In Vitro and In Vivo Studies of Different Liposomes Containing Topotecan

Hao, Yan-Li,Deng, Ying-Jie,Chen, Yan,Wang, Xiu-Min,Zhong, Hai-Jun,Suo, Xu-Bin The Pharmaceutical Society of Korea 2005 Archives of Pharmacal Research Vol.28 No.5

Liposome as a carrier of topotecan (TPT), a promising anticancer drug, has been reported in attempt to improve the stability and antitumor activity of TPT. However, the biodistr ibution pattern of TPT liposome in vivo and PEG-modified liposome containing TPT have not been studied systemically. In this paper, the in vitro stability and in vivo biodistribution behavior of several liposomes containing TPT with different lipid compositions and PEG-modification were studied. Compared with the 'fluid' liposome (S-Lip) composed of soybean phosphatidylcholine (SPC), the 'solid' liposome (H-Lip) composed of hydrogenated soybean phosphatidylcholine HSPC decreased the leaking efficiency of TPT from liposome and enhanced the stability of liposome in fetal bovine serum (FBS) or human blood plasma (HBP). The results of biodistribution studies in S$_{180}$ tumor-bearing mice showed that liposomal encapsulation increased the concentrations of total TPT and the ratio of lactone form in plasma. Compared with free TPT, S-Lip and H-Lip resulted in 5- and 19- fold increase in the area under the curve (AUC$_{0\rightarrow\propto}$), respectively. PEG- modified H-Lip (H-PEG) showed 3.7-fold increase in AUC$_{0\rightarrow\propto}$ compared with H-Lip, but there was no significant increase in t$_{1/2}$ and AUC$_{0\rightarrow\propto}$ for PEG-modified S-Lip (S-PEG) compared with S-Lip. Moreover, the liposomal encapsulation changed the biodistribution behavior, and H-Lip and H-PEG dramatically increased the accumulation of TPT in tumor, and the relative tumor uptake ratios were 3.4 and 4.3 compared with free drug, respectively. There was also a marked increase in the distribution of TPT in lung when the drug was encapsulated into H-Lip and H-PEG. Moreover, H-PEG decreased the accumulation of TPT in bore marrow compared with unmodified H-Lip. All these results indicated that the membrane fluidity of liposome has an important effect on in vitro stability and in vivo biodistribution pattern of liposomes containing TPT, and PEG-modified 'solid' liposome may be an efficient carrier of TPT.

Applicability Analysis of Microseismic Technology in Tunnel Water Inrush Monitoring

Yan-hao Chen,Shuai Cheng,Li-Ping Li,Jun-yan Yang,Hong-liang Liu,Wen-feng Tu 대한토목학회 2021 KSCE JOURNAL OF CIVIL ENGINEERING Vol.25 No.7

Water inrush disaster is one of the most serious geological disasters in tunnel construction. There are still some problems in the existing researches, such as the activity information of surrounding rock is difficult to obtain, the mechanism of water inrush disaster is unclear, the correlation between water inrush disaster and microseismic (MS) information is missing, which have caused the water inrush disaster to be passively controlled. Combining with the practical experience of tunnel engineering, the application problems of MS technology in tunnel engineering is summarized, which provides ideas for monitoring of surrounding rock activity. The formation mechanism of water inrush disaster caused by rock mass fracturing and filling medium instability has been revealed. The MS characteristics of the water inrush channel in different water inrush disasters have also been revealed. The MS response characteristics of water inrush and rockburst disasters are compared, which provides guidance for the improvement of MS monitoring technology and the analysis of effective MS information. The compression failure test of limestone under saturated and natural conditions is carried out. The results show that the presence of water weakens the ability of rock to store energy. The acoustic emission (AE) phenomenon is weaker in the process of saturated limestone failure, which increases the difficulty of AE monitoring. The number of AE events of natural limestone and saturated limestone shows a slow increase to a sudden increase in the process stress loading, which can be regarded as an important precursor of rock failure.

In Vitro and In Vivo Studies of Different Liposomes Containing Topotecan

Yan-Li Hao,Ying-Jie Deng,Yan Chen,Xiu-Min Wang,Hai-Jun Zhong,Xu-Bin Suo 대한약학회 2005 Archives of Pharmacal Research Vol.28 No.5

Two new sesquiterpenoids from endophytic fungus J3 isolated from Mangrove Plant Ceriops tagal

Yan-Bo Zeng,Hai-Gang Gu,Wen-Jian Zuo,Li-Li Zhang,Hong-Jin Bai,Zhi-Kai Guo,Peter Proksch,Wen Li Mei,Hao Fu Dai 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5

Two new sesquiterpenoids, named 2a-hydroxyxylaranolB (1) and 4b-hydroxyxylaranol B (2), togetherwith a known diterpenoid 3,4-seco-sonderianol (3) wereisolated from the fermentation of endophytic fungus J3 ofCeriops tagal. Their structures were elucidated based onspectroscopic methods including 1D and 2D NMR(HMQC, 1H-1H COSY and HMBC). All compounds wereevaluated for their cytotoxic activities by MTT method,and compound 3 exhibited cytotoxic activities againstK562, SGC-7901, and BEL-7402 cell lines.

