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ABSTRACT: C4d has been used as an evaluation marker for antibody-mediated rejection for solid organ transplantation. Although some studies have proposed that complement activation is involved in renal diseases, very little information is available on pathogenesis. This study was conducted to investigate C4d deposition in IgA nephropathy and to find its relations with histopathology and albuminuria.
This retrospective study included 23 patients who underwent renal biopsy at our medical center. The WHO grade of IgA nephropathy, interstitial inflammation and fibrosis, C4d staining and medical records including sex, age, and urine albumin were reviewed.
Thirteen patients (56.5%) were positive for C4d staining in the glomerulus and eleven patients (47.8%) were positive in the tubular epithelium. Glomerular C4d deposition was associated with albuminuria (p=0.044), and tubular C4d deposition was associated with a higher grade of IgA nephropathy (p=0.014).
Activation of the complement system was involved in renal damage and was identified through deposition of C4d in the glomerulus and tubules. Positive C4d staining in the glomerulus and the tubules may be associated with functional damage related to glomerular filtration and poor renal outcome.
International journal of clinical and experimental pathology 01/2013; 6(5):904-10. · 1.89 Impact Factor
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Mijin Gu,
Young Kyung Bae,
Ae Ri Kim,
Seung-Mo Hong,
Eunsil Yu,
Jihun Kim,
Kee-Taek Jang,
Hee-Kyung Chang,
Eun Sun Jung,
Han-Ik Bae, [......],
Young-Ha Oh,
Kyu Yun Jang,
Sun-Young Jun,
Dae Woon Eom,
Kye Won Kwon,
Gyeong Hoon Kang, Jae Bok Park,
Soonwon Hong,
Soo Jin Jung,
Ji Shin Lee
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ABSTRACT: Background/Aims: Although primary small intestinal carcinoma (SIC) is morphologically similar to colorectal carcinoma and shares many of the genetic changes of carcinogenesis, little is known about the role of defective mismatch repair (MMR) genes involved in the SIC. The aim of this study is to investigate the role of defective MMR genes and correlation between clinicopathological factors and loss of MMR protein in SIC. Methodology: A total of 195 SIC cases were collected from 20 institutions in Korea and tissue microarrays (TMA) were made. The loss of expression of hMLH1, hMSH2 and hMSH6 was examined by immunohistochemistry (IHC). Results: The loss of expression of hMLH1, hMSH2 and hMSH6 was identified in 25/193 (13.0%), 25/193 (13%) and 29/195 (15%), respectively. The loss of hMSH2 expression was associated with retroperitoneal seeding. Patients with loss of hMSH6 expression had a tendency to invade deeply and a higher frequency of pancreas invasion. The loss of hMSH6 expression was associated less frequently with peritumoral adenoma. There was no survival difference by MMR protein expression status. Conclusions: The loss of MMR protein was associated with some distinct clinicopathological features. MMR pathway seems to be major pathway in carcinogenesis of SICs. MMR defect seems to be related with sporadic-microsatellite instability (MSI).
Hepato-gastroenterology 03/2012; 59(119). · 0.66 Impact Factor
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ABSTRACT: Intratumoral electroporation (IT-EP) with IL-12 cDNA (IT-EP/IL12) can lead to the eradication of established B16 melanoma tumors in mice. Here, we explore the immunological mechanism of the antitumor effects generated by this therapy. The results show that IT-EP/IL12 applied only once resulted in eradication in 70% animals with large established B16 tumors. Tumor eradication required the participation of CD8+ T cells, but not CD4+ T cells and NK cells. IT-EP/IL12 induced antigen-specific CD8+ T cell responses against the immunodominant Trp2(180-188) epitope and generated a systemic response, resulting in significant therapeutic effects against distal, untreated tumors. The therapeutic effect of IT-EP/IL12 was absent in perforin-deficient mice, indicating that tumor elimination occurred through conventional perforin/granzyme lysis by CTLs. Moreover, this therapy induced some degree of immunological memory that protected approximately one-third of the cured mice against a subsequent tumor challenge. Moreover, antitumor efficacy and long-term protection against B16 were significantly improved by concurrent Trp2 peptide immunization through more induction of Ag-specific CTL responses and more attraction of IFN-γ-expressing CD8+ T cells into tumor sites. The antitumor effect of IT-EP/IL12 required the participation of IFN-γ, which was shown to induce MHC class I expression on B16 cells and increase the lytic activity of the CD8+ CTL generated by IT-EP/IL12. The results from these animal studies may help in the development of IT-EP/IL12 for cancer patients.
