原发性食管小细胞癌16例临床分析

目的探讨原发性食管小细胞癌的临床特点、治疗及预后。方法回顾分析16例原发性食管小细胞癌患者的临床资料。结果1年总生存率为56．2％，2年总生存率25．0％，3年总生存率12．5％。中位生存期15．7个月。结论对于原发性食管小细胞癌应采用以化疗占主要地位的综合治疗，局限期以手术联合化疗，广泛期以放疗联合化疗为宜。     

原发性肝细胞癌中5种细胞周期蛋白的表达及其临床意义

目的探讨原发性肝细胞癌中5种细胞周期蛋白(cyclin)的表达及其与肝癌细胞的增殖状态、侵袭转移和乙型肝炎病毒(HBV)感染的相关性。方法应用Instrumedics公司生产的组织芯片制作仪,将273例原发性肝癌组织、144例癌旁肝组织和10例尸检非肝病死亡肝组织制成组织芯片,取样针直径2．0am,采用免疫组织化学方法分别检测了cyclin A、cyclin B、cyclin D1、cyclin D3及cyclin E在肝癌、癌旁肝及尸检肝组织的表达率,并分析了肝癌、癌旁肝组织中HBV感染与这5种cyclin表达间的相关性。结果共获得3个肝癌组织芯片蜡块,分别含136、143和148个位点。在273例肝癌组织标本中5种cyclin的阳性表达率分别为cyclin A 52．7％、cyclin B 45．4％、cyclin D1 35．9％、cyclin D3 44．3％和cyclin E 23．1％;在144例癌旁肝组织中分别为8．3％、5．6％、4．9％、6．3％和1．4％;10例尸检肝组织除1例cyclin D1阳性外,其余均为阴性。5种cyclin在肝癌组织中的阳性表达率均显著高于癌旁肝组织(P＜0．01);组织学分级为Ⅱ、Ⅲ级的肝癌组织5种cyclin的表达高于Ⅰ级(P＜0．05);除cyclinA外,伴有门静脉癌栓组的阳性率高于无癌栓组(P＜0．01);HBV感染与cyclin的表达无明显相关性(P＞0．05)。结论各个cyclin在肝癌细胞中呈不同程度的高表达,使癌细胞周期缩短,处于细胞增殖活跃状态,并有利于肝癌细胞的侵袭转移;未发现与HBV感染有关。     

NF-κB在人肝细胞肝癌中的表达及与HBV X蛋白的关系

目的：研究核转录因子NF－-κB在人肝细胞肝癌组织中的表达及其与乙型肝炎病毒（HBV ）X蛋白的关系。方法；用免疫组织化学S－P法，检测52例人肝细胞肝癌组织中核转录因子NF－-κB及HBV X蛋白的表达；用脂质体介导的基因转染法将HBV x基因真核表达载体pcDNA3.1-HBX转染入人肝癌细胞系HCC－9204，检测肝癌细胞内核转录因子NF－-κB的表达。结果：52例人肝细胞肝癌组织均有核转录因子NF－-κB的广泛表达，并且在11例HBV X蛋白阳性的肝癌组织，核转录因子NF－-κB位于细胞胞质和胞核，而在41例HBV X蛋白阴性的肝癌组织，核转录因子NF－-κB位于肝癌细胞的胞质。将HBV x基因真核表达载体pcDNA3.1-HBX转染 入人肝癌细胞系HCC－9204，并在稳定表达X蛋白 的肝癌细胞，核转录因子NF－-κB定位于其胞质和胞核，而未进行基因转染的亲体细胞，核转录因子NF－-κB仅定位于细胞质，细胞核无核转录因子NF－-κB的表达。结论：核转录因子NF－-κB在人肝细胞肝癌组织中广泛表达，人肝细胞肝癌中存在着核转录因子NF－-κB的异常激活，并且核转录因子NF－-κB的异常激活与HBV X蛋白有关，X蛋白激活核转录因子NF－-κB， 使其从细胞转位于细胞核，这可能在HBV相关的人原发性肝癌肝癌的发生中起一定作用。     

