independent risk factors for LNM in early gastric cancers (all P<0.05). Receiver operating characteristic curve indicated that AUC of training set was 0.818 (95%CI: 0.790-0.847) and AUC of external validation set was 0.765 (95%CI: 0.688-0.843). The calibration curve showed that the LNM probability predicted by nomogram was consistent with the actual situation (C-index: 0.818 in training set and 0.765 in external validation set). Conclusions: Females, tumor morphology as ulcer type, vascular invasion, lymphatic cancer thrombus, tumor length≥3 cm, deeper invasion of mucosa and poor differentiation are independent risk factors for LNM of early gastric cancer. The establishment of a nomogram prediction model for LNM in early gastric cancer has great diagnostic value and can provide reference for treatment selection.


Subject(s)
Female , Humans , Gastrectomy , Lymph Node Excision , Lymph Nodes , Lymphatic Metastasis , Nomograms , Retrospective Studies , Risk Factors , Stomach Neoplasms/surgery
6.
Chinese Journal of Gastrointestinal Surgery ; (12): 153-159, 2021.
Article in Chinese | WPRIM | ID: wpr-942879

ABSTRACT

Objective: At present, there are few studies focusing on the factors short-term complications after total gastrectomy in patients with advanced gastric cancer receiving neoadjuvant chemotherapy (NACT). The purpose of this study is to provide a reference for clinical prevention of complications in these patients. Methods: A retrospective case-control study was conducted. Case inclusion criteria: (1) clinical stage II-III gastric cancer diagnosed by preoperative gastroscopy, pathology, abdominal CT, EUS or PET-CT; (2) evaluated suitable for NACT by MDT discussion; (3) no previous history of other malignant tumors and no concurrent tumor; (4) undergoing total gastrectomy+ D2 lymphadenectomy after NACT. Exclusion criteria: (1) age <18 or >80 years old; (2) severe concurrent diseases, and ASA classification>grade III; (3) stump gastric cancer or history of gastric surgery; (4) incomplete clinicopathological data. According to the above criteria, clinicopathological data of 140 advanced gastric cancer patients who underwent total gastrectomy after NACT in Chinese PLA General Hospital between June 2012 and June 2019 were collected, including 109 males and 31 females with mean age of (56.9±11.4) years and body mass indey (BMI) of (23.3±3.1) kg/m(2). Logistic analysis was used to analyze the relationship between postoperative complication and clinicopathological data. Factors in univariate analysis with P<0.05 were included in the multivariate analysis. Results: Postoperative complications (Clavien-Dindo classification ≥ II) occurred in 35 cases (25.0%) and severe complications (Clavien-Dindo classification ≥ IIIa) occurred in 4 cases (2.9%), including 1 case of esophago-jejunal anastomotic leakage, 1 case of vena cava thrombosis, 1 case of pleural effusion, 1 case of septic shock during perioperative days resulting in death. Univariate analysis showed that BMI (P=0.011), cycle of NACT (P=0.027), tumor diameter (P=0.021), and vascular invasion (P=0.033) were associated with postoperative complication within 30 days, while open/laparoscopic total gastrectomy were not associated with postoperative complication (P=0.926). Multivariate analysis revealed that BMI ≥ 25 kg/m(2) (OR=3.294, 95% CI: 1.343-8.079, P=0.009) and < 4 cycles of NACT (OR=2.922, 95% CI: 1.217-7.016, P=0.016) were independent risk factors for postoperative complication. The 3-year overall survival rates of patients with or without complication were 54.4% and 64.0%, respectively (P=0.395), and 3-year disease-free survival rates were 47.4% and 52.9%, respectively (P=0.587). Conclusions: Higher BMI and fewer cycles of NACT are independent risk factors of postoperative complication in advanced gastric cancer patients undergoing total gastrectomy after NACT. No obvious association is found between postoperative complication and surgical approaches.