Cancer Immunology and Immunotherapy 03/2012; 61(10):1671-82. · 3.70 Impact Factor
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Journal of the American Academy of Dermatology 07/2011; 65(1):247-9. · 3.99 Impact Factor
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ABSTRACT: DNA vaccines are known to be lacking in immunogenicity in humans. Presently, electroporation (EP) is thought to overcome this limitation. Here, we investigate whether human papillomavirus 16 E7 DNA vaccines delivered by EP might elicit potent antitumor activity in animal cervical cancer models, with a focus on the underlying mechanism(s). Intramuscular (IM)-EP delivery of E7 DNA vaccines induced more potent antitumor therapeutic and antimetastatic activity compared with IM delivery. Moreover, the tumor-controlled animals by IM-EP possessed long-term memory responses to parental tumor cells. This improved antitumor effect was concomitant with augmented Ag-specific CTL activities. IM-EP also induced IgG and Th-cell responses higher than IM delivery. Finally, IM-EP resulted in more antigen production in and more attraction of immune cells into the site of DNA injection, suggesting that these biological and immunological changes made by IM-EP might be responsible for enhanced CTL activities and antitumor resistance. Thus, this study shows that IM-EP can induce more potent antitumor activity by augmenting CTL responses possibly through more antigen production in and more attraction of immune cells into the muscle sites. This study also suggests that IM-EP of E7 DNA vaccines might be a potential approach toward treating patients with cervical cancer.
DNA and cell biology 06/2011; 30(12):975-85. · 2.28 Impact Factor
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Mee-Yon Cho,
Jin Hee Sohn,
Joon Mee Kim,
Kyoung-Mee Kim,
Young Su Park,
Woo Ho Kim,
Jin Sook Jung,
Eun Sun Jung,
So-Young Jin,
Dae Young Kang, [......],
Yun Kyung Kang,
Hye Kyung Kim,
Hee-Kyung Chang,
Soon Won Hong,
Young Hee Choi,
Okran Shin,
MiJin Gu,
Youn Wha Kim,
Gwang Il Kim,
Sei Jin Chang
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ABSTRACT: Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.