原发性胆汁性肝硬化基因易感性的研究进展

原发性胆汁性肝硬化（PBC）是一种由自身免疫机制介导的慢性进行性胆汁淤积性肝脏疾病。近年来，其发病率逐年增长，研究表明谷胱甘肽S转换酶（GST）、细胞毒性T淋巴细胞相关抗原4（CTLA-4）、血管内皮细胞一氧化氮合成酶（eNOS）、人类白细胞分化抗原（HLA）、IL-10、细胞角蛋白19（CK19）、甘露糖结合凝集素（MBL）、IL-1、TNF-α基因以及x染色体关联的基因等可能与PBC相关。我对与PBC易感性相关的基因的研究进展进行综述，为今后的研究提供一定的依据。     

Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival

We have shown recently that the hyaluronan receptor, CD44, and matrix metalloproteinase 9 (MMP-9) form a complex on the surface of TA/St mouse mammary carcinoma cells that activates latent transforming growth factor-beta (TGF-β) and is required for tumor invasion. Disruption of the CD44/MMP-9 complex by expression of soluble CD44 results in the loss of tumor invasiveness and abrogates tumor cell survival in host lung parenchyma following intravenous injection into syngeneic mice. To explore the molecular nature of the survival signals derived from the CD44/MMP-9 complex during the development of tumor metastasis, we investigated the possibility that activation of latent TGF-β by the CD44/MMP-9 complex is responsible for tumor cell survival in host lung parenchyma. TA3 cells overexpressing dominant negative soluble CD44 (TA3sCD44), which compromises native CD44 function and the ability of TA3 cells to develop metastases, were transfected with constitutively active or latent TGF-β2 and tested for their ability to form tumors in syngeneic mice. Our results demonstrate that expression of the constitutively active, but not the latent, form of TGF-β2 rescues TA3sCD44 cells from apoptosis during lung colonization. These observations provide evidence that activation of latent TGF-β constitutes an event downstream of CD44-dependent signals that is required for tumor cell survival and metastatic colony formation. The functional axis composed of CD44, MMP-9 and TGF-β may therefore play an important role in the metastatic proclivity of selected tumor types. Abbreviations: ECM – extracellular matrix; HA – hyaluronan; HSPG – heparan sulfate proteoglycan; MMP – matrix metalloproteinase; TGF-β– transforming growth factor β This revised version was published online in July 2006 with corrections to the Cover Date.     

Comparison of anatomical location of squamous cell carcinoma within the oral cavity and oropharynx with the incidence of in vitro hyperdiploidy

The anatomical location of the squamous cell carcinoma (SCCA) within the oral cavity and oropharynx influenced the association of SCCA with the biomarker in vitro hyperdiploidy in human dermal fibroblast cultures (IVH). There was a strong association of IVH with the occurrence of SCCA in the anterior 2/3 of the tongue, floor of the mouth and lower alveolar ridge of the oral cavity and in the base of the tongue and pharyngeal wall of the oropharynx. There was a lower association of SCCA with IVH in the tonsillar region of the oropharynx. IVH showed no association with SCCA located in other anatomical parts of the oral region. The patient group whose diagnosis of SCCA in the anterior 2/3 of the tongue occurred prior to the age of 50 years were invariably IVH-, whereas those diagnosed after the age of 50 years were IVH+, providing evidence for heterogeneity. There was no such correlation of biomarker subgrouping with age of diagnosis demonstrated for SCCA at any other anatomical location within the oral cavity or oropharynx.     

Human telomerase catalytic subunit gene re-expression is an early event in oral carcinogenesis

AIMS: Detection of telomerase catalytic subunit (hTERT) mRNA has been used as a surrogate marker for estimation of telomerase activity. The exact role and timing of telomerase re-activation, a key enzyme implicated in cellular immortalization and transformation, in the multistep process of oral carcinogenesis is still unknown. The aim was to test the hypothesis that (i) quantitative rather than qualitative differences exist in the level of hTERT mRNA expression between normal oral mucosa, different grades of oral epithelial abnormalities and squamous cell carcinomas of the oral cavity, and that (ii) hTERT gene re-expression is an important, probably early event in oral carcinogenesis. METHODS AND RESULTS: The relative quantity of hTERT mRNA was analysed in 45 frozen oral epithelia representing different morphological stages of oral carcinogenesis classified according to the Ljubljana classification and in 37 oral squamous cell carcinomas, using a commercially available LightCycler Telo TAGGG hTERT Quantification kit. hTERT mRNA was not detected in normal or reactive hyperplastic oral epithelia, but was present in 43% of atypical hyperplasias (premalignant lesions), 60% of intraepithelial carcinomas and 68% of oral squamous cell carcinomas. Statistical analysis revealed two groups of oral epithelial changes, with significant differences in the levels of hTERT mRNA expression: 1, normal and reactive hyperplastic oral epithelium, and 2, atypical hyperplasia, intraepithelial carcinomas and squamous cell carcinomas. CONCLUSION: These data suggest that hTERT gene re-expression represents an early event in the multistep process of oral carcinogenesis, already detectable at the stage of precancerous oral epithelial changes. Nevertheless, other genetic aberrations appear to be necessary for progression of oral epithelial abnormalities towards invasive squamous cell carcinoma.     