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Case-Control Studies , Gastrectomy/adverse effects , Lymph Node Excision , Neoadjuvant Therapy , Postoperative Complications/etiology , Retrospective Studies , Risk Factors , Stomach Neoplasms/surgery
7.
Acta Pharmaceutica Sinica ; (12): 257-2016.
Article in Chinese | WPRIM | ID: wpr-779163

ABSTRACT

Mitochondrion is one of the most vital organelles in cells of human body, and it is involved in many metabolic processes. Mitochondrion dysfunction is closely related to many diseases such as cancers, neurodegenerative diseases, obesity and ischemia reperfusion injury. As a result, mitochondrial drug delivery has gained more and more attention in the drug discovery against these diseases. This review gives a brief introduction to the relationship between mitochondria and human diseases (e.g., cancer), and summarizes the latest trend of mitochondrial targeting drug delivery system (MTDDS).

8.
Acta Pharmaceutica Sinica ; (12): 746-751, 2013.
Article in Chinese | WPRIM | ID: wpr-259555

ABSTRACT

To develop estradiol transdermal film-forming spray (TFS), various polymers were screened using solvent appearance, spray ability, film-forming rate and appearance as indices. The influence of polymer type, plasticizer and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model, and transdermal flux of TFS was compared with commercial patch and gel. The drug existing state in the formed film was investigated by differential scanning calorimetry (DSC). The solvent appearances, spray abilities, film-forming rates and appearances of eudragit E PO, RL PO, hydroxypropyl cellulose EF, polyvinylpyrrolidone K30, Plasdone S630 and Agrimer VA64 were suitable for the preparation of TFS. TFS prepared by Eudragit RL PO had the biggest transdermal flux of estradiol among all the polymers investigated. Triethyl citrate, the plasticizer, decreased the transdermal flux. Azone increased the transdermal flux, while oleic acid, isopropyl myristate and menthol had opposite effects. TFS had a higher transdermal rate and a higher accumulative penetrated estradiol of 24 h than commercial patch and gel. The DSC result showed that estradiol was spread as molecule in the formed film of TFS. It was indicated that TFS could be expected to be an effective transdermal drug delivery system.


Subject(s)
Animals , Administration, Cutaneous , Aerosols , Azepines , Chemistry , Calorimetry, Differential Scanning , Cellulose , Chemistry , Citrates , Chemistry , Drug Delivery Systems , Estradiol , Pharmacokinetics , Plasticizers , Chemistry , Polymers , Chemistry , Skin Absorption , Swine
9.
Acta Pharmaceutica Sinica ; (12): 1209-1220, 2013.
Article in Chinese | WPRIM | ID: wpr-259492

ABSTRACT

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.


Subject(s)
Animals , Humans , Cell Movement , Genetics , Drug Carriers , Gene Targeting , Methods , Gene Transfer Techniques , Genetic Therapy , Methods , Genetic Vectors , Mesenchymal Stem Cells , Cell Biology , Metabolism , Physiology , Neoplasms , Genetics , Therapeutics , Recombinant Proteins , Genetics , Metabolism , Transfection
10.
Journal of Zhejiang University. Medical sciences ; (6): 523-529, 2013.
Article in Chinese | WPRIM | ID: wpr-252595

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug.</p><p><b>METHODS</b>Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated.</p><p><b>RESULTS</b>Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/μg protein which had significant difference with control group [(38.54 ± 0.34)ng/μg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/μg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/μg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug.</p><p><b>CONCLUSION</b>Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.</p>


Subject(s)
Humans , Anions , Cations , Coumarins , Pharmacokinetics , Emulsions , Endocytosis , HeLa Cells , Surface-Active Agents , Pharmacokinetics , Thiazoles , Pharmacokinetics
11.
Journal of Zhejiang University. Medical sciences ; (6): 408-413, 2011.
Article in Chinese | WPRIM | ID: wpr-247238

