Mobile website
Volume 3,Issue 4,1996 Table of Contents
1996, 3(4):251-258.
DOI: 10.3872/j.issn.1007-385X.1996.4.002
Abstract:
The aim of the current study was to determine whether tumor-specific T cells can be primed in and obtained from sponge implants loaded with tumor associated peptides. Naive C57BL/6 mice as well as C57BL/6 mice previously primed with FBL-3 tumor cells were implanted with small polyurethane sponges containing FBL-3 gag peptides CCLCLTVFL(gPr80 gag 85-93)or RSPTNLAKV(Pr65 gag p30 131-139). Both FBL-3 gag peptides were shown could bind to H-2 Db molecules. Ten days later, cells that had accumulated in the sponges were harvested, stimulated in vitro with the immunizing peptide, and tested for cytolytic activity against FBL-3 tumor and FBL-3 gag peptides. The results demonstrated that peptide-specific CD8 CTL could be elicited and obtained from the sponge implants of both naive and immune mice. The FBL-3 gag p85-93 peptide induced CTL could specifically lyse syngeneic targets pulsed with the FBL-3 gag p85-93 peptide as well as FBL-3 tumor. However, the FBL-3 gag p131-139 peptide induced CTL lysed only the FBL-3 gag p131- 139 peptide pulsed syngeneic targets but not the FBL- 3 tumor. Tumor-specific T cells obtained from peptide-loaded sponge implants could be induced to grow to large numbers in vitro by periodic restimulation with the immunizing peptide plus syngeneic APC and low concentrations of IL- 2. Adoptive transfer of the resultant expanded FBL-3 gag p85-93 peptide-induced CTL into mice with disseminated FBL-3 could mediate effective anti-tumor therapy. Thus,in vivo immunization with peptide-loaded sponges provides a potentially useful technique for procuring primed peptide- specific T cells for tumor therapy.
The aim of the current study was to determine whether tumor-specific T cells can be primed in and obtained from sponge implants loaded with tumor associated peptides. Naive C57BL/6 mice as well as C57BL/6 mice previously primed with FBL-3 tumor cells were implanted with small polyurethane sponges containing FBL-3 gag peptides CCLCLTVFL(gPr80 gag 85-93)or RSPTNLAKV(Pr65 gag p30 131-139). Both FBL-3 gag peptides were shown could bind to H-2 Db molecules. Ten days later, cells that had accumulated in the sponges were harvested, stimulated in vitro with the immunizing peptide, and tested for cytolytic activity against FBL-3 tumor and FBL-3 gag peptides. The results demonstrated that peptide-specific CD8 CTL could be elicited and obtained from the sponge implants of both naive and immune mice. The FBL-3 gag p85-93 peptide induced CTL could specifically lyse syngeneic targets pulsed with the FBL-3 gag p85-93 peptide as well as FBL-3 tumor. However, the FBL-3 gag p131-139 peptide induced CTL lysed only the FBL-3 gag p131- 139 peptide pulsed syngeneic targets but not the FBL- 3 tumor. Tumor-specific T cells obtained from peptide-loaded sponge implants could be induced to grow to large numbers in vitro by periodic restimulation with the immunizing peptide plus syngeneic APC and low concentrations of IL- 2. Adoptive transfer of the resultant expanded FBL-3 gag p85-93 peptide-induced CTL into mice with disseminated FBL-3 could mediate effective anti-tumor therapy. Thus,in vivo immunization with peptide-loaded sponges provides a potentially useful technique for procuring primed peptide- specific T cells for tumor therapy.
1996, 3(4):259-263.
