No abstract available.
Oncogenes*

Four proto-oncogenes commonly associated with well-differentiated thyroid carcinoma, rearranged during transfection (RET)/papillary thyroid cancer, BRAF, RAS, and PAX8/peroxisome proliferator activated receptor-gamma, may carry diagnostic and prognostic significance. These oncogenes can be used to improve the diagnosis and management of well-differentiated thyroid carcinoma. Limited therapeutic options are available for patients with metastatic well-differentiated thyroid cancer, necessitating the development of novel therapies. Vascular endothelial growth factor (VEGF)- and RET-directed therapies such as sorafenib, motesanib, and sunitinib have been shown to be the most effective at inducing clinical responses and stabilizing the disease process. Further clinical trials of these therapeutic agents may soon change the management of thyroid cancer.
Diagnosis ; Humans ; Oncogenes ; Proto-Oncogenes ; Thyroid Neoplasms* ; Transfection ; Vascular Endothelial Growth Factor A

There are a lots of evidences that colorectal cancer arise as a result of multiple alterations of genes. Many attempts were made to understand the role of oncogenes and suppressor genes as a prognostic indicator, recently. Although histopathologic staging of tumor is the most important prognostic factor up to now, it is not enough to be used with full confidence. Apoptosis or programmed cell death represents a deletion of damaged or natural cell mechanism. The bel-2 proto-oncogene is known as a inhibitor of apoptosis that may allow accumulation and propagation of cells containing genetic alterations. Overexpression of bcl-2 probably plays a role in colorectal carcinogenesis. The aim of this study was to determine bcl-2 and p53 expression in colorectal carcinoma in correlation with apoptosis, clinical parameters, and histopathology, and to test their prognostic significance in patient with colorectal carcinoma. The bel-2 and p53 protein were identified by immunohistochemical staining using monoclonal and polyclonal antibody. The apoptotic index was detetermined by microscopic examination of hematoxyln and rosin-stained sections at x400. The materials subiected to this study were 54 paraffin-embedded colorectal carcinomas, which were collected randomly from January of 1992 to December of 1994 at Department of Surgery, Chosun University Hospital. Of 54 cases, 21 (38.9%) and 22(40.7%) showed positive expression of bel-2 and p53 protein respectively. Mean apoptotic index(AI) was 2.99% in colorectal carcinoma. Bcl-2 expression did not correlated with p53 expression or apoptotic index. Positive expression of p53 or AI was not correlate with any other clinical and pathologic parameters. An inverse correlation was found between bel-2 expression and increased tumor stage or Iymph node metastasis (P<0.05). In conclusion, these results suggest that bcl-2 expression is significant associated with early stage in colorectal carcinoma. But bcl-2 p53 and AI can`t be a independent prognostic factor in colorectal carcinoma. Further investigations to clarity its possible role in controlling the tumor decelopment and growth of colorectal carcinoma are needed.
Apoptosis ; Carcinogenesis ; Cell Death ; Colorectal Neoplasms* ; Genes, Suppressor ; Humans ; Neoplasm Metastasis ; Oncogenes ; Proto-Oncogenes

A large number of studies for genes involved in oncogenesis have been done during last decade. Over 20 oncogenes have been isolated characterized, and the oncogene expressions in human tumors have been examined. The proto-oncogenes of c-Myc, c-Fos and c-Jun, which modulate the transcription factors, have overexpressed in a variety of human cancers. Immunohistochemical method was used in this study to examine c-Myc, c-Fos and c-Jun oncoprotein expression in 31 patients with human pheochromocytoma 28(90.0%) were benign and 3(10.0%) malignant. C-Myc oncoprotein immunoreactivity was found in 24 cases(77.4%), c-Fos in 29(93.5%), and c-Jun in 25(80.6%). Twenty-one(67.7%) showed positive immunoreactivity for all these oncoproteins, six(19.4%) for 2 oncoproteins, 3 for one oncoprotein. Only 1 case showed negative immunoreactivity for all 3 oncoproteins. The oncoprotein immunoreactivity did not correlate with the amount of 24 hour urinary catecholamine excretion. Although the number of malignant pheochromocytomsa was not so many, most of them showed that the immunoreactivity for oncoprotein was more than 30 percent of tumor cells.The expression of c-Myc, c-Fos and c-Jun oncoprotein were frequently found in human pheochromocytoma. These results suggest that the oncoprotein expression may play an important role in tumorogenesis and proliferation of human pheochromocytoma.
Carcinogenesis ; Humans ; Methods ; Oncogene Proteins ; Oncogenes ; Pheochromocytoma ; Proto-Oncogenes ; Transcription Factors