Langerhans cells and serum precipitating antibodies against fungal antigens in bronchioloalveolar cell carcinoma: possible association with pulmonary eosinophilic granuloma

In an ultrastructural study of 37 cases of bronchioloalveolar cell carcinoma (BAC), we identified seven cases (19%) in which Langerhans cells (LC) were closely associated with tumor cells. Serum precipitating antibodies against Aspergillus species and/or thermophilic actinomyces were present in five BAC patients whose tumors contained LC and in six patients whose tumors lacked LC. In a simultaneous study we identified marked atypical bronchiolar and alveolar lining cell hypertrophy and hyperplasma in pulmonary eosinophilic granuloma (PEG). Our data plus current information suggesting that PEG is a form of hypersensitivity pneumonitis support our hypothesis that those cases of BAC in which LC are present may arise in localized or diffuse pulmonary scars caused by PEG.     

Characterisation of axon terminals in the rat dorsal horn that are immunoreactive for serotonin 5-HT3A receptor subunits

Serotonin 5-HT₃ receptors are abundant in the superficial dorsal horn and are likely to have an involvement in processing of nociceptive information. It has been shown previously that 5-HT₃ receptors are present on primary afferent terminals and some dorsal horn cells. The primary aim of the present study was to determine what classes of primary afferent possess 5-HT₃A receptor subunits. We performed a series of double- and triple-labelling immunofluorescence experiments. Subunits were labelled with an anti-peptide antibody and primary afferent axons were identified by the presence of calcitonin gene-related peptide (CGRP) and binding of the lectin IB4. Quantitative confocal microscopic analysis revealed that approximately 10% of axons displaying 5-HT₃A immunoreactivity were also labelled for CGRP but that only 3% of these fibres bind IB4. We also investigated the relationship between immunoreactivity for the subunit and descending serotoninergic systems, axons originating from inhibitory neurons that contain glutamic acid decarboxylase, and axons of a subpopulation of excitatory neurons that contain neurotensin. None of these types of axon was associated with immunoreactivity for receptor subunits. Ultrastructural studies confirmed that punctate immunoreactive structures observed with the light microscope were axon terminals. These terminals invariably formed asymmetric synaptic junctions with dendritic profiles and often contained a mixture of granular and agranular vesicles. Some terminals formed glomerular-like arrangements. Immunoreactive cells were also examined and were found to contain intense patches of reaction product within the cytoplasm. We conclude that the majority (about 87%) of dorsal horn axons that are immunoreactive for 5-HT₃A receptor subunits do not originate from the subtypes of primary afferent fibres that bind IB4 or contain CGRP. It is likely that most of these axons have an excitatory action and they may originate from dorsal horn interneurons and/or fine myelinated primary afferent fibres. Electronic Publication     

Peripheral lung carcinomas associated with central fibrosis and mixed small cell and other histologic components

Three cases of peripheral small cell lung carcinoma (SCLC) with central fibrosis are presented. Central fibrosis is usually present in adenocarcinomas. Cases 1 and 2 are combined SCLCs with components of papillary adenocar-cinoma, and case 3 is a mixed SCLC with a large cell component. Small cell Components showed intermediate cell type in ail cases. In cases 1 and 2, there was a gradual transition between small cell carcinoma and papillary ade-nocarcinoma. Small cell components showed Grimelius argyrophilia, but other neuroendocrine markers such as neuronspecific enorase, chromogranin A, Leu-7 and syn-aptophysln were negative. The chest X-ray examination of case 1 demonstrated rapid enlargement of a tumor shadow, which was present two years before, for a recent year. Central fibrosis, coexistence of small cell carcinoma and papillary adenocarcinoma, and a change of growth rate in the chest x-ray may suggest that some SCLC derive from papillary adenocarcinomas.