ABSTRACT

<p><b>OBJECTIVE</b>To compare the differences in antitumor activity between cisplatin (CDDP)-loaded liposomes and nanoparticles in vitro.</p><p><b>METHODS</b>CDDP-gelatin nanoparticles (GPs-Pt) and CDDP-liposomes with similar size, zeta potential, drug loading efficiency and in vitro release property were prepared. The uptake in A549 cells and elimination kinetics were evaluated and antitumor activity was determined by MTT test. The internalization pathways of nanocarriers were studied with inhibitors.</p><p><b>RESULTS</b>Internalization of two nanocarriers was clathrin and actin dependent. Pt accumulation delivered by GPs-Pt was significantly higher than that of liposomes. However, the results of kinetic analysis showed that liposomes had longer cellular retention, and the MRT and AUC were 3 times and twice of GPs-Pt, respectively. The IC(50) of liposomes was significantly lower than GPs-Pt. The values were 2.94±0.21 and 20.70±1.05 μg/ml, respectively.</p><p><b>CONCLUSION</b>Nanocarriers with similar pharmaceutical parameters can induce differences in cellular internalization and elimination, which influence the antitumor activity eventually. Compared with gelatin nanoparticle, liposome is preferable for cisplatin delivery.</p>


Subject(s)
Humans , Adenocarcinoma , Pathology , Antineoplastic Agents , Pharmacology , Cell Line, Tumor , Cisplatin , Pharmacokinetics , Pharmacology , Drug Carriers , Liposomes , Lung Neoplasms , Pathology , Nanoparticles
12.
Acta Pharmaceutica Sinica ; (12): 838-844, 2009.
Article in Chinese | WPRIM | ID: wpr-344032

ABSTRACT

Modern drug delivery system demands high therapeutic efficacy and low toxicity which depends on efficient intracellular transportation of therapeutics to specific organisms, cells, even targeted organelles such as cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum. Intracellular barriers which prevent drug molecules accessing to their targets mainly include cell membrane, lysosomal degradation and the endomembrane system. Nanocarriers can preserve the bioactivities of protein, enzyme and DNA, and also they are easy to be modified and functionalized. In this paper, we summarized the intracellular fate of nanocarriers, especially how to bypass intracellular barriers and then target cytosol, nucleus, mitochondria, lysosome and endoplasmic reticulum by pharmaceutical modifications.


Subject(s)
Animals , Humans , Drug Carriers , Drug Delivery Systems , Nanoparticles , Organelles
13.
China Journal of Chinese Materia Medica ; (24): 1252-1255, 2008.
Article in Chinese | WPRIM | ID: wpr-295373

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effects of different kinds and concentration of transdermal enhancers on Lappaconitine transcutaneous permeation when used individually or together.</p><p><b>METHOD</b>Using modified Franz-type diffusion cell and excised human body skin as an in vitro transdermal model, the concentration of lappaconitine was determined by HPLC, then cumulative permeation quantity (Q) and stability rate (J) of progesterone were calculated.</p><p><b>RESULT</b>Penetration enhancers such as propylene glycol, dodecanol, IPM, and particularly 3% OA and Azone, can significantly enhance the penetration rate of lappaconitine. Concentration effect of penetration enhancers concentration on lappaconitine transcutaneous permeation were found in experiments, the permeation effect of Azone was better than Azone + OA and Azone + propylene glycol.</p><p><b>CONCLUSION</b>The transdermal rate of lappaconitine from batch which contains 3% OA or Azone is higher than others. Combination of Azone with other penetration enhancers is not recommended for Lappaconitine transcutaneous permeation.</p>


Subject(s)
Humans , Aconitine , Metabolism , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Metabolism , Permeability , Skin , Cell Biology , Metabolism
14.
China Journal of Chinese Materia Medica ; (24): 393-396, 2007.
Article in Chinese | WPRIM | ID: wpr-245969

