COMBINATION OF CHOLECYSTOJEJUNOSTOMY OR CHOLEDOCHJEJUNOSTOMY PERFUSION CHEMOTHERAPY AND RADIOTHERAPY FOR CANCER OF THE PANCRE

ＣＯＭＢＩＮＡＴＩＯＮＯＦＣＨＯＬＥＣＹＳＴＯＪＥＪＵＮＯＳＴＯＭＹＯＲＣＨＯＬＥＤＯＣＨＪＥＪＵＮＯＳＴＯＭＹＰＥＲＦＵＳＩＯＮＣＨＥＭＯＴＨＥＲＡＰＹＡＮＤＲＡＤＩＯＴＨＥＲＡＰＹＦＯＲＣＡＮＣＥＲＯＦＴＨＥＰＡＮＣＲＥＡＴＩＣＨＥＡＤＸｕｅＨｕ...     

THE EFFECT OF RETINOIC ACID ON CELL MEMBRANE AND METASTATIC ABILITY OF MOUSE FORESTOMACH CARCINOMA C

ＴＨＥＥＦＦＥＣＴＯＦＲＥＴＩＮＯＩＣＡＣＩＤＯＮＣＥＬＬＭＥＭＢＲＡＮＥＡＮＤＭＥＴＡＳＴＡＴＩＣＡＢＩＬＩＴＹＯＦＭＯＵＳＥＦＯＲＥＳＴＯＭＡＣＨＣＡＲＣＩＮＯＭＡＣＥＬＬＹｕＸｉａｏｄａｎ于晓；ＺｈａｏＸｕｅｍｅｉ赵雪梅；ＧａｏＪｉｎ高进（Ｉｎ...     

THE BLOCKING EFFECTS OF GLYCYRRHIZE URALENSIS AND CHELIDONIUM MAJUS ON MUTAGENESIS INDUCED BY AFLATOXIN B1

ＴＨＥＢＬＯＣＫＩＮＧＥＦＦＥＣＴＳＯＦＧＬＹＣＹＲＲＨＩＺＥＵＲＡＬＥＮＳＩＳＡＮＤＣＨＥＬＩＤＯＮＩＵＭＭＡＪＵＳＯＮＭＵＴＡＧＥＮＥＳＩＳＩＮＤＵＣＥＤＢＹＡＦＬＡＴＯＸＩＮＢ１ＳｈｉＧｕｉｚｎｉ；史桂芝；ＪｉＸｉｎｈｕａ；纪新华；ＬｉａｎｇＹ...     

IMMUNOCYTOCHEMICAL CHARACTERIZATION OF CD44 MOLECULES EXPRESSED IN HUMAN BRAIN METASTASES

ＩＭＭＵＮＯＣＹＴＯＣＨＥＭＩＣＡＬＣＨＡＲＡＣＴＥＲＩＺＡＴＩＯＮＯＦＣＤ４４ＭＯＬＥＣＵＬＥＳＥＸＰＲＥＳＳＥＤＩＮＨＵＭＡＮＢＲＡＩＮＭＥＴＡＳＴＡＳＥＳＬｉＨｏｎｇ李宏；ＬｉｕＪｉａ刘佳；ＭａｒｔｉｎＨｏｆｍａｎｎ；Ｍａｒｉａｅ－Ｆｒａｎｃｅ...     

COMPARATIVE PATHOLOGICAL AND FCM STUDIES ON THE PRIMARY AND METASTATIC CANCERS IN STOMACH AND BREAST

ＣＯＭＰＡＲＡＴＩＶＥＰＡＴＨＯＬＯＧＩＣＡＬＡＮＤＦＣＭＳＴＵＤＩＥＳＯＮＴＨＥＰＲＩＭＡＲＹＡＮＤＭＥＴＡＳＴＡＴＩＣＣＡＮＣＥＲＳＩＮＳＴＯＭＡＣＨＡＮＤＢＲＥＡＳＴ￥ＺｈａｎｇＸｉａｎｇｈｏｎｇ；张祥宏；ＺｈａｎｇＪｉｅｙｉｎｇ；张杰英；Ｘｉ...     