DOI: 10.3872/j.issn.1007-385X.1996.4.003
Abstract:
T lymphocytes play a very important role in tumor immunity, which recognize tumor antigenic peptide presented by MHC molecules on the surface of tumor cells through T cell receptor ( TCR) . Cytotoxic T lymphocytes kill tumor cells after recognizing antigenic peptide in the cleft of MHC class I molecules. It is now generally accepted that peptides naturally presented by a given MHC class I molecule have a specific motif which is referred to as MHC class I allele-specific consensus motif and that synthetic peptide corresponding to the identified naturally presented antigens exhibit remarkable activity in inducing T-cell responses. FBL-3 is a transplantable Friend virus-induced leukemia of B6 (H-2b) origin,which can induce the CTL against FBL-3 by immunizing B6 mice with atenuated FBL-3.Seven peptides were predicted as candidates of FBL-3 antigenic peptides in the light of H-2Db specific peptide binding motif and gag gene sequence of Friend virus. The synthetic peptides, named gagl to gag7, were obtainted. The results showed that CTL specific to gag3 could be induced by in vivo immunizing B6 mice with gag3 in IFA, but a primary T cell response could not be induced by in vitro immuniztion with the peptides. gag3 and gag5 could be recognized by specific CTL to FBL-3,because the CTLs obviously killed target cells (EL-4) pulsed with gag3 or gag5. Immunization with gag3 and gag5 could not induce an immune response to protect the subsequent challenge of FBL-3 in B6 mice which could be induced by immunizing B6 mice with parental FBL-3 tumor cells. This indicates these 7 synthetic peptides may not be the same antigens of the FBL-3.
T lymphocytes play a very important role in tumor immunity, which recognize tumor antigenic peptide presented by MHC molecules on the surface of tumor cells through T cell receptor ( TCR) . Cytotoxic T lymphocytes kill tumor cells after recognizing antigenic peptide in the cleft of MHC class I molecules. It is now generally accepted that peptides naturally presented by a given MHC class I molecule have a specific motif which is referred to as MHC class I allele-specific consensus motif and that synthetic peptide corresponding to the identified naturally presented antigens exhibit remarkable activity in inducing T-cell responses. FBL-3 is a transplantable Friend virus-induced leukemia of B6 (H-2b) origin,which can induce the CTL against FBL-3 by immunizing B6 mice with atenuated FBL-3.Seven peptides were predicted as candidates of FBL-3 antigenic peptides in the light of H-2Db specific peptide binding motif and gag gene sequence of Friend virus. The synthetic peptides, named gagl to gag7, were obtainted. The results showed that CTL specific to gag3 could be induced by in vivo immunizing B6 mice with gag3 in IFA, but a primary T cell response could not be induced by in vitro immuniztion with the peptides. gag3 and gag5 could be recognized by specific CTL to FBL-3,because the CTLs obviously killed target cells (EL-4) pulsed with gag3 or gag5. Immunization with gag3 and gag5 could not induce an immune response to protect the subsequent challenge of FBL-3 in B6 mice which could be induced by immunizing B6 mice with parental FBL-3 tumor cells. This indicates these 7 synthetic peptides may not be the same antigens of the FBL-3.
1996, 3(4):264-267.
DOI: 10.3872/j.issn.1007-385X.1996.4.004
Abstract:
The inhibition of pulmonary metastasis by inhalation of aerosolized recombinant 1L-2 (rIL-2) in BCG-primed mice is reported in this paper . (TA2 x 615) Fl mice were given ip BCG twice in two-week apart.Right after the second BCG injection, MA891 cells, a murine mammary adenocarcinoma of TA2 origin, were injected into the tail vein.Treatment with aerosolized rIL -2 by inhalation was given for 1 hr, 3 times a day and lasted for 14 days. After sacrifice, bronchoalveolar lavage was performed and the lavage fluid was examined for nitric oxide content. The number of tumor nodules on the lung surface was recorded as a measure of the extent of pulmonary metastasis. The results showed that in mice so treated, pulmonary metastasis was very significantly inhibited. When rIL-2 treatment was given in BCG-unprimed mice, inhibition of pulmonary metastasis was also observed albeit to a much lesser extent. Significant inhibition of lung metastasis was associated with significant increase in nitric oxide content in the broncho-alveolar lavage fluid. Moreover, when nitric oxide synthase inhibitor, NG monomethyl-L-arginine (7mg/kg) was given ip shortly before each inhalation of rIL-2, accompanied with a significant reduction of nitric oxide in the lavage fluid, the inhibitory effect of rIL-2 in both BCG-primed and -unprimed mice was almost completely abrogated. Taken together, the results clearly indicate that pulmonary metastasis can be effectively treated by the induction of endogenous release of nitric oxide from activated alveolar macrophages.
