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Objective To establish a subcutaneous and orthotopic transplatation tumor model of human esophageal cancer in nude mice .Methods Fresh tissues of human esophageal cancer were collected and transplanted into subcutaneous places of nude mice .The successfully transplanted primary generation tumor was passed down three times .Then tumor were implanted into the subcutaneous and esophageal submucous tissues of nude mice .The formation rate ,morphology ,invasion and metastasis of tumor were observed .Results The tumor formation rate of subcutaneous transplatation model was 60% ,it was low grade squamous cell carcinoma without lymph node and distant organ metastasis .The tumor formation rate of orthotopic transplatation model was 80% , the morphological characteristics were consistent with human original tumor .Lymph node and organ metastasis could be found ex-tensive .Conclusion We preliminary established effective subcutaneous and orthotopic transplatation tumor model of human esopha-geal cancer in nude mice .It might be an available model for further research of esophageal cancer .
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Objective To investigate influence of cisplatin (DDP) on the tumor inhibition rate,transcriptional levels of CyclinB1 and CyclinD1 of CNE-1 xenograft in nude mice.Methods Tumor mode of nude mice CNE-1 xenograft was established.Then mice were divided into control arm,DDP arm,high speed irradiation arm,simulated intensity modulated radiation therapy (IMRT) arm and simulated IMRT + DDP arm,with 12 mice in each arm.Irradiation dose was 20 Gy with a single fraction.DDP was 15 μg/g weight.The maximum diameter of tumor base was measured every other day.The growth curve was drawn and tumor inhibition rate werevcalculated after 40 days.The transcriptional level of CyclinB1 and CyclinD1 of xenograft was measured by RT-PCR.The results of different groups were compared with one-factor analysis of variance.Results Tumor inhibition rates of the control arm,DDP arm,high speed irradiation arm,simulated IMRT arm and simulated IMRT + DDP arm were-129.1％,-71.2％,42.5％,35.3％ and 47.1％,respectively.There was significant difference between the high speed irradiation arm and simulated IMRT arm (P =0.034),but not between the high speed irradiation arm and simulated IMRT + DDP arm (P =0.222).The transcriptional levels of CyclinB1 in the arms were 0.429,0.386,0.322,0.354 and 0.268.There were significant differences between the high speed irradiation arm and the simulated IMRT arm or the simulated IMRT + DDP arm (P =0.007 and 0.000).The transcriptional levels of CyclinD1 in the arms were 0.716,0.583,0.348,0.495 and 0.296,respectively.There was significant difference between the acute irradiation arm and the simulated IMRT arm (P =0.000),but there was no significant difference between the high speed irradiation arm and the simulated IMRT + DDP arm (P =0.072).Conclusions Irradiation of 20 Gy single fraction,or combined with DDP are effective on the CNE-1 xenograft in nude mice,but DDP alone can only lower the tumor growth speed.Irradiation of 20 Gy single fraction,or combined with DDP,or DDP alone can reduce the transcriptional levels of CyclinB1 and CyclinD1.As the single therapeutic time is prolonged in IMRT mode,the tumor inhibition rate is reduce,and the reduce of the transcriptional levels of CyclinB1 and CyclinD1 is depressed,while combined DDP can compensate the decline of the biological effect.
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Objective To investigate the influence of gonadotropin-releasing hormone (GnRH) analogues on ovarian cancer and ovarian function in vivo.Methods ES-2 cells were cultured and xenotransplanted into 36 nude mice,which were divided into 6 groups:normal saline (NS) group:NS 0.1 nd/day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; cisplatin (DDP) group:NS 0.1 ml/day subcutaneous injection,and then DDP 5 mg/kg ( diluted to 0.2 ml ) per week peritoneal injection; goserelin group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; goserelin + DDP group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; cetrorelix group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and NS 0.2 ml/week peritoneal injection; cetrorelix + DDP group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and DDP 5 mg/kg ( diluted to 0.2 ml) per week peritoneal injection.All the peritoneal injection started from subcutaneous injection one week later.To compare the weight of nude mice,the volumes of transplanted tumors,the expression of Ki-67 antigen in transplanted tumors,the estrus,the ratio of atretic follicles,the ratio of primary and preantral follicles,the levels of serum anti-Mullerian hormone ( AMH ),folliclestimulating hormone ( FSH),estradio ( E2 ) and progesterone (P) in each group.Results There were no significant difference in the weight of nude mice among 6 groups ( P ＞ 0.05 ),which on day 29 in NS group was ( 19.8 ±2.2) g,DDP group (20.5 ± 1.4) g,gosereline group ( 19.6 ±0.9) g,goserelin + DDP group ( 19.7 ± 1.6) g,cetrorelix group (20.7 ±2.2) g,and cetrorelix + DDP group ( 19.0 ± 1.7) g.The tumor volumes of