Female ; Genes, p53 ; immunology ; Humans ; Ovarian Neoplasms ; genetics ; pathology ; Ovary ; pathology ; Proto-Oncogene Proteins ; immunology ; metabolism ; Proto-Oncogene Proteins p21(ras) ; Proto-Oncogenes ; immunology ; Sertoli-Leydig Cell Tumor ; genetics ; pathology ; ras Proteins ; immunology ; metabolism

The protein encoded by the Bcl-2 proto-oncogene has been shown to prolong cell su-rvival by preventing cell death(Apoptosis) induced by many insults including cancer therap-eutic drugs. Recently many researches have elucidated the bcl-2 expression in several hu-man solid cancers. However, there is still a few avaiable data to determine the role of Bcl-2 expression in the ovarian carcinogenesis and its prognostic significance in ovarian can-cers. Hence, we examined the expression of Bcl-2 in 68 ovarian epithelial cancers using immunohistochemistry and determined whether Bcl-2 expression has prognostic significance in the ovarian epithelial cancers. We found Bcl-2 expression(>5% positive cell) in 31 patients(40%). Bcl-2 expression were exclusively negative in the mucinous type of the ovarian epithelial cancer. Bcl-2 exp- ression was not correlated with tumor stage(stage I & II vs III & IV, p=0.63). The patients with Bcl-2 positivity had lower recurrence rate than the patients with negativity at the se- cond look operation(p<0.01). Although there was a trend that the patients with Bcl-2 posi- tivity had better acturial survival than the patient with negativity, the stastical significance was not present(3 years acturial survival;+vs-;63%, 29%;p>0.05). These results sug- gest the Bcl-2 expression appears an early event in the ovarian carcinogenesis and has an inhibiting role in progression of ovarian tumor.
Carcinogenesis ; Humans ; Immunohistochemistry ; Mucins ; Ovarian Neoplasms* ; Proto-Oncogenes ; Recurrence

PURPOSE: We compared c-erbB-2 oncogene amplification and oncoprotein expression, trying to identify the biologic and prognostic significance of c-erbB-2 in adendegrees Carcinoma of the stomach. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded tissue sections from 43 cases of gastric cancer were analyzed for amplification of c-erbB-2 by differential polymerase chain reaction and for overexpression of gene product by immunohistdegrees Chemistry. RESULTS: The amplification was detected in 13 cases (30%). Enhanced c-erbB-2 immunoreactivity was observed in 30% (13/43) of tumors. Tumors with gene amplification generally stained strongly (p=0.003). Although the frequency of amplification and overexpression of c-erbB-2 was increased with advanced gastric cancer and with lymph node metastasis, this difference was not statistically significant. c-erbB-2 gene amplification or protein overexpression showed a trend toward a better five year survival rate, but this did not reach a statistical significance. CONCLUSION: Amplification and/or overexpression of the c-erbB-2 may be of value in clarifying the biologic characteristics of the human gastric cancer. However, more sensitive and more speci fic methods of identifying gene amplification are needed and the standardization of the staining method as well as guidelines for interpreting the staining result are mandatory for this purpose.
Chemistry ; Gene Amplification ; Genes, erbB-2 ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Oncogenes ; Polymerase Chain Reaction ; Population Characteristics ; Proto-Oncogenes ; Stomach ; Stomach Neoplasms* ; Survival Rate