IMMUNOHISTOCHEMICAL STUDY OF SIXTEEN CASES OF CHORDOMA

ＩＭＭＵＮＯＨＩＳＴＯＣＨＥＭＩＣＡＬＳＴＵＤＹＯＦＳＩＸＴＥＥＮＣＡＳＥＳＯＦＣＨＯＲＤＯＭＡＹａｎｇＪｉａｎ；杨践；ＣｈｅｎＺｈｉｒａｎｇ；陈志让；ＳｈｉＤａｒｅｎ；施达仁（ＲａｉｊｉｎｇＨｏｓｐｉｔａｌ，ＳｈａｎｇｈａｉＳｅｃｏｎｄＭｅｄｉｃａ...     

REVERSION OF MALIGNANT PHENOTYPES OF HUMAN LUNG SQUAMOUS CARCINOMA CELLS BY ORNITHINE DECARBOXYLASE ANTISENSE RNA

ＲＥＶＥＲＳＩＯＮＯＦＭＡＬＩＧＮＡＮＴＰＨＥＮＯＴＹＰＥＳＯＦＨＵＭＡＮＬＵＮＧＳＱＵＡＭＯＵＳＣＡＲＣＩＮＯＭＡＣＥＬＬＳＢＹＯＲＮＩＴＨＩＮＥＤＥＣＡＲＢＯＸＹＬＡＳＥＡＮＴＩＳＥＮＳＥＲＮＡＧｕａｎＪｕｎ关钧，ＦａｎＭｕｚｈｅｎ范慕贞，Ｃａｏ...     

SIMULTANEOUS THORACO－CRANIAL OPERATION FOR THE TREATMENT OF LUNG CANCER WITH BRAIN METASTASES

ＳＩＭＵＬＴＡＮＥＯＵＳＴＨＯＲＡＣＯ－ＣＲＡＮＩＡＬＯＰＥＲＡＴＩＯＮＦＯＲＴＨＥＴＲＥＡＴＭＥＮＴＯＦＬＵＮＧＣＡＮＣＥＲＷＩＴＨＢＲＡＩＮＭＥＴＡＳＴＡＳＥＳＣｈｅｎＪｉａｎ陈建；ＬｉｕＤａｏｋｕｎ刘道坤；ＬｉｕＪｕｎｈｕａ刘俊华；ＳｈｉＺｈｏ...     

STUDIES ON THE GAP JUNCTIONAL INTERCELLULARCOMMUNICATION OF HUMAN NASOPHARYNGEALCARCINOMA CELLS AND THE EFFECT OF RII

ＳＴＵＤＩＥＳＯＮＴＨＥＧＡＰＪＵＮＣＴＩＯＮＡＬＩＮＴＥＲＣＥＬＬＵＬＡＲＣＯＭＭＵＮＩＣＡＴＩＯＮＯＦＨＵＭＡＮＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣＩＮＯＭＡ　ＣＥＬＬＳＡＮＤＴＨＥＥＦＦＥＣＴＯＦＲＩＩＨａｎＬｉｑｕｎ韩立群；ＧａｏＪｉｎ高进；...     

THE ANTICANCER EFFECT AND ANTI－DNA TOPOISOMERASE II EFFECT OF EXTRACTS OF CAMELLIA PTILOPHYLLA CHANG AND CAMELLIA SINENSIS

ＴＨＥＡＮＴＩＣＡＮＣＥＲＥＦＦＥＣＴＡＮＤＡＮＴＩ－ＤＮＡＴＯＰＯＩＳＯＭＥＲＡＳＥＩＩＥＦＦＥＣＴＯＦＥＸＴＲＡＣＴＳＯＦＣＡＭＥＬＬＩＡＰＴＩＬＯＰＨＹＬＬＡＣＨＡＮＧＡＮＤＣＡＭＥＬＬＩＡＳＩＮＥＮＳＩＳＸｉｅＢｉｎｓｆｅｎ；谢冰芬；ＬｉｕＺ...     

Inhibitory effect of a serine protease inhibitor, FOY-305 on the invasion and metastasis of human pancreatic cancers

We examined the inhibitory effect of a serine protease inhibitor, FOY-305, on the invasion and metastasis of human pancreatic cancers. The in vitro matrigel invasion assay showed that the invasiveness of Capan-1 human pancreatic cancer cells was inhibited by FOY-305 treatment in a dose-dependent manner at concentrations greater than 100 nM. Intrasplenic injection of Capan-1 cells in nude mice resulted in frequent metastases to liver, however, its incidence was significantly decreased by FOY-305 treatment. These findings suggest that a serine protease inhibitor, FOY-305 can inhibit tumor invasion and metastasis by blocking the serine protease-mediated activation cascade.     

