To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.
Antineoplastic Agents ; chemistry ; Cell-Penetrating Peptides ; chemistry ; DNA ; chemistry ; Drug Delivery Systems ; HeLa Cells ; Humans ; Neoplasms ; drug therapy ; Particle Size ; Plasmids

The systematic treatment based on gemcitabine plus cisplatin is recommended as the current standard chemotherapy for unresectable or metastatic biliary tract cancers.However,the exact benefits from the recognized regime are still dismal.We thus elicit this study in an attempt to analyze whether targeted therapy coupled with various chemotherapy could produce improvement of survival benefits.The clinical trials were searched electronically from databases till July 2016 published in English and Chinese.Nine hundred and sixty-four patients from 7 trials were identified in our analysis.The overall analysis achieved a significantly higher overall response rate (ORR) among the patients treated with targeted drugs plus chemotherapy than chemotherapy alone (OR=1.87;95％ CI:1.37-2.57;P=0.000),but failed in the overall progression-free survival (PFS) [mean difference (MD)=0.63;95％ CI:-0.45-1.72;P=0.26] and overall survival (OS) (MD=-0.67;95％ CI:-2.54-1.20;P=0.49).In the sub analysis,better ORR was obtained with the addition of EGFR (OR=1.75;95％ CI:1.20-2.56;P=0.004) and VEGFR (OR=2.5;95％ CI:1.28-4.87;P=0.007) targeted therapy.Furthermore,the sub analysis of EGFR target showed an significant improvement on PFS (MD=l.36;95％ CI:0.29-2.43;P=0.01).No significant differences were observed in the incidences ofneutropenia (OR=1.37;95％ CI:0.89-2.12),thrombocytopenia (OR=l.40;95％ CI:0.83-2.39),anemia (OR=l.21;95％ CI:0.62-2.38),peripheral neuropathy (OR=1.52;95％ CI:0.81-2.88),increased AST/ALT (OR=l.40;95％ CI:0.82-2.39) as well as fatigue (OR=1.65;95％ CI:0.96-2.84) in either of the treatment groups.In conclusion,better ORR associated with chemotherapy combined with targeted therapy (both targeting EGFR and VEGF) is found in the present mcta-analysis without the cost of increased unacceptable toxicities,but regretfully not for the OS.The sub-analysis of targeting EGFR instead of VEGF obtains a superior PFS.Otherwise,there is no statistically significant difference in the overall PFS between the combination regime and chemotherapy alone.Given the paucity of favorable data,we need further studies to characterize optimal targeted agents to confirm the potential value to biliary tract cancer.

OBJECTIVETo evaluate the role and the performance of diffusion weighted imaging (DWI) for predicting the early response to neoadjuvant chemotherapy (NAC) in local advanced breast cancer (LABC) and to assess the accuracy of DWI in evaluating residual lesion after NAC.

METHODS88 women with LABC (89 lesions) underwent DWI before and after the first and final cycle of NAC. For each patient, the apparent diffusion coefficient (ADC) values were compared between the baseline and follow-up to predict the early response to NAC. The residual tumor volumes were obtained using 3D maximum intensity projections (MIP) of DWI map, and were compared with pathological findings to assess the accuracy of DWI in detecting and measuring residual tumor. All results were proved or analyzed comparing with the data from histopathology.

RESULTSThere were 68 lesions responding to NAC, while 21 non-responders. The baseline ADC values of responders and non-responders were (1.049 +/- 0.135) x 10(-3) mm(2)/s and (1.171 +/- 0.134) x 10(-3)mm(2)/s, respectively, with a significant difference (t = -2.731, P = 0.009 < 0.01). The ADC value measured prior to treatment was (1.087 +/- 0.146) x 10(-3)mm(2)/s, and the degree of the changes in tumor volume after NAC was (70.4% +/- 55.1)%. A negative correlation was observed (r = -0.430, P = 0.025 < 0.05). In the response group, there was a significant difference in ADC value between prior to NAC and 1st cycle of NAC, the final cycle of NAC, respectively (P < 0.001). While no significant differences were found in non-responders during NAC (P > 0.05). The tumor volume correlation coefficient between DWI and pathology measurements was very high (r = 0.749, P < 0.01).

CONCLUSIONDWI appears to provide functional information regarding changes in ADC value of tumors due to NAC. DWI may be useful in monitoring the early pathological response of tumor after the initiation of treatment and in evaluating the residual tumor after NAC.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; Carcinoma, Lobular ; drug therapy ; pathology ; Diffusion Magnetic Resonance Imaging ; methods ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; methods ; Neoplasm, Residual ; pathology ; Paclitaxel ; administration & dosage ; Prospective Studies ; Young Adult

OBJECTIVETo analyze and investigate the rules for drug utilization of Chinese medicine for the treatment of psoriasis vulgaris with blood-heat syndrome.

METHODSThe literatures that met the following inclusion criteria were screened out from China National Knowledge Infrastructure (CNKI) from January 1998 to December 2008, including the compositions and dosages of the recipes reported completely and accurately, the sample size being [Symbol: see text] 30 cases and the total effective rate being [Symbol: see text] 70%.

