ABSTRACT
OBJECTIVE: To explore the clinical efficacy of GEMOX regimen on patients with refractory non-hodgkin's lymphoma. METHODS: Eighty-two cases of non-Hodgkin's lymphoma were divided into 2 groups: gemcitabine+oxaliplation(Gem+Oxa) group (42 cases) and vinorelbine+oxaliplatin(Vin+Oxa) group (40 cases) according to chemotherapy regimens. The clinical efficacy, side effects, progression-free survival situation in 2 groups were compared. RESULTS: There was no significant difference on the clinical effects of 2 groups (P>0.05); The therapeutic efficacy for B cell lymphoma was higher than that for T cell lymphoma(P<0.05); The therapeutic effects for I-II stages was lower than that for III-IV stages(P<0.05); The incidences of platelet decline, nausea and vomit, peripheral nerve symptoms in Gem+Oxa group were lower than those in Vin+Oxa group(P<0.05); There was no significant difference in the median progression free survival(P>0.05). CONCLUSION: The efficacy of GEMOX regimen for refractory non-Hodgkin's lymphoma has been confirmed to be good, it has distinct clinical curative effect, it can prolong the progression-free survival time in patients with B cell lymphoma, specially for III-IV stages. It can be used as the preferred method for the treatment of patients with refractory NHL.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lymphoma, Non-Hodgkin/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Humans , Lymphoma, B-Cell , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/analogs & derivatives , VinorelbineABSTRACT
The TAM receptor tyrosine kinase family member Mer has been recognized as an attractive therapeutic target for pediatric leukemia. Beside Mer the family contains other two kinases, namely, Tyro3 and Axl, which are highly homologues with Mer and thus most existing small-molecule inhibitors show moderate or high promiscuity across the three kinases. Here, the structural basis and energetic property of selective binding of small-molecule inhibitors to the three kinases were investigated at molecular level. It is found that the selectivity is primarily determined by the size, shape and configuration of kinase's ATP-binding site; the Mer and Axl possess a small, closed active pocket as compared to the bulky, open pocket of Tyro3. The location and conformation of active-site residues of Mer and Axl are highly consistent, suggesting that small-molecule inhibitors generally have a low Mer-over-Axl selectivity and a high Mer-over-Tyro3 selectivity. We demonstrated that the difference in ATP binding potency to the three kinases is also responsible for inhibitor selectivity. We also found that the long-range interactions and allosteric effect arising from rest of the kinase's active site can indirectly influence inhibitor binding and selectivity.
Subject(s)
Leukemia/drug therapy , Protein Kinase Inhibitors/chemistry , Protein Kinase Inhibitors/therapeutic use , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Small Molecule Libraries/chemistry , Small Molecule Libraries/therapeutic use , Amino Acid Sequence , Child , Crystallography, X-Ray , Enzyme Assays , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Models, Molecular , Protein Domains , Receptor Protein-Tyrosine Kinases/chemistry , Sequence AlignmentABSTRACT
OBJECTIVE: To evaluate the efficacy of artificial liver support system (ALSS) in the treatment of liver failure patients. METHODS: This is a prospective, multi-center, controlled, large sample clinic trial. 518 patients with liver failure from 5 hospitals were studied and followed. All the patients received similar pharmacological manipulation according to one and the same protocol but were divided into an ALSS treatment group and a control group without ALSS treatment. The ALSS treatment procedures included plasma exchange, molecular adsorbent recirculating system (MARS), plasma exchange plus hemofiltration and other combined nonbioartificial methods. The analysis of survival time was computed using the Kaplain-Maier method, and comparison among groups was done using Log-Rank, Breslow and/or the Tarone-Ware test. RESULTS: Survival time of acute liver failure patients was prolonged from 4.0+/-0.2 days to 8.0+/-0.4 days (P=0.004). ALSS was shown to be two times more effective. ALSS increased the survival time of acute on chronic (A on C) liver failure patients from 27.0+/-1.6 days to 39.0+/-4.0 days (P less than 0.01). In addition, it increased the survival time of the patients in the middle and end stage of subacute liver failure and A on C liver failure, but had no significant effects on early stage patients. The survival time of middle stage patients was 38.0+/-17.5 days in the control group vs 66.0+/-18.6 days in the ALSS group (P less than 0.05). The survival time of end stage patients of the control group and the ALSS group was 18.0+/-4.0 days vs 26.0+/-2.5 days (P less than 0.01). CONCLUSIONS: Multi ALSS treatment is more effective than the standard medicinal liver care treatment. Multi-ALSS treatment could increase survival time of patients suffering from acute liver failure or A on C liver failure, especially in their middle and end stages. It is important and necessary to treat these patients with ALSS.