胰腺癌神经转移原位移植瘤动物模型的构建及其生物学特性研究

目的建立人类胰腺癌细胞系MIA PaCa—Ⅱ裸鼠胰腺原位移植瘤模型,观察神经侵袭情况,并研究其生物学特性。方法将MIA PaCa—Ⅱ细胞接种于裸鼠背部皮下和胰腺被膜下,建立皮下和原位移植瘤模型,分别于4、6、8周处死裸鼠行原位移植瘤病理学检查,HE和银染观察神经侵袭情况,对K—ras、C—erbB2、环氧合酶-2（COX-2）、前列腺干细胞抗原（PSCA）、p53、DPC4行SABC免疫组织化学染色。结果皮下移植瘤接种成瘤率为100％（10／10）,呈局限性生长,无脏器和神经转移。原位移植4、6、8周时成瘤率均为100％（10／10）,神经转移率分别为50％（5／10）、80％（8／10）和60％（6／10）,并可见多个脏器转移。MIA PaCa—Ⅱ细胞、皮下及原位移植瘤细胞对K—ras、C—erbB2、COX-2、PSCA呈阳性表达,且高于裸鼠正常胰腺细胞,而p53、DPC4表达则低于正常胰腺组织细胞。结论成功建立神经侵袭原位移植瘤动物模型,研究嗜神经转移以6周为宜。K—ras、C—erbB2、COX-2、PSCA高表达与p53、DPC4低表达可能参与了胰腺癌的发生。     

Genetically induced pancreatic adenocarcinoma is highly immunogenic and causes spontaneous tumor-specific immune responses

Treatment options for pancreatic cancer are limited and often ineffective. Immunotherapeutic approaches are one possible option that needs to be evaluated in appropriate animal models. The aim of the present study was to analyze tumor-specific immune responses in a mouse model of pancreatic cancer, which mimics the human disease closely. C57BL/6 EL-TGF-alpha x Trp53-/- mice, which develop spontaneous ductal pancreatic carcinoma, were generated. EL-TGF-alpha x Trp53-/- mice developed spontaneous pancreatic tumors with pathomorphologic features close to the human disease. Tumor-specific CD8+ T-cell responses and IgG responses were analyzed in EL-TGF-alpha x Trp53-/- mice during tumor development and compared with mice with s.c. growing pancreatic tumors. In contrast to spontaneous pancreatic tumors, cell lines generated from these tumors were rejected after s.c. injection into wild-type mice but not in nude or RAG knockout mice. Direct comparison of spontaneous and s.c. injected tumors revealed an impaired infiltration of CD8+ T cells in spontaneous pancreatic tumors, which was also evident after adoptive transfer of tumor-specific T cells. Intratumoral cytokine secretion of tumor necrosis factor-alpha, IFN-gamma, IL-6, and MCP-1 was lower in spontaneous tumors as well as the number of adoptively transferred tumor-specific T cells. Our data provide clear evidence for tumor-specific immune responses in a genetic mouse model for pancreatic carcinoma. Comparative analysis of s.c. injected tumors and spontaneous tumors showed significant differences in tumor-specific immune responses, which will help in improving current immune-based cancer therapies against adenocarcinoma of the pancreas.     

Restoration of p53 functions suppresses tumor growth of pancreatic cells with different p53 status

Pancreatic tumor cells show a very high frequency of p53 mutation. Our aim in this study was to determine if the restoration of wild-type p53 function could be used to eliminate the tumorigenic phenotype in these cells. Pancreatic tumor cell lines, CRL1420, which contains elevated levels of mutant p53, and CRL1682, with no detectable p53 protein, were stably transfected with the exogenous wild-type p53 gene. The growth rate and tumorigenicity in nude mice of wild-type p53 expressing clones were measured. Our data showed that the expression of wild-type p53 decreased the growth rate of CRL1420 and completely suppressed its potential for tumor formation in nude mice. Moreover, the size of the tumor formed in nude mice by CRL1682 was reduced drastically. G1 arrest as a possible cause for tumor suppression was investigated by flowcytometry. Neither of the cell lines irrespective of the status of p53 was arrested at G1 in response to x-irradiation. Thus, our results provide functional evidence that the deletion or mutational inactivation of the p53 gene represents an important step in the tumorigenicity of pancreatic cancer. Furthermore, the extent of the restoration of p53 function by introduction of the p53 gene depends on both the cell type and the cell settings (in vitro or in vivo conditions).     

