食管鳞状细胞癌伴Paget病1例报道并文献复习

目的 探讨食管Paget病的临床病理学特点、免疫表型及组织学发生.方法 对1例食管鳞状细胞癌伴Paget病进行临床特点、组织形态学观察和免疫组化检测,并复习相关文献.结果 患者男性,62岁,进食时胸骨后疼痛1个月余,以进食干硬食物明显.胃镜示食管距门齿33～39 cm处有一环状新生物,考虑为食管癌.距食管癌标本上切缘2 cm处见一溃疡型肿块,其组织学表现为中分化鳞状细胞癌;上切缘黏膜及黏膜下腺体、导管见Paget细胞.免疫组化:鳞癌细胞CK14、CK5/6、p63、高分子CK阳性;Paget细胞CK8、低分子CK、EMA、CEA、CKpan阳性,CK20阴性.结论 食管Paget病罕见,分为原发性和继发性两种,需与鳞状细胞癌及恶性黑色素瘤的Paget样播散等鉴别.     

伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤1例并文献复习

目的探讨伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤的临床病理学特征、诊断及鉴别诊断。方法回顾性分析1例伴皮脂腺分化的腺样囊性癌和鳞癌构成的发生在食管的碰撞瘤,分析其临床表现、组织病理学特征和免疫表型,并复习相关文献。结果胃镜下见距门齿34～37cm处食管见一隆起型灰黄色肿物,组织学表现为双原发肿瘤,糜烂区为中分化鳞癌,浸润黏膜下层,周围可见鳞状上皮不典型增生;隆起型灰黄色肿物主要由3种不同组织构型区域融合构成。免疫表型:未分化基底样细胞CK8/18、CAM5. 2、p63、p40、GATA-3、S-100均(+),CK5/6、CK7均灶(+),AR、GCDFP-15、SMA均(-);腺样囊性癌样区域:腺上皮CK8/18、CAM5. 2、CK7均(+),基底细胞p63、p40、CK5/6、S-100、CD117均(+),SMA、AR、GCDFP-15、GATA-3均(-);皮脂腺分化区域:CK5/6、p40、GATA-3、EMA均(+),SMA灶(+); AR、GCDFP-15、vimentin、CD117、CD15均(-);鳞癌区域:p40、p63、CK5/6均(+)。随访56个月,患者无复发及转移。结论伴皮脂腺分化的腺样囊性癌和鳞癌构成的食管碰撞瘤临床罕见,需与基底细胞样鳞癌、黏液表皮样癌、腺鳞癌及MuiR-Torre综合征鉴别。     

联合检测TTF1、CK5/6、p63和napsinA在肺鳞癌和腺癌鉴别诊断中的价值

目的 探讨TTF1、CK5/6、p63和napsinA联合检测在肺鳞状细胞癌和腺癌鉴别诊断中的价值.方法 应用免疫组化EnVision法分别检测30例肺鳞状细胞癌和30例肺腺癌中TTF1、CK5/6、p63和napsinA的表达.结果 CK5/6、p63、TTF1和napsinA在肺鳞状细胞癌中的阳性率分别为96.7%、100%、20%和0,同时在肺腺癌中的阳性率分别为10%、20%、86.7%和90%.单个标志物中,CK5/6阳性和napsinA阴性对肺鳞状细胞癌与腺癌的鉴别诊断具有较高的特异性和敏感性;联合标志物检测中,p63和CK5/6共同表达阳性与TTF1和napsinA共同表达阴性在肺鳞状细胞癌的诊断中具有较高的特异性.结论 TTF1、CK5/6、p63和napsinA联合检测可鉴别肺鳞状细胞癌和腺癌,p63和CK5/6共同阳性表达与TTF1和napsinA共同阴性表达更加支持肺鳞状细胞癌,而非肺腺癌,反之亦然.     

