Poly ADP ribose polymerases (PARP) play an important role in DNA damage repair and genome stability.So,PARP inhibitors can inhibit the DNA damage repairing of tumor cells and enhance the sensitivity of the DNA of tumor cells to damage factors.In recent years,PARP inhibitors have been more and more concerned.PARP inhibitors can kill tumor cells with certain genetic mutations alone by synthetic lethal effect.In addition,PARP inhibitors in combination with chemotherapy or radiotherapy can increase the sensi tivity of tumor cells to the chemotherapy or radiotherapy.PARP inhibitors are expected to play an important role in cancer therapy.

Aim To investigate the reversal effect of PARP-1 inhibitor PJ34 on cisplatin-resistance in hu-man lung adenocarcinoma A549/DDP cells and the mechanism. Methods A549/DDP cells were treated with PJ34 alone or combined with cisplatin. The effects of proliferation inhibition were assayed by MTT meth-
od. The apoptosis ratios of cells were analyzed by flow cytometry. The protein expression of PARP-1 and LRP, GST-π were measured by Western blot assay. Results PJ34 could inhibit the proliferation of A549/DDP cells alone. The non-toxic dose of PJ34 could signifi-cantly resensitize A 5 4 9/ DDP cells to cisplatin , induce
apoptotic,lower the expression of PARP-1 and resist-ance-associated protein LRP and GST-π. Conclusion PJ34 could inhibit the proliferation of A549/DDP cells and resensitize A549/DDP cells,partially reverse cisplatin-resistance in A549/DDP cells, with a proba-
ble mechanism relating to increased apoptotic rate,and lowered expression of PARP-1 and resistance-associat-ed protein LRP and GST-π.

Aim To investigate the possible mechanism of antitumor in human lung cancer cell lines A549 and NCI-H460 induced by lumiracoxib.Methods The expression of COX-2 was detected by Western blot and the levels of PGE2 and cAMP was determined by radioimmunoassay (RIA).Results COX-2 protein was highly expressed in A549 and NCI-H460 cells.After treatment with 15~240 ?mol?L-1 LUM for 24 hrs,LUM significantly decreased the level of COX-2 in A549 cells,but not in NCI-H460 cells.Compared with the control,the PGE2 production was reduced and the level of cAMP was increased after the treatment with 15,30,60,120,240 ?mol?L-1 of LUM,respectively.Conclusion The effect of Lumiracoxib on antitumor is in COX-2-dependent or-independent manner. The antitumor effect of LUM may be related to inhibiting the COX-2 activities by decreasing its secretion,up-regulating the level of cAMP,and down-regulating the level of PGE2.

Objective To evaluate the efficacy and safety of low-dose dexamethasone pretreatment regimen in prevention of hypersensitive reaction (HR) related to docetaxel in elderly tumor patients. Methods According to the order for admission and the ratio of 3:2, 91 elderly patients with docetaxel weekly therapy were randomly divided into two groups: experimental group and control group. All patients aged from 65 to 82 years with a median age of 68 years old. There were 54 patients in the experimental group and 37 patients in the control group. In the experimental group, patients received oral dexamethasone 4. 5 mg once daily on 1 day before treatment, the day of treatment and continuing for 3 days after treatment, while patients received 8 mg twice daily in the control group. All patients were scored according to MCIRS by the physician. The side effects were evaluated by NCI-CTCAE3.0. Results Four cases in the experimental group (7.4 %) and three cases in the control group (8. 1%) occurred HR, and there was no significant statistical difference (P=1. 000). Conclusions The low dose dexamethasone is efficient and safe compared with the conventional dose dexamethasone, and there is no significant difference in HR incidence between two groups.

AIM To study the analgesic effects of melatonin (MT) and related mechanisms. METHODS The threshold was measured by hot plate test.? endorphine (? EP) was determined by radioimmunoassay (RIA). RESULTS MT (40～160 mg?kg -1 , ip) had significant dose and time dependent analgesic effects in hot plate test. The analgesia was also induced by injection (icv) of MT (0 25 mg?kg -1 ). The day night rhythm of pain threshold was not observed in 7 d after pinealectomy, but it appeared in sham operated rats.? EP content of rat brain measured by RIA indicated that the level of ? EP in hypothalamus and pituitary decreased significantly 1 h after ip MT(100 mg?kg -1 ). The analgesic effect of MT was attenuated by pretreatment of reserpine (3 mg?kg -1 ip) or ? receptor blocker phentolamine (100 mg?kg -1 , sc). CaCl 2 (230 mg?kg -1 ) antagonized the analgesic effect of MT, and EGTA and verapamil significantly enhanced the analgesia of MT in the same situation. CONCLUSION MT has significant analgesic action which may be related to opiate system, adrenergic system, and Ca 2+ content.