Establishment and characterization of a carcinoembryonic antigen (CEA)-producing cell line from a human carcinoma of the exocrine pancreas

A human carcinoembryonic antigen (CEA)-producing cell line, T3M-4, has been established from explant cultures of a primary human pancreatic exocrine adenocarcinoma transplanted into nude mice. The tumor had metastasized in the patient. The tumor obtained from metastatic lymph nodes was the initial source for implantation in athymic nude mice. In the primary culture, host fibroblasts were eliminated by the use of the antiserum raised against nude mouse cells. T3M-4 cells have been continuously propagated in vitro during the past 26 months. The cells grew in a monolayered sheet with about 31 hours of population doubling time. The cells exhibited epithelial morphologic features resembling the structure of the original tumor, and they showed tumor takes when inoculated into athymic nude mice. Xenografts established from the cell line have retained a similar histology to the original tumor on serial transplantation. Chromosomal analysis revealed the cell line to be a human aneuploid one with a hyperdiploid mode. T3M-4 cells possess the characteristic function of CEA secretion in vitro in culture and in vivo in nude mice bearing the tumors produced by inoculation with the cultured cells. In view of these characteristics, T3M-4 cell line represents a new human pancreatic exocrine adenocarcinoma cell line that produces CEA.     

MIA PaCa-Ⅱ胰腺癌细胞系神经转移动物模型建立的实验研究

目的建立MIA PaCa-Ⅱ人胰腺癌细胞系裸鼠胰腺原位移植瘤模型并观察神经侵袭情况。方法将MIA PaCa-Ⅱ细胞行裸鼠背部皮下接种,建立高转移特性胰腺癌裸鼠皮下移植瘤模型,然后将高转移性移植瘤组织接种于裸鼠胰腺被膜下,分别于4周、6周和8周处死裸鼠行移植瘤组织解剖和病理学检查,测量移植瘤大小和重量,并用HE和银染方法观察神经侵袭情况。结果MIA PaCa-Ⅱ细胞裸鼠皮下接种成瘤率为100.0%（10/10）,皮下移植瘤呈局限性生长,无脏器和神经转移。原位移植4周、6周和8周后,胰腺癌原位移植瘤成瘤率均为100.0%（10/10）,神经转移率分别为50.0%（5/10）、80.0%（8/10）和60.0%（6/10）,并可见多个脏器转移,以肝脏、肝门淋巴结、胃窦转移和腹膜播散多见。结论人胰腺癌细胞系MIA PaCa-Ⅱ裸鼠胰腺原位移植瘤模型为一较理想的＂拟人＂神经浸润转移模型,可用于胰腺癌体内嗜神经性机制的研究。     

Prevention of human prostate tumor metastasis in athymic mice by antisense targeting of human angiogenin.

PURPOSE: Angiogenin is a potent positive mediator of neovascularization, a process required for both primary tumor growth and metastasis. In the present study, the effect of a fully phosphorothioated antisense oligodeoxynucleotide, designated JF2S, targeting the AUG translation initiation codon region of human angiogenin, on human prostate tumor development and metastasis in athymic mice was examined. EXPERIMENTAL DESIGN: JF2S was evaluated for its capacity to affect in vitro synthesis of angiogenin and subsequent tumorigenicity of transiently transfected prostate tumor cells in mice. In vivo treatment experiments were then conducted in which JF2S was used to prevent formation of tumors in an ectopic model and metastasis in an orthotopic model. RESULTS: Transient transfection of tumor cells with JF2S inhibited both angiogenin gene expression in vitro and tumorigenicity of these transfected cells in athymic mice. In therapy experiments, local treatment with JF2S completely protected mice from developing prostate tumors after s.c. injection of PC-3 human prostate tumor cells (P < 0.0001, survivor analysis). Most importantly, systemic prophylactic administration of JF2S prevented, in 47% of mice, formation of regional iliac lymph node micrometastases arising from primary tumors growing in the more natural orthotopic prostate setting (P = 0.0003, Fisher's exact test). Furthermore, total protection from regional metastasis occurred in those mice in which JF2S treatment successfully diminished human angiogenin expression in vivo. Tumor-associated angiogenesis was also impaired by JF2S treatment. When therapy was delayed until all of the mice harbored primary tumors in the prostate, the incidence of regional metastasis was still significantly decreased (P < 0.005, survivor analysis). Conclusions: These findings demonstrate that human prostate cancer establishment and spread in athymic mice is extremely susceptible to targeted disruption of tumor-derived human angiogenin gene expression. Therefore, angiogenin is a valid target against which to devise preventative strategies for prostate cancer metastasis.     

