Sang Hee Park

Publications (16)35.48 Total impact

• Article: Comparison of diffusion-weighted MR imaging and FDG PET/CT to predict pathological complete response to neoadjuvant chemotherapy in patients with breast cancer.

  Sang Hee Park, Woo Kyung Moon, Nariya Cho, Jung Min Chang, Seock-Ah Im, In Ae Park, Keon Wook Kang, Wonshik Han, Dong-Young Noh
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  ABSTRACT: To compare the use of diffusion-weighted MR imaging (DWI) and (18)F-FDG PET/CT to predict pathological complete response (pCR) in breast cancer patients receiving neoadjuvant chemotherapy. Thirty-four women with 34 invasive breast cancers underwent DWI and PET/CT before and after chemotherapy and before surgery. The percentage changes in the apparent diffusion coefficient (ADC) and the standardised uptake value (SUV) were calculated, and the diagnostic performances for predicting pCR were evaluated using receiver operating characteristic (ROC) curve analysis. After surgery, 7/34 patients (20.6%) were found to have pCR. A( z ) values for DWI, PET/CT and the combined use of DWI and PET/CT were 0.910, 0.873 and 0.944, respectively. The best cut-offs for differentiating pCR from non-pCR were a 54.9% increase in the ADC and a 63.9% decrease in the SUV. DWI showed 100% (7/7) sensitivity and 70.4% (19/27) specificity and PET/CT showed 100% sensitivity and 77.8% (21/27) specificity. When DWI and PET/CT were combined, there was a trend towards improved specificity compared with DWI. DWI and FDG PET/CT show similar diagnostic accuracy for predicting pCR to neoadjuvant chemotherapy in breast cancer patients. The combined use of DWI and FDG PET/CT has the potential to improve specificity in predicting pCR.
  European Radiology 08/2011; 22(1):18-25. · 3.22 Impact Factor
• Article: Enhanced detection of Coxiella burnetii with a complementary locked primer-based real-time PCR method.

  Eun-Ju Kim, Hong Yong Kang, Kyu-Jam Hwang, Sang-Hee Park, Mi-Yeoun Park, Sungdo Park, Jin Seok Yu, Ji Sung Park, Sang Hyeon Kang, Hyuk Chu
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  ABSTRACT: Coxiella burnetii is the bacterial causative agent of Q fever in humans. Because Q fever can establish itself with an initial inoculation of fewer than ten C. burnetii cells, a sensitive detection method for C. burnetii infection is needed for early detection. We aimed to evaluate the effectiveness of a complementary locked primer (CLP)-based real-time PCR method for sensitive detection of C. burnetii infection. To evaluate the ability of CLPs to enhance the efficiency of the real-time PCR assay for the C. burnetii IS1111 insertion sequence, the mean threshold cycle values from 20 real-time PCR replicates with either CLPs or conventional primers were determined using tenfold serial dilutions (102-108) of purified C. burnetii Nine Mile genomic DNA. In addition, the cross-reactivity between C. burnetii and 31 non-Coxiella species was examined. The CLP-based real-time PCR allowed specific and reliable detection of as few as 59 copies of the IS1111 element present in the genome of C. burnetii, which represents approximately 2.96 genome equivalents or three cells of C. burnetii. These results demonstrate the effectiveness of CLP-based real-time PCR for sensitive detection of C. burnetii infection. It can be concluded that the CLP-based real-time PCR assay is a more appropriate method for sensitive detection and quantification of C. burnetii than previously reported methods.
  Molecular diagnosis & therapy 03/2011; 15(2):103-7. · 1.71 Impact Factor
• Article: Computer-aided analysis of ultrasound elasticity images for classification of benign and malignant breast masses.