Journal of Korean medical science 06/2010; 25(6):853-62. · 0.84 Impact Factor
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Hee-Kyung Chang,
Eunsil Yu,
Jihun Kim,
Young Kyung Bae,
Kee-Taek Jang,
Eun Sun Jung,
Ghil Suk Yoon,
Joon Mee Kim,
Young-Ha Oh,
Han-Ik Bae, [......],
Kyu Yun Jang,
Sun-Young Jun,
Dae Woon Eom,
Kye Won Kwon,
Gyeong Hoon Kang, Jae Bok Park,
SoonWon Hong,
Ji Shin Lee,
Jason Y Park,
Seung-Mo Hong
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ABSTRACT: Small intestinal adenocarcinoma is a rare malignant neoplasm, and its clinicopathologic characteristics have not been well elucidated. A total of 197 small intestinal adenocarcinoma cases were collected from 22 institutions in South Korea and were evaluated for clinicopathologic factors that affect the prognosis of small intestinal adenocarcinoma patients using univariate and multivariate analyses. The mean patient age was 59 years, and the male-to-female ratio was 1.7:1. Tumors were located in the duodenum of 108 cases (55%), the jejunum in 59 (30%), and the ileum in 30 (15%). Predisposing conditions were observed in 23 cases (12%), including 17 cases with sporadic adenomas, 3 with Peutz-Jeghers syndrome, 2 with Meckel diverticulum, and 1 with Crohn disease. Synchronous or metachronous malignant tumors were identified in 31 cases (16%), including 13 colorectal and 10 stomach cancers. About 90% of tumors were classified as either pT3 (63 cases) or pT4 (112 cases). The median survival time for all small intestinal adenocarcinoma patients was 39.7 months. Compared with small intestinal adenocarcinomas without accompanying sporadic adenomas, small intestinal adenocarcinomas with accompanying adenomas were more well differentiated (P < .0001), with a more polypoid growth pattern (P < .0001), a lower pT classification (P < .0001), less perineural invasion (P = .01), and less lymphatic invasion (P = .03). Small intestinal adenocarcinoma patients with associated sporadic adenomas (77%) had a significantly better 5-year survival rate than those without sporadic adenomas (38%, P = .02). By univariate analysis, small intestinal adenocarcinoma patients had significantly different survival based on pT classification (P = .003), lymph node metastasis (P < .0001), distal location (jejunal and ileal carcinomas) (P = .003), retroperitoneal tumor seeding (P < .0001), vascular invasion (P = .007), lymphatic invasion (P = .001), peritumoral dysplasia (P = .004), and radiation therapy (P = .006). By multivariate analysis, lymph node metastasis (P = .01) and distal location (P = .003) were independent predictors of a worse prognosis. In conclusion, (1) small intestinal adenocarcinomas are diagnosed at an advanced disease stage; therefore, the development of strategies for detection at an earlier stage is needed. (2) Small intestinal adenocarcinoma patients with an adenomatous component had a better survival than those without an adenomatous component. (3) Lymph node metastasis and distal location (jejunum and ileum) of tumor are the most important independent prognostic factors.
Human pathology 03/2010; 41(8):1087-96. · 3.03 Impact Factor
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ABSTRACT: Liver fibrosis is characterized by the excessive accumulation of extracellular matrix (ECM). Recent advances in the knowledge about the cellular, molecular and genetic aspects of fibrosis have opened a new era of research on liver cirrhosis. A transcription factor, Sp1, originally described as a ubiquitous transcription factor, is involved in the basal expression of ECM genes and may be important in the fibrotic processes.
The chronic hepatic damage received intraperitoneal injection of carbon tetrachloride (2 mg/kg) dissolved in corn oil (1 : 3 ratio) three times a weekly for 8 weeks. The delivery of decoy oligodeoxynucleotide (ODN) was performed by injection of 10 microg of scrambled decoy ODN or 10 microg of ring type (R)-Sp1 decoy ODN through the mouse tail vein. All animals of each group were sacrificed, DNA binding activity, expression of cytokines and histological analysis were measured.
We have generated a R-Sp1 decoy ODN that effectively blocks Sp1 binding to the promoter region for transcription regulation of transforming growth factor (TGF)-beta1. The expression of fibrotic cytokines and inflammatory cytokines was decreased by using the R-Sp1 decoy ODN in liver cirrhosis.
The present study demonstrates that the R-Sp1 decoy ODN inhibits TGF-beta1 expression in liver cirrhosis. These results indicate that targeting Sp1 can efficiently block ECM expression, and suggest that such an approach may represent an interesting therapeutic alternative towards the treatment of cirrhosis.
