ABSTRACT
Objective To explore the effects of hepatocyte nuclear factor 1 homeobox A(HNF1A) on drug resistance of PANC1 cells to gemcitabine plus abaraxane and explore the potential mechanism. Methods 78 pancreatic cancer patients with locally advanced or distant metastasis who received gemcitabine plus abaraxane chemotherapy after surgery in Biliary and Pancreatic Surgery Department of Sun Yat-sen Memorial Hospital from March 2012 to May 2017 were enrolled. qPCR was used to detect HNF1A mRNA levels in pancreatic cancer tissue. The patients were divided into high-expression group ( n=39 ) and low-expression group (n=39) according to the median expression level of HNF1A, and the correlation of HNF1A expression with cancer clinicopathologic parameters and survival was analyzed. qPCR was used to detect HNF1A mRNA of 3 drug-sensitive cell lines (BxPC-3, CFPAC-1 and L3. 6pl) and 4 drug-resistant pancreatic cancer cell lines (PANC1, MIA PaCa-2, Hs766T and Mpanc96). Lentivirus with plasmids carrying HNF1AcDNA infection was used to establish HNF1A overexpressing PANC1 cells ( HNF1A group), and lentivirus with empty plasmids were used to infect PANC1 cells to construct the control group. The mRNA and protein expression of HNF1A and ATP binding cassette transporter family ABCC1 in HNF1A group and control group were measured by qPCR and Western Blot, respectively. The half inhibition concentration ( IC50 ) of gemcitabine plus abaraxane was detected by MTT, and cell apoptosis was examined by flow cytometry. Results Pancreatic cancer patients with high HNF1A expression had a better overall survival than those with low HNF1A expression (17. 9 months vs 12.4 months), and the difference was statistically significant (P<0.001). HNF1A low expression in pancreatic cancer tissue was significantly associated with advanced TNM stage, perineural invasion ( PNI) and short overall survival. The expression level of HNF1A was significantly down-regulated in drug-resistant PANC1 cells compared to drug-sensitive BxPC-3 cells by an average fold change of 6. 73, and the difference was statistically significant ( P<0. 001 ). In HNF1A group, the mRNA and protein levels of ABCC1 were significantly decreased compared with those in control group (0. 012 ± 0. 004vs 0. 047 ± 0. 008,0. 281 ± 0. 040 vs 0. 832 ± 0. 046,P=0. 003,P <0. 001). IC50 of HNF1A group to gemcitabine plus abraxane was decreased compared with that of control group [(26. 31 ± 2. 91)μmol/L vs (72. 63 ± 4. 07) μmol/L], and the cell apoptosis rate of HNF1A group was increased compared with that of control group [(40. 18 ± 1. 64)％ vs (21. 31 ± 1. 98)％], and the differences were statistically significant (P<0. 01). Conclusions HNF1A may induce resistance of pancreatic cancer cell to gemcitabine plus abraxane by downregulating ABCC1.
ABSTRACT
Objective To compare the analgesia effects of Oxycodone hydrochloride with Sufentanil in laparoscopic cholecystectomy (LC) anesthesia induction. Method Sixty patients scheduled for elective LC, ASAⅠ or Ⅱ , were randomly divided into two groups (30 in each): Oxycodone group (group O) and Sufentanil group (Group S). Induction of anesthesia: group O: Propofol 1.0 ~ 2.0 mg/kg, Oxycodone 0.3 mg/kg, Vecuronium 0.1 mg/kg. Group S: Propofol 1.0 ~ 2.0 mg/kg, Sufentanil 0.3 μg/kg and Vecuronium 0.1 mg/kg. The value of HR, SBP, DBP of the two groups were recorded in the operation room (T0), after anesthesia induction (T1), 1 min after insertion laryngeal mask (T2), the instant of pneumoperitoneum establishment (T3), separation of the gallbladder (T4), the time of wake up (T5), leave the recovery room (T6). The numeric pain rating scale (NRS) were recorded at T4, T5, 4 hours later (T7), 8 hours later (T8), one day later (T9). Then recorded the wake time and additional analgetic cases. Recorded the adverse reactions. Results The average HR, SBP and DBP fluctuations in the two groups were not more than 20.0 % of the basal values. There was no significant difference in wake time between the two groups. There were 11 cases of patients, the NRS>4, in Sufentanil group requires additional analgesics after they wake up, more than Oxycodone group (P = 0.040). The NRS score was lower in Oxycodone group than group S in T5, T7, T8, T9, but they had no statistically significant difference. There was no significant difference in adverse reactions between the two groups. Conclusion 0.3 mg/kg Oxycodone and 0.3 μg/kg Sufentanil for anesthesia induction of LC, the anesthesia and analgesia effect is good, can satisfy the clinical anesthesia and postoperative analgesic requirements. The analgesic effect of 0.3 mg/kg Oxycodone may be comparable or better than 0.3 μg/kg Sufentanil.
ABSTRACT
Objective To determine the optimum dose of Oxycodone for anesthesia induction in patients undergoing laparoscopic cholecystectomy. Methods Ninety patients, ASA Ⅰ or Ⅱ , scheduled for elective LC, were randomly divided into 3 groups using random number table (O 1~O 3 groups, n = 30 each). Anesthesia was induced with iv Propofol 1.00~2.00 mg/kg, Oxycodone 0.20 mg/kg, 0.3 mg/kg and 0.4 mg/kg (O 1~O 3 groups, respectively), and Vecuronium 0.10 mg/kg. Before anesthesia induction ( T0 ), 1 min after Laryngeal Mask intubating ( T1 ), the instant of pneumoperitoneum ( T2 ), separation of the gallbladder ( T3 ), wake up immediately ( T4 ), leaving the recovery room ( T5 ), the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. At T4, leaving the recovery room ( T5 ), 4 hours after the operation ( T6 ), 8 hours after operation (T7), the numeric pain rating scale (NRS) were recorded. The overall amount of remifentanil and Oxycodone were record. The wake up time, additional analgetic cases and the adverse reactions were recorded. Results The average HR, SBP and DBP fluctuations in the O 2 and O 3 groups were not more than 20.00% of the basal values. There was no significant difference in wake up time between the three groups. There were 22 cases of patients, the NRS> 4, in O1 group requires additional analgesics after they wake up, more than O 2 and O 3 group (7, 3 respectively, P < 0.05). The overall Oxycodone consumption of the three groups were O1: (18.93 ± 4.34) mg (0.90~2.60 mg),O2: (25.50 ± 4.49) mg (1.40~3.00 mg), O3: (26.10 ± 4.55) mg (1.80~3.40 mg) (F = 23.79, P = 0.000). There was no significant difference in adverse reactions between the three groups, but one patient had respiratory depression in O3 group. Conclusion The optimum dose of Oxycodone for anesthesia inducing in laparoscopic cholecystectomy were 0.30 mg/kg.