  Woo Kyung Moon, Ji Won Choi, Nariya Cho, Sang Hee Park, Jung Min Chang, Mijung Jang, Kwang Gi Kim
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  ABSTRACT: The purpose of this study was to evaluate computer-aided analysis of ultrasound elasticity images for the classification of benign and malignant breast tumors. Real-time ultrasound elastography of 140 women (mean age, 46 years; age range, 35-67 years) with nonpalpable breast masses (101 benign and 39 malignant lesions) was performed before needle biopsy. A region of interest (ROI) was drawn around the margin of the mass, and a score for each pixel was assigned; scores ranged from 0 for the greatest strain to 255 for no strain. The diagnostic performances of a neural network based on the values of the six elasticity features were compared with visual assessment of elasticity images and BI-RADS assessment using B-mode images. The values for the area under the receiver operating characteristic curve (A(z)) of the six elasticity features--mean hue histogram value, skewness, kurtosis, difference histogram variation, edge density, and run length--were 0.84, 0.69, 0.63, 0.75, 0.68, and 0.71, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the neural network based on all six features were 92% (36/39), 74% (75/101), 58% (36/62), and 96% (75/78), respectively, with an A(z) value of 0.89, which is significantly higher than the A(z) of 0.81 for visual assessment by radiologists (p = 0.01) and 0.76 for BI-RADS assessment using B-mode images (p = 0.002). Computer-aided analysis of ultrasound elasticity images has the potential to aid in the classification of benign and malignant breast tumors.
  American Journal of Roentgenology 12/2010; 195(6):1460-5. · 2.78 Impact Factor
• Article: A genetic comparison of Brucella abortus isolates from animals and humans by using an MLVA assay.

  Moon Her, Sung-Il Kang, Jong-Wan Kim, Ji-Yeon Kim, In-Yeong Hwang, Suk-Chan Jung, Sang Hee Park, Mi Yeoun Park, Hansang Yoo
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  ABSTRACT: The MLVA assay is known to have a high ability to identify and discriminate Brucella species, so that it can be used as an epidemiological tool to discriminate Brucella isolates originating from restricted geographic sources. In this study, the genetic profiles of 38 B. abortus isolates from humans were analyzed and compared with genotypes from animal isolates in South Korea. As a result, it was found that they did not show high genetic diversity and were compacted. They were clustered together with animal isolates, showing a significant correlation to regional distributions. With its ability to prove a significant genetic correlation among B. abortus isolates from animals and humans in South Korea, the MLVA assay could be utilized as part of a program to control and eradicate brucellosis, one of the major zoonoses. This study represents the first data of genetic correlation of B. abortus isolates from humans and animals in South Korea.
  Journal of Microbiology and Biotechnology 12/2010; 20(12):1750-5. · 1.38 Impact Factor
• Article: Diffusion-weighted MR imaging: pretreatment prediction of response to neoadjuvant chemotherapy in patients with breast cancer.

  Sang Hee Park, Woo Kyung Moon, Nariya Cho, In Chan Song, Jung Min Chang, In-Ae Park, Wonshik Han, Dong-Young Noh
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  ABSTRACT: To evaluate the potential of diffusion-weighted (DW) magnetic resonance (MR) imaging with an apparent diffusion coefficient (ADC) map in the prediction of response to neoadjuvant chemotherapy in patients with breast cancer. This retrospective study was approved by the institutional review board, which waived the informed consent requirement. Fifty-three consecutive women (mean age, 43.7 years; median age, 42.0 years; age range, 24-65 years) with 53 invasive breast cancers (mean diameter, 5.0 cm; median diameter, 4.2 cm; diameter range, 2.0-13.3 cm) who had undergone chemotherapy were included. Both DW MR imaging (b values, 0 and 750 sec/mm(2)) and dynamic contrast material-enhanced (DCE) MR imaging were performed at 1.5 T before and after chemotherapy prior to surgery. Mean time from initiation of chemotherapy to posttreatment ADC measurement was 54 days (range, 48-62 days). Average ADC for three regions of interest per tumor on ADC maps was calculated. Patients with a reduction in tumor diameter of at least 30% after chemotherapy at DCE MR imaging were defined as responders. Pretreatment ADCs and percentage increases in ADC after chemotherapy in responders and nonresponders were compared. The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was calculated with receiver operating characteristic curve analysis. After chemotherapy, 36 (68%) patients were classified as responders, and 17 (32%) were classified as nonresponders. Pretreatment mean ADC ([1.036 ± 0.015] × 10(-3) mm(2)/sec [standard error]) of responders was significantly lower than that of nonresponders ([1.299 ± 0.079] × 10(-3) mm(2)/sec) (P = .004). Furthermore, mean percentage ADC increase of responders (47.9% ± 4.8) was higher than that of nonresponders (18.1% ± 4.5) (P < .001). The best pretreatment ADC cutoff with which to differentiate between responders and nonresponders was 1.17 × 10(-3) mm(2)/sec, which yielded a sensitivity of 94% (95% confidence interval [CI]: 81%, 99%) and a specificity of 71% (95% CI: 44%, 90%). Patients with breast cancer and a low pretreatment ADC tended to respond better to chemotherapy. Prediction of response to neoadjuvant chemotherapy with DW MR imaging might help physicians individualize treatments and avoid ineffective chemotherapy.
  Radiology 10/2010; 257(1):56-63. · 5.73 Impact Factor
• Article: Phylogenetic clustering of 4 prevalent virulence genes in Orientia tsutsugamushi isolates from human patients.