The inhibition of pulmonary metastasis by inhalation of aerosolized recombinant 1L-2 (rIL-2) in BCG-primed mice is reported in this paper . (TA2 x 615) Fl mice were given ip BCG twice in two-week apart.Right after the second BCG injection, MA891 cells, a murine mammary adenocarcinoma of TA2 origin, were injected into the tail vein.Treatment with aerosolized rIL -2 by inhalation was given for 1 hr, 3 times a day and lasted for 14 days. After sacrifice, bronchoalveolar lavage was performed and the lavage fluid was examined for nitric oxide content. The number of tumor nodules on the lung surface was recorded as a measure of the extent of pulmonary metastasis. The results showed that in mice so treated, pulmonary metastasis was very significantly inhibited. When rIL-2 treatment was given in BCG-unprimed mice, inhibition of pulmonary metastasis was also observed albeit to a much lesser extent. Significant inhibition of lung metastasis was associated with significant increase in nitric oxide content in the broncho-alveolar lavage fluid. Moreover, when nitric oxide synthase inhibitor, NG monomethyl-L-arginine (7mg/kg) was given ip shortly before each inhalation of rIL-2, accompanied with a significant reduction of nitric oxide in the lavage fluid, the inhibitory effect of rIL-2 in both BCG-primed and -unprimed mice was almost completely abrogated. Taken together, the results clearly indicate that pulmonary metastasis can be effectively treated by the induction of endogenous release of nitric oxide from activated alveolar macrophages.
1996, 3(4):268-271.
DOI: 10.3872/j.issn.1007-385X.1996.4.005
Abstract:
以分化绣导剂苯乙酸钠处理肿瘤细胞,以ELISA检测肿瘤细胞表面HLA Ⅰ、Ⅱ类分子表达的变化。结果发现MCF-7、MDA-453、MKN-45以及Hela细胞表面HLA Ⅰ类分子表达较低,而MKN-28和3AO细胞表面HLA Ⅰ类分子高表达。MDA-453、MKN-28、MKN-45、Hela以及3AO细胞表面亦表达HLA Ⅱ类分子,而MCF-7细胞表面缺乏HLA Ⅱ类分子。苯乙酸钠能够诱导MCF-7细胞表面表达HLA Ⅱ类分子;增强MCF-7细胞表面HLA Ⅰ类分子,MDA-453、MKN-28、MKN-45、Hela以及3AO细胞表面HLA Ⅰ、Ⅱ类分子的表达。并且肿瘤细胞表面HLA Ⅰ类分子的表达与苯乙酸钠的作用时间和剂量呈正相关。
以分化绣导剂苯乙酸钠处理肿瘤细胞,以ELISA检测肿瘤细胞表面HLA Ⅰ、Ⅱ类分子表达的变化。结果发现MCF-7、MDA-453、MKN-45以及Hela细胞表面HLA Ⅰ类分子表达较低,而MKN-28和3AO细胞表面HLA Ⅰ类分子高表达。MDA-453、MKN-28、MKN-45、Hela以及3AO细胞表面亦表达HLA Ⅱ类分子,而MCF-7细胞表面缺乏HLA Ⅱ类分子。苯乙酸钠能够诱导MCF-7细胞表面表达HLA Ⅱ类分子;增强MCF-7细胞表面HLA Ⅰ类分子,MDA-453、MKN-28、MKN-45、Hela以及3AO细胞表面HLA Ⅰ、Ⅱ类分子的表达。并且肿瘤细胞表面HLA Ⅰ类分子的表达与苯乙酸钠的作用时间和剂量呈正相关。
1996, 3(4):272-276.