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of different permeation enhancer on transdermal permeation of anemonin through human skin.</p><p><b>METHOD</b>The permeation experiments were performed using human skin on modified Franz diffusion cells in vitro. The concentrations of anemonin in receptor compartment at specified time points were determined by HPLC. The steady flux and the cumulative quantity of anemonin through skin were calculated.</p><p><b>RESULT</b>The flux of anemonin permeating through human skin from 30% ethanol, 50% ethanol solution and a combination of 3% laurocapm -5% polysorbate 20 and 30% ethanol -3 % laurocapm -5% polysorbate 20 of anemonin was (9.30 +/- 0.32), (18.56+/-0.58), (7.29+/-0.35), (13.77+/-0. 16) microg x cm(-2) x h(-1) and 7.9, 15.9, 6.2, 11.8 times higher than from saturated water solution respectively.</p><p><b>CONCLUSION</b>Ethanol and laurocapm can remarkably improve the transdermal permeation of anemonin and the anemonin have the potential to be developed to new transdermal preparation.</p>


Subject(s)
Humans , Administration, Cutaneous , Azepines , Pharmacology , Clematis , Chemistry , Ethanol , Pharmacology , Furans , Pharmacokinetics , In Vitro Techniques , Permeability , Plants, Medicinal , Chemistry , Skin , Metabolism , Skin Absorption
15.
China Journal of Chinese Materia Medica ; (24): 484-487, 2007.
Article in Chinese | WPRIM | ID: wpr-283451

ABSTRACT

<p><b>OBJECTIVE</b>To prepare the alpha-asarone reservoir patch and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug's permeation rate.</p><p><b>METHOD</b>The alpha-asarone reservoir patch was prepared using 1% hydroxypropyl methylcellulose (HPMC) of ethanol solution as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and several permeation enhancers were evaluated. High performance liquid chromatorgraphy (HPLC) was used to determine alpha-asarone's content and permeation rate.</p><p><b>RESULT</b>The release mechanisms of alpha K-asarone patch in vitro coincided with zero-order kinetic. 30% ethanol cooperates with 1% Isopropyl Myristate (IPM) have the best effect on permeation of the patch. The permeation rate reaches (20.67 +/- 1.33) microg x cm(-2) h(-1).</p><p><b>CONCLUSION</b>Ethanol combined with IPM is good permeation enhancer, which facilitated the permeation of alpha K-asarone to fit the clinical requirements. However, the further studies of the skin's stimulation and bioavailability are needed.</p>


Subject(s)
Humans , Acorus , Chemistry , Administration, Cutaneous , Anisoles , Pharmacokinetics , Delayed-Action Preparations , Pharmacokinetics , Ethanol , Pharmacology , Hypromellose Derivatives , In Vitro Techniques , Methylcellulose , Chemistry , Myristates , Pharmacology , Plants, Medicinal , Chemistry , Polyvinyls , Chemistry , Skin , Metabolism , Skin Absorption
16.
China Journal of Chinese Materia Medica ; (24): 805-807, 2007.
Article in Chinese | WPRIM | ID: wpr-283382

ABSTRACT

<p><b>OBJECTIVE</b>To prepare the quercetin self-emulsified formulation and evaluate its quality.</p><p><b>METHOD</b>The quercetin self-emulsified formulation was optimized based on the quercetin solubility in different oils, and the self-microemulsified efficiency of various combinations of emulsifier and co-emulsifier evaluated using the pseudo-ternary phase diagram. The microemulsion of morphology, size and zeta potential were examined. The quercetin of solubility in self-emulsified system was tested and the formulation stability was investigated by accelerated experiment.</p><p><b>RESULT</b>The blank self-emulsified system was composed of ethyl oleate/Cremophor EUL/butanol with weight ratio of 10: 54: 36. After being dilutied with water, the morphology of microemulsion was homogeneous small spherical drops observed under the electro-microscopy. The particle size and the zeta potential were 16.3 +/- 4.6 nm and 2.1 +/- 0.8 mV, respectively. The solubility of quercetin in self-emulsifing system was (62.42 +/- 0.11) mg x mL(-1), increased 2 229 folds compared with that of in water. The quality of quercetin self-emulsified formulation was stable during the 3 months storage at 40 degrees C.</p><p><b>CONCLUSION</b>The solubility of quercetin is significantly increased in self-emulsified system and the formulation is stable and easy to prepare.</p>