Encapsulation, Pharmacokinetics and Tissue Distribution of Interferon α-2b Liposomes after Intramuscular Injection to Rats

Hao Li,Li Yang,Gang Cheng,Hong-Yan Wei,Qun Zeng 대한약학회 2011 Archives of Pharmacal Research Vol.34 No.6

The aim of the present study was to investigate the effect of liposome-encapsulation and liposome-size on the in vivo pharmacokinetics of interferon α-2b (IFNα-2b) following i.m. administration to rats, and whether there was any liver-targeting of these liposomes. Since liposomes of different sizes can be obtained by homogenization, the effect of homogenization on the IFNα-2b activity was also investigated. The pharmacokinetics of IFNα-2b solution (12.8 μg/kg) and IFNα-2b prepared in liposomes, including three mean sizes of 172 nm (12.2 μg/kg), 113 nm (44.2, 11.0, and 2.8 μg/kg, respectively), and 82 nm (13.1 μg/kg), were studied after a single i.m. dose to rats. Compared to a solution of IFNα-2b. administration of liposomal IFNα-2b resulted in a significantly prolonged t_max, the apparent elimination half life (t_(1/2β)) was 2.3 times longer, both AUC_(0-∞) and MRT_(0-∞) were also clearly enhanced and greater accumulation was obtained in the liver (p < 0.05). The AUC_(0-∞) increased proportionally to the administered dose of IFNα-2b liposomes. Moreover, the size of liposomes ranging from 82 nm to 172 nm had no significant difference on the pharmacokinetic behavior in vivo (p > 0.05). In sum, compared with the free form, IFNα-2b encapsulated in liposomes can alter strikingly the pharmacokinetics properties following i.m. injection and if a liposomal size ranging from 82 nm to 172 nm was used, consistent pharmacokinetic behaviors of IFNα-2b was exhibited. The liposomal formulation apparently targeted the liver, offering a potential advantage for hepatitis B treatment.

Colorectal Cancer Concealment Predicts a Poor Survival: A Retrospective Study

Li, Xiao-Pan,Xie, Zhen-Yu,Fu, Yi-Fei,Yang, Chen,Hao, Li-Peng,Yang, Li-Ming,Zhang, Mei-Yu,Li, Xiao-Li,Feng, Li-Li,Yan, Bei,Sun, Qiao Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.7

Objectives: Understanding the situation of cancer awareness which doctors give to patients might lead to prognostic prediction in cases of of colorectal cancer (CRC). Methods: Subsets of 10,779 CRC patients were used to screen the risk factors from the Cancer Registry in Pudong New Area in cancer awareness, age, TNM stage, and gender. Survival of the patients was calculated by the Kaplan-Meier method and assessed by Cox regression analysis. The views of cancer awareness in doctors and patients were surveyed by telephone or household. Results: After a median observation time of 1,616 days (ranging from 0 to 4,083 days) of 10,779 available patients, 2,596 of the 4,561 patients with cancer awareness survived, whereas 2,258 of the 5,469 patients without cancer awareness and 406 of the 749 patients without information on cancer awareness died of the disease. All-cause and cancer-specific survival were poorer for the patients without cancer awareness than those with (P < 0.001 for each, log-rank test). Cox multivariate regression analysis showed that cancer concealment cases had significantly lower cancer-specific survival (hazard ratio (HR) = 1.299; 95 % confidence interval (CI): 1.200-1.407)and all-cause survival (HR = 1.324; 95 % CI: 1.227-1.428). Furthermore, attitudes of cancer awareness between doctors and patients were significantly different (P < 0.001). Conclusion: Cancer concealment, not only late-stage tumor and age, is associated with a poor survival of CRC patients.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

Li, Xing,Dong, Min,Wen, Jing-Yun,Wei, Li,Ma, Xiao-Kun,Xing, Yan-Fang,Deng, Yun,Chen, Zhan-Hong,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wang, Tian-Tian,Wu, Dong-Hao,Liu, Xu,Hu, Hai-Tao,Lin, Jia-Yu,Li, Zhu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

Neutrophil Count and the Inflammation-based Glasgow Prognostic Score Predict Survival in Patients with Advanced Gastric Cancer Receiving First-line Chemotherapy

Li, Qing-Qing,Lu, Zhi-Hao,Yang, Li,Lu, Ming,Zhang, Xiao-Tian,Li, Jian,Zhou, Jun,Wang, Xi-Cheng,Gong, Ji-Fang,Gao, Jing,Li, Jie,Li, Yan,Shen, Lin Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2