Objective To retrospectively observe and compare the efficacy and safty of irinotecan or oxaliplatin combined with fluoropyrimidine in the first line treatment of advanced gastric cancer. Methods 71 patients were divided into two groups. The irinotecan group consisted of 37 patients. Irinotecan 180 mg/m2 was injected in 90 minutes on d1. And the oxaliplatin group consisted of 34 patients. Oxaliplatin 85 mg/m2 was injected on d1. All the groups combined fluoropyrimidine. 5-Fluorouracil (5-Fu) 400 mg/m2 and leucovorin 200 mg/m2 were injected on d1,2 and 5-Fu 600 mg/m2 was 22 h continuous injected on d1,2, every 2 weeks was a cycle. It could also take capecitabine 1.0 g/m2 or tegafur-gimeracil-oteracil potassium 25 mg/m2 Bid for d1~14 orally, every 3 weeks was a treatment. Results 65 patients were evaluated. The response rates were 32.35% and 22.58%, the disease con-trol rates were 76.47% and 70.97%, and the median progression free survival (PFS) were 5 (3.962~6.038) months and 4 (2.730~5.270) months in irinotecan group and oxaliplatingroup, respectively, with no significant difference (P>0.05). Toxicity was tolerable, major adverse events were neutropenia, nausea and vomiting in two group. The incidence rate of diarrhea (45.95%) was higher in irinotecan group, and the peripheral nerve toxicity was 29. 41% in oxaliplatin group. Conclusion The effects of irinotecan or oxaliplatin combined with fluoropyrimi-dine in the treatment of advanced gastric cancer are comparable, and their toxicities are tolerable.

Objective To investigate the inhibition and possible mechanism of SAHA alone and combined with Er-lotinib on EGFR-TKI resistant lung cancer cell line H1975 cells. Methods The inhibitory effects of SAHA, Erlo-tinib and combined effect on cells were evaluated by CCK-8, colony formation assay and Transwell invasion assay. Western blot analysis was used to analyze the expression of PI3K, AKT, p-AKT, mTOR and p-mTOR protein in cells. Results SAHA and Erlotinib showed growth inhibition effects on H1975 cells with a dose-dependent man-nerand displayed synergistic inhibition effect. The combination of the drugs was significantly stronger than the single drug in the formation and invasion inhibition of tumor cells. The combined group had a strong inhibitory effect on the PI3K/AKT/mTOR signaling pathway. Conclusion SAHA combined with Erlotinib has synergistic inhibitory effects on the growth, cloning and invasion of EGFR-TKI lung cancer cell line H1975, which may be associated with inhibitory effects on the PI3K/AKT/mTOR signaling pathway.

Objective To investigate the impact of vorinostat(SAHA) on the erlotinib-resistance of human lung adenocarcinoma cell line PC-9/ER.Methods PC-9/ER cells were treated with erlotinib and SAHA,alone or in combination.The effects of proliferation inhibition were assayed by MTT method,the apoptosis ratios of cells were analyzed by flow cytometry.Results The results showed that SAHA inhibited the proliferation of PC-9/ER cells in a dose-dependent manner alone.The non-toxic doses of SAHA (1 μmol/L) significantly improved the sensitivity of PC-9/ER to Erlotinib,and induce apoptosis.Conclusion SAHA could partially improve PC-9/ER sensitivity to erlotinib.

Purpose: This study was to investigate the prognostic significance of the preoperative fibrinogen and systemic inflammation response index (F-SIRI) in a Chinese cohort of resectable gastric cancer. Materials and Methods: Baseline characteristics, preoperative fibrinogen levels and peripheral neutrophil, monocyte, and lymphocyte counts were retrospectively reviewed in 240 patients who underwent radical gastrectomy. The optimal cut-off values for fibrinogen and SIRI were defined as 4.0 g/L and 1.2. Then patients with hyperfibrinogenemia (≥4.0 g/L) and high SIRI (≥1.2) were assigned with an F-SIRI of 2 (both of these hematological abnormalities), 1 (one of these abnormalities), and 0 (neither abnormality), respectively. The prognostic value was examined by univariate and multivariate survival analysis. Results: Preoperative F-SIRI was significantly correlated with tumor size, fibrinogen level, and adjuvant chemotherapy. Whereas there was no significant difference in age, gender, tumor location or other characteristics between groups. In addition, high preoperative F-SIRI was significantly associated with worse disease-free survival (DFS) (hazard ratio [HR], 2.299; 95% confidence interval [CI], 1.482–3.566; P<0.001) and overall survival (OS) (HR, 2.461; 95% CI, 1.584–3.824; P<0.001) by univariate survival analysis. Moreover, it remained an independent predictor for impaired DFS (HR, 2.023; 95% CI, 1.273–3.215; P=0.003) and OS (HR, 2.341; 95% CI, 1.480–3.705; P<0.001) in multivariate Cox regression analysis. Conclusions Preoperative F-SIRI could serve as a significantly prognostic marker for long-term survival in Chinese patients who underwent radical gastrectomy.