As a hot topic, biomarkers can provide reliable evidence for the individualized treatment of non-small cell lung cancer. With the further study of molecular biology and development of new drugs,biomarkers have shown a broad prospect in clinical application. Combining with the research in recent years,this review describes the progress in biomarkers for non-small-cell lung cancer.

Multi-drug resistance (MDR) of cancer cells is a major cause of failure in chemotherapy. To the majority of anti-cancer drugs, tumor cells are able to generate a multi-drug resistance; but there is no common views on the mechanism of MDR. This review summarizes the use of drug delivery system based on nanoparticles to overcome MDR in recent years. Three kinds including non-modified, ligand-modified and multifunctional drug delivery systems are described. Especially, the mechanism of reversing MDR based on nanoparticles is covered. Through efficiently offsetting and antagonizing the action of pumping drugs out of the tumor cells, drug delivery system based on nanoparticles can increase the concentration of the drug in tumors, while reduce the side effects on normal cells and overcome multi-drug resistance. The use of drug-loaded nanoparticles, which combines nanotechnology with the strategy of active and passive targeting administration, has shown significant prospect improving cancer therapy.
Animals ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Drug Delivery Systems ; methods ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Humans ; Nanoparticles ; therapeutic use ; Neoplasms ; drug therapy

Current treatments for cancer and the central nervous system diseases are limited,partly due to the difficulties posed by the insolubility,poor distribution of drugs among cells and lack of selectivity of drugs,the inability of drugs to cross cellular barriers and blood brain barrier (BBB).Carbon nanotubes (CNTs) possess many distinct properties including good electronic properiies,remarkably penetrating capability on the cell membrane,high drug-loading and pH-dependent therapeutic unloading capacities,thermal properties,large surface area and easy modification with molecules,which render them as a suitable candidate to deliver drugs to cancer and brain.CNTs as a drug delivery could achieve a high efficacy,enhance specificity and diminish side effects.Whereas CNTs have been primarily employed in cancer treatment,a few studies have focused on the treatment and diagnosis of the central nervous system diseases using CNTs.Here,we review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to cancer involving CNTs-based tumor-targeted drug delivery systems (DDS),photodynamic therapy (PDT) and photothermal therapy (PTT).Meanwhile,we also review the current progress of in vitro and in vivo researches of CNTs-based drug delivery to brain.

OBJECTIVEThe aim of this study was to investigate the association between preoperative C-reactive protein (CRP) level and pathologic features in patients with stage I non-small cell lung cancer (NSCLC), and also to analyze if CRP provides prognostic information for NSCLC patients.

METHODSThe clinicopathological data of 105 patients with stage I NSCLC, who underwent pulmonary resection in Shanghai Chest hospital from Mar 1999 to Jul 2004, were retrospectively reviewed. The association between preoperative CRP levels and several clinical variables was analyzed by chi square test. Logistic regression analysis was used for multivariate analysis. Kaplan-Meier method and Cox multivariate regression model was used to examine the prognostic significance of the covariates on survival.

RESULTSAmong the 105 cases, 69 had CRP at normal level (≤ 5 mg/L) and 36 at increased level (> 5 mg/L). The patients who were male (P < 0.001), smoking (P = 0.002), with squamous cell carcinoma (P < 0.001), poor differentiation (P < 0.001), tumor size larger than 3 cm (P < 0.001) had a higher serum CRP level. The maxmal tumor diameter (P = 0.037) was an independent risk factor for preoperative serum CRP level elevation. The five-year survival rate and five-year disease free survival rate of the higher CRP group were lower than that in the normal CRP group (55.6% vs. 79.7%, P < 0.05, and 41.7%vs. 68.1%, P < 0.05, respectively). Cox regression analysis demonstrated that the CRP level had effect on overall survival (P = 0.009) and disease free survival (P = 0.019).

CONCLUSIONSOur findings indicate that the maximal tumor diameter is an independent risk factor for preoperative serum CRP level elevation. The overall survival, disease free survival, five-year survival rate and five-year disease free survival rate of the higher CRP group are lower than that in the normal CRP group.

Aged ; C-Reactive Protein ; metabolism ; Carcinoma, Non-Small-Cell Lung ; blood ; pathology ; surgery ; Disease-Free Survival ; Female ; Follow-Up Studies ; Humans ; Logistic Models ; Lung Neoplasms ; blood ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Pneumonectomy ; methods ; Preoperative Period ; Proportional Hazards Models ; Retrospective Studies ; Smoking ; Survival Rate ; Tumor Burden

OBJECTIVETo study the distribution of 5-FU in rat plasma and liver tissue following systemic or local 5-FU infusion.

METHODS5-FU was administered at the dose of 20 mg/kg systemically via bolus injection through the jugular vein or locally via infusion through the hepatic artery and portal vein of the rats. High-performance liquid chromatography was used to measure 5-FU concentration in the plasma and liver tissue, and the pharmacokinetic parameters, penetration rate and therapeutic dominance of 5-FU were calculated.