annexin Ⅰ对胰腺癌细胞生物学行为影响的体内研究

目的 探讨annexin Ⅰ在胰腺癌发生过程中的作用.方法 应用RNA干扰技术,敲低annexin Ⅰ基因在mRNA水平的表达,并经Western blot检测证实.分别接种人胰腺癌Suit-Ⅱ细胞及转染annexin Ⅰ-siRNA2、annexin Ⅰ-siRNA3、annexin Ⅰ-siRNAN的Suit-Ⅱ细胞,建立裸鼠胰腺癌移植瘤模型,观察胰腺癌细胞的成瘤能力、肿瘤生长速度的变化,测定肿瘤体积和瘤重.结果 (1)Westernblot检测结果显示,转染pSilencer-annexin Ⅰ-siRNA1的Suit-Ⅱ细胞annexin Ⅰ表达显著降低,转染pSilencer-annexin Ⅰ-siRNA2和pSilencer-annexin Ⅰ-siRNA3的Suit-Ⅱ细胞annexin Ⅰ的表达几乎被完全抑制.(2)接种转染annexin Ⅰ-siRNA2、annexin Ⅰ-siRNA3细胞组的肿瘤生长速度较接种亲本Suit-Ⅱ细胞组明显减慢,肿瘤生长被抑制,抑制率分别达76.6%和68.4%.接种肿瘤细胞后44 d,接种转染annexin Ⅰ-siRNA2细胞组、接种转染annexin Ⅰ-siRNA3细胞组的瘤重分别为0.8987和0.8992 g,显著低于接种亲本Suit-Ⅱ细胞组和接种转染annexin Ⅰ-siRNAN细胞组(分别为2.5866和2.4070 g,P<0.001).结论 annexin Ⅰ基因在胰腺癌发生过程中起到了促进胰腺癌细胞生长增殖、增强胰腺癌细胞成瘤能力的重要作用,可作为基因治疗的潜在靶点.     

转染 p53基因对肺腺癌细胞株裸鼠 移植瘤生长的影响

目的：探讨转染野生型 p53（ wt-p53）和突变型 p53（ mt-p53）基因对人肺腺癌细胞株 GLC-82裸鼠移植瘤生长的影响。方法：采用脂质体介导法,分别将 wt-p53和 mt-p53基因导入人肺腺癌细胞株 GLC-82,在裸鼠体内、体外实验中检测转导细胞的生长状况和裸鼠致瘤性。结果：转染 mt-p53 基因的细胞株 G418筛选的细胞集落数、 3H-TDR掺入实验、软琼脂平皿细胞集落数,以及裸鼠瘤组织重量和体积均高于对照组（ P<0.01）,而转染 wt p53基因的细胞株均显著低于对照组（ P< 0.01）,表明导入 wt p53基因的细胞株瘤细胞生长速度明显低于对照组细胞株和导入 mt p53基因的细胞株,即导入 mt p53基因的细胞株瘤细胞生长速度最快,而导入 wt p53基因的细胞株瘤细胞生长速度最慢。结论： wt p53基因能有效抑制人肺腺癌细胞生长; mt p53基因则可以明显地促进瘤细胞生长。     

p53基因对鼻咽癌细胞株CNE－3裸鼠致瘤抑制作用的研究

分别将野生型和突变型ｐ５３基因导入鼻咽癌的体外培养细胞系ＣＮＥ－３．裸鼠致瘤试验表明，导入野生型ｐ５３基因的细胞系，肿瘤生长速度明显低于对照细胞系及导入突变型ｐ５３基因的细胞系；导入突变型ｐ５３基因的细胞系肿瘤生长速度最快；导入野生型ｐ５３基因的细胞系肿瘤生长速度最慢，而且肿瘤出现时间也较导入突变型ｐ５３的细胞及对照细胞晚１～２周。这说明野生型ｐ５３基因能有效地抑制肿瘤的生长，而实变型ｐ５３基因则可以促进肿瘤生长。这是首次有关ｐ５３基因对鼻咽癌细胞作用的报道。这一研究更进一步说明了ｐ５３基因的功能，对于鼻咽癌发生机理的探讨以及肿瘤的防治具有重要意义。