食管鳞状细胞癌中Beclin1、LC3和mTOR的表达及其临床意义

目的探讨Beclin1、LC3和m TOR在食管鳞状细胞癌中的表达,并分析其临床意义。方法采用免疫组化En Vision法检测食管30例正常黏膜、32例低级别上皮内瘤变、34例高级别上皮内瘤变、35例早期癌及126例进展期癌中Beclin1、LC3和m TOR的表达,并分析其相关性及其与临床病理特征的关系。结果 Beclin1在进展期癌组中的表达高于其他四组(P0.005)。LC3在食管进展期癌组的表达高于正常黏膜组、低级别上皮内瘤变及早期癌组(P0.005)。m TOR在进展期癌组中的表达高于正常黏膜组、低级别上皮内瘤变及高级别上皮内瘤变组(P0.005)。Beclin1、LC3、m TOR表达与肿瘤TNM分期、淋巴结转移具有显著相关性(P0.05)。Beclin1与LC3、Beclin1与m TOR在食管进展期癌中的表达均呈正相关(P0.05),m TOR与LC3在高级别上皮内瘤变组及进展期癌中的表达呈正相关(P0.05)。结论在食管癌的发生、发展中,Beclin1作为抑癌基因激活自噬,导致肿瘤细胞过度自我消耗死亡;m TOR通过抑制自噬及促进血管生成,促进肿瘤生长。联合检测Beclin1、LC3和m TOR在食管癌中的表达,有助于评估进展程度和预后判断。     

p63蛋白在食管磷状细胞癌中的表达及意义

目的检测p63蛋白在食管癌组织中的表达情况,并探讨其与食管癌临床病理特征的关系。方法采用免疫组化检测p63蛋白在53例食管磷癌及癌旁组织中的表达情况。结果p63蛋白在食管癌组织中的阳性表达率为71.7%（38/53）,而在癌旁食管组织中的阳性表达率为35.8%（19/53）,两者比较有显著性差异（P〈0.01）。p63蛋白的表达与食管磷癌分化程度密切相关（P〈0.05）,其在低分化磷癌中的阳性表达率（89.5%）显著高于在高分化磷癌中的阳性表达率（46.2%）。p63蛋白的表达与食管磷癌的TNM分期、淋巴结转移、浸润深度均无明显相关性（P〉0.05）。结论p63蛋白在食管磷癌组织中呈高表达,表明其可能参与食管磷癌的发生发展。     

PTEN和mTOR在食管鳞癌组织中的表达及意义

目的观察食管鳞癌组织中PTEN与m TOR的表达,探讨其与临床病理特征的关系。方法应用免疫组化染色检测148例食管鳞癌组织、癌旁组织及其正常食管组织中PTEN和m TOR表达,分析其与常见临床病理特征的关系。结果PTEN在癌组织中阳性表达率为43.9%,癌旁组织为67.6%,而正常组织为93.2%,食管癌组织中PTEN表达率均低于癌旁组织及正常食管黏膜组织,差异有统计学意义（P〈0.05）;m TOR在癌组织中阳性表达率为85.8%,癌旁组织为35.1%,而正常组织为3.4%,食管癌组织中m TOR表达明显高于癌旁组织及正常食管组织,差异有统计学意义（P〈0.05）。PTEN的表达与m TOR的表达强度呈负相关（P〈0.05）。m TOR表达与性别、年龄、肿瘤长度差异无统计学意义（P〉0.05）,而与肿瘤浸润深度、肿瘤分化程度以及有无淋巴结转移上差异无统计学意义（P〈0.05）。结论 m TOR信号通路的激活与PTEN的抑制,可能在食管鳞癌的发生发展中起重要的作用,PTEN低表达与m TOR高表达与肿瘤恶性程度有关,两者联合检测可能有助于预后的判断。     

大蒜素抑制Wnt/β-catenin通路对晚期食管癌中VEGF的调控作用

目的探讨大蒜素(garlicin)抑制Wnt/β-catenin通路对晚期食管癌中VEGF的调控作用。方法采用甲基苄基亚硝胺食管内灌注方法构建SD大鼠食管癌模型,随机分为对照组、模型组和大蒜素[剂量为10 mg/(kg·d)]组,每组20只。HE染色进行食管组织病理学观察;免疫组织化学染色检测食管组织中VEGF表达;Western blot法检测食管癌细胞wnt3a、β-catenin、Cyclin D1和VEGF蛋白表达水平。结果与模型组相比,大蒜素组大鼠食管内瘤体总体积、瘤体总质量及瘤体个数明显减少(P0.05),大蒜素组瘤体抑制率为39.93%;大蒜素组食管组织病理学分级明显减轻,差异有统计学意义(χ2=7.734,P=0.021);大蒜素可以显著下调食管wnt3a、β-catenin、Cyclin D1和VEGF蛋白表达水平(P0.05)。结论大蒜素下调VEGF/Wnt/β-catenin通路的表达来有效抑制食管癌。     