The Journal of Gene Medicine 06/2009; 11(9):824-33. · 2.48 Impact Factor
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Kyung-Woon Kim,
Yong-Seung Shin,
Kap-Sung Kim,
Young-Chae Chang,
Kwan-Kyu Park, Jae-Bok Park,
Jung-Yoon Choe,
Kwang-Gill Lee,
Mi-Suk Kang,
Young-Guk Park,
Cheorl-Ho Kim
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ABSTRACT: The effect of bee venom (BVA) on the development of type II collagen (CII)-induced arthritis (CIA) in rats has been studied. Male rats were immunized with an emulsion of 200 microg of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneally (i.p.) injection of a suspension of BVA or saline during the experiment. The effect of BVA on cellular responses to CII was examined. In the control rats, the onset of arthritis was observed at the 24th day after the CII-immunization, and the severity of CIA was developed gradually. As compared with rats treated with saline, BVA i.p. injected at doses of more than 20 microl/100g mouse once a day for 14 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-1beta, -2, -6, tumor necrosis factor-alpha and interferon-gamma when the cells were obtained from rats 24 days after immunization and cultured in vitro with CII. When rats were injected i.p. with sheep red blood cells, hemagglutination titers in BVA-treated and control rats did not differ significantly when low doses of BVA was given to rats. However, i.p. injection of BVA at doses of more than 10 microl/100g/day suppressed antibody production. Pretreatment of rats with BVA could inhibit the development of collagen arthritis even when 10-20 microl/100g/day of the BVA were used for pretreatment. Interestingly, higher doses than 10 microlBVA/100g mouse were much effective for arthritis incidence. Treatment of rats with BVA prevented the development of collagen arthritis in a dose-dependent manner. Doses of BVA (15 and 20 microl/100g) resulted in decreased incidence of arthritis. In conclusion, therapeutic i.p injection with BVA improved the clinical course of the disease and the immune response to CII.
Phytomedicine: international journal of phytotherapy and phytopharmacology 05/2008; 15(12):1099-107. · 2.17 Impact Factor
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Yoon-Seup Kum,
Kyung-Hyun Kim,
Tae-In Park,
In-Soo Suh,
Hoon-Kyu Oh,
Chang-Ho Cho, Jae-Bok Park,
Young-Chae Chang,
Ji-Hyun Park,
Kwang-Gil Lee,
Kwan-Kyu Park
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ABSTRACT: The aim of this study is to evaluate the antifibrotic effect of ring-type Sp1 decoy oligonucleotides (ODNs) through blocking the transcription of transforming growth factor (TGF)-beta1 and its downstream target genes. In this experiment, the expression of TGF-beta1, metalloproteinase (MMP)-13, and fibronectin was decreased in the group with the treatment of the ring-type Sp1 decoy ODNs. Also, alpha-smooth muscle actin positive bronchial lining cells and alveolar epithelial cells were observed, especially around the lesions of extracellular matrix (ECM) deposition. These findings provide evidences for the finding of pulmonary epithelial-mesenchymal transition (EMT) and the effectiveness of Sp1 transcription factor as a target for the gene therapy on lung fibrosis.
Biochemical and Biophysical Research Communications 12/2007; 363(2):368-74. · 2.48 Impact Factor
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Hyun-Ji Cho,
Tae-Sung Lee, Jae-Bok Park,
Kwan-Kyu Park,
Jung-Yoon Choe,
Doo-Il Sin,
Yoon-Yub Park,
Yong-Suk Moon,
Kwang-Gill Lee,
Joo-Hong Yeo,
Sang-Mi Han,
Young-Su Cho,
Myeong-Rak Choi,
Nam-Gyu Park,
Yun-Sik Lee,
Young-Chae Chang
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ABSTRACT: Cancer cells, characterized by local invasion and distant metastasis, are very much dependent on the extracellular matrix. The expression of matrix metalloproteinases (MMPs) has been implicated in the invasion and metastasis of cancer cells. In this study, we reported the effects of disulfiram, a clinically used anti-alcoholism drug, on tumor invasion suppression, as well as its effects on the activity of MMP-2 and MMP-9 in human osteosarcoma cells (U2OS). Disulfiram has been used for alcohol aversion therapy. However, recent reports have shown that disulfiram may have potential in the treatment of human cancers. Herewith, we showed that the anti-tumor effects of disulfiram, in an invasion assay using U2OS cells and that disulfiram has a type IV collagenase inhibitory activity that inhibits expression of genes and proteins responsible for both cell and non-cell mediated invasion on pathways. In conclusion, disulfiram inhibited expression of MMP-2 and MMP-9 and it regulated the invasion of human osteosarcoma cells. These observations raise the possibility of disulfiram being used clinical for the inhibition of cancer invasion.