DOI: 10.3872/j.issn.1007-385X.1996.4.006
Abstract:
将热稳定抗原(Heat-stable Antigen,简称HSA)的cDNA与质粒载体(PcDNA3)连接,构建成真核表达载体,通过电穿孔的方法将重组质粒导入到小鼠淋巴瘤细胞EL-4中,使其表达抗性基因和HSA分子,通过高剂量G418(400μg/ml)选择培养和有限稀释法克隆,获得高比例表达HSA的阳性细胞克隆,以提供活化T细胞所必需的协同刺激信号,从而诱导宿主体内有效的抗肿瘤免疫应答。实验发现:表达HSA的EL-4淋巴瘤细胞在同系小鼠(C57BL/6)体内的致瘤性明显较野生型肿瘤弱。HSA~ EL-4瘤细胞经丝裂霉素灭活后,腹腔免疫同系小鼠后可获得对低剂量(2×10~3/鼠)野生型瘤细胞EL-4攻击的免疫保护效应。用HSA~ 瘤细胞灭活后作为瘤苗治疗早期带瘤动物显示一定的治疗效果。
将热稳定抗原(Heat-stable Antigen,简称HSA)的cDNA与质粒载体(PcDNA3)连接,构建成真核表达载体,通过电穿孔的方法将重组质粒导入到小鼠淋巴瘤细胞EL-4中,使其表达抗性基因和HSA分子,通过高剂量G418(400μg/ml)选择培养和有限稀释法克隆,获得高比例表达HSA的阳性细胞克隆,以提供活化T细胞所必需的协同刺激信号,从而诱导宿主体内有效的抗肿瘤免疫应答。实验发现:表达HSA的EL-4淋巴瘤细胞在同系小鼠(C57BL/6)体内的致瘤性明显较野生型肿瘤弱。HSA~ EL-4瘤细胞经丝裂霉素灭活后,腹腔免疫同系小鼠后可获得对低剂量(2×10~3/鼠)野生型瘤细胞EL-4攻击的免疫保护效应。用HSA~ 瘤细胞灭活后作为瘤苗治疗早期带瘤动物显示一定的治疗效果。
Huang Xin
,
Cao Xuetao
,
Zhang Weiping
,
Ju Tianwen
,
Zhang Minghui
,
Xiao Nong
,
Chen Guoyou
,
Wan Tao
,
HirofumiHamada
1996, 3(4):280-284.
DOI: 10.3872/j.issn.1007-385X.1996.4.008
Abstract:
To evaluate whether in vitro and in vivo transfer of E. Coli cytosine deaminase gene will confer sensitivity of a solid tumor to prodrug 5-fluorocytosine(5FC), we used an adenovirus vector(AdexCMV. CD) carrying the cytosine deaminase gene driven by the CMV promoter, infected SMMC-7721 or HepG2 cells hepatocellular carcinoma cells in vitro, and found AdexCMV. CD vector could effectively suppressed the growth of SMMC-7721 and HepG2 cells. When the two cells were infected with AdexAFP. CD vector in which the CD gene was driven by the AFP gene 5'-flanking region, only HepG2 cells were conferred sensitivity to 5FC. (Infection with AdexCMV.CD, when as few as 20% of cells transfected the CD gene, SMMC-7721 cells were associated with a bystander effect when combined with 5FC in cell mixing studies.) Consistent with these in vitro observations, AdexCMV. CD was directly injected into established subcutaneous SMMC-7721 tumors in nude mice receiving 5FC,there was a 60% reduction in tumor size at day 8, 70% reduction at day 24. Our results suggested that adenovirus-mediated tumor-specific gene transfer of CD gene and concomitant administration of 5 FC may have potential as a strategy for local control of tumor growth.
To evaluate whether in vitro and in vivo transfer of E. Coli cytosine deaminase gene will confer sensitivity of a solid tumor to prodrug 5-fluorocytosine(5FC), we used an adenovirus vector(AdexCMV. CD) carrying the cytosine deaminase gene driven by the CMV promoter, infected SMMC-7721 or HepG2 cells hepatocellular carcinoma cells in vitro, and found AdexCMV. CD vector could effectively suppressed the growth of SMMC-7721 and HepG2 cells. When the two cells were infected with AdexAFP. CD vector in which the CD gene was driven by the AFP gene 5'-flanking region, only HepG2 cells were conferred sensitivity to 5FC. (Infection with AdexCMV.CD, when as few as 20% of cells transfected the CD gene, SMMC-7721 cells were associated with a bystander effect when combined with 5FC in cell mixing studies.) Consistent with these in vitro observations, AdexCMV. CD was directly injected into established subcutaneous SMMC-7721 tumors in nude mice receiving 5FC,there was a 60% reduction in tumor size at day 8, 70% reduction at day 24. Our results suggested that adenovirus-mediated tumor-specific gene transfer of CD gene and concomitant administration of 5 FC may have potential as a strategy for local control of tumor growth.
1996, 3(4):285-288.
