BACKGROUND: Identification of the genes expressed differentially in renal cell carcinoma (RCC)but not in the non-cancerous kidney is important for understanding the molecular basis ofrenal cell carcinoma and for defining possible prognostic value and therapeutic intervention.We investigated the changes in gene expression accompanying the development and progression of kidney cancer by cDNA microarrays. METHODS: To identify molecular alterations in renal cell carcinoma, we measured expression profiles for paired neoplastic and noncancerouskidney samples from an individual by means of a cDNA microarry representing 7, 500genes. Of the differentially expressed genes, we assessed the decorin gene at the proteinlevel using immunohistochemistry. RESULTS: The 60 genes were noted to have more than a fivefold change in expression (either increased or decreased) in RCC compared to the noncancerouskidney. The changed genes are those associated with signal transduction, metabolizingenzymes, the cytoskeleton, cell adhesion, cell cycle control, modulation of transcription, the tumor suppressor gene and tumor antigens. Under immunohistochemistry, the expressionof decorin was significantly decreased in the tumor than in the non-cancerous kidney.The expression rate of decorin was not associated with the patient's sex, age, histologic type, Fuhrmann nuclear grade and T stage. CONCLUSION: The author predicted that these geneexpression profiling experiments will lead to improvements in the basic understanding of renaltumor pathogenesis and will promote the discovery of novel molecular markers for renal tumordiagnosis and therapy.
Antigens, Neoplasm ; Carcinoma, Renal Cell* ; Cell Adhesion ; Cell Cycle Checkpoints ; Cytoskeleton ; Decorin* ; DNA, Complementary* ; Gene Expression* ; Genes, Tumor Suppressor ; Immunohistochemistry ; Kidney ; Kidney Neoplasms ; Oligonucleotide Array Sequence Analysis* ; Signal Transduction

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1 alpha (HIF-1 alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1 alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1 alpha positive carcinomas, MVD was significantly higher in HIF-1 alpha positive SCCs than in HIF-1 alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1 alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1 alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.
Adenocarcinoma/metabolism* ; Adenocarcinoma/pathology ; Animals ; Antigens, CD34/metabolism ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology ; Carcinoma, Non-Small-Cell Lung/surgery ; Carcinoma, Squamous Cell/metabolism* ; Carcinoma, Squamous Cell/pathology ; Cell Division/physiology* ; Human ; Immunohistochemistry ; Proliferating Cell Nuclear Antigen/metabolism ; Survival Rate ; Transcription Factors/metabolism* ; Vascular Endothelial Growth Factor A/metabolism

BACKGROUND: The role of Smad4 in carcinogenesis is important, because of its function as a central mediator of TGF-beta signaling. In the present study we analyzed the expressions of Smad4 mRNA and protein in human gastric cancer cell lines and tissues and we also analyzed their clinicopathological significance. METHODS: We used semi-quantitative RT-PCR for Smad4 mRNA expression in 13 cases of fresh gastric cancer tissues and two gastric cancer cell lines (MKN-28, SNU-1). We also used immunohistochemistry for Smad4 protein expression in 88 cases of formalin fixed gastric cancers tissues. RESULTS: The mRNA level of Smad4 was higher in MKN-28 cell line (intestinal type) than in the SNU-1 cell line (diffuse type). Fresh frozen gastric cancer tissues showed that the intestinal type of gastric cancer had higher Smad4 mRNA expressions than the diffuse type of gastric cancer (p<0.05). Immunohistochemical staining for Smad4 revealed that cytoplasmic and nuclear expressions of Smad4 were significantly correlated with histologic types of gastric cancer (p<0.05). That is, the intestinal type of gastric cancer showed more cytoplasmic and nuclear smad4 expressions than did the diffuse type of gastric cancer. Reduced cytoplasmic expressions and positive nuclear expressions of Smad4 were more prominent in the advanced gastric cancer than in the early gastric cancer. CONCLUSION: Taken together, we suggest that loss of Smad4 expression might be associated with the intestinal type of gastric cancer. Also reduced cytoplasmic Smad4 expressions and increased nuclear Smad4 expressions may be associated with the advanced stage of gastric cancer.
Adenocarcinoma* ; Carcinogenesis ; Cell Line ; Cytoplasm ; Formaldehyde ; Humans ; Immunohistochemistry ; RNA, Messenger ; Smad4 Protein ; Stomach Neoplasms ; Transforming Growth Factor beta

