Biomedical subjects

Hoguen Kim

Publications and source records attributed to Hoguen Kim.

39 records · Page 3Linked to original sources

PubMed2002

Proteomic analysis and molecular characterization of tissue ferritin light chain in hepatocellular carcinoma.

To investigate a molecular basis for iron depletion in human hepatocellular carcinoma (HCC), 19 cases of HCC were analyzed by two-dimensional electrophoresis (2DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). Results were compared with those of paired adjacent nontumorous liver tissues. Comparative analysis of the respective spot patterns in 2DE showed that tissue ferritin light chain (T-FLC), an iron-storage protein, was either severely suppressed or reduced to undetectable levels in HCC, which was further supported by Western blot and immunohistochemical analysis. In contrast, transferrin receptor (TfR) was shown to be overexpressed in the same HCC samples. Interestingly, the relative levels of messenger RNA (mRNA) expression of T-FLC in HCC, which were measured by a real-time quantitative reverse-transcription polymerase chain reaction (PCR), exhibited almost the same levels as those in normal tissues, suggesting that the translational or posttranslational modification of T-FLC may be the cause of T-FLC suppression in HCC. Furthermore, with PCR-based loss of heterozygosity analysis, only 1 of 19 HCCs showed chromosomal deletions at 19q13.3-q13.4 where T-FLC is located, indicating that the suppression of T-FLC is unlikely due to structural genomic changes with HCC. In conclusion, both proteomic and genomic evidence support not only a basis for the suppression of T-FLC in HCC but also provide a new clue to the unresolved question of iron depletion during hepatocarcinogenesis.

Biomarkers, Tumor↗

PubMedDate not supplied

Expression of Bcl-2 family member Bid in normal and malignant tissues.

Bid is the only known Bcl-2 family member that can function as an agonist of proapoptotic Bcl-2-related proteins such as Bax and Bak. Expression of the proapoptotic Bcl-2 family protein Bid was assessed by immunoblotting and immunohistochemical methods in normal murine and human tissues, and in several types of human cancers and tumor cell lines. Bid expression in normal tissues varied widely, with prominent Bid immunostaining occurring in several types of short-lived cells (e.g., germinal center B cells, peripheral blood granulocytes, differentiated keratinocytes) and in apoptosis-sensitive cells (e.g., adult neurons). Analysis of Bid expression by immunostaining of 100 colon, 95 ovarian, and 254 prostate cancers, as well as 59 brain tumors and 50 lymphomas, revealed evidence of altered Bid regulation in some types of cancers. Correlations with clinical outcome data revealed association of higher levels of Bid with longer recurrence-free survival in men with locally advanced (T3 stage) prostate cancer (P=0.04). Immunoblot analysis of Bid protein levels in the NCI's panel of 60 human tumor cell lines revealed a correlation between higher levels of Bid and sensitivity to ribonucleotide reductase (RR)-inhibiting drugs (P<0.0005). Overexpression of Bid in a model tumor cell line by gene transfection resulted in increased sensitivity to apoptosis induction by a RR inhibitor. Taken together, these observations suggest a potential role for Bid in tumor responses to specific chemotherapeutic drugs, and lay a foundation for future investigations of this member of the Bcl-2 family in healthy and diseased tissues.

Animals↗

PubMedDate not supplied

Clinicopathologic characteristics related to the high variability of coding mononucleotide repeat sequences in tumors with high-microsatellite instability.

Frameshift mutation at coding mononucleotide repeat sequences are common in tumors with microsatellite instability (MSI-H), but the incidences are different among the target genes. We analyzed the mutational profiles of 12 known target genes containing polydeoxyadenosine repeats in their coding sequences in 39 MSI-H colorectal carcinomas and 40 MSI-H gastric carcinomas by using polymerase chain reaction and sequencing, and compared the results with the clinicopathologic characteristics. Frameshift mutations of target genes in the MSI-H colorectal and gastric carcinomas are increased according to the length of the polydeoxyadenosine repeats in the target genes. The mean mutational rates of MSI-H colorectal carcinomas and MSI-H gastric carcinomas were 2.03 and 1.95 in the 4 genes containing (A)10 repeats, 1.23 and 0.73 in the 4 genes with (A)9 repeats and 0.61 and 0.48 in the 4 genes containing (A)8 repeats, respectively (p<0.001). Among the evaluated clinicopathologic findings, intestinal type gastric carcinomas had more frameshift mutations than the diffuse type carcinomas (3.5 vs. 1.9, p=0.01). These findings suggest that mutational rates of the target genes in MSI-H tumors are diverse, and higher mutational rates are related to the length of mononucleotide repeat sequences of the target genes and histologic type of tumors.

Adult↗