DOI: 10.3872/j.issn.1007-385X.1996.4.009
Abstract:
In this research, we apply the antisense strategy to study the function of IGF- I in human hepatoma lines(7402) by Lipofectin mediated gene transfer. The effect of antisense IGF-I on the expression of MHC and the sensitivity of LAK cytotoxicity of tumor cell were studied. The results showed that human hepotoma lines(7402) were transfected with an amplifiable antisense IGF- I gene. The expression antisense IGF-I RNA in the transfected cells after hygromycin resistant selection was confirmed by northern blot analysis. The transfectants expressed higher level of MHC class I and class II molecules. The susceptibility of the transfected cell to LAK cytotoxicity was greater than that of 7402 parent cells(P<0.05). It suggests that transfecting cells can enhance the expression of MHC class I and class II molecules and suceptibility of 7402 cells to the cytotoxicity of LAK cells.
In this research, we apply the antisense strategy to study the function of IGF- I in human hepatoma lines(7402) by Lipofectin mediated gene transfer. The effect of antisense IGF-I on the expression of MHC and the sensitivity of LAK cytotoxicity of tumor cell were studied. The results showed that human hepotoma lines(7402) were transfected with an amplifiable antisense IGF- I gene. The expression antisense IGF-I RNA in the transfected cells after hygromycin resistant selection was confirmed by northern blot analysis. The transfectants expressed higher level of MHC class I and class II molecules. The susceptibility of the transfected cell to LAK cytotoxicity was greater than that of 7402 parent cells(P<0.05). It suggests that transfecting cells can enhance the expression of MHC class I and class II molecules and suceptibility of 7402 cells to the cytotoxicity of LAK cells.
Chen Chengwei
,
Ni Liuda
,
Ru Sujuan
,
Zhou Feng
,
Chen Hui
,
Ren Huiqiong
,
Lu Jinyu
,
Feng Xiaoling
1996, 3(4):289-291.
DOI: 10.3872/j.issn.1007-385X.1996.4.010
Abstract:
A comparison of effectiveness of chemo-immunotherapy (CIT) using LAK/CD3AK 1-2 weeks after TACE in 74 patients with no surgical indication and TACE alone in 41 patients with moderately advanced HCC was carried out. The rates of remission between CIT group and TACE alone group were 72.4% and 40.4%(P<0.05) in stage II HCC and 48.9% and 14.3% (P<0.05) in stage III HCC respectively (P<0.05). The 6 and 12 months survival of stage III HCC and 2 years survival rates of stage II of CIT group were 62.2%,46.0% and 48. 3% respectively, significantly higher than those of TACE alone group (23.8%,9.5% and 15% respectively,P<0.05). The rates of extrahepatic metastasis within 12 month of CIT group was 25.9%, significantly lower than that of TACE alone group(58.1%,P<0.05). The results show chemo-immunotherapy is a rational and effective treatment for moderately advanced HCC.
A comparison of effectiveness of chemo-immunotherapy (CIT) using LAK/CD3AK 1-2 weeks after TACE in 74 patients with no surgical indication and TACE alone in 41 patients with moderately advanced HCC was carried out. The rates of remission between CIT group and TACE alone group were 72.4% and 40.4%(P<0.05) in stage II HCC and 48.9% and 14.3% (P<0.05) in stage III HCC respectively (P<0.05). The 6 and 12 months survival of stage III HCC and 2 years survival rates of stage II of CIT group were 62.2%,46.0% and 48. 3% respectively, significantly higher than those of TACE alone group (23.8%,9.5% and 15% respectively,P<0.05). The rates of extrahepatic metastasis within 12 month of CIT group was 25.9%, significantly lower than that of TACE alone group(58.1%,P<0.05). The results show chemo-immunotherapy is a rational and effective treatment for moderately advanced HCC.
1996, 3(4):292-294.
DOI: 10.3872/j.issn.1007-385X.1996.4.011
Abstract:
Murine interleukin-4 gene(mIL-4) was transfected into mice glioblastoma cell line G422 by recombinant adenovirus vector. We detected mRNA transcription of target gene in gene modified tumor cells(G422-mIL4). High level of mouse IL-4 could be detected in the culture supernatant of G422-mIL4. When inoculated subcuatneously, the tumor growth of G422-mIL4 was significantly inhibited as compared to wild type G422 and LacZ gene modified G422( G422-LacZ) . The period of survival of mice inoculated with G422-mlL4 was significantly prolongated(p<0.01).