Journal of biochemistry and molecular biology 12/2007; 40(6):1069-76. · 2.02 Impact Factor
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ABSTRACT: The development of therapeutic vaccines has important implications for the treatment of cancer patients. Here we investigate whether human papillomavirus (HPV) E7 subunit vaccines can enhance tumor radioresponse using an established cervical cancer animal model. Radiation plus E7 subunit vaccines improved complete response, cure, and recurrence rates of tumors dramatically compared with single therapy alone. In particular, both components of the E7 subunit vaccines (E7 protein and CpG-oligodeoxynucleotide) were required for the induction of antigen (Ag)-specific cytotoxic T-lymphocyte (CTL) responses and for therapeutic synergy with radiotherapy. Moreover, with combined therapy the radiation dose could be reduced by 16 Gy to achieve an equivalent anti-tumor efficacy to radiation treatment alone. This therapeutic synergy was found to be mediated by CD8(+) CTLs and was concomitant with histological changes (presence of apoptotic bodies and multinucleated giant cells; heavy infiltration of lymphocytes), as determined by in vivo T-cell depletion and histological analysis. Finally, phenotypic changes of radiated tumors and their increased sensitivity to CTL-mediated killing appeared to be responsible for therapeutic synergy. These results show that E7 subunit vaccines act as a potent enhancer of tumor radioresponse and that this is mediated by increased sensitivity of radiated tumors to CTL-mediated killing. This study further suggests that E7-targeted therapeutic vaccines have the potential to improve radiotherapy in patients with cervical cancer.
Molecular Therapy 09/2007; 15(8):1564-70. · 6.87 Impact Factor
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ABSTRACT: The goal of this study was to investigate the therapeutic potentials of combining chemotherapy with human papillomavirus (HPV) E7 subunit vaccines in an animal tumor model and to determine the underlying therapeutic mechanisms.
Animals bearing HPV E6/E7-expressing tumors were treated intratumorally with a selected cytotoxic drug, cisplatin, twice at 1-week interval and s.c. with E7 subunit vaccines thrice at 1-week interval. Tumor chemoimmunoresponse was measured by tumor size. Ag-specific CTL activities and tumor histology were checked in mice under treatments. Apoptosis, in vivo T-cell subset depletion, adoptive CTL transfer, and tumor regression were used to determine the mechanisms for antitumor therapeutic effects.
Combined therapy using cisplatin plus E7 subunit vaccines improved cure and recurrence rates of tumors and long-term antitumor immunity dramatically more than single therapy alone. In particular, both components of E7 subunit vaccines were required for induction of Ag-specific CTL as well as therapeutic synergy when combined with cisplatin. This therapeutic synergy was abrogated by depletion of CD8(+) T cells in vivo and was concomitant with histologic changes (such as heavy infiltration of lymphocytes and reduced tumor cell density). Finally, the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing was found to be responsible for therapeutic synergy.
E7 subunit vaccines plus cisplatin mediate antitumor therapeutic synergy through the increased sensitivity of cisplatin-treated tumors to CTL-mediated killing. Moreover, E7-based therapeutic vaccines have the potential to improve chemotherapy in patients with cervical cancer.