Subject(s)
Antioxidants , Chemistry , Butanols , Chemistry , Chromatography, High Pressure Liquid , Drug Delivery Systems , Drug Stability , Emulsions , Glycerol , Chemistry , Oleic Acids , Chemistry , Particle Size , Quercetin , Chemistry , Solubility , Solvents , Technology, Pharmaceutical , Methods
17.
Acta Pharmaceutica Sinica ; (12): 1116-1120, 2006.
Article in Chinese | WPRIM | ID: wpr-294878

ABSTRACT

<p><b>AIM</b>To construct an efficient recombinant viral vector for gene therapy.</p><p><b>METHODS</b>First-generation adenovirus (Ad) vector was modified with the RGD peptide inserted into the fiber. Both in vitro and in vivo experiments of gene expression in different tumor cells with conventional and recombinant vectors were conducted. RT-PCR was used for detecting the expression of coxackievirus and adenovirus receptor and integrin at the surface of Meth-A cells.</p><p><b>RESULTS</b>Fiber-mutant adenovirus vector showed a notably enhanced gene expression in A2058, B16BL6, OV-HM, and Meth-A tumor cells compared with that of conventional ones. In vivo study carried out using Meth-A tumor-bearing mice also demonstrated that the intra-tumoral injection of recombinant adenovirus induced strong gene expression in these CAR-deficient tumor cells.</p><p><b>CONCLUSION</b>The recombinant vector can be a promising one for effective cancer gene therapy.</p>


Subject(s)
Animals , Female , Humans , Mice , Adenoviridae , Genetics , Amino Acid Sequence , Base Sequence , Cell Line , Cell Line, Tumor , Enterovirus , Genetics , Gene Expression Regulation, Neoplastic , Genetic Therapy , Methods , Genetic Vectors , Green Fluorescent Proteins , Genetics , Metabolism , Integrins , Genetics , Metabolism , Luciferases , Genetics , Metabolism , Mice, Inbred BALB C , Microscopy, Fluorescence , Mutation , Neoplasm Transplantation , Neoplasms, Experimental , Genetics , Pathology , Therapeutics , Oligopeptides , Genetics , Receptors, Virus , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transfection
18.
Acta Pharmaceutica Sinica ; (12): 493-497, 2006.
Article in Chinese | WPRIM | ID: wpr-271419

ABSTRACT

<p><b>AIM</b>To prepare cells scaffolds with the characteristics of sustained release of proteins.</p><p><b>METHODS</b>Chitosan scaffolds was prepared by freeze-drying. Porosity and water content of scaffolds were determined. Bovine serum album (BSA) was selected as a model protein. Poly (lactic-co-glycolic acid) (PLGA) microspheres were prepared by double emulsion solvent evaporation and encapsulated into chitosan scaffolds. The morphology of PLGA microspheres and various scaffolds were observed using scanning electron microscope. Release behavior of BSA from various chitosan scaffolds was investigated.</p><p><b>RESULTS</b>The chitosan scaffold represents porous. At the -70 degrees C of quenching temperature, the porosity and water content of chitosan scaffolds were 78.6% +/- 1.5% and 85.1% +/- 6.2%, respectively. PLGA microspheres can be uniformly encapsulated into scaffolds without any morphology change. Significant sustained release of BSA from PLGA microspheres encapsulated into scaffolds was obtained. The cumulative release at 168 h was only 33.5%, while that of BSA from chitosan scaffolds at 24 h was above 90%. The release behavior can be controlled by adjusting the amount of chitosan in scaffolds and the type of PLGA.</p><p><b>CONCLUSION</b>The novel chitosan scaffolds encapsulating PLGA microspheres proved to be a promising cells scaffolds with controlling the release of growth factors in tissue engineering.</p>


