PURPOSE:Studying the multidrug resistance(MDR) phenotype occurring in retinoblastoma and its mechanism.
METHODS:Using the procedure of stepwise increase in drug concentrations to obtain a retinoblastoma subline which resistant to 600ng/ml vincristine (HXO-RB/VCR). Characteristics of this drug-resistant cell line were investigated by cell
counting,drugcontents determinatin,drug sensitivity evaluation and radiation sensitivity test. RESULTS:This cell line was cross-resistant to VDS,MMC VP16，ADM ,DDP,CBP,but not resistant to BCNU and 5-Fu. It was proved to be collaterally sensitive to MTX,and the response to 60Co gamma;-ray was modified slightly in HXO-RB/VCR cell line. Intracellular levels of VCR was much higher in HXO-RB44 cells than in the resistant subline. Those cross-resistances can be reversed by verapamil partly.
CONCLUSIONS:MDR and radiation resistance of retinoblastoma can be induced by exposing to VCR and reversed by verapamil partly.
（Chin J Ocul Fundus Dis,1997,13: 6-9）
Objective To evaluate the safety and tolerance of pegfilgrastin (PEG-G-CSF) in Chinese healthy volunteers. Methods Thirty healthy volunteers were randomly divided into five single-dose groups to receive PEG-G-CSF 15, 30, 50, 60 or 75μg/kg by hypodermic injection. The safety profile and tolerability were evaluated by observing symptoms, vital signs, laboratory tests and electro cardiogram. Results No serious adverse event was reported for any volunteer. Transient dizziness occurred in one person in the 50 μg/kg dose group, and mild dizziness and ostalgia was found in all six people in the 75μg/kg dose group, of whom one experienced transient fever and two experienced mild diarrhea. No clinically significant changes in laboratory tests and electrocardiogram were found during the follow-up period. Conclusions The maximum tolerated dose of PEG-G-CSF injection in Chinese healthy volunteers is 60 μg/kg. Doses below 60μg/kg can be well tolerated. The recommended dose for phase II clinical trials is 60 μg/kgone, one dose for each cycle of chemotherapy.
Objective To evaluate the safety and tolerance of medicinal charcoal enteric-coated tablets in healthy volunteers. Methods A total of 44 healthy volunteers were randomly divided into 6 single-dose groups (0.5 g, 2 g, 4 g, 6 g, 8 g and 10 g) and a multiple-dose group (3 g, 3 times a day, for 14 days). The safety profile and tolerance were evaluated by observing symptoms, vital signs, and laboratory tests. Results No serious adverse event was reported for any volunteer. Abdominal distension occurred in 2 volunteers in the 4 g dose group and the 6 g dose group. One volunteer in the 8 g dose group experienced nausea and vomiting. Transient decrease in white blood cell count was observed in one volunteer in the 10 g dose group. Abdominal distension occurred in 2 volunteers of the multiple-dose group. Conclusion Based on our findings, the maximum tolerated dose of medicinal charcoal enteric-coated tablets in Chinese healthy volunteers is 10 g. The recommended dose for subsequent clinical trials is 3 g, 3 times a day.
Objective
To analyze the distribution of pathogens, drug susceptibility and multi-drug resistant bacteria (MDRB) in elderly patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with pneumonia.
Methods
The clinical data of patients whose discharge diagnosis included AECOPD with pneumonia or pulmonary infection from January 2012 to December 2015 were retrospectively analyzed. Strain identification and drug sensitivity analysis were performed in the pathogenic bacterias isolated from sputum culture.
Results
A total of 1 978 patients were enrolled in this study, and pathogenic bacterias were isolated from the sputum of 708 patients, including 485 cases of community-acquired pneumonia (CAP) and 223 cases of hospital-acquired pneumonia (HAP); and 786 strains of pathogens were isolated (501 strains from CAP cases, 285 strains from HAP cases), including 448 strains of Gram-negative (G–) bacilli (57.0%), 117 strains of Gram-positive (G+) cocci (14.9%), and 221 strains of fungi (28.1%). Susceptibility testing results showed that G– bacilli were highly resistant to penicillins, third generation cephalosporins, ciprofloxacin, gentamicin, etc., and G+ cocci were highly resistant to penicillin, clindamycin and erythromycin. There were 238 strains of MDRB, mainly including 69 strains of Acinetobacter baumanii [multiple drug resistance rate (MDRR)=67.6%], 27 strains of Escherichia coli (MDRR=52.9%), 25 strains of Klebsiella pneumoniae (MDRR=34.2%), 33 strains of Pseudomonas aeruginosa (MDRR=33.0%) and 24 strains of Stenotrophomonas maltophilia (MDRR=100.0%). MDRR of Enterococcus genus and methicillin-resistant Staphylococcus aureus was 50.0% and 48.0%, respectively.
Conclusions
The pathogenic bacterias in elderly AECOPD patients complicated with pneumonia are mainly G– bacterias, and the proportion of fungal infection tends to increase. Bacterial drug resistance is serious and the MDRB tends to increase, especially in patients with HAP. Physicians should early find out the characteristics of local pathogenic bacteria and drug sensitivity, rationally select antibiotics, reduce the occurrence of drug-resistant strains and superinfection when treating the elderly patients with AECOPD complicated with pneumonia.
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
Objective To review the recent studies on the multidrug resistance of breast cancer. Methods The literatures of recent years on the studies of multidrug resistance, multidrug resistance protein and breast cancer resistance protein were reviewed. Results Multidrug resistance resulted from multiple factors. How to identify the sensibility of chemotherapy drugs and select individual therapeutic regime early were important to improve the survival rate and life quality of breast cancer patients. Conclusion These studies on multidrug resistance of breast cancer are helpful to predicting the effect and outcome of chemotherapy and overcoming the barrier of drug resistance.