贲门三源性碰撞瘤1例并文献复习

目的观察食管胃交界处三源性碰撞瘤的临床病理学特征,初步探讨其病理诊断标准、发病机制、常规病理镜下形态、免疫表型及预后。方法回顾性分析1例贲门三源性碰撞瘤的临床病理学特征及免疫表型,并复习相关文献。结果眼观:食管及近端胃切除标本,食管胃交界处见一溃疡型肿物;肿瘤由食管延续至胃黏膜小弯侧,侵犯食管壁及胃壁全层。镜检:贲门溃疡型肿物由三种完全不同类型的组织学成分构成,包括高分化鳞形细胞癌、神经内分泌肿瘤(G3)及中分化腺癌,三者分界清楚,且三种肿瘤成分均发生淋巴结转移。免疫表型:肿瘤的三种成分中,鳞状细胞癌成分表达p40、p63、CK5/6,Ki-67增殖指数为30%,p53阳性率为60%;神经内分泌癌成分表达CgA、Syn、CD56;腺癌成分表达CK7;神经内分泌癌与腺癌成分均表达CDX2和Villin,且两者Ki-67增殖指数均为40%,p53阳性率均为80%。结论目前食管胃交界处三源性碰撞瘤的诊断主要依赖组织形态学及免疫表型;根据碰撞瘤中各种肿瘤成分不同的侵犯及转移程度,并结合其他肿瘤诊断相关指标,对患者行个体化治疗。     

乳腺导管不同类型增生性病变中p63和 CK5/6的表达及意义

目的：明确不同类型的乳腺导管增生性病变中p63和Cytokeratin 5/6(CK5/6)的表达和意义。方法：对150例乳腺导管增生性病变中的368个病灶分别进行p63和CK5/6染色。结果：CK5/6在正常乳腺组织中的肌上皮和导管上皮均阳性表达，35例普通型增生中，33例CK5/6呈马赛克式阳性表达，仅2例弥漫阳性；在非典型性增生、原位癌和浸润癌中，CK5/6主要呈阴性表达，仅6例阳性，其中有2例雌激素受体（estrogen receptor, ER）、孕激素受体（progesterone receptor, PR）和CerbB 2阴性，符合基底细胞样癌的特点。p63在良性病变和非浸润性肿瘤性增生病变中的肌上皮细胞阳性表达，3例原位癌不表达p63和CK5/6。浸润癌中有3例（3/43）p63散在肿瘤细胞阳性，其余均阴性。结论：不同类型乳腺增生性病变中p63及CK5/6的染色模式存在一定规律，有助于这些病变的诊断和鉴别诊断。     

食管鳞状细胞癌基因组改变的确认

食管癌是最具侵袭性的癌症之一,居全球恶性肿瘤病死率的第六位。全球约70%的食管癌患者在中国,食管鳞状细胞癌是最常见的病理类型(>90%)。目前,临床上对于食管鳞状细胞癌的早期诊断和治疗非常有限,患者5年生存率仅为10%。然而,直到目前对于导致食管鳞状细胞癌发病的完整基因组事件仍知之甚少。本组对158例食管鳞状细胞癌病例进行一次全面的基因组分析：其中17例食管鳞状细胞癌病例进行全基因组测序,71例进行外显子测序,在71例进行外显子测序的53例加上另外的70例未使用全基因组和全外显子测序,并进行阵列比较基因组杂交分析。本实验确定8个明显突变的基因,其中有6个是众所周知的肿瘤相关基因( TP53、 Rb1、CDKN2A、PIK3CA、 NOTCH1、NFE2L2),另两个基因在食管鳞状细胞癌中未被描述(AD-AM29、FAM135B)。值得注意的是,FAM135B被确定为新的肿瘤相关基因,并鉴定其促进食管鳞状细胞癌细胞恶性程度的能力。此外,MIR548K是编码在扩增11q13．3~13．4区域的microRNA,它是一种新的癌基因,功能实验证明MIR548K增强食管鳞状细胞癌细胞的恶性表型。本组还发现几个重要的组蛋白调控基因MLL2(又称作KMT2D)、ASH1L、MLL3(KMT2C)、SETD1B、CREBBP 和EP300在食管鳞状细胞癌中频繁发生改变。信号通路分析结果揭示一些体细胞变异主要与Wnt、细胞周期以及Notch信号通路相关。基因组分析结果表明,食管鳞状细胞癌和头颈部鳞状细胞癌共享某些共同的致病机制,且食管鳞状细胞癌的形成与饮酒有关。本文着重探讨新的生物学标志物和致瘤性的途径,提高食管鳞状细胞癌的治疗策略。     

Trastuzumab anti-tumor efficacy in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models

ABSTRACT: BACKGROUND: Trastuzumab is currently approved for the clinical treatment of breast and gastric cancer patients with HER-2 positive tumors, but not yet for the treatment of esophageal carcinoma patients, whose tumors typically show 5 ~ 35% HER-2 gene amplification and 0 ~ 56% HER-2 protein expression. This study aimed to investigate the therapeutic efficacy of Trastuzumab in patient-derived esophageal squamous cell carcinoma xenograft (PDECX) mouse models. METHODS: PDECX models were established by implanting patient esophageal squamous cell carcinoma (ESCC) tissues into immunodeficient (SCID/nude) mice. HER-2 gene copy number (GCN) and protein expression were determined in xenograft tissues and corresponding patient EC samples by FISH and IHC analysis. Trastuzumab anti-tumor efficacy was evaluated within these PDECX models (n = 8 animals/group). Furthermore, hotspot mutations of EGFR, K-ras, B-raf and PIK3CA genes were screened for in the PDECX models and their corresponding patient's ESCC tissues. Similarity between the PDECX models and their corresponding patient's ESCC tissue was confirmed by histology, morphology, HER-2 GCN and mutation. RESULTS: None of the PDECX models (or their corresponding patient's ESCC tissues) harbored HER-2 gene amplification. IHC staining showed HER-2 positivity (IHC 2+) in 2 PDECX models and negativity in 3 PDECX models. Significant tumor regression was observed in the Trastuzumab-treated EC044 HER-2 positive model (IHC 2+). A second HER-2 positive (IHC 2+) model, EC039, harbored a known PIK3CA mutation and showed strong activation of the AKT signaling pathway and was insensitive to Trastuzumab treatment, but could be resensitised using a combination of Trastuzumab and AKT inhibitor AZD5363. In summary, we established 5 PDECX mouse models and demonstrated tumor regression in response to Trastuzumab treatment in a HER-2 IHC 2+ model, but resistance in a HER-2 IHC 2+/PIK3CA mutated model. CONCLUSIONS: This study demonstrates Trastuzumab-induced tumor regressions in HER-2 positive tumors, and highlights PIK3CA mutation as a potential resistance mechanism to Trastuzumab treatment in pre-clinical patient-derived EC xenograft models.     

Development of recombinant varicella-zoster viruses expressing luciferase fusion proteins for live in vivo imaging in human skin and dorsal root ganglia xenografts

Varicella-zoster virus (VZV) is a host specific human pathogen that has been studied using human xenografts in SCID mice. Live whole-animal imaging is an emerging technique to measure protein expression in vivo using luminescence. Currently, it has only been possible to determine VZV protein expression in xenografts postmortem. Therefore, to measure immediate early (IE63) and late (glycoprotein E [gE]) protein expression in vivo viruses expressing IE63 or gE as luciferase fusion proteins were generated. Viable recombinant viruses pOka-63-luciferase and pOka-63/70-luciferase, which had luciferase genes fused to ORF63 and its duplicate ORF70, or pOka-gE-CBR were recovered that expressed IE63 or gE as fusion proteins and generated luminescent plaques. In contrast to pOka-63/70-luciferase viruses, the luciferase gene was rapidly lost in vitro when fused to a single copy of ORF63 or ORF68. IE63 expression was successfully measured in human skin and dorsal root ganglia xenografts infected with the genomically stable pOka-63/70-luciferase viruses. The progress of VZV infection in dorsal root ganglia xenografts was delayed in valacyclovir treated mice but followed a similar trend in untreated mice when the antiviral was withdrawn 28 days post-inoculation. Thus, IE63-luciferase fusion proteins were effective for investigating VZV infection and antiviral activity in human xenografts.     

Distribution of p63, cytokeratins 5/6 and cytokeratin 14 in 51 normal and 400 neoplastic human tissue samples using TARP-4 multi-tumor tissue microarray