BACKGROUND: Under hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is known to activate the expression of various genes, including angiogenesis-related genes. The aim of this study was to evaluate the expression of HIF-1alpha protein and its relationship with p53 protein expression and angiogenesis in the squamous cell carcinoma (SCC) of the uterine cervix. METHODS: Using immunohistochemical methods, the expression of HIF-1alpha protein, p53 protein, vascular endothelial growth factor (VEGF), and microvessel count were evaluated in seventy cases of FIGO stages I and II SCC; and their results were compared with age, stage, and pelvic lymph node metastasis. RESULTS: Positive nuclear staining for HIF-1alpha protein was noted in 19 cases (27.1%). Carcinoma in situ or dysplastic lesions also revealed positive nuclear reaction along the lower part of the epithelium. The expression of HIF-1alpha protein was significantly related with those of p53 protein and VEGF (p<0.05), but not with other clinicopathologic parameters. The microvessel count showed a significant difference regarding stage and VEGF expression (pand<0.05). CONCLUSION: These findings suggest that HIF-1alpha expression in SCCs of the uterine cervix might be the early event of carcinogenesis and could be associated with p53 protein and VEGF expression. However, the prognostic significance of HIF-1alpha expression in stages I and II SCCs is undetermined.
Anoxia ; Carcinogenesis ; Carcinoma in Situ ; Carcinoma, Squamous Cell* ; Cervix Uteri* ; Epithelium ; Female ; Lymph Nodes ; Microvessels ; Neoplasm Metastasis ; Vascular Endothelial Growth Factor A*

Little is known about the involvement of Smad-related molecules in the regulation of the Transforming Growth Factor (TGF)-beta signaling pathway during hepatocarcinogenesis, particularly with respect to preneoplastic lesions of a rat liver. The aims of this study were to investigate the localizations and temporal expressions of TGF-beta Receptor Type 1 (TGR1) and Smads during the promotion stage of chemical hepatocarcinogenesis in rats. We investigated expressions and localizations of TGR1, Smad2, Smad4, and Smad7 by using semi-quantitative RT-PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber's method. The down-regulation of TGR1, Sma-d2, and Smad4 was evident during the later steps of the promotion stage of chemical hepatocarcinogenesis. In contrast with other Smads, increased Smad7 expression was evident during the later steps of the promotion stage. Also immunohistochemistry revealed that the main site of TGR1, Smad2, Smad4, and Smad7 expression was mainly in hepatocytes of the preneoplastic lesions of a rat liver. Dysregulation of the downstream effectors of TGF-beta such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.
Activin Receptors, Type I/*biosynthesis ; Animals ; Apoptosis ; DNA-Binding Proteins/*biosynthesis ; Disease Progression ; Glutathione Transferase/metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; Liver/metabolism ; Liver Neoplasms/chemically induced ; Male ; Peptides/chemistry ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, Transforming Growth Factor beta/*biosynthesis ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Time Factors ; Trans-Activators/*biosynthesis

BACKGROUND: Transforming growth factor (TGF)-beta1 inhibits hepatocyte proliferation by inducing apoptosis. Expression of TGF-beta1 is tightly associated with the TGF-betatype II receptor (TGR2) expression level, and has been regarded as an important change of TGF-beta1 and TGR2 during hepatocarcinogenesis. We investigated the gene expressions and protein localizations of TGF-beta1 and TGR2 in chemical hepatocarcinogenesis. METHODS: Solt and Farber's method was used as the chemical hepatocarcinogenesis model of the rat. Northern blot analyses and immunohistochemistry for TGF-beta1 and TGR2 were performed to investigate the gene expressions and protein localizations, respectively. RESULTS: The Northern blot analyses showed a slight increase of TGF-beta1 transcripts one month after partial hepatectomy, which is more than in sham operated control liver, and a decrease of transcripts for TGR2 two months after partial hepatectomy. The number of TGF-beta-positive preneoplastic hepatocytes was increased and correlated with the increase of the number of TGR2 negative hepatocytes or reduction of expressions of TGR2 in preneoplastic lesions. HCC tissues showed an increase of TGF-beta1 protein expressions and a decrease of TGR2 compared to the adjacent liver parenchyme. CONCLUSION: Our data suggest that down regulation of TGR2 in preneoplastic lesions and HCC might contribute to the resistance to the growth inhibitory effects of TGF-beta.
Animals ; Apoptosis ; Blotting, Northern ; Down-Regulation ; Gene Expression ; Hepatectomy ; Hepatocytes ; Immunohistochemistry ; Liver ; Rats* ; Transforming Growth Factor beta ; Transforming Growth Factor beta1* ; Transforming Growth Factors

Pleuropulmonary blastoma (PPB) is a rare malignant dysontogenetic neoplasm primarily affecting children and is characterized histologically by a variably mixed blastematous and sarcomatous patterns. We herein report a very exceptional adult case of PPB. A 21-yr-old male patient presented with a left chest pain of two weeks' duration. A computed tomography scan revealed a large, multicystic tumor occupying the left lower hemithorax, leading to the impression of a ruptured mediastinal cystic teratoma. A thoracotomy for resection of the tumor was performed. On histologic examination, the tumor consisted of cystic walls and associated solid lesions which showed undifferentiated blastemal tissues with focal fibrosarcomatous and rhabdoid features. Immunohistochemically the tumor cells only showed diffuse strong positivity for vimentin. The histologic findings corresponded to a type II PPB. The authors suggest that PPB, especially of type I or II, should be included in the radiologic differential diagnosis of mediastinal cystic neoplasms in a young adult.
Adult ; Diagnosis, Differential ; Human ; Immunohistochemistry ; Lung Neoplasms/*diagnosis/radiography/surgery ; Male ; Pulmonary Blastoma/*diagnosis/radiography/surgery ; Teratoma/*diagnosis/*radiography/surgery ; Tomography, X-Ray Computed ; Vimentin/biosynthesis