RESULTSSystemic administration of 5-FU resulted in the peak 5-FU concentration (Cmax) and area under curve (AUC) in the liver tissue of 13.79-/+4.56 microg/g and 342.20-/+108.20 microg.min(-1).g(-1)g-1, with the plasma Cmax and AUC of 36.85-/+5.96 microg/g and 842.00-/+158.00 microg.min(-1).ml(-1), respectively. Local 5-FU administration through the hepatic artery resulted in Cmax and AUC in the liver tissue of 29.58-/+4.30 microg/g and 794.60-/+115.40 microg.min(-1).g(-1) and Cmax and AUC in the plasma of 24.39-/+4.63 microg/g and 639.70-/+133.80 microg.min(-1).ml(-1), respectively. After administration through the portal vein, the Cmax and AUC of 5-FU was 28.21-/+4.46 microg/g and 733.60-/+180.3 microg.min(-1).g(-1) in the liver tissue, and 21.02-/+4.06 microg/ml and 529.80-/+111.50 microg.min(-1).ml(-1) in the plasma, respectively.

CONCLUSIONCompared with systemic venous bolus injection, administration through the hepatic artery and portal vein can significantly increase 5-FU concentration in the liver, and decrease its concentration in the peripheral blood.

Animals ; Area Under Curve ; Female ; Fluorouracil ; administration & dosage ; blood ; pharmacokinetics ; Hepatic Artery ; Immunosuppressive Agents ; administration & dosage ; blood ; pharmacokinetics ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver ; metabolism ; pathology ; Liver Neoplasms, Experimental ; blood ; drug therapy ; Male ; Metabolic Clearance Rate ; Portal Vein ; Rats ; Rats, Wistar

OBJECTIVETo retrospectively investigate the diagnosis and the outcome of Caroli's disease treated by surgical procedures.

METHODSThe clinical data of 68 patients with Caroli's disease treated by surgical procedures between 1996 and 2002 were reviewed, retrospectively.

RESULTSThe patients, with a M/F ratio of 1:1.35 and a mean age of 46, presented mainly with recurrent cholangitis. Of all the patients, 26 had a history of operation for cholelithiasis or cholangitis. On admission, the image investigations suggested that the lesions located at left lobe in 44 patients, right lobe in 9 patients, and whole liver in 15 patients. The coexisting cyst in common bile duct was found in 20 patients. The malignant transformation was found in 5 patients (8.8%). Hepatectomy was performed in 82.4% of patients, with a morbidity rate of 15.0% and mortality rate of 0 after the surgery. The long-term outcome of symptom-free in hepatectomy group was 90.2%, significantly higher than the 33.3% in non-hepatectomy group (P < 0.01) after a 3 to 10 years of follow-up.

CONCLUSIONSHepatectomy offers a curative procedure for local Caroli's disease, and liver transplantation is a good option for diffuse sufferers.

Adolescent ; Adult ; Aged ; Caroli Disease ; surgery ; Female ; Follow-Up Studies ; Hepatectomy ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome

BACKGROUNDPrevious studies have suggested that interrupted clearance of nuclear DNA-protein complexes after cell death might initiate and propagate systemic lupus erythematosus (SLE). Deoxyribonuclease I (DNaseI) may be responsible for the removal of DNA from nuclear antigens at sites of high cell turnover, thus preventing the onset of SLE. The purpose of this study was to genotype the single nucleotide polymorphisms (SNPs) of DNase1 and characterize its gene expression and alternatively spliced transcripts in Chinese patients with SLE in order to understand the pathogenic role of DNase1 in human SLE.

METHODSFour SNPs located at the 3' end of the DNase1 gene, as listed on the SNP website, were selected for analysis. Those SNPs with relatively high heterozygosity were chosen for genotyping in 312 Chinese SLE families using the Taqman minor groove binder (MGB) allelic discrimination method. Haplotypes were constructed and linkage disequilibrium tests were performed using GeneHunter. DNase1 mRNA expression was detected using real-time polymerase chain reaction (PCR), and alternatively spliced transcripts were isolated using capillary electrophoresis. Any effects the specific SNP haplotypes had on DNase1 gene expression and the alternatively spliced transcripts were also assessed.

RESULTSrs179982 and rs1053874 had high heterozygosity, about 0.5 in this Chinese cohort, while rs1059857 was also found to be heterozygous. Analysis of the haplotype combining rs179982-rs1030874 (C-G) and rs179982-rs1030874-rs1059857 (C-G-G) revealed a skewed transmission in favor of affected offspring. DNase1 gene expression was higher in SLE patients than in normal controls (P < 0.001), but this was not related to disease activity or SNP haplotype. Capillary electrophoresis revealed that the pattern of alternatively spliced transcripts in patients differed from that of normal controls. Furthermore, different SNP haplotype combinations generated different transcript patterns in SLE patients.

