No abstract available.
Carcinogenesis*

Astrocytes play important roles in normal brain development and the physiological processes. In particular, 30% of the brain volume consists of astrocytes, and they are the primary target cell in the brain for cellular injuries from chemical exposures. The present study attempts to establish an immortalized murine astrocyte cell line to study the mechanisms of chemical-induced carcinogenesis of astrocytes. Primary astrocytes isolated from mice were transfected with plasmid carrying the SV40 T antigen. Clonal cells obtained after G418 selection were continuously subcultured to establish an immortalized astrocyte cell line. The cell line was positive on GFAP expression and was sensitive to exposure to such chemicals as MNNG. Cells were treated with MNNG for 5 days, with doses ranging from 0.001ug/ml to 1ug/ml. Dose-dependent cellular transformations of astrocytes were observed. Treatments at 0.01ug/ml showed the most distinct characteristics of neoplastic transformation. Subsequent treatment with TPA produced higher levels of neoplastic cell transformation than MNNG treatment alone, as evidenced by increases of saturation density, soft-agar colony formation and cell aggregation. Promotional effects of TPA on cell transformation was further demonstrated by the shortening duration of foci appearance. Addition of hydrocortisone to the culture media resulted in further promotion of cell transformation in astrocytes treated with MNNG and TPA, suggesting that glucocortocoid also plays a role in the promotion of chemical-induced astrocyte transformation. The present study demonstrates that astrocytes are susceptible to chemical-induced carcinogenicity and subject to mechanisms of multistage carcinogenesis. Analysis of MNNG-transformed astrocytes showed that, while the expression of TGF-beta was decreased, expression of GFAP, IL-1betaand fibronectin were increased. The results suggest that these factors are associated with mechanisms of MNNG-induced astrocyte transformation and may be used as potential candidates for biomarkers representing astrocyte-related tumors and cell toxicities. The study showed scientific evidence that growth factors, cytokine and the extracellular matrix are involved in processes of chemical-induced transformation of astrocytes. In addition, the present work provided an excellent opportunity to develop an immortalized astrocyte cell line that can be used for studying mechanisms of astrocyte-related diseases.
Animals ; Antigens, Viral, Tumor ; Astrocytes* ; Biomarkers ; Brain ; Carcinogenesis* ; Cell Aggregation ; Cell Line ; Cell Transformation, Neoplastic ; Culture Media ; Extracellular Matrix ; Fibronectins ; Hydrocortisone ; Intercellular Signaling Peptides and Proteins ; Methylnitronitrosoguanidine ; Mice ; Physiological Processes ; Plasmids ; Transforming Growth Factor beta

Carcinogenesis ; Cell Transformation, Neoplastic ; Heme Oxygenase-1 ; Humans

No abstract available.
Apoptosis* ; Carcinogenesis*

BACKGROUND: Philadelphia(Ph) chromosome is found in about 95 percent of chronic myelogenous leukemia(CML) patients. Ph chromosome results from a reciprocal translocation between the long arms of chromosomes 9 and 22, and the fusion gene, BCR-ABL contribute to oncogenesis. Three to five years after first diagnosis, CML progresses to the blast crisis, and is accompanied by secondary cytogenetic changes in about 85% of cases. In this study, we investigated the incidence of ABL deletion of derivative 9 chromosome in CML and evaluated the association between this deletion and progression to the blast crisis by interphase fluorescence in situ hybridization(FISH). METHOD: The subjects included in this study were a consecutive series of 58 patients who were diagnosed as CML at Seoul National University Hospital between January 1997 and April 2000. On 90 archival bone marrow aspirate samples from these 58 CML patients, interphase FISH was performed with a commercially available probe. RESULTS: The ABL deletion of derivative 9 chromosome was detected in 17(29.3%) of 58 patients with CML. Eighteen of 58 patients progressed to blast crisis in this period. ABL deletion was found in 7 of 18 patients with blast crisis, and not in 11 remainders. The mean duration from the diagnosis to blast crisis was 37.1 months in 7 patients with the ABL deletion, while the mean duration was 74.2 months in 11 patients without the ABL deletion. The mean duration from the diagnosis to blast crisis in patients with ABL deletion was significantly shorter than in patients without ABL deletion(P=0.043). CONCLUSIONS: We found that 29.3% of patients with CML had the ABL deletion on derivative 9 chromosome. In these patients, the time taken for evolution to blast crisis was significantly shorter than that of the patients without ABL deletion.
Arm ; Blast Crisis* ; Bone Marrow ; Carcinogenesis ; Cytogenetics ; Diagnosis ; Fluorescence* ; Humans ; Hydrogen-Ion Concentration ; In Situ Hybridization* ; Incidence* ; Interphase* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive* ; Philadelphia Chromosome ; Seoul

Thyroid carcinogenesis is traditionally thought to originate 'de novo'. However, it is debatable whether a malignant transformation can possibly arise from a benign thyroid nodule, as suggested for the malignant transformation of a thyroid adenoma. To the best of our knowledge, no studies have been performed addressing the malignant transformation of nodular hyperplasia in the thyroid gland. Here, we report a case of nodular hyperplasia with focally malignant degeneration.
Carcinogenesis ; Cell Transformation, Neoplastic ; Focal Nodular Hyperplasia ; Hyperplasia* ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule

Cancer-associated fibroblasts (CAFs) and tumor-infiltrating immune cells are the most essential components of the tumor microenvironment (TME). They communicate with each other in tumor microenvironment and play a critical role in tumorigenesis and development. CAFs are very heterogeneous and different subtypes of CAFs display different functions. At the same time, it can contribute to the regulation of the function of tumor-infiltrating immune cells and eventually result in the carcinogenesis, tumor progression, invasion, metastasis and other biological behaviors of tumors by producting various growth factors and cytokines etc. Based on the current research results at home and abroad, this paper reviews the recent research progress on the regulation of CAFs on infiltrating immune cells in tumor microenvironment.
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Cancer-Associated Fibroblasts/metabolism* ; Carcinogenesis ; Cell Transformation, Neoplastic/metabolism* ; Humans ; Lung Neoplasms/metabolism* ; Tumor Microenvironment

Carcinogenesis ; Cell Transformation, Neoplastic ; Hepatoblastoma ; Humans ; Liver ; Liver Neoplasms ; Organoids ; YAP-Signaling Proteins

BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
Humans ; Female ; Genomics ; Carcinogenesis ; Carcinoma ; Breast Neoplasms ; Cell Transformation, Neoplastic ; Nucleotides ; Tumor Microenvironment

To investigate the involvement of expression of the Fragile Histidine Triad(FH1T) gene product in the process of carcinogenesis and progression in cervical carcinoma, we examined its expression by immunohistochemical method in 15 cervical invasive carcinomas, 10 low grade cervical intraepithelial neoplasias(CINs) and 30 high grade CINs(CMI and III). We detected expression of FHIT gene product in 4 of 15(27%) of invasive carcinomas, 3 of 10(30%) low grade CIN and 7 of 30(23%) of high grade CIN, while we detected expression of FHIT gene product in 28 of 45(62%) normal and metaplastic epithelium near the tumor. Thesc data indicate that loss of expression of FH1T gene product has some role in the early tumorigenesis of uterine cervical carcinoma, but not the consequence of the pregression of the tumor.
Carcinogenesis ; Epithelium ; Histidine* ; Immunohistochemistry