different groups on the 12th day:NS group (241 ± 179) mm3,DDP group (78 ±20) mm3,gosereline group (78 t±55) mm3,goserelin + DDP group (64 ±48) mm3,cetrorelix group (78 ±64) mm3,or cetrorelix + DDP group (70 ± 19) mm3,in which there were significant difference between NS group and the other groups ( P ＜ 0.05 ) ; and the same result was obtained on day 15,19,22,26 and 29 ( P ＜ 0.05 ).The expression of Ki-67 in NS group was ( 33 ± 10 ) ％,in which it was higher than those in DDP group 3.5％,goserelin group 8.8％,goserelin + DDP group 1.5％,cetrorelix group (23 ± 11 ) ％,or cetrorelix + DDP group ( 8 ± 6 ) ％ ( P ＜ 0.05 ).The ratio of primary and preantral follicles in goserehn group was (71.5 ± 8.1 ) ％,in goserelin + DDP group was (62.4 ± 4.1 ) ％,in cetrorelix group was (71.2 ± 7.4) ％,and in cetrorelix + DDP group was (63.8 ±3.1 )％,in which they were much higher than that in DDP group ( 47.0 ± 4.8 ) ％ ( P ＜ 0.05 ).The level of AMH in goserelin group was ( 98 ± 27 ) ng/ml,which was much higher than that in NS group (66.2 ± 17.4) ng/ml (P ＜0.05),while there were no difference in the levelsof FSH,E2 or P among different groups ( P ＞ 0.05).Conclusion GnRH analogues could inhibit the growth of transplanted tumors in nude mice,meanwhile increase the secretion of AMH,decrease the frequencies and prolong the lasting time of estrus,decrease the ratio of atretic follicles,raise the ratio of primary and preantral follicles,which may be protect the ovarian function of nude mice.
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AIM: To investigate antitumor effect of allotri-tridecyl diethylamine (D-108) in vivo and in vitro. METHODS: The cytotoxic effects of D-108 on various tumor cell lines, human gingival fibroblast and marrow stromal cell cultured in vitro were determined with trypan blue dye exclusion test and MTT method. The acute toxicity of mice by administration of D-108 was evaluated by Bliss method. At a tolerable dose level, D-108 was administrated to treat transplanted solid tumor U14, and tumor weight inhibition was observed. Apoptosis morphological transformation of HL 60 cell induced by D-108 was detected by the Giemsa staining. RESULTS: The cytotoxic effects in vitro of D-108 on various tumor cell lines (IC_ 50 : 0.22 to 2.19 mg?L~ -1 ) were more powerful than both human gingival fibroblast and marrow stromal cell (IC_ 50 : 5.55 and 3.57 mg?L~ -1 ). LD_ 50 of D-108 was 36.49 mg?kg~ -1 (mice, i.g.). D-108 inhibited in vivo growth of implanted solid tumor U14 of mice effectually. The inhibition rate of tumor weight of D-108 (100 mg?kg~ -1 ?d~ -1 i.g.) was 45.27 %. HL 60 cell appearanced typical apoptosis morphological transformation induced by D-108. CONCLUSION: D-108 had obvious antitumor activity in vivo and in vitro and little toxicity. D-108 could induce the apoptosis of HL 60 cell.
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Objective To investigate the effect of integrin-?1 antisense oligodeoxynucleotide(ASODN) on(human) pancreatic cancinoma transplanted subcutaneously in nude mice.Methods The models of human(pancreatic) cancinoma transplanted subcutaneously were established in nude mice,then divided randomly into 3 groups and different treatment was given respectively(control group,random oligodeoxynucleotide group and ASODN group).After treatment,the weight of nude mice and tumor volume were observed,and the tumor growth inhibitory rate and the tumor response rate were calculated.The expressions of integrin-?1 mRNA and protein in tumor tissue were determined by RT-PCR and Western-blot.Results The tumor growth inhibitory rate in the random oligodexynucleotide group and the ASODN group was 4.75% and 72.70%,respectively.The tumor decrease rate of the ASODN group was 10.91%.The expression level of integrin-?1 mRNA and protein was decreased in the ASODN group compared with other 2 control groups. Conclusions Our findings suggest that integrin-?1 antisense oligodeoxynucleotides result in marked inhibition of human pancreatic(cancinoma) growth in nude mice.It may be a novel treatment approach for human pancreatic carcinoma.
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PURPOSE To provide evidence for the relationship between degree of invasion and tumor metastasis. The tumor cells of transplantable mouse histiocytic sarcoma (L1) were inoculated at the right hind footpads of inbred 615-strain mice. METHODS Once bearing the tumor, all the mice were sacrificed respectively on the 1st. 3th, 5th. 10th, 20th, 30th, and 40th day as to observe the degree of tumor invasion and the process of tumor metastasis. RESULTS When the degree of tumor invasion was grade Ⅲ or Ⅳ , the metastasis of tumor cells was found earliest in draining lymph nodes. However, the tumor metastasis in lung appeared later than in lymph nodes. CONCLUSION According to the time of tumor growth and degree of invasion and metastasis, the authors suggest a new classification for cancer staging, namely, latent, invasive and metastatic stages. During the stage of tumor invasion, it is redivided into early, middle and late invasive phases. During the stage of tumor metastasis, it is redivided into early, middle and late metastatic phases.