Clinical Cancer Research 02/2007; 13(1):341-9. · 7.74 Impact Factor
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ABSTRACT: Primary adenosquamous carcinoma of the liver is generally considered as an extremely rare subtype of cholangiocarcinoma. It has been reported mostly in a form of case studies. As far as we know, there was only one case report on tumor related with biliary fistula. Recently, we experienced a case of primary adenosquamous carcinoma of liver with a formation of tumor-colonic fistula. A 54-year-old man was transferred to our hospital due to liver mass detected by abdominal ultrasonogram. Dynamic computed tomogram of liver showed a large irregular hypodense mass without rim enhancement in right lobe of liver and also suggested a fistula formation between the tumor and hepatic flexure of right colon. Colonoscopic examination showed a large colonic wall defect in hepatic flexure and a friable, nodular mucosa around the defected colonic wall. Extended right lobectomy and right hemicolectomy were done. Microscopically, the tumor was composed of squamous cell carcinoma mainly with foci of the adenocarcinoma component.
The Korean journal of gastroenterology = Taehan Sohwagi Hakhoe chi 12/2006; 48(5):360-4.
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Bon Chul Koo,
Mo Sun Kwon,
Bok Ryul Choi,
Jin-Hoi Kim,
Seong-Keun Cho,
Sea Hwan Sohn,
Eun Jung Cho,
Hoon Taek Lee,
Wonkyung Chang,
Iksoo Jeon,
Jin-Ki Park, Jae Bok Park,
Teoan Kim
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ABSTRACT: The Moloney murine leukemia virus (MoMLV) -based retrovirus vector system has been used most often in gene transfer work, but has been known to cause silencing of the imported gene in transgenic animals. In the present study, using a MoMLV-based retrovirus vector, we successfully generated a new transgenic chicken line expressing high levels of enhanced green fluorescent protein (eGFP). The level of eGFP expression was conserved after germline transmission and as much as 100 microg of eGFP could be detected per 1 mg of tissue protein. DNA sequencing showed that the transgene had been integrated at chromosome 26 of the G1 and G2 generation transgenic chickens. Owing to the stable integration of the transgene, it is now feasible to produce G3 generation of homozygous eGFP transgenic chickens that will provide 100% transgenic eggs. These results will help establish a useful transgenic chicken model system for studies of embryonic development and for efficient production of transgenic chickens as bioreactors.
The FASEB Journal 12/2006; 20(13):2251-60. · 5.71 Impact Factor
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Kyoung-Mee Kim,
Dong Wook Kang,
Woo Sung Moon, Jae Bok Park,
Cheol Keun Park,
Jin Hee Sohn,
Jin Sook Jeong,
Mee-Yon Cho,
So-Young Jin,
Jong Sang Choi,
Dae Young Kang
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ABSTRACT: Gastrointestinal stromal tumor is characterized by a gain of function mutation of KIT gene and the expression of c-kit protein, but in 5% of cases, c-kit expression is negative although histological findings of gastrointestinal stromal tumor are most suspicious. The existence of c-kit-negative gastrointestinal stromal tumors points to the need of additional markers for making the diagnosis. In this study, we studied the expression of PKCtheta and correlated their expression with other immunohistochemical profiles of gastrointestinal stromal tumors and evaluated their usability as a diagnostic marker. For this purpose, 220 gastrointestinal stromal tumors were immunohistochemically stained for PKCtheta, c-kit, CD34, alpha-smooth muscle actin and S-100 protein. Additionally, genetic studies of KIT and PDGFRA genes were performed using c-kit-negative or PKCtheta-negative cases. All the 220 masses were either PKCtheta-positive or c-kit-positive. PKCtheta was positive in 212 (96%) cases and c-kit was positive in 216 (98%) cases in the cytoplasm of tumor cells with a diffuse staining pattern. Out of 212 PKCtheta-positive GISTs, 208 (98%) cases were c-kit-positive, 174 (82%) cases were CD34-positive, 62 (29%) cases were SMA-positive and S-100 protein was positive in 54 cases (26%). Genetic analyses on eight PKCtheta-negative cases showed exon 11 mutations of KIT gene in four cases. Two PKCtheta-positive and c-kit-negative GISTs showed mutations of PDGFRA gene. Our study shows that PKCtheta is a useful marker and it may play a role in the development of gastrointestinal stromal tumors. Together with c-kit, PKCtheta immunostaining can be used as an important diagnostic tool in the pathologic diagnosis of gastrointestinal stromal tumors with its high specificity and sensitivity.
