A double blind multicenter study of patients suffering from presenile and senile cataracts was performed, bendazac Iysine salt (Bendaline(R))or a placebo was administered orally to the patients and the results were analyzed. Although subjective variability in visual acuity and in the clinical course of cataracts should be taken into consideration together with the short duration of the observation period, the results obtained demonstrate an improvement in the Bendaline(R) treated group with regard to visual acuity and lens opacity, and an aggravation in the group of patients receiving the placebo.
Administration, Oral ; Adult ; Aged ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Cataract/*drug therapy ; Clinical Trials as Topic ; Double-Blind Method ; Female ; Humans ; Indazoles/*administration & dosage ; Male ; Middle Aged ; Pyrazoles/*administration & dosage ; Random Allocation ; Tablets ; Visual Acuity/*drug effects

OBJECTIVETo study the inhibitory effect and toxicity of axitinib combined with 5-FU in nude mice bearing transplanted tumor of colon cancer LoVo cells.

METHODSNude mouse models bearing LoVo colon cancer xenograft were randomized into vehicle control group, untreated control group, axitinib-treated group, 5-FU-treated group and combined treatment group for corresponding treatments. The tumor dimensions, body weight and tumor weight were recorded, and the efficacy and toxicity were evaluated in terms of complete remission (CR), partial remission (PR), tumor growth delay (TGD), mortality rate and net body weight loss.

RESULTSThe combined treatment showed a significantly stronger efficacy than axitinib or 5-FU used alone. TGD of the combined treatment group was 16.73 days, longer than that of axitinib (8.53 days) and 5-FU (9.72 days) used alone. No mouse died during the treatments in the untreated control group, and 1 died in each of the other 4 groups. The mortality rate and weight loss were both less than 20%. One mouse had PR in axitinib-treated group and another in the combination treatment group. Axitinib, alone and in combination with 5-FU, reduced ABCG2 expression in the tumor tissue, and 5-FU has no such effect.

CONCLUSIONCombination of axitinib and 5-FU produces better antitumor effect than either drug used alone and is well tolerated in nude mice bearing colon cancer xenograft.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Colonic Neoplasms ; drug therapy ; Female ; Fluorouracil ; administration & dosage ; Humans ; Imidazoles ; administration & dosage ; Indazoles ; administration & dosage ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays

OBJECTIVETo investigate the effect of the selective PI3K inhibitor and MEK inhibitor on KRAS and PTEN co-mutated non-small cell lung cancer cell line NCI-H157 and the relevant mechanisms.

METHODSNCI-H157 was cultured routinely and treated with different concentrations of the two inhibitors. Cell proliferation was detected by MTT cell cycle assay. Based on the MTT results the cells were divided into four groups: the control group, PI3K inhibitor group (GDC-0941, 0.5 and 5.0 µmol/L), combination group I (0.5 µmol/L AZD6244 + 0.5 µmol/L GDC-0941) and combination group II (5.0 µmol/L AZD6244 + 5.0 µmol/L GDC-0941). Colony formation assay was performed to detect colony formation efficiency. The cell cycle and apoptosis were analyzed by flow cytometry. The expression of protein related to apoptosis was tested with Western blot.

RESULTSCell growth was inhibited by the two inhibitors. Combination groups led to stronger cell proliferation inhibition: combination group Ishowed synergistic effect of their actions and combination group II showed an additive effect; in both groups, there were decreased colony number [(77.2 ± 1.54)/well vs (61.50 ± 2.12)/well, P < 0.01] and [(51.00 ± 4.00)/ well vs (22.50 ± 3.53)/well, P < 0.01]; and enhanced apoptotic ratios [(18.30 ± 0.82)% vs (21.32 ± 0.56)%, P < 0.01] and [(27.14 ± 1.58)% vs (42.45 ± 4.42)%, P < 0.01]. In addition, compared to the PI3K inhibitor alone group, the NCI-H157 cells in the combination groups showed increased G0/G1 phase and decreased S phase (P < 0.01). Western blotting showed that the combination groups demonstrated significantly decreased expression of cyclin D1 and cyclin B1, increased p21 and cleaved PARP and decreased bcl-2/bax ratio, compared to the PI3K inhibitor only group.

CONCLUSIONThe combined inhibition of PI3K (AZD6244) and MEK (GDC-0941) has synergistic effects on the proliferation of NCI-H157 cells, but such effects appear to be in a dose-dependent manner.

Apoptosis ; drug effects ; Benzimidazoles ; administration & dosage ; pharmacology ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Dose-Response Relationship, Drug ; Drug Synergism ; Humans ; Indazoles ; administration & dosage ; pharmacology ; Lung Neoplasms ; genetics ; pathology ; Mitogen-Activated Protein Kinase Kinases ; antagonists & inhibitors ; metabolism ; Mutation ; PTEN Phosphohydrolase ; genetics ; Phosphatidylinositol 3-Kinases ; antagonists & inhibitors ; metabolism ; Poly(ADP-ribose) Polymerases ; metabolism ; Proto-Oncogene Proteins ; genetics ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Proto-Oncogene Proteins p21(ras) ; metabolism ; Signal Transduction ; Sulfonamides ; administration & dosage ; pharmacology ; bcl-2-Associated X Protein ; metabolism ; ras Proteins ; genetics