Murine interleukin-4 gene(mIL-4) was transfected into mice glioblastoma cell line G422 by recombinant adenovirus vector. We detected mRNA transcription of target gene in gene modified tumor cells(G422-mIL4). High level of mouse IL-4 could be detected in the culture supernatant of G422-mIL4. When inoculated subcuatneously, the tumor growth of G422-mIL4 was significantly inhibited as compared to wild type G422 and LacZ gene modified G422( G422-LacZ) . The period of survival of mice inoculated with G422-mlL4 was significantly prolongated(p<0.01).
1996, 3(4):295-298.
DOI: 10.3872/j.issn.1007-385X.1996.4.012
Abstract:
In this experiment, the murine melanoma cell B16-F10 oncolysates transfected by recombinant vaccinia viruses encoding human IL-2(IL-2VBO) were used as vaccine. When the tumor-bearing mice were treated by following injection of IL-2VBO into tumor site, the tumor growth was inhibited and the survival time prolonged. The PBL from IL-2VBO treated mice showed higher cytotoxicity to the wild type B16-F10 but not to YAC-1 cells than that from control groups. The results showed the active specific immunity was induced by the IL-2VBO. On accout of its stronger immuogenicity and some advantages in preparing and storing, the IL-2VBO might be used as a kind of effective vaccine in the cancer active specific immunotherapy.
In this experiment, the murine melanoma cell B16-F10 oncolysates transfected by recombinant vaccinia viruses encoding human IL-2(IL-2VBO) were used as vaccine. When the tumor-bearing mice were treated by following injection of IL-2VBO into tumor site, the tumor growth was inhibited and the survival time prolonged. The PBL from IL-2VBO treated mice showed higher cytotoxicity to the wild type B16-F10 but not to YAC-1 cells than that from control groups. The results showed the active specific immunity was induced by the IL-2VBO. On accout of its stronger immuogenicity and some advantages in preparing and storing, the IL-2VBO might be used as a kind of effective vaccine in the cancer active specific immunotherapy.
1996, 3(4):299-301.
DOI: 10.3872/j.issn.1007-385X.1996.4.013
Abstract:
In this article, the plasma half life of IL-2 and its bio-distribution were studied using radio-nucleus Technetium-99M labeled IL-2. The results showed the plasma half life of IL-2 was merely 10 minutes mainly due to IL-2 distribute to its target organ such as liver, kidney etc,rather than clear out of the body. Our results indicated that IL-2 is a high organ-specific drug. It's plasma half life is short under high concentration in its target organ. So it might have advantages of high effectiveness and low whole body toxicity in treatment of tumor of liver and kidney.
In this article, the plasma half life of IL-2 and its bio-distribution were studied using radio-nucleus Technetium-99M labeled IL-2. The results showed the plasma half life of IL-2 was merely 10 minutes mainly due to IL-2 distribute to its target organ such as liver, kidney etc,rather than clear out of the body. Our results indicated that IL-2 is a high organ-specific drug. It's plasma half life is short under high concentration in its target organ. So it might have advantages of high effectiveness and low whole body toxicity in treatment of tumor of liver and kidney.
1996, 3(4):305-307.
DOI: 10.3872/j.issn.1007-385X.1996.4.015
Abstract:
A new modification of Merril's silver staining of proteins in sodium dodecylsulfate polyacrylamide gels is introduced.The use of a prolonged period step after fixation and adjusting of oxidant incubation time considerably decrease the background, therefore increase the sensitivity. The detection limit is fivefold lower than original method.
A new modification of Merril's silver staining of proteins in sodium dodecylsulfate polyacrylamide gels is introduced.The use of a prolonged period step after fixation and adjusting of oxidant incubation time considerably decrease the background, therefore increase the sensitivity. The detection limit is fivefold lower than original method.
联系方式
- 《中国肿瘤生物治疗杂志》
- 1994年创刊
- 主办单位：Chinese Society of Immunology, Chinese Anti-cancer Association
- 邮编：200433
- 电话：021-81871002-22
- 电子邮箱：cjcb@biother.cn
- 网址:http://www.biother.cn
- 刊号：ISSN 1007-385X
- CN 31-1725/R
- 国内定价： ￥20元/册
您是第位访问者
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.
Chinese Journal Of Cancer Biotheray ® 2025 All Rights Reserved
Supported by:Beijing E-Tiller Technology Development Co., Ltd.