RESULTSIn total, 289 papers meeting the inclusion criteria were retrieved, involving 301 recipes; in which 111 recipes consisting of 145 individual drugs were the function for clearing the heat, accounting for 52.84%. The three drugs with the highest utilized frequency were Radix Rehmanniae, Radix Arnebiae seu Lithospermi and Cortex Moutan. Meridian adscription of the drugs was mainly the Gan-meridian.

CONCLUSIONThere were rules for the treatment of psoriasis vulgaris of blood-heat syndrome with Chinese medicine prescriptions.

Chemistry, Pharmaceutical ; Drugs, Chinese Herbal ; therapeutic use ; Hematologic Diseases ; drug therapy ; etiology ; Hot Temperature ; Humans ; Medicine, Chinese Traditional ; methods ; Psoriasis ; complications ; drug therapy ; Review Literature as Topic ; Syndrome

OBJECTIVETo assess the value of dynamic contrast-enhanced MRI (DMRI) in predicting early response to neoadjuvant chemotherapy (NAC) in patients with locally advanced breast cancer (LABC) and to assess the accuracy of MRI in evaluation of residual disease after NAC.

METHODSForty-three women with LABC (44 lesions, all were invasive ductal carcinoma) underwent DMRI before, after the first and final cycles of NAC. For each patient, the tumor volume, early enhancement ratio (E1), maximum enhancement ratio (Emax), and maximum enhancement time (Tmax), dynamic signal intensity-time curve were obtained during treatment. The residual tumor volumes obtained by DMRI were compared with pathological findings to assess the accuracy of DMRI.

RESULTSAfter the first cycle of NAC, the mean volume of responders decreased insignificantly (P = 0.055), but after NAC, mean volume of residual tumor decreased significantly (P = 0.000). Morphological changes: 29 cases showed a concentric shrinkage pattern while 7 cases showed a dendritic shrinkage pattern. Significant differences were found in E1, Emax and Tmax between responders and non-responders (P < 0.05). After the first cycle of NAC, E1, Emax and Tmax of responders changed significantly (P < 0.001), while there was no significant change in non-responders (P > 0.05). After NAC, the dynamic signal intensity-time types were changed in responders, and tended to be significantly flattening, while no significant change was found in non-responders. The residual tumor volume correlation coefficient between MRI and pathology measurements was very high (r = 0.866, P < 0.01).

CONCLUSIONDMRI is useful to evaluate the early response to NAC in LABC. The presence and volume of residual tumor in LABC patients treated with NAC can be accurately evaluated by DMRI.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Carboplatin ; administration & dosage ; Carcinoma, Ductal, Breast ; drug therapy ; pathology ; Chemotherapy, Adjuvant ; Contrast Media ; Female ; Humans ; Magnetic Resonance Imaging ; methods ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Neoplasm, Residual ; Paclitaxel ; administration & dosage

OBJECTIVETo explore the relationship between mutant p53 and multidrug resistance in gastric cancer.

METHODSMutant p53 (mp53) and mp53+sv40Tag were transferred to gastric cancer cell line SGC-7901. The MDR-1 mRNA was examined using RT-PCR, and the difference in chemotherapeutic sensitivity of SGC-7901 cells with mutant p53 was compared with those with mp53+sv40Tag and controls by MTT method.

RESULTSSGC-7901 cells with mutant p53 showed higher MDR-1 mRNA than that of other two groups. SGC-7901 cells with mutant p53 showed higher chemotherapeutic sensitivity to 5-Fu than that with mp53+sv40Tag and control (P<0.05), but no difference between those with mp53+sv40Tag and control (P>0.05). SGC-7901 cells with mutant p53 and those with mp53+sv40Tag showed higher chemotherapeutic sensitivity to ADM than control (P<0.05), but no difference between those with mp53 and with mp53+sv40Tag (P>0.05). There was no difference in chemotherapeutic sensitivity of SGC-7901 cells with mutant p53 compared with those with mp53+sv40Tag and control to CDDP (P>0.05).

CONCLUSIONMutante p53 genes relates to multidrug resistance of gastric cancer.

ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; Adenocarcinoma ; genetics ; Drug Resistance, Multiple ; genetics ; Humans ; Mutation ; RNA, Messenger ; biosynthesis ; genetics ; Stomach Neoplasms ; genetics ; Tumor Cells, Cultured ; Tumor Suppressor Protein p53 ; genetics