p63, cytokeratin (CK) 5/6 and CK 14 have been employed in diagnostic pathology as markers of basal, squamous and myoepithelial differentiation in several types of human neoplasms; however, there is scant data on the concurrent expression of these markers in large series of human neoplasms. We analyzed the distribution of these three immunohistochemical markers in 51 normal human tissue samples, 350 carcinomas, 25 malignant melanomas (MMs), and 25 glioblastomas using three serial sections of tissue array research program (TARP)-4 multi-tumor tissue microarray. Also, we performed double immunostainings to characterize the differential distribution of p63/CK 5/6 and p63/CK 14 in normal breast, salivary gland and skin. p63, CK 5/6 and CK 14 were expressed in basal cells of the prostate and respiratory epithelia and in breast and bronchial myoepithelial cells. p63 was also expressed in cytotrophoblast cells of human placenta and in scattered cells of lymph node germinal center. CK 5/6 and CK 14 also stained the cytoplasm of basal cells of esophageal stratified squamous epithelium and transitional epithelial cells of the bladder. No mesenchymal, neural, endothelial, smooth muscle or adipose cells were stained by any of the markers. p63, CK 5/6, and CK 14 were respectively expressed in 92.6%, 75.0%, and 52.9% of the squamous cell carcinomas of the lung, 10.2%, 20.0%, and 7.4% of the ductal carcinomas of the breast, 12.9%, 34.4%, and 11.8% of the serous and 25.0%, 0%, and 0% of the endometrioid carcinomas of the ovary. Lung, prostate and colonic adenocarcinomas, as well as MMs and glioblastomas were only rarely decorated by one of the markers. Only matched samples of 16 squamous cell carcinomas and two ductal carcinomas of the breast co-expressed these three markers. In double immunostainings, p63-CK 5/6, as well as p63-CK 14 were co-expressed by basal/myoepithelial cells of the salivary glands and basal cells of the epidermis. Our results demonstrate that p63, CK 5/6 and CK 14 may be used together in immunohistochemical panels to characterize squamous differentiation in poorly differentiated carcinomas or carcinomas of unknown origin.     

p63 correlates with both BRCA1 and cytokeratin 5 in invasive breast carcinomas: further evidence for the pathogenesis of the basal phenotype of breast cancer

AIMS: To study the expression of p63, cytokeratin (CK) 5 and CK8/18 in invasive ductal carcinomas and their relationship with BRCA1 and other pathological and immunohistochemical features of clinical significance. METHODS AND RESULTS: Immunohistochemistry with the antibodies p63, CK5, CK8/18, BRCA1, oestrogen receptor, progesterone receptor, p53, c-erbB-2 and Ki67 was performed in 102 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. The CK5+ cases were submitted to a double-immunolabelling study with p63. There was a strong relationship between CK5 and p63 expression and both markers were associated with hormonal receptor-negative high-grade carcinomas with high proliferative rate. Furthermore, there was coexpression of CK5 and p63 in neoplastic cells, indicating that p63, like CK5, is a marker of the basal phenotype of breast cancer. There was a strong relationship between reduced expression of BRCA1 with both p63 and CK5 expression as well as an inverse correlation between p63 and CK8/18 expression, suggesting that loss of p63 expression is required for the transition between a basal to a luminal phenotype of breast carcinoma. CONCLUSIONS: Since p63 is thought to be a marker of stem cells and may act as an oncogene, our data support the idea that BRCA1 acts as stem cell regulator.     

黄芩苷对CA46细胞裸鼠异种移植瘤的作用及机制

目的: 研究黄芩苷抗CA46细胞裸鼠异种移植瘤的作用并探讨其机制。方法: 构建CA46细胞裸鼠异种移植瘤模型,将荷瘤裸鼠随机分为5组:阴性对照组、15 mg/kg黄芩苷组、30 mg/kg黄芩苷组、60 mg/kg黄芩苷组和4 mg/kg依托泊甙 (VP-16) 阳性对照组。采用腹腔注射方式给药,12 d后处死部分裸鼠,对剥取的瘤块称重计算抑瘤率,并进行透射电镜、病理学和Western blotting检测;观察各组未处死的裸鼠直至全部死亡,研究黄芩苷对荷瘤裸鼠生存时间的影响。结果: 黄芩苷明显抑制了CA46细胞裸鼠异种移植瘤的生长,引起肿瘤细胞的凋亡、坏死以及p-Akt、NF-κB、mTOR和p-mTOR蛋白表达的下调;随着黄芩苷剂量的增加,黄芩苷治疗组荷瘤裸鼠的生存时间明显延长。结论: 黄芩苷可抑制CA46细胞裸鼠异种移植瘤的生长,诱导肿瘤细胞的凋亡,并延长荷瘤裸鼠的生存时间,其机制可能与下调PI3K/Akt/NF-κB和PI3K/Akt/mTOR信号通路有关。     

