ABSTRACT
Spinocerebellar ataxia type-2 (SCA2) is an autosomal dominant cerebellar ataxia that occurs due to expanded CAG trinucleotide repeats in the ATXN2 gene. Clinical features of parkinsonism in SCA2 vary from phenotypes of levodopa-responsive parkinsonism to multiple system atrophy. We described a patient with SCA2 presenting typical clinical manifestations of multiple system atrophy-c type with levodopa responsive parkinsonism whose dopamine transporter (DAT) image showed atypically reduced DAT uptake in in the striatum.
ABSTRACT
PURPOSE: Histone deacetylase inhibitors (HDACIs) induce accumulation of acetylated histones in nucleosomes, which lead to reactivate gene expression and inhibit the growth and survival of tumor cells. This study evaluated the efficacy of HDACIs in breast cancer cells in comparison with other established drug regimens. METHODS: Drug responses of tumor samples from mastectomy specimens of 78 breast cancer patients were evaluated using the histoculture drug response assay (HDRA). Tumor inhibition rates (IRs) of established drug regimens such as doxorubicin, cyclophosphamide, doxorubicin with cyclophosphamide (AC), paclitaxel, docetaxel and doxorubicin with docetaxel (AT), as well as those of three HDACIs (SAHA, PXD101, and a novel compound CG-2) were evaluate. RESULTS: The percentages of chemosensitive tumors (chemoresponsiveness) were 26.9-60.3% with established regimens and 61.5-73.1% with HDACIs when the cutoff value for inhibition rate was set at 30%. Breast cancer cells appeared to be more chemoresponsive to HDACIs than to established drug regimens. Chemoresponsiveness to AT was the highest among the established drug regimens. A combination regimen offered higher activity than did a single drug (doxorubicin vs AT; p<0.001). HER2/Neu-overexpressing breast cancers were chemosensitive to SAHA and AT (p=0.031 and 0.04, respectively). CONCLUSION: Our findings show that breast cancer cells were sensitive to HDACIs, with therapeutic efficacies comparable to those of established drug regimens. Specific biological markers such as HER2/Neu could be assessed for effectiveness as HDACIs chemosensitivity markers in further clinical trials.
Subject(s)
Humans , Biomarkers , Breast , Breast Neoplasms , Cyclophosphamide , Doxorubicin , Gene Expression , Histone Deacetylase Inhibitors , Histone Deacetylases , Histones , Hydroxamic Acids , Mastectomy , Nucleosomes , Paclitaxel , Sulfonamides , TaxoidsABSTRACT
BACKGROUND: Hepatitis B virus (HBV) is major source of chronic liver disease in Korea. However this virus might have different nucleotide sequence according to races, different region, etc. Recently the novel method that allows sensitive amplification with dramatically decreased mis-incorporation has developed. We determined to get the major form of HBV nucleotide sequence from whole sequencing data of 26 Korean HBV carriers. METHODS: HBV DNA were collected from 26 Korean chronic HBV carriers. We used the novel PCR with pfu for the amplification of HBV DNA, and specific primers were made with combination sequence bases of non-HBV part and HBV parts which were located head and tail in the virion. Then whole length of HBV were directly sequenced and analysed. RESULT: HBV DNA was consisted of 3215 bases in 20 cases of 26 Korean chronic HBV carriers. And the remainder had smaller or larger number due to deletion, insertion or both in pre-S2 and S gene. They were 99.03% homology of their nucleotide sequence and belong to genotype C. The variability of nucleotide sequence was significantly higher in the singly coding region (SCR) than doubly coding region (DCR), and also high in pre-S1 and pre-S2 gene among the DCR. Hot-spots were more frequently found in the SCR, pre-S1 and pre-S2 gene. CONCLUSION: In Korean chronic HBV carriers, HBV is consisted of 3215 nucleotides, and belongs to genotype C. And it might exist one genotype with the variability in Korea.