Dioscin has a wide range of biological effects and broad application prospects. However the studies concerning the toxicology and mechanism of dioscin is small. This article is to study the hepatotoxicity of dioscin and the effect of dioscin treatment on expression of aryl hydrocarbon receptor (AhR) mRNA and CYP1A mRNA and protein in HepG2 cells in vitro. Dioscin 0.5-32 µmol · L(-1) exposed to HepG2 cells for 12 h, cell viability was examined by CCK-8 assay and the release rate of lactate dehydrogenase (LDH) was to evaluate cell membrane damage. HepG2 cells morphologic changes were quantified by inverted Microscope, and the effect on production of reactive oxygen species (ROS) was detected by flow cytometry. The mRNA expression of CYP1A and AhR was evaluated by RT-RCR. The protein expression of CYP1A1 was detected by western blot. The cell viability was significantly inhibited after HepG2 cells were exposed to dioscin 0.5-32 µmol · L(-1). Compared with the control, the LDH release rate and ROS were significantly increased. The expression of CYPlA and AhR mRNA was increased. The expression of CYP1Al protein was increased after dioscin treatment, and resveratrol, an AhR antagonist, could downregulate the expression of CYP1A1. It follows that large doses dioscin has potential hepatotoxicity. The possible mechanism may be dioscin can active aryl hydrocarbon receptor (AhR) and induce the expression of CYP1A.
Cell Survival ; drug effects ; Chemical and Drug Induced Liver Injury ; etiology ; Cytochrome P-450 CYP1A1 ; genetics ; Diosgenin ; analogs & derivatives ; toxicity ; Hep G2 Cells ; Humans ; L-Lactate Dehydrogenase ; secretion ; RNA, Messenger ; analysis ; Reactive Oxygen Species ; metabolism ; Receptors, Aryl Hydrocarbon ; genetics

Objective To study the influence on the tumor after percutaneous intra-tumor injection of ~(32)P-GMS in liver cancer as well as its suitable dose.Methods 24 New Zealand rabbits were used to establish the animal model of VX-2 liver cancer,and divided into A,B,C and D groups with individually 37,74,111 and 148 MBq of ~(32)P-GMS being injected,respectively;and then pathological changes of tumor were observed by light and electron microscope respectively.Result The dose of ~(32)P-GMS was obviously correlated with the radioactivity damage of tumor cells.In the A and B groups,the tumor cells were not observed to disappear completely after injection of ~(32)P-GMS,but in C group,tumor cells were almost completely disappeared and surrounded by a lot of connective tissue.Although the tumor cells were found to disappear completely in D group,normal liver tissues were also involved.Conclusion Percutaneous intra-tumor injection of ~(32)P-GMS with suitable dose that may induce the tumor tissue to be maximally damaged and may also provide some significances to prevent the tumor metastasis.

Constitutive activation of nuclear transcription factor-κB (NF-κB) exists in a variety of leukemia, and induction of apoptosis through blocking NF-κB activation may be an alternative strategy for leukemia treatment. The aim of this study was to investigate the inducing effect of modified adenovirus 5-based adenovirus vector (i.e. chimeric Ad5F35 Vec)-mediated expression of mutant IκBα (IκBαDN) on apoptosis of HL-60 cells. The recombinant Ad5F35-IκBαDN Vec carrying IκBαDN cDNA which deleted the first 1-70 amino acids coding sequences at 5' terminal of human IκBα was transfected into HL-60 cells. The apoptosis, NF-κB DNA binding activity, the expressions of IκBα, cIAP-2 and xIAP in HL-60 cells were detected by DNA binding assay, flow cytometry, real-time quantitative polymerase chain reaction and Western blot respectively. The results showed that apoptosis rates were 22.53 ± 2.999%, 6.08 ± 2.464% and 4.86 ± 1.366% for Ad5F35-IκBαDN Vec-infected or blank vector of Ad5F35-EGFP Vec-transfected and untransfected HL-60 cells respectively, which showed a significant difference between Ad5F35-IκBαDN Vec-transfected and untransfected cells (p < 0.001) and between Ad5F35-IκBαDN Vec-transfected and Ad5F35-EGFP Vec-transfected cells (p < 0.001, p < 0.002), while NF-κB DNA binding activity was decreased, the truncated IκBα was expressed, and IκBα mRNA expression was up-regulated, but the expression of cIAP-2 and xIAP mRNA was down-regulated after transduction for 48 hours. It is concluded that the chimeric Ad5F35 Vec can effectively mediate the expression of IκBαDN cDNA in HL-60 cells, leading to the inhibition of NF-κB DNA binding activity and inducing apoptosis of HL-60 cells.
Adenoviridae ; genetics ; Apoptosis ; Genetic Vectors ; HL-60 Cells ; Humans ; I-kappa B Proteins ; genetics ; NF-KappaB Inhibitor alpha ; NF-kappa B ; genetics ; Transfection

OBJECTIVETo establish the methods of calculating and analyzing the multi-coefficient of variation significance test for the toxicology study.

METHODSThe paper aimed to confirm the significance level with the method of Bonferroni and then compared the methods of calculating and analyzing of the experiment groups with the control group respectively.

RESULTSThe significance level of multi-coefficient of variation significance test was confirmed as alpha1=0.0167. Compared with the control groups, the activity of ALT in serum both in 30 mg/kg and 60 mg/kg groups did not change in the average significance test, which was not statistically significant (P>0.05), while it changed in the variation significance test, which was of statistical significance (P<0.0167). The activity of AST in serum in 60 mg/kg group did not change in the average significance test (P>0.05), while it changed in the variation significance test (P<0.0167).

CONCLUSIONThe complete changes of the indexes can only be shown by use of both the average significance test and the variation significance test together.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Disease Models, Animal ; Female ; Lead Poisoning ; enzymology ; Rats ; Rats, Wistar ; Statistical Distributions