Modern Pathology 12/2006; 19(11):1480-6. · 4.79 Impact Factor
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ABSTRACT: We previously reported that E7 subunit and DNA vaccines are both capable of inducing antitumor protection through induction of antigen-specific CTL. In this study, we investigated their ability to control established tumors according to tumor size, vaccine doses, and vaccine delivery routes. Antitumor therapeutic efficacy of both vaccine types was dependent on tumor burden. However, E7 subunit vaccines induced a higher level of antitumor therapeutic activities at the tested dose compared to DNA vaccines. This was concomitant with induction of antibody, CTL, and IFN-gamma responses, as well as histologic changes (heavy infiltration of lymphocytes and presence of apoptotic bodies). In vaccine dose titration assays, 50 and 100 microg of DNA vaccines exhibited an equivalent antitumor efficacy to 0.5 and 1 microg of E7 subunit vaccines, respectively, i.e., a 100-fold difference in E7 dosage, suggesting the importance of vaccine doses for achieving antitumor immunity. Furthermore, tumors of a larger size were controlled by intratumoral injection with E7 subunit vaccines, underscoring the importance of vaccine delivery routes for antitumor therapeutic efficacy. Thus, these data suggest that antitumor therapeutic efficacy of E7 therapeutic vaccines is determined by vaccine doses, vaccine delivery routes, and tumor sizes, and that these vaccines could be another addition to conventional therapy modalities against cervical cancer.
DNA and Cell Biology 06/2006; 25(5):277-86. · 2.07 Impact Factor
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Kyoung-Mee Kim,
Dong Wook Kang,
Woo Sung Moon, Jae Bok Park,
Cheol Keun Park,
Jin Hee Sohn,
Jin Sook Jeong,
Mee-Yon Cho,
So-Young Jin,
Jong Sang Choi,
Dae Young Kang
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ABSTRACT: Seven hundred forty seven cases of gastrointestinal stromal tumors (GISTs) in Koreans who were diagnosed between 2001 and 2002 were analyzed to evaluate their occurrence and their clinical, pathologic and immunohistochemical findings. The most frequent location of tumor was in the stomach (63%), followed by the small intestine (30%), the colorectum (5%), and the esophagus (2%). c-kit expression was found in 93.6% of the cases, while CD34, SMA and S-100 protein was positive in 80.1%, 28.2%, and 20.2%, respectively. c-kit positivity was high in the stomach (94.2%) and small intestine (94.6%), while it was relatively low in the colorectum (85.0%), and esophagus (81.2%). The positivity for CD34 was correlated with the higher risk of GISTs (p = 0.04). Follow up of the patients showed that 58 primary GISTs patients died and 20 of these patients were recurrent or metastatic at the time of diagnosis. The pathologic diagnosis to predict the risk of aggressive behavior of GISTs was correlated with the numbers of tumor, clinical stage, epithelioid histologic type, cellularity, cellular atypia, necrosis, and mucosal invasion (p = 0.00). GISTs with a poor prognosis were closely related to the clinical stage at presentation, the locations of the tumor, and the ages of the patients.