PURPOSE: The expression of the PIM-1 gene, which is a proto-oncogene that encodes a serine/threonine kinase, is associated with multiple cellular functions such as proliferation, differentiation, apoptosis and tumorigenesis. In particular, several studies have reported that the PIM-1 gene is associated with the development of lymphoma, leukemia and prostate cancer. Therefore, this study was conducted to evaluate the association between the single nucleotide polymorphisms in the PIM-1 gene and the risk of lung cancer occurrence in the Korean population. MATERIALS AND METHODS: To evaluate the role of the PIM-1 gene in the development of lung cancer, the genotypes of the PIM-1 gene were determined in 408 lung cancer patients and 410 normal subjects. RESULTS: We found that the T-C-T-C haplotypes of the PIM-1 gene (-1196 T>C, IVS4 +55 T>C, IVS4 +1416 T>A and +3684 C>A) were associated with an increased risk of lung cancer [adjusted odds ratio (aOR): 3.98; 95% CI: 1.24~12.75, p-value: 0.020]. In particular, these haplotypes showed an increased risk of lung cancer in males (aOR: 5.67; 95% CI: 1.32~24.30, p-value: 0.019) and smokers (aOR: 7.82; 95% CI: 1.75~34.98, p-value: 0.007). CONCLUSIONS: The present results suggest that the T-C-T-C haplotype of the PIM-1 gene could influence the risk of developing smoking-related lung cancer in the Korean population. Additional functional studies with an larger sample sized analysis are warranted to reconfirm our findings.
Apoptosis ; Cell Transformation, Neoplastic ; Genotype ; Haplotypes ; Humans ; Leukemia ; Lung ; Lung Neoplasms ; Lymphoma ; Male ; Odds Ratio ; Oncogenes ; Phosphotransferases ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms ; Proto-Oncogenes

BACKGROUND: The proto-oncogene c-met encodes the tyrosine kinase receptor for hepatocyte growth factor (HGF), which is a pleiotropic cytokine that controls growth, survival, motility, invasive migration, and differentiation of epithelial cells. Like several other epithelial neoplasms, thyroid carcinomas have been found to overexpress the c-met oncogene. We presently examine the expression of c-met protein in thyroid tumors and the correlation of c-met protein expression with prognostic factors in thyroid cancers. METHOD: We have examined the expression of the c-met oncogene in 62 paraffin-embedded thyroid cancer specimens (54 papillary carcinomas, 5 follicular carcinomas, 2 medullary carcinomas, and 1 anaplastic carcinoma), 20 benign tumors and 20 normal tissues using immunohistochemistry. We measured both the proportion and the intensity of stained cells and then calculated the staining index by multiplying the proportion and intensity scores. The staining index were categorized to be negative/low (staining index < or = 5) or high(staining index >5). The most important prognostic factors were age (over 45), tumor size (over 1.5 cm), lymph node metastasis, capsular invasion, vascular invasion and peripheral metastasis. RESULT: 1) The rate of expression of the c-met oncogene were 100%, 100% and 60% in thyroid cancer, benign tumors and normal thyroid tissue respectively. The expression of the c-met oncogene was restricted to the membrane. 2) The staining index of normal tissue, benign tumors and thyroid carcinomas was 1.8, 4.3 and 5.8 respectively. In malignancies, the staining index of papillary carcinoma was 5.7, follicular carcinoma 5.4, medullary carcinoma 7.5, and anaplastic cancer 9. 3) A high expression of c-met was not correlated with prognostic factors in papillary, follicular carcinomas or medullay carcinomas. CONCLUSION: The c-met oncogene might not play a role in the pathogenesis of thyroid neoplasia. There was no correlation between the high expression rate of the c-met oncogene and prognostic factors in papillary and follicular carcinomas.
Carcinoma, Medullary ; Carcinoma, Papillary ; Epithelial Cells ; Hepatocyte Growth Factor ; Immunohistochemistry ; Lymph Nodes ; Membranes ; Neoplasm Metastasis ; Neoplasms, Glandular and Epithelial ; Oncogenes* ; Protein-Tyrosine Kinases ; Proto-Oncogenes ; Thyroid Gland* ; Thyroid Neoplasms

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.
Biosynthetic Pathways ; Carcinogenesis ; Glucose ; Glycolysis ; Homeostasis ; Kynurenine ; Lactic Acid ; Metabolism ; Oncogenes ; Oxidation-Reduction ; Oxygen ; Proto-Oncogenes ; Protons ; Quality Control ; T-Lymphocytes ; Tumor Microenvironment ; Yeasts