CONCLUSIONSThe SNP haplotypes are in linkage disequilibrium in Chinese SLE patients and may induce the disease through a modification of DNase1 mRNA splicing rather than at the level of mRNA expression. There is a relatively unique transcript band in SLE patients independent of special haplotype, which suggests that other unknown factors might be involved in adjusting gene expression.

Adolescent ; Adult ; Alternative Splicing ; Deoxyribonuclease I ; genetics ; Female ; Haplotypes ; Humans ; Linkage Disequilibrium ; Lupus Erythematosus, Systemic ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

BACKGROUNDIntractable secondary glaucoma with severe ocular contusion involving the posterior segment is difficult to treat. In this study, we evaluated the safety and efficacy of combined trabeculectomy and vitrectomy for intractable glaucoma with severe ocular contusion involving the posterior segment.

METHODSThis retrospective interventional study enrolled 18 eyes from 18 consecutive cases with uncontrolled intraocular pressure, angle recession exceeding 180°, dense vitreous hemorrhage, and/or limited retinal detachment after severe ocular contusion. Combined trabeculectomy and vitrectomy was performed after giving the patient sufficient anti-inflammatory and intraocular pressure (IOP)-lowering medication. Follow-up averaged 26.2 (range, 6.0- 48.0) months.

RESULTSThe mean IOP decreased from (36.4 ± 10.0) mmHg on maximum IOP-lowering medications to (14.6 ± 4.4) mmHg on (0.7 ± 1.2) topical medications at the final follow-up (P < 0.0001). During the first postoperative month, four eyes (22%) had a short hypertensive phase and six eyes (33%) had early hypotony, including one case (5.6%) of bleb leakage. Seven eyes (39%) developed recurrent hypertension 3- 6 months postoperatively, five of which were controlled by topical medications. Ten (55.6%) eyes were classified as a complete success, five (27.8%) as a qualified success, and three eyes (16.7%) as failures. Kaplan-Meier survival analysis for complete and cumulative success showed 53.5% and 80.0% survival at 48 months, respectively. Visual acuity was improved in 15 eyes (83.3%). Three eyes (16.7%) had unchanged visual acuity, one (5.6%) of which developed atrophia bulbi despite a normal intraocular pressure. No recurrent retinal detachment or vitreous hemorrhage developed.

CONCLUSIONCombined trabeculectomy and vitrectomy is a viable surgical procedure for the management of intractable glaucoma with severe ocular contusion involving the posterior segment in selected cases.

Adult ; Aged ; Female ; Glaucoma ; physiopathology ; surgery ; Humans ; Intraocular Pressure ; physiology ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Retrospective Studies ; Trabeculectomy ; methods ; Vitrectomy ; methods

OBJECTIVETo test the dissolution rate of silymarin dropping pill as well as to be compared with other three commercial products of the silymarin.

METHODBy UV spectrophotometry, we studied the dissolution conditions of silymarin dropping pill and compared its dissolution rate with Yiganling tablets (film-coating, sugar-coating) and Legalon capsule which are available in the market.

RESULTThe dissolution parameters T50 and Td of silymarin dropping pill, Yiganling tablet (film-coating), Yiganling tablet (sugar-coating) and Legalon capsule are 6.78, 9.85 min, 51.01, 73.78 min, 74.35, 86.97 min and 53.10, 72.65 min.

CONCLUSIONThe dissolution rate of silymarin dropping pill is superior to that of two kinds of Yiganling tablets and Legalon capsule.

Capsules ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Silymarin ; administration & dosage ; chemistry ; Solubility ; Spectrophotometry, Ultraviolet ; Tablets

OBJECTIVETo observe whether deoxyribonuclease I (DNASE1) gene expression and its DNASE1 mRNA expression was detected by real-time polymerase chain reaction and its alternatively spliced transcripts were performed by capillary electrophoresis. An analysis was also made to disclose whether specific single nucleotide polymorphisms (SNPs) haplotype had effects onDNASE1 gene expression and its alternatively spliced transcripts.

RESULTSDNASE1 gene expression was higher in SLE patients than in normal controls (P<0.001), and in patients it was found to be of no relationship with SLE disease activity index score. However, it was increased in female patients. Capillary electrophoresis revealed that the pattern of alternatively spliced transcripts in patients was not the same as that in normal controls. Moreover, it seemed that different SNPs haplotype combination might show different transcript pattern in SLE patients.

CONCLUSIONIn SLE patients, DNASE1 gene expression is abnormal and there are alternatively spliced transcripts different from those in normal controls. DNASE1 gene is a critical factor in the pathogenesis of SLE.

Adolescent ; Adult ; Alternative Splicing ; Deoxyribonuclease I ; genetics ; Female ; Gene Expression ; Humans ; Lupus Erythematosus, Systemic ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide