Comparison of glycopeptide in lung cancer tissues of different histological types

The glycopeptide was studied in the pulmonary cancer tissues of three different histological types including squamous cell carcinoma, undifferentiated cell carcinoma, and adenocarcinoma. The glycopeptide preparation was made by digesting the lung cancer tissues with proteolytic enzymes followed by removal of enzymes and undigested protein. The comparison of the relative proportion of the glycopeptide, which migrated toward the anode slower than hyaluronic acid, and was stained with both alcian blue and PAS, and contained higher sialic acid, was carried out among three different histologic types of lung cancer. This glycopeptide was highest in adenocarcinoma, followed by undifferentiated cell carcinoma, and was lowest in squamous cell carcinoma.     

Telomerase activity could be used as a marker for neoplastic transformation in gastric adenocarcinoma: but it does not have a prognostic significance

Telomerase activity is responsible for telomere maintenance and is believed to be crucial in most immortal cells and cancer cells; however, its clinicopathological significance in gastric cancer remains to be clarified. The aim of the present study was to assess whether malignant progression of gastric adenocarcinoma correlates with telomerase activity. We also investigated the correlation between telomerase activity and histopathological findings. We examined telomerase activity in tumor specimens and adjacent normal tissues from 43 patients with gastric adenocarcinoma. Telomerase activity was measured quantitatively by the TRAPEZE Gel Based Telomerase Detection Kit. Approximately 98% of the tumor tissues were telomerase positive, but telomerase activity was detected not only in tumor tissues but also in normal gastric mucosa. Although telomerase activity was found to be higher in tumor samples than normal tissue for each subject, we could not find a general cut-off level for telomerase activity in gastric adenocarcinoma. In addition, telomerase activity was not correlated with tumor invasion, lymph node involvement and histological stage. Our results support the idea that telomerase reactivation is a common event in gastric adenocarcinoma and it is not related to histopathological parameters. Since it is difficult to set a cut-off level for this type of cancer, we suggest that the prognostic utility of telomerase assay has not yet reached the clinic in terms of predicting outcome for patients with gastric adenocarcinoma. For the assessment of gastric carcinoma, telomerase activity should be evaluated in both tumor and normal tissues, because normal gastric mucosa samples show appreciable telomerase activity.     

Cerebroside sulfotransferase activity in human lung tissues. An elevated level in lung adenocarcinoma.

Cerebroside sulfotransferase activity was demonstrated in particulate fractions from human lung and its carcinoma tissues. The activity in human lung adenocarcinoma was significantly higher than those in a different histological type of carcinoma (squamous cell carcinoma) and in normal tissue from which each carcinoma was derived.     

Comparative characterization of pulmonary surfactant aggregates and alkaline phosphatase isozymes in human lung carcinoma tissue

Alkaline phosphatase (AP) isozymes are surfactant-associated proteins (SPs). Since several different AP isozymes have been detected in the pneumocytes of lung cancer patients, we attempted to identify the relationship between pulmonary surfactant aggregate subtypes and AP isozymes. Pulmonary surfactant aggregates were isolated from carcinoma and non-carcinoma tissues of patients with non-small cell carcinoma of the lung. Upon analysis, ultraheavy, heavy, and light surfactant aggregates were detected in the non-carcinoma tissues, but no ultraheavy surfactant aggregates were found in the carcinoma tissues. Surfactant-associated protein A (SP-A) was detected as two bands (a 27-kDa band and a 54-kDa band) in the ultraheavy, heavy, and light surfactant aggregates found in the non-carcinoma tissues. Although both SP-A bands were detected in the heavy and light surfactant aggregates from adenocarcinoma tissues, the 54-kDa band was not detected in squamous cell carcinoma tissues. Liver AP (LAP) was detected in the heavy and light surfactant aggregates from both non-carcinoma and squamous carcinoma tissues, but not in heavy surfactant aggregates from adenocarcinoma tissues. A larger amount of bone type AP (BAP) was found in light surfactant aggregate fractions from squamous cell carcinomas than those from adenocarcinoma tissues or non-carcinoma tissues from patients with either type of cancer. LAP, BAP, and SP-A were identified immunohistochemically in type II pneumocytes from non-carcinoma tissues and adenocarcinoma cells, but no distinct SP-A staining was observed in squamous cell carcinoma tissues. The present study has thus revealed several differences in pulmonary surfactant aggregates and AP isozymes between adenocarcinoma tissue and squamous cell carcinoma tissue.     

Irisin immunohistochemistry in gastrointestinal system cancers

Cancer is the leading cause of morbidity and mortality worldwide. Some studies have shown that high heat kills cancer cells. Irisin is a protein involved in heat production by converting white into brown adipose tissue, but there is no information about how its expression changes in cancerous tissues. We used irisin antibody immunohistochemistry to investigate changes in irisin expression in gastrointestinal cancers compared to normal tissues. Irisin was found in human brain neuroglial cells, esophageal epithelial cells, esophageal epidermoid carcinoma, esophageal adenocarcinoma and neuroendocrine esophageal carcinoma, gastric glands, gastric adenosquamous carcinoma, gastric neuroendocrine carcinoma, gastric signet ring cell carcinoma, neutrophils in vascular tissues, intestinal glands of colon, colon adenocarcinoma, mucinous colon adenocarcinoma, hepatocytes, hepatocellular carcinoma, islets of Langerhans, exocrine pancreas, acinar cells and interlobular and interlobular ducts of normal pancreas, pancreatic ductal adenocarcinoma, and intra- and interlobular ducts of cancerous pancreatic tissue. Histoscores (area × intensity) indicated that irisin was increased significantly in gastrointestinal cancer tissues, except liver cancers. Our findings suggest that the relation of irisin to cancer warrants further investigation.     

Neuronatin在人体常见肿瘤中的表达及对肿瘤细胞增殖的影响

目的:研究印记基因Neuronatin(NNAT)在人体常见肿瘤中的表达情况及其两种编码产物NNATα和NNATβ对肿瘤细胞增殖的影响。方法:运用组织芯片免疫组化技术对一些人体常见肿瘤及其对应正常组织中NNAT的表达进行系统检测;同时利用腺病毒载体技术,将NNATα和NNATβ分别导入人结肠癌细胞系SW620,并用实时细胞分析仪和平板克隆实验分析细胞增殖能力的变化。结果:①免疫组化结果显示:NNAT在食道鳞癌,结肠腺癌,直肠腺癌,胰腺腺癌,乳腺非特殊性浸润性导管癌,宫颈鳞癌,子宫内膜癌,膀胱移行上皮癌,肺鳞癌,皮肤鳞癌以及前列腺腺癌11种肿瘤组织,肾上腺,皮肤,睾丸,脑,骨骼肌,胰腺6种正常人体组织,以及慢性结肠黏膜炎与慢性肝炎2种炎性组织中呈阳性。②体外细胞增殖实验结果显示,NNATα对人结肠癌肿瘤细胞增殖有一定的抑制作用。结论:NNAT基因在多种人体肿瘤组织中表达,其α片段的表达对于结肠癌细胞系SW620增殖具有轻微抑制作用。     

Enzyme activities in human breast tumours.

The activities of six enzymes associated with carbohydrate metabolism were measured both in carcinomas and in normal breast tissues. The following differences were observed. 1. The carcinoma showed higher enzyme activities than the normal mammary tissue. 2. The ratios of glutamate dehydrogenase, hydroxybutyrate dehydrogenase, glutathione reductase and catalase to lactate dehydrogenase were lower in carcinomas than in normal tissues. Similarly, the ratios of glutamate dehydrogenase, hydroxybutyrate dehydrogenase, glutathione reductase and catalase to glucose-6-phosphate dehydrogenase were also significantly lower in carcinomas. 3. There were no significant differences in enzyme activities between I and II stage of the disease and the metastatic tissues, however, there were significant differences between I and III stage. The significance of these findings is discussed in terms of the alterations in the balance between the metabolic pathways.     

Expression level of enzymes related to in situ estrogen synthesis and clinicopathological parameters in breast cancer patients

In order to evaluate the importance of estrogen production in tumor and surrounding tissues, we measured mRNA expression levels of 5 enzymes participating to estrogen synthesis in situ and 4 breast cancer-related proteins in 27 pairs of tumor and non-malignant tissues. Steroid sulfatase (STS) mRNA was more frequently detected in tumor tissues rather than in their non-malignant counterparts. Estrogen sulfotransferase (EST) was constantly expressed with high level not only in tumor tissues but also in their surrounding non-malignant counterparts. In contrast, mRNA expression levels of aromatase, and 17β-hydroxysteroid dehydrogenase type I and II were relatively low and detected only in small proportion of the patients. We also measured the mRNA expression levels of the same nine genes in tumor tissues of 197 breast cancer patients, and analyzed relationship between the mRNA expression level and the clinicopathological parameters. The mRNA expression levels of STS, aromatase and erbB2 in tumor tissues increased as breast cancer progressed. The tumoral mRNA expression levels of STS, estrogen receptor β, and erbB2 in patients with recurrence were higher than those in patients without recurrence. Upregulation of STS expression plays an important role in tumor progression of human breast cancer and is considered to be responsible for estrogen production in tumor and surrounding tissues.     

Immunohistochemical distribution of inter-alpha-trypsin inhibitor chains in normal and malignant human lung tissue.

The inter-alpha-trypsin inhibitor (ITI) family is a group of plasma proteins built up from heavy (HC1, HC2, HC3) and light (bikunin) chains synthesized in the liver. In this study we determined the distribution of ITI constitutive chains in normal and cancerous lung tissues using polyclonal antibodies. In normal lung tissue, H2, H3, and bikunin chains were found in polymorphonuclear cells, whereas H1 and bikunin proteins were found in mast cells. Bikunin was further observed in bronchoepithelial mucous cells. In lung carcinoma, similar findings were obtained on infiltrating polymorphonuclear and mast cells surrounding the tumor islets. Highly differentiated cancerous cells displayed strong intracytoplasmic staining with H1 and bikunin antiserum in both adenocarcinoma and squamous cell carcinoma. Moreover, weak but frequent H2 expression was observed in adenocarcinoma cells, whereas no H3-related protein could be detected in cancer cells. Local lung ITI expression was confirmed by RT-PCR. Although the respective role of inflammatory and tumor cells in ITI chain synthesis cannot be presently clarified, these results show that heavy chains as well as bikunin are involved in malignant transformation of lung tissue.(J Histochem Cytochem 47:1625-1632, 1999)     

Characterization of a new tumor associated antigen from mammary carcinoma cells by monoclonal antibodies

A new tumor associated glycoprotein antigen was identified in the soluble fraction of adenocarcinoma of the mammary gland. Immunoprecipitation with a monoclonal antibody revealed an antigen with a molecular weight of 300.000 daltons and a pI of 4.3. Immunoblotting of sera from patients with mammary carcinoma indicated the presence of the antigen at various concentrations. This antigen was not detected in any of the normal sera tested so far and was absent on non-malignant breast tissue.     

非小细胞肺癌组织MMP-2、MMP-9的表达与组织学类型及临床分期的关系

目的:探究非小细胞肺癌组织基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)的表达及其与患者组织学类型及其临床分期的关系。方法:选取2014年1月至2017年1月于我院进行就诊并确诊为非小细胞肺癌的96例患者为实验组,另选取30例肺良性病变患者为对照组,使用免疫组织化学的方法检测患者肺癌组织或肺良性病变组织中MMP-2、MMP-9的表达,并分析MMP-2、MMP-9的表达与患者组织学类型及临床分期之间的关系。结果:非小细胞肺癌组织MMP-2及MMP-9表达水平显著高于肺良性病变组织(P0.05)。非小细胞肺癌鳞癌组织MMP-2、MMP-9表达明显高于腺癌和腺鳞癌(P0.05),而鳞癌与腺鳞癌组织MMP-2、MMP-9表达相比差异无统计学意义(P0.05)。随着非小细胞肺癌临床分期的增加,癌组织MMP-2及MMP-9表达逐渐上升,各分期比较差异均具有统计学意义(P0.05)。结论:MMP-2、MMP-9在非小细胞肺癌组织中的表达水平明显上调,以鳞癌最高,且与临床分期显著相关,提示其对组织学类型、临床分期、病情评估和预后判断均具有一定的参考意义。     

Influence of Sodium Selenite on the mRNA Expression of the Mammalian Selenocysteine-Containing Protein Genes in Testicle and Prostate Cancer Cells

The sodium selenite concentration that reduces the viability of Du-145 human prostate adenocarcinoma cells and F-9 mouse testicular teratocarcinoma cells was determined. We investigated the effect of sodium selenite on the mRNA expression level of the genes encoding mammalian selenocysteine-containing glutathione peroxidases and thioredoxin reductases (key antioxidant enzymes involved in the regulation of intracellular thiol redox balance), endoplasmic reticulum selenoproteins, and selenoproteins located in the testes and prostate.     

Comparison of the activity levels and localization of dipeptidyl peptidase IV in normal and tumor human lung cells

Dipeptidyl peptidase IV (DPPIV) was studied in three human lung cells - P (fetal lung-derived cells), A549 (lung adenocarcinoma) and SK-MES-1 (squamous cell carcinoma) using a fluorescent cytochemical procedure developed on the basis of the substrate 4-(glycyl-l-prolyl hydrazido)-N-hexyl-1,8-naphthalimide. The observed differences in the enzyme expression were confirmed by measuring the enzyme hydrolysis of glycyl-l-prolyl-para-nitroanilide. The surface and total dipeptidyl peptidase activities of P cells were correspondingly 7-8 and 3-10 times higher than those of SK-MES-1 and A549 cells. The ratio surface per total activity showed that in P (95%) and A549 (93%) cells the enzyme is associated with the plasmalemma while in SK-MES-1 cells (35%) it is bound to intracellular membranes. In order to compare the results from cell cultures with those in human tumor, the enzyme activity was investigated in cryo-sections of three cases of diagnosed squamous lung carcinoma. DPPIV activity was restricted to the connective tissue stroma surrounding the DPPIV-negative tumor foci.     

Immunohistochemical detection of human gastrointestinal glutathione peroxidase in normal tissues and cultured cells with novel mouse monoclonal antibodies.

This is the first report to describe the successful detection of human gastrointestinal glutathione peroxidase in normal tissues by Western blotting and immunohistochemical staining techniques. Four hybridoma clones producing monoclonal antibodies (MAbs) against the human gastrointestinal glutathione peroxidase were established from mice immunized with a gastrointestinal glutathione peroxidase-derived peptide. The MAbs did not crossreact with other members of the glutathione peroxidase family, be it cellular glutathione peroxidase, phospholipid hydroperoxide glutathione peroxidase, or extracellular glutathione peroxidase. Although the MAbs were found to react with a 24-kD protein in a Western blotting assay using gastric carcinoma cell extracts as antigen, they did not react with a B-lymphoblastoid cell extract. Immunohistochemical staining showed gastrointestinal glutathione peroxidase localized in the cytoplasm and in the nucleus of gastric carcinoma cells. Moreover, gastrointestinal glutathione peroxidase was detected in tissue extracts of human stomach, small intestine, large intestine, liver, and gallbladder by Western blotting, and its localization was immunohistochemically confirmed in the mucosal epithelia of the basal area of gastric pits and intestinal crypts.     

Proteomic signatures for histological types of lung cancer

We performed proteomic studies on lung cancer cells to elucidate the mechanisms that determine histological phenotype. Thirty lung cancer cell lines with three different histological backgrounds (squamous cell carcinoma, small cell lung carcinoma and adenocarcinoma) were subjected to two-dimensional difference gel electrophoresis (2-D DIGE) and grouped by multivariate analyses on the basis of their protein expression profiles. 2-D DIGE achieves more accurate quantification of protein expression by using highly sensitive fluorescence dyes to label the cysteine residues of proteins prior to two-dimensional polyacrylamide gel electrophoresis. We found that hierarchical clustering analysis and principal component analysis divided the cell lines according to their original histology. Spot ranking analysis using a support vector machine algorithm and unsupervised classification methods identified 32 protein spots essential for the classification. The proteins corresponding to the spots were identified by mass spectrometry. Next, lung cancer cells isolated from tumor tissue by laser microdissection were classified on the basis of the expression pattern of these 32 protein spots. Based on the expression profile of the 32 spots, the isolated cancer cells were categorized into three histological groups: the squamous cell carcinoma group, the adenocarcinoma group, and a group of carcinomas with other histological types. In conclusion, our results demonstrate the utility of quantitative proteomic analysis for molecular diagnosis and classification of lung cancer cells.     

