ABSTRACT
Genetic variants in glioma tumor suppressor candidate region gene 1 (GLTSCR1)and ATM serine/threonine kinase (ATM) have been associated with various cancer risks.Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors.However,little is known about the relationship between both gene polymorphisms and lung cancer risk.We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls.No significant differences in the single polymorphism (GLTSCR1 rs1035938 and ATM rs11212592)association were found in five genetic models (co-dominant,dominant,recessive,overdominant and log-additive models) (adjusted by smoking duration).Join effect of three SNPs (PPP1R13L rs1970764,CD3EAP rs967591,GLTSCR1 rs1035938) on chromosome 19q 13.3 showed that the designated haplotype2 (rs 1970764<rs967591A-rs 1035938c) [OR (95％ CI)=1.60 (1.11-2.32),P=0.012] and haplotype8 (rs 1970764G-rs967591G-rs 1035938T)[OR (95％ CI)=2.45 (1.17-5.12),P=0.018] were associated with increased risk of lung cancer (adjusted by smoking duration).The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci (P＜0.001)or 4 loci (P=0.015-0.016).The entropy-based analysis indicated the strongest synergistic effect between PPP1R13L rs1970764 and ATM rs11212592 in analysis of four genes.In conclusion,our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3,interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592,and synergistic action of PPP1R13L rs1970764 and ATMrs11212592 may associate with lung cancer risk in the Chinese population.
ABSTRACT
Genetic variants in glioma tumor suppressor candidate region gene 1 (GLTSCR1)and ATM serine/threonine kinase (ATM) have been associated with various cancer risks.Epidemiological studies also revealed the association of variants of GLTSCR1 and ATM genes with different brain tumors.However,little is known about the relationship between both gene polymorphisms and lung cancer risk.We conducted a Chinese hospital-based casecontrol study involving 384 lung cancer cases and 387 cancer-free controls.No significant differences in the single polymorphism (GLTSCR1 rs1035938 and ATM rs11212592)association were found in five genetic models (co-dominant,dominant,recessive,overdominant and log-additive models) (adjusted by smoking duration).Join effect of three SNPs (PPP1R13L rs1970764,CD3EAP rs967591,GLTSCR1 rs1035938) on chromosome 19q 13.3 showed that the designated haplotype2 (rs 1970764<rs967591A-rs 1035938c) [OR (95％ CI)=1.60 (1.11-2.32),P=0.012] and haplotype8 (rs 1970764G-rs967591G-rs 1035938T)[OR (95％ CI)=2.45 (1.17-5.12),P=0.018] were associated with increased risk of lung cancer (adjusted by smoking duration).The analysis ofmultifactor dimensionality reduction revealed that two 3-way models were the best fit models in analyses of 2 loci (P＜0.001)or 4 loci (P=0.015-0.016).The entropy-based analysis indicated the strongest synergistic effect between PPP1R13L rs1970764 and ATM rs11212592 in analysis of four genes.In conclusion,our study suggests that haplotypes consisting of PPP1R13L rs1970764-CD3EAP rs967591-GLTSCR1 rs1035938 on Chr19q13.3,interaction of smoking and GLTSCR1 rs1035938-ATM rs11212592,and synergistic action of PPP1R13L rs1970764 and ATMrs11212592 may associate with lung cancer risk in the Chinese population.
ABSTRACT
Objective: To observe the antitumor effect and mechanism of recombinant human endostatin (Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats. Methods: A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm3. Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg kg-1 d-1 for 10 d. Group C was given the injection of Endostar 5 mg kg-1 d-1 combined with intraperitoneal injection of cisplatin 5 mg kg-1 d-1 for 10 d. All the rats in three groups were executed the day after the 10 d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor (VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density (MVD) in each group. Results: The volume and mass of tumor in Groups B and C were significantly lower than Group A (P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B (P < 0.05). The antitumor rate in Group C was significantly higher than Group B (P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B (P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A (P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor. Conclusions: Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.
ABSTRACT
OBJECTIVE@#To observe the antitumor effect and mechanism of recombinant human endostatin (Endostar) injection in tumor combined with intraperitoneal injection of cisplatin on subcutaneous transplanted Lewis lung cancer in rats.@*METHODS@#A total of 30 C57 rats were selected, and the monoplast suspension of Lewis lung cancer was injected into the left axilla to prepare the subcutaneous transplanted tumor models in the axilla of right upper limb. The models were randomly divided into Groups A, B, and C. Medication was conducted when the tumor grew to 400 mm(3). Group A was the control group without any interventional treatment. Group B was injected with Endostar 5 mg kg(-1) d(-1) for 10 d. Group C was given the injection of Endostar 5 mg kg(-1) d(-1) combined with intraperitoneal injection of cisplatin 5 mg kg(-1) d(-1) for 10 d. All the rats in three groups were executed the day after the 10 d medication and the tumor was taken off for measurement of volume and mass changes and calculation of antitumor rate, after which the vascular endothelial growth factor (VEGF) concentration in rats' plasma was determined by ELISA. The tumor tissues were cut for the preparation of conventional biopsies. After hematoxylin-eosin staining, the pathologic histology was examined to observe the structures of tumor tissues, VEGF score and microvessel density (MVD) in each group.@*RESULTS@#The volume and mass of tumor in Groups B and C were significantly lower than Group A (P < 0.05) while the tumor volume and mass in Group C were significantly lower than Group B (P < 0.05). The antitumor rate in Group C was significantly higher than Group B (P < 0.05), but the tumor VEGF score, MVD and plasma VEGF level in Group C were significantly lower than Groups A and B (P < 0.05). In Group B, the tumor VEGF score, MVD and plasma VEGF level were significantly lower than Group A (P < 0.05). The microscopic image of Group C showed that its number of active tumor cells and the blood capillary around tumor was significantly smaller than that of Groups A and B, and meanwhile atrophy and liquefactive necrosis were seen in local tumor.@*CONCLUSIONS@#Endostar injection combined with intraperitoneal injection of cisplatin is effective in reducing tumor VEGF score and MVD of transplanted tumor tissues in rats with Lewis lung cancer to obstruct the nutrient supply of tumor cells and kill tumor cells, so that the inhibition of tumor cell proliferation and metastasis can be achieved with a remarkable effect.