Journal of Korean Medical Science 01/2006; 20(6):977-84. · 0.99 Impact Factor
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ABSTRACT: Chukmesundan (CMSD) is composed of 8 medicinal herbs including Panex ginseng C.A. MEYER, Atractylodes macrocephala KOID, Poria cocos WOLF, Pinellia ternata BREIT, Brassica alba BOISS, Aconitum carmichaeli DEBX, Cynanchum atratum BGE, and Cuscuta chinensis LAM and used for the treatment of various symptoms accompanying hypertension and cerebrovascular disorders. This study was carried out to examine the effects of CMSD on N-methyl-D-aspartate (NMDA)-evoked, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-evoked nitric oxide synthase (NOS) activity in mouse brain. In adult forebrain, CMSD influences neuronal maintenance and is neuroprotective in several injury models through mechanisms that are incompletely understood. Interaction is observed between CMSD and nitric oxide (NO). Because NO affects both neural plasticity and degeneration, we hypothesized that CMSD might rapidly modulate NO production. Using in vivo microdialysis we measured conversion of L-[14C] arginine to L-[14C] citrulline as an accurate reflection of NOS activity in adult mouse hippocampus. CMSD significantly reduced NOS activities to 62% of basal levels within 2 days of onset of delivery and maintained NOS activity at less than 45% of baseline throughout 3 days of delivery. These effects did not occur with control (distilled water) and were not mediated by effect of CMSD on glutamate levels. In addition, simultaneous delivery of CMSD treatment prevented significant increases in NOS activity triggered by the glutamate receptor agonists NMDA and AMPA. Rapid suppression by CMSD of basal and glutamate-stimulated NOS activity may regulate neuromodulatory functions of NO or protect neurons from NO toxicity and suggests a novel mechanism for rapidly mediating functions of CMSD. It is shown that NMDA receptor stimulation leads to activation of p21ras (Ras) through generation of NO via neuronal NOS. The competitive NOS inhibitor, L-nitroarginine methyl ester, and CMSD prevents Ras activation elicited by NMDA, thus supporting the physiologic relevance of endogenous NO regulation of Ras. These results suggest that Ras is a physiologic target of endogenously produced NO and indicates a signaling pathway for NMDA receptor activation that may be important for long-lasting neuronal responses.
Immunopharmacology and Immunotoxicology 02/2005; 27(3):499-514. · 1.83 Impact Factor
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ABSTRACT: Epidemiological studies suggest that a high consumption of fruits can reduce the risk of some cancers and cardiovascular disease, and this may be attributable to the antioxidant activity of vitamins and phenolic compounds. The present study investigated the variations in vitamin C, total phenolic, hesperidin, and naringin contents, and total antioxidant activity of yuzu (Citrus junos Sieb ex Tanaka)-which is a popular citrus fruit in Korea and Japan-between cultivars and during maturity. The amounts of phenolics and vitamin C and the antioxidant activity in all tested yuzu cultivars were higher in peel than in flesh. Ripening increased the total antioxidant activity and vitamin C content in both peel and flesh of yuzu. However, the amounts of all total phenolics, hesperidin, and naringin in peel increased with ripening, whereas they decreased slightly in flesh. There was a highly linear relationship between the vitamin C content and the total antioxidant activity in both peel (r(2) = 1.000) and flesh (r(2) =0.998), suggesting that vitamin C plays a key role in the antioxidant activity of yuzu. In addition, the contribution of each antioxidant to the total antioxidant activity of yuzu was determined using a 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assay and is expressed here in terms of the vitamin C equivalent antioxidant capacity (VCEAC). The means of vitamin C, naringin, and hesperidin in yuzu were 90.4, 63.8, and 65.7 mg/100 g fresh yuzu, respectively. The relative VCEAC values of these compounds were in the following order: vitamin C (1.00) > naringin (0.195) > hesperidin (0.162). Therefore, the estimated contribution of each antioxidant to the total antioxidant capacity of 100 g of fresh yuzus is as follows (in mg of VCEAC): vitamin C (90.36 mg) > naringin (12.44 mg) > hesperidin (10.64 mg). Our results indicate that mature yuzu contains higher amounts of vitamin C and phenolics than other citrus fruits and could therefore be used as a significant dietary source of antioxidants.
Journal of Agricultural and Food Chemistry 09/2004; 52(19):5907-13. · 2.82 Impact Factor