3.0T 1H-MRS对脑胶质瘤及脑转移瘤的鉴别诊断

目的：利用3.0T氢质子磁共振波谱对胶质瘤和转移瘤的肿瘤组织区、瘤周水肿区进行细胞代谢物水平的检测,试图找出胶质瘤和脑转移瘤的鉴别诊断的依据,以及胶质瘤高、低级别组间的差别。方法：对经病理证实的20例高级别胶质瘤组、16例低级别胶质瘤组和19例脑转移瘤组患者,先行MRI平扫及增强扫描,波谱均在增强扫描的基础上获得,使用MR点分辨波谱序列,检测肿瘤组织区、瘤周水肿组织区NAA/Cr、Cho/Cr、NAA/Cho、NAA、Cho、Cr、Lip/Lac等值,进行比较。结果：（1）高级别胶质瘤与转移瘤在肿瘤组织区NAA/Cr代谢物浓度的比值有统计学意义。（2）高、低级别胶质瘤肿瘤组织内Cho/Cr比值有统计学意义。（3）转移瘤与高、低级别胶质瘤在瘤周水肿区NAA/Cr,以及低级别胶质瘤与转移瘤Cho/Cr代谢物浓度的比值有统计学意义;高级别胶质瘤与转移瘤瘤周区NAA代谢物浓度有明显差异。（4）胶质瘤高、低级别组间在肿瘤周围区NAA峰、Cho峰及NAA/Cho Cho/Cr代谢物浓度比值有统计学意义。（5）高级别胶质瘤和转移瘤分别与低级别胶质瘤在肿瘤组织区及瘤周水肿区Lip/Lac有显著性差异（P〈0.01）。结论：利用氢质子波谱可对胶质瘤和转移瘤进行鉴别诊断;Cho/Cr及NAA/Cho比值可对胶质瘤进行分级;Lip/Lac峰的出现与肿瘤的恶性度呈正相关,但不特异。     

Cancer stem cell model in oral squamous cell carcinoma

The concept of "field cancerization" describes the presence of histological abnormal tissue surrounding oral squamous cell carcinoma (OSCC). Molecular model of multistep carcinogenesis indicates that an accumulation of genetic alterations forms the basis for the OSCC progression with genetic heterogeneity. Furthermore, we reviewed cancer stem cell (CSC) model, which suggests functional heterogeneity in the tumor mass and current supporting evidence in OSCC. According to CSC model, prevention from carcinogen exposure and eliminating the particular CSCs instead of targeting tumor mass could help obtain a more long-lasting therapeutic effect.     

MNX1-AS1 is a novel biomarker for predicting clinical progression and poor prognosis in lung adenocarcinoma

Motor neuron and pancreas homeobox 1-antisense RNA1 (MNX1-AS1) is a novel long noncoding RNA and has been suggested to be overexpressed in human ovarian cancer and glioma. The role of MNX1-AS1 in lung cancer was still unknown. In our study, we observed levels of MNX1-AS1 expression through analyzing The Cancer Genome Atlas and found MNX1-AS1 expression was highly expressed in lung adenocarcinoma tissues compared with normal lung tissues, but there was no statistical difference between lung squamous cell carcinoma tissues and normal lung tissues. Furthermore, we conducted quantitative real-time polymerase chain reaction, and confirmed that the expression of MNX1-AS1 was definitely higher in lung adenocarcinoma tissue samples, but not in lung squamous cell carcinoma tissue samples. In addition, high MNX1-AS1 expression was found to be associated with the low differentiated degree, advanced clinical stage, big tumor size, lymph node metastasis, and distant metastasis in lung adenocarcinoma patients. High expression of MNX1-AS1 was negatively correlated with overall survival time and served as an independent unfavorable prognostic factor in patients with lung adenocarcinoma. The in vitro functional studies suggested that suppression of MNX1-AS1 inhibited lung adenocarcinoma cell proliferation and migration, and promoted apoptosis. In conclusion, MNX1-AS1 is overexpressed in lung adenocarcinoma, and associated with clinical progression and poor prognosis.