Experimental liver disease models of rats have many similarities with those of humans, especially in morphological characteristics. Rat liver disease models can be categorized as models of hepatic fibrosis, hepatic stem cell and hepatocarcinogenesis. The purpose of this article is to review experimental liver disease models, with a major emphasis on morphologic features, including routine morphological, immunohistochemical, and electron microscopic features.
Animals ; Fibrosis ; Humans ; Liver Diseases* ; Liver* ; Rats* ; Stem Cells

Hyalinizing trabecular adenoma of the thyroid gland is a rare benign neoplasm predominantly diagnosed in middle-aged women. Carney et al. first described this entity that may mimic paraganglioma, medullary carcinoma and papillary carcinoma in 1987. We describe cytologic and histopathologic features of a case of hyalinizing trabecular adenoma combined with occult papillary carcinoma in the opposite lobe. A 55-year-old woman presented with nontender palpable mass of the right neck for 6 months. The aspirate was cellular and contained small clusters and sheets of epithelial cells with abundant filamentous, vacuolated, and ill-defined cytoplasm. The nuclei were slightly pleomorphic and showed nuclear overlapping, nuclear grooves, and intranuclear cytoplasmic inclusions. Histologic examination showed hyalinizing trabecular adenoma in the right lobe and occult papillary carcinoma in the left lobe.
Adenoma* ; Carcinoma, Medullary ; Carcinoma, Papillary* ; Cytoplasm ; Epithelial Cells ; Female ; Humans ; Hyalin* ; Inclusion Bodies ; Middle Aged ; Neck ; Needles* ; Paraganglioma ; Thyroid Gland*

OBJECTIVE: Diabetic nephropathy and ablation nephropathy are characterized by sclerotic processes in the glomeruli. To elucidate the site, degree and time-honored changes of glomerular sclerosis, morphometric analysis was performed using the experimental animals models. METHODS: The animals used were male Sprague Dowley rats and separated into 4 groups as young normal control, old control, streptozotocin-injected group, and right nephrectomized group. Chronologically kidney specimens were obtained after each treatment and processed to evaluated histologic changes. To evaluated the glomerular area, interstitial fibrosis and glomerular tuft fibrosis, the kidney specimens were fixed in Buin's solution, paraffin-embedded and 2 micrometer sections were Sirius red stained. To study the mesangial area, mesangial matrix area, glomerular basement membrane, and tubu lar basement membrane, the specimens were fixed in 2.5% glutaraldehyde, epon-embedded, double-stained and examined under the transmission electron microscope. All the specimens were analyzed morphometrically using the Image Pro Plus software. The obtained morphometric data were statistically analyzed to evaluate the differences of fibrotic processes and degree between experimental groups. RESULTS: Diabetic group revealed statistically significant increase of glomerular area from 8th week after streptozotocin injection to 24th week of experimental date. The parenchymal fibrosis and glomerular tuft fibrosis was prominent from the 2nd week of injection and steadily increased until the end of experimental date. The thickness of glomerular basement membrane was significantly increased even at the first week of injection and the tubular basement membrane also increased in thickness at the 3rd week of experiment. Ablation nephropathy model made by right nephrectomy showed increased glo merular area at the 7th week of ablation and the degree were intensified after 16th week of experimental date. The amount of stainable collagen in the renal parenchyme and glomerular tuft increased in the second week kidney sample and steadily increased thereafter until the end of experimental date. The increase of thickness of GBM and TBM also started to appear at the second week of operation. The old control also revealed fibrosis but the degree was less than the diabetic and ablation groups. Both diabetic and ablation nephropathy groups exhibited extensive increase of glomerular area, stainable colla gen, thickness of GBM and TBM at the end of experimental date and the ablation group revealed more extensive evidences of fibrosis without statistical significance. Comparison between the experimental groups were meaningless because the duration of the experimental manipulation was not the same. CONCLUSION: Glomerular and renal interstitial sclerosis and thickening of GBM and TBM are not the specific lesions of the diabetic glomerulopathy and are the common histologic changes occur in the kidney of partial parenchymal loss of any etiology. And it is suggested by this study that the common hemodynamic change involving the diabetic nephropathy, ablation nephropathy and physiologic aging is one of the important pathogenetic factors of glomerular sclerosis.
Aging ; Animals ; Basement Membrane ; Collagen ; Diabetic Nephropathies ; Fibrosis ; Glomerular Basement Membrane ; Glutaral ; Hemodynamics ; Humans ; Hyperglycemia* ; Kidney ; Male ; Models, Animal* ; Nephrectomy ; Rats* ; Sclerosis ; Streptozocin