Purpose: To explore the value of systemic inflammatory markers as independent prognostic factors and the extent these markers improve prognostic classification for patients with inoperable advanced or metastatic gastric cancer (GC) receiving palliative chemotherapy. Methods: We studied the prognostic value of systemic inflammatory factors such as circulating white blood cell count and its components as well as that combined to form inflammation-based prognostic scores (Glasgow Prognostic Score (GPS), Neutrophil-Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio (PLR), Prognostic Index (PI) and Prognostic Nutritional Index (PNI)) in 384 patients with inoperable advanced or metastatic gastric cancer (GC) receiving first-line chemotherapy. Univariate and multivariate analyses were performed to examine the impact of inflammatory markers on overall survival (OS). Results: Univariate analysis revealed that an elevated white blood cell, neutrophil and/or platelet count, a decreased lymphocyte count, a low serum albumin concentration, and high CRP concentration, as well as elevated NLR/PLR, GPS, PI, PNI were significant predictors of shorter OS. Multivariate analysis demonstrated that only elevated neutrophil count (HR 3.696, p=0.003) and higher GPS (HR 1.621, p=0.01) were independent predictors of poor OS. Conclusion: This study demonstrated elevated pretreatment neutrophil count and high GPS to be independent predictors of shorter OS in inoperable advanced or metastatic GC patients treated with first-line chemotherapy. Upon validation of these data in independent studies, stratification of patients using these markers in future clinical trials is recommended.

Combination of Tumor Volume and Epstein-Barr Virus DNA Improved Prognostic Stratification of Stage II Nasopharyngeal Carcinoma in the Intensity Modulated Radiotherapy Era: A Large-Scale Cohort Study

Qiu-Yan Chen,Shao-Yan Guo,Lin-Quan Tang,Tong-Yu Lu,Bo-Lin Chen,Qi-Yu Zhong,Meng-Sha Zou,Qing-Nan Tang,Wen-Hui Chen,Shan-Shan Guo,Li-Ting Liu,Yang Li,Ling Guo,Hao-Yuan Mo,Rui Sun,Dong-Hua Luo,Chong Zha 대한암학회 2018 Cancer Research and Treatment Vol.50 No.3

Purpose Little is known about combination of the circulating Epstein-Barr viral (EBV) DNA and tumor volume in prognosis of stage II nasopharyngeal carcinoma (NPC) patients in the intensity modulated radiotherapy (IMRT) era. We conducted this cohort study to evaluate the prognostic values of combining these two factors. Materials and Methods By Kaplan-Meier, we compare the differences of survival curves between 385 patients with different EBV DNA or tumor volume levels, or with the combination of two biomarkers mentioned above. Results Gross tumor volume of cervical lymph nodes (GTVnd, p < 0.001) and total tumor volume (GTVtotal, p < 0.001) were both closely related to pretreatment EBV DNA, while gross tumor volume of nasopharynx (GTVnx, p=0.047) was weakly related to EBV DNA. EBV DNA was significantly correlated with progress-free survival (PFS, p=0.005), locoregional-free survival (LRFS, p=0.039), and distant metastasis-free survival (DMFS, p=0.017), while GTVtotal, regardless of GTVnx and GTVnd, had a significant correlation with PFS and LRFS. The p-values of GTVtotal for PFS and LRFS were 0.008 and 0.001, respectively. According to GTVtotal and pretreatment EBV DNA level, patients were divided into a low-risk group (EBV DNA 0 copy/mL, GTVtotal < 30 cm3; EBV DNA 0 copy/mL, GTVtotal  30 cm3; or EBV DNA > 0 copy/mL, GTVtotal < 30 cm3) and a high-risk group (EBV DNA > 0 copy/mL, GTVtotal  30 cm3). When patients in the low-risk group were compared with those in the high-risk group, 3-year PFS (p=0.003), LRFS (p=0.010), and DMFS (p=0.031) rates were statistically significant. Conclusion Pretreatment plasma EBV DNA and tumor volume were both closely correlated with prognosis of stage II NPC patients in the IMRT era. Combination of EBV DNA and tumor volume can refine prognosis and indicate for clinical therapy.

Anatomical Study of the Accessory Tendon of the Extensor Hallucis Longus Muscle and Its Clinical Application

Yue Li,Jing-Ying Zhang,Xin-Yue Zhao,Li-Ya Pan,De-Hao Jin,He-Xing Xu,Hu-Zhe Cui,Yan-Qun Liu,Xiang-Zheng Qin,Qingyuan Li 대한정형외과학회 2021 Clinics in Orthopedic Surgery Vol.13 No.2

Background: The accessory tendon of the extensor hallucis longus (ATEHL) muscle is a common abnormal structure, and its clinical significance remains debatable. In this study, we provide the incidence of the ATEHL and characterize its morphological types in Asian cadavers and investigate its clinical applications. Methods: The tendons from 50 adult cadaveric feet, fixed in 10% formalin, were analyzed. We measured the length and width of both the ATEHL and the extensor hallucis brevis (EHB). Results: All dissected specimens had an ATEHL. The first metatarsophalangeal joint was surrounded by an accessory tendon that inserted onto the joint capsule and the dorsal base of the proximal phalanx. We classified the ATEHL into 3 types based on their directions. Differences in ATEHL type based on sex were not statistically significant. Conclusions: We found an ATEHL in all cadaveric specimens in this study. We surmise that the ATEHL acts as an antagonist with the EHB when the toe is extending, which might help prevent the occurrence of hallux valgus deformity.