  Hyuk Chu, Sang-Hee Park, Eun-Ju Kim, Kyu-Jam Hwang, Soo-Kyoung Shim, Sungdo Park, Mi-Yeoun Park
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  ABSTRACT: The pathogenicity of microbes is involved in many kinds of virulence genes. The relationships between these virulence genes and strains are not clear in Orientia tsutsugamushi yet. In this study, we confirmed the presence of the virulence genes and classified into O. tsutsugamushi isolates using phylogenetic analysis of the virulence genes. We also compared the fatality rates of every isolate via an infection experiment in BALB/c mice using the O. tsutsugamushi isolates, Deajeon03-01, Wonju03-01, and Muju03-01. Moreover, we compared the phylogenetic analysis, in basis with 56 kDa protein sequence which determined from serotype, and virulence genes of O. tsutsugamushi. Our results showed remarkably different fatality rates between Deajeon03-01 and Muju03-01, which are both Boryong strains of O. tsutsugamushi. Also, clustering analyses including these two isolates gave slightly different results depending on whether they were clustered based on virulence genes or on the 56 kDa protein sequences. Consequently, we conclude that fatality rates in O. tsutsugamushi are correlated with differences in both serotypes and virulence genes. We identified some variations within the virulence genes dnaA, virB8, tolR, and trxA among the isolates.
  The Journal of Microbiology 02/2010; 48(1):124-8. · 1.10 Impact Factor
• Article: Sonoelastographic strain index for differentiation of benign and malignant nonpalpable breast masses.

  Nariya Cho, Woo Kyung Moon, Ha Young Kim, Jung Min Chang, Sang Hee Park, Chae Yeon Lyou
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  ABSTRACT: The purpose of this study was to evaluate the diagnostic potential of the sonoelastographic strain index for differentiation of nonpalpable breast masses. Ninety-nine nonpalpable breast masses (79 benign and 20 malignant) in 94 women (mean age, 45 years; range, 21-68 years) who had been scheduled for a sonographically guided core biopsy were examined with B-mode sonography and sonoelastography. Radiologists who had performed the biopsies analyzed the B-mode sonograms and provided American College of Radiology Breast Imaging Reporting and Data System categories. The strain index (fat to lesion strain ratio) was calculated by dividing the strain value of the subcutaneous fat by that of the mass. The histologic result from the sonographically guided core biopsy was used as a reference standard. The diagnostic performance of the strain index and that of B-mode sonography were compared by receiver operating characteristic (ROC) curve analysis. The mean strain index values +/- SD were 6.57 +/- 6.62 (range, 1.29-28.69) in malignant masses and 2.63 +/- 4.57 (range, 0.54-38.76) in benign masses (P = .019). The area under the ROC curve values were 0.835 (95% confidence interval [CI], 0.747-0.902) for B-mode sonography and 0.879 (95% CI, 0.798-0.936) for the strain index (P = .490). The sensitivity, specificity, positive predictive value, and negative predictive value were 95% (19 of 20), 75% (59 of 79), 48% (19 of 39), and 98% (59 of 60), respectively, when a best cutoff point of 2.24 was used. The strain index based on the fat to lesion strain ratio has diagnostic performance comparable with that of B-mode sonography for differentiation of benign and malignant breast masses.
  Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 01/2010; 29(1):1-7. · 1.25 Impact Factor
• Article: Comparison of diagnostic methods for detection of Brucella species in dog blood samples

  Soon Oh Kwon, Truong Quang Lam, Moon Her, Dong Chun Ahn, Sang Hee Park, Mi Yeoun Park, Young Ju Lee, Tae Wook Hahn
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  ABSTRACT: Canine brucellosis produce abortions and infertility in dogs and currently is diagnosed by serological methods such as rapid slide agglutination test with 2-mercaptoethanol (2-ME RSAT) and immunochromatographic assay (ICA). Bacterial isolation is considered gold standard for Brucella diagnosis and the polymerase chain reaction (PCR) is an alternative method to bacterial isolation. A total of 36 whole blood samples were collected from dogs reared in area of Chuncheon and were subjected to serology (2-ME RSAT and ICA for B. canis, Rose Bengal test and C-ELISA for B. abortus), blood culture and 3 types of PCRs (BSCP31, 16s rRNA, and OMP-2). All blood samples were negative by serology and blood cultures. The BCSP31 and the OMP-2 PCR detected 5 samples were positive whereas the 16S rRNA PCR detected all samples were negative as serological methods and blood culture did. From the results observed in the present study, we conclude that 16S rRNA PCR could be used for direct PCR for canine blood samples.
  Korean Journal of Veterinary Service. 12/2009; 32(4):335-341.
• Article: Ultrasonography-guided vacuum-assisted biopsy of microcalcifications: Comparison of the diagnostic yield of calcified cores and non-calcified cores on specimen radiographs.

  Nariya Cho, Woo Kyung Moon, Jung Min Chang, Sang Hee Park, Chae Yeon Lyou, In Ae Park
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  ABSTRACT: Microcalcifications found on mammography of asymptomatic women can be sampled by ultrasound (US)-guided percutaneous breast biopsy when stereotactic core biopsy is unavailable or unsuccessful. The role of specimen radiograph needs to be reevaluated after US-guided biopsy. Purpose: To compare retrospectively the histological diagnoses of calcified cores and non-calcified cores as depicted on specimen radiographs after a US-guided, 11-gauge, vacuum-assisted biopsy using surgical histology as the reference standard. A total of 135 consecutive patients underwent a US-guided vacuum-assisted biopsy for calcifications with malignant histological results from 135 lesions. For each lesion, calcification was identified in at least one core on specimen radiographs. Calcified cores and non-calcified cores depicted on specimen radiographs were separately submitted to the pathology department. The pathological diagnoses of calcified cores and non-calcified cores were compared with final diagnoses at surgical excision. Of a total of 2049 core specimens that were obtained (mean, 15 per lesion; range, 4-35 per lesion), 794 cores (mean, 5.9 per lesion; range, 1-17 per lesion) contained calcifications and 1255 cores (mean, 9.3 cores per lesion; range, 1-34 cores per lesion) did not contain calcifications. Calcified cores were more likely to enable an accurate diagnosis of cancer as compared to non-calcified cores (67%, 91 of 135 versus 52%, 70 of 135; P = 0.009). A diagnosis of cancer was more likely to be missed with non-calcified cores as compared to calcified cores (16%, 21 of 135 versus 4%, 5 of 135; P = 0.002). There was no difference in the underestimation of malignancy between calcified cores (29%, 39 of 135) and non-calcified cores (33%, 44 of 135) (P = 0.510). Calcified cores depicted on specimen radiographs are more accurate for a diagnosis of cancer as compared to non-calcified cores obtained during US-guided vacuum-assisted biopsy of microcalcifications.
  Acta Radiologica 11/2009; 51(2):123-7. · 1.37 Impact Factor
• Source

  Available from: PubMed Central

  Article: Cytokine response in Balb/c mice infected with Francisella tularensis LVS and the Pohang isolate.

  Eun-Ju Kim, Sang-Hee Park, Young-Sill Choi, Soo-Kyoung Shim, Mi-Yeoun Park, Man Suck Park, Kyu-Jam Hwang
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  ABSTRACT: We investigated the immune response induced by the Francisella (F.) tularensis live vaccine strain (LVS) and the Pohang isolate. After the Balb/c mice were infected intradermally (i.d) with 2 x 10(4) cfu of F. tularensis LVS and Pohang, respectively, their blood and organs were collected at different times; 0, 3, 6, 24, 72, 96, 120 and 168 h after infection. Using these samples, RT-PCR and ELISA analysis were carried out for the comparative study of the cytokines, including TNF-alpha, INF-gamma, IL-2, IL-4, IL-10 and IL-12. In the Pohang-infected mice at 120 h, the liver showed a 53 times higher level of TNF-alpha and a 42 times higher level of IFN-gamma than the respective levels at the early time points after infection. The levels of TNF-alpha and IFN-gamma induced by LVS were 5 times lower than those induced by the Pohang isolate. Also, the organs from the Pohang-infected mice showed higher levels of TNF-alpha, IFN-gamma, IL-10 and IL-12 than the levels in the LVS-infected mice. The blood from the Pohang-infected mice at 120 h revealed about a 40 times increased level of IFN-gamma, and IL-10 was also increased by 4 times at 96 h compared to an early infection time point, while IL-4 was not induced during the whole infection period. These results suggest that F. tularensis may induce a Th1-mediated immune response to in vivo infection and the Pohang isolate has a higher capacity than the LVS to induce an acute immune response in Blab/c mice.
  Journal of Veterinary Science 10/2008; 9(3):309-15. · 1.16 Impact Factor
• Article: UV-irradiation induces oxidative damage to mitochondrial DNA primarily through hydrogen peroxide: analysis of 8-oxodGuo by HPLC.

  Daisaku Takai, Sang-Hee Park, Yasunari Takada, Shizuko Ichinose, Masanobu Kitagawa, Makoto Akashi
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  ABSTRACT: Roles of reactive oxygen species (ROS) in damage to mitochondrial DNA (mtDNA) following ultraviolet (UV)-irradiation were investigated in the human hepatoma cell line SK-HEP-1. We altered the intracellular status of ROS by the overexpression of manganese superoxide dismutase (MnSOD) and/or catalase. Using HPLC, we analyzed 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo), known as a marker of damage to DNA molecules. UV-irradiation resulted in the accumulation of 8-oxodGuo in these cells. The overexpression of MnSOD enhanced the accumulation of 8-oxodGuo by UV. The co-overexpression of catalase inhibited the accumulation of 8-oxodGuo by UV in MnSOD-transfectants. The overexpression of MnSOD reduced the colony forming capacity in SK-HEP-1 cells and the co-overexpression of catalase with MnSOD stimulated the capacity compared to control. UV-irradiation inhibited the colony forming capacity in these cells; no difference was observed among the capacities of control, MnSOD- and catalase-transfectants. However, the overexpression of MnSOD/catalase significantly rescued the reduction of colony forming capacity by UV-irradiation. Our results suggest that the accumulation of hydrogen peroxide plays a key role in the oxidative damage to mtDNA of UV-irradiated cells, and also that the overexpression of both MnSOD and catalase reduces the mtDNA damage and blocks the growth inhibition by UV. Our results also indicate that the increased activity of MnSOD may lead to a toxic effect on mtDNA by UV-irradiation.
  Free Radical Research 12/2006; 40(11):1138-48. · 2.88 Impact Factor
• Source

  Available from: msk.or.kr

  Article: Characterization of recombinant Drosophila melanogaster myo-inositol-1-phosphate synthase expressed in Escherichia coli.

  Sang-Hee Park, Jong-Il Kim
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  ABSTRACT: Cloned myo-inositol-1-phpsphate synthase (INOS) of Drosophila melanogaster was expressed in Escherichia coli, and purified using a His-affinity column. The purified INOS required NAD+ for the conversion of glucose-6-phosphate to inositol-1-phosphate. The optimum pH for myo-inositol-1-phosphate synthase is 7.5, and the maximum activity was measured at 40 degrees C. The molecular weight of the native enzyme, as determined by gel filtration, was approximately Mr 271,000 +/- 15,000. A single subunit of approximately Mr 62,000 +/- 5,000 was detected upon SDS-polyacrylamide gel electrophoresis. The Michaelis (Km) and dissociation constants for glucose-6-phosphate were 3.5 and 3.7 mM, whereas for the cofactor NAD+ these were 0.42 and 0.4 mM, respectively.
  The Journal of Microbiology 04/2004; 42(1):20-4. · 1.10 Impact Factor
• Article: Polyphenol (-)-epigallocatechin gallate inhibits apoptosis induced by irradiation in human HaCaT keratinocytes.

  Hisayoshi Kondo, Sang-Hee Park, Keiko Watanabe, Yasuhiro Yamamoto, Makoto Akashi
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  ABSTRACT: Green tea is a rich source of polyphenols, and (-)-epigallocatechin-3-gallate (EGCG) is a major constituent of green tea polyphenols. In the present study, we investigated the effect of EGCG on apoptosis induced by irradiation in the human keratinocytic cell line HaCaT. Irradiation by gamma-ray induced apoptosis with concomitant cleavage of caspase-3 and its in vivo substrate poly(ADP-ribose) polymerase. Treatment of cells with EGCG inhibited irradiation-induced apoptosis as detected by Hoechst staining and internucleosomal cleavage of DNA, and prevented the cleavage of these proteins by irradiation. We also found that the treatment of cells with EGCG alone suppressed cell growth and induced apoptosis in these cells. Our results suggest that EGCG inhibits irradiation-induced apoptosis by inactivating the caspase pathway in HaCaT cells. Our study also indicates that EGCG has a dual effect on the survival of these keratinocytes.
  Biochemical and Biophysical Research Communications 04/2004; 316(1):59-64. · 2.48 Impact Factor
• Article: Role of reactive oxygen species in cells overexpressing manganese superoxide dismutase: mechanism for induction of radioresistance.

  Yasunari Takada, Misao Hachiya, Sang-Hee Park, Yoshiaki Osawa, Toshihiko Ozawa, Makoto Akashi
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  ABSTRACT: Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide anions (O(2)(-)) into hydrogen peroxide (H(2)O(2)). We altered the intracellular status of reactive oxygen species by introducing human MnSOD cDNA into the human ovarian cancer cell line SK-OV-3. The overexpression of MnSOD inhibited cell growth and induced a concomitant increase in the level of H(2)O(2) in SK-OV-3 cells. The cells overexpressing MnSOD were more resistant to irradiation than parental cells. MnSOD overexpression shortened the G(2)-M duration in irradiated cells. Either inhibition of p38 mitogen-activated protein kinase (p38MAPK) or scavenging free radicals blocked the induction of radioresistance by MnSOD and also abolished the shortening of the G(2)-M duration with concomitant inhibition of p38MAPK phosphorylation. Irradiation increased the generation of H(2)O(2) even more in these transfectants. These results suggest that the accumulated H(2)O(2) potentiated the activation of p38MAPK after irradiation in cells overexpressing MnSOD, which led to the protection of cells from irradiation-mediated cell death through the G(2)-M checkpoint. SK-OV-3 cells had no constitutive expression of p53, and the overexpression of MnSOD and/or irradiation did not induce p53 or p21(WAF1), which causes cell cycle arrest. Thus, our results suggest that MnSOD alters the cell cycle progression of irradiated cells independently of p53 and p21(WAF1).
  Molecular Cancer Research 01/2003; 1(2):137-46. · 4.29 Impact Factor
• Article: Heat-shock protein 25 (Hspb1) regulates manganese superoxide dismutase through activation of Nfkb (NF-kappaB).