Subject(s)
Chitosan , Chemistry , Drug Carriers , Freeze Drying , Methods , Lactic Acid , Chemistry , Microspheres , Polyglycolic Acid , Chemistry , Polymers , Chemistry , Serum Albumin, Bovine , Metabolism , Tissue Engineering , Methods
19.
Acta Pharmaceutica Sinica ; (12): 182-186, 2005.
Article in Chinese | WPRIM | ID: wpr-241350

ABSTRACT

<p><b>AIM</b>To elevate the encapsulation efficiency, decrease the burst release and improve the release of protein entrapped in poly (lactic-co-glycolic acid) (PLGA) microspheres. The bovine serum albumin (BSA) composite microspheres of alginate-chitosan-PLGA were prepared and the release characteristics of BSA from this composite microspheres were studied.</p><p><b>METHODS</b>The much smaller calcium alginate microcapsules were first prepared by a modified emulsification method in an isopropyl alcohol-washed way and coated with chitosan, then the alginate-chitosan microcapsules were further entrapped in PLGA to form the composite microspheres. The protein concentration was determined using a BCA protein assay kit. The release profiles were changed with various formulation factors.</p><p><b>RESULTS</b>The average diameter of the composite microcapsules was about 30 microm. Comparing with 60% to 70% of the conventional PLGA microspheres, the average encapsulation efficiency was more than 80%, and the burst releases in phosphate buffer solution of the composite microspheres decreased from 40% and 50% to 25% and further to 5% in saline solution.</p><p><b>CONCLUSION</b>The novel composite microspheres were prepared, the drug encapsulation efficiency increased and the burst release decreased. The desired release profiles could be obtained by regulating the ratios of PLG and PLA in the composite microspheres.</p>


Subject(s)
Alginates , Chemistry , Chitosan , Chemistry , Drug Delivery Systems , Methods , Lactic Acid , Chemistry , Microspheres , Particle Size , Polyglycolic Acid , Chemistry , Polymers , Chemistry , Serum Albumin, Bovine , Chemistry
20.
Acta Pharmaceutica Sinica ; (12): 950-953, 2005.
Article in Chinese | WPRIM | ID: wpr-253534

ABSTRACT

<p><b>AIM</b>To survey the uptake behavior and subcellular distribution of antisense oligodeoxynucleotide polymethacrylate submicroparticles (AS-ODN-SMP) and infer its mechanism in MGC cell lines.</p><p><b>METHODS</b>MGC cells were incubated at certain concentration of AS-ODN-SMP or AS-ODN for 8 h at 4 degrees C or 37 degrees C. Then the fluorescence oligodeoxynucleotide- labeled cells were counted by flow cytometer and the intracellular fluorescence intensity was determined after incubated with chloroquine for 2 h.</p><p><b>RESULTS</b>Cellular uptake of oligodeoxynucleotides was significantly increased following application of AS-ODN-SMP and total intracellular fluorescence intensity was enhanced by 683 folds with the vehicle concentration of 20 microg x mL(-1). AS-ODN-SMP entranced to cells profoundly with temperature-dependent manner. Rare cells took on fluorescence when incubated at 4 degrees C, while 37 degrees C they were significantly increased. But the intracellular fluorescence intensity appeared same level in present or absent of chloroquine.</p><p><b>CONCLUSION</b>With the help of polyacrylate submicroparticles, oligonucleotides efficiently entranced the cells via endocytosis and could successfully escape the degradation in lysosome.</p>


Subject(s)
Animals , Cell Line , Drug Carriers , Drug Delivery Systems , Endocytosis , Giant Cells , Cell Biology , Lysosomes , Metabolism , Nanoparticles , Oligodeoxyribonucleotides, Antisense , Pharmacokinetics , Particle Size , Polymethacrylic Acids , Chemistry , Pharmacology , Temperature
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