腺病毒介导的ING4对裸鼠人骨肉瘤移植瘤的生长抑制作用

目的:研究腺病毒介导的人ING4基因(Ad-ING4)对MG-63人骨肉瘤细胞移植瘤的生长抑制作用及其机制.方法:将本室构建好的重组腺病毒表达载体Ad-ING4,经QBI-293A细胞感染多轮扩增后获得高效价重组病毒子以用于肿瘤基因治疗试验,首先建立MG-63人骨肉瘤细胞移植瘤裸鼠模型,然后将15只荷瘤裸鼠随机分为阴性对照组(PBS组)、空载体对照组(Ad-GFP组)、Ad-ING4实验组(Ad-ING4组),3组均使用瘤体内注射干预用药,隔日一次,共5次.分别于用药前和用药后测量皮下瘤的体积,治疗开始后的第15天将裸鼠脱颈处死,摘取瘤体称重,计算抑瘤率.HE染色观察移植瘤细胞形态,免疫组化法检测瘤体中Bcl-2、Bax、Caspase-3、VEGF、CD34细胞因子的表达.结果:获得了高滴度(10~9pfu/ml)的重组腺病毒Ad-ING4;经瘤体基因治疗后,Ad-ING4组与PBS组及Ad-GFP组相比,可以明显抑制裸鼠MG-63人骨肉瘤细胞移植瘤生长,瘤重抑制率可达59.3%,移植瘤组织中可出现典型的细胞凋亡、坏死现象,其分子机制可能与Ad-ING4明显上调瘤体中促进凋亡的细胞因子Bax、Caspase-3的表达,下调抑制凋亡因子Bcl-2及血管形成细胞因子VEGF、CD34的表达有关.结论:Ad-ING4可以显著抑制MG-63人骨肉瘤细胞荷瘤生长,其机制可能通过激活细胞凋亡和抑制血管形成等途径来发挥抑瘤作用.     

Growth of human tumor xenografts in SCID mice quantified using an immunoassay for tumor marker protein in serum

The accurate measurement of the response of a tumor to a given treatment is critical to evaluating novel therapeutic modalities. An experimental design is reported here that can be generally applied to monitoring human tumor xenografts growing in immunodeficient mice. A human non-small cell lung tumor cell line was transfected with a mammalian expression vector containing the gene encoding human prostate specific antigen (PSA) and has been shown to grow progressively following the subcutaneous, intraperitoneal and intravenous inoculation of the tumor into severe combined immunodeficient (SCID) mice. The transfected human tumor cells produce PSA that accumulates in the sera of all tumor inoculated SCID mice. An enzyme-linked immunoassay using a rabbit polyclonal and a mouse monoclonal antibody specific for PSA was designed and tested for the detection and quantification of serum PSA in tumor-bearing mice. Over a 5-week period, the serum levels of PSA of mice inoculated subcutaneously with the tumor increased progressively, and the estimated tumor volumes correlated with the amount of PSA detected in the serum. Serum PSA levels correlated even better with total tumor mass following the intraperitoneal inoculation of tumor cells into SCID mice. Serum PSA levels fell rapidly following the surgical debulking of tumor xenograft, reaching background levels of PSA in the serum 1 week after tumor removal. Serum PSA levels were also observed in SCID mice inoculated intravenously with a PSA transfected human lung tumor cell line adapted to grow orthotopically in the lung. The transfection of human tumors with a tumor marker and the use of an immunoassay to detect this marker establish an experimental design that provides a reliable, non-invasive, accurate and simple approach to monitor and quantify the growth of human tumor xenografts in SCID mice.     

人M5型白血病-SCID小鼠模型的建立及白血病病理变化的分析

目的:建立人M5型白血病细胞系SHI-1/SCID(重症联合免疫缺陷)小鼠模型,探讨白血病细胞的接种密度与SCID小鼠成瘤率及病理变化的关系。方法:将不同密度的人白血病细胞SHI-1注射至SCID小鼠腹腔。定期尾静脉取血并以流式细胞术(FCM)监测肿瘤细胞表面标志CD14及CD137L的变化。通过病理组织学检查和FCM分析SCID小鼠的骨髓、肝脏、脾脏和肾脏中白血病细胞的浸润及病理变化。结果:将不同密度的SHI-1细胞移植至小鼠腹腔,均可发现瘤块生长。同时中、高剂量组小鼠的主要组织器官呈现不同程度的肿瘤细胞的浸润。最早在移植3周后即可在尾静脉检测到肿瘤细胞,并与注射细胞量相关。结论:建立的SHI-1/SCID小鼠模型为人M5型白血病的研究提供了有价值的动物模型。