  Min-Jeong Yi, Sang-Hee Park, Hye-Nyun Cho, Hee Yong Chung, Jong-Il Kim, Chul-Koo Cho, Su-Jae Lee, Yun-Sil Lee
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  ABSTRACT: We previously demonstrated that overexpression of HSP25 (now known as Hspb1) conferred increased resistance to ionizing radiation (Radiat Res. 154, 421-428, 2000). In the present study, L929 cells overexpressing Hspb1 were shown to have increased expression of the manganese superoxide dismutase gene (now known as SOD2) and its enzyme activity. To elucidate Hspb1-induced pathways leading to activation of these antioxidant enzymes, the production of the tumor necrosis factor alpha (Tnf) and interleukin 1 beta (Il1b) genes was examined. Increased expression of Tnf and Il1b resulting from Hspb1 overexpression was detected by RT-PCR. Increased activation of Nfkb (degradation of Ikb, a member of the Nfkb family) was also found in Hspb1-overexpressing cells. When treated with Tnf, Nfkb activation and SOD2 gene expression were increased more by Hspb1 overexpression. Moreover, transfection with the Hspb1 antisense gene abrogated all of the Hspb1-mediated phenomena. To further elucidate the exact relationship between induction of SOD2 and Nfkb activation, a dominant negative I-kBalpha (now known as Nfkb1a) construct was transfected into Hspb1-overexpressing cells. The dominant negative Nfkb1a inhibited Hspb1-mediated SOD2 gene expression. In addition, Hspb1-mediated radioresistance was blocked by dominant negative Nfkb1a transfection. When the SOD2 gene was transfected into L929 cells, a somewhat increased radioresistance was detected by a clonogenic survival assay compared to control cells. Hspb1 produced Tnf and Il1b and facilitated SOD2 gene expression through Nfkb activation, possibly resulting in Hspb1-mediated radioresistance.
  Radiation Research 12/2002; 158(5):641-9. · 2.68 Impact Factor
• Article: Hsp25 regulates the expression of p21(Waf1/Cip1/Sdi1) through multiple mechanisms.

  Sang-Hee Park, Yun-Sil Lee, Yoshiaki Osawa, Misao Hachiya, Makoto Akashi
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  ABSTRACT: Exposure of cells to external stresses leads to the induction or activation of certain proteins. Expression of heat shock proteins (Hsps) is induced in response to these stresses. Hsps are known to have molecular chaperone activities; but recent studies have shown that Hsps have a variety of functions such as the triggering of proliferation, differentiation, and apoptosis of cells. Previously, we found that overexpression of a 25 kDa Hsp (Hsp25) induced expression of cell cycle inhibitory protein p21 (Waf1/Cip1/Sdi1) in murine fibroblastoid L929 cells. However, the mechanisms underlying the induction of p21 by Hsp25 are unknown. In the present study, we investigated the mechanisms underlying the regulation of p21 expression by Hsp25 in these cells. The introduction of Hsp25 cDNA stimulated the accumulation of p21 transcripts through transcriptional but not posttranscriptional regulation in these cells. We also found that overexpression of Hsp25 markedly increased the translational rate of p21 and stabilized the protein. Studies involving proteasome inhibitors and Western blot analysis for ubiquitination of p21 demonstrated that the stabilization of p21 is regulated through a ubiquitin-independent pathway. However, no direct association of Hsp25 with p21 was observed. These findings suggest that Hsp25 induces p21 expression through multiple mechanisms, and that transcriptional, translational, and post-translational regulation are important in the regulation of p21.
  Journal of Biochemistry 07/2002; 131(6):869-75. · 2.37 Impact Factor