1.Treadmill Exercise Ameliorates Chemotherapy-Induced Muscle Weakness and Central Fatigue by Enhancing Mitochondrial Function and Inhibiting Apoptosis
Sang Seo PARK ; Hye Sang PARK ; Hyungmo JEONG ; Hyo Bum KWAK ; Mi Hyun NO ; Jun Won HEO ; Su Zi YOO ; Tae Woon KIM
International Neurourology Journal 2019;23(Suppl 1):S32-S39
PURPOSE:
Chemotherapy is associated with the side effects including damage to the mitochondrial DNA. Doxorubicin (DOX) serves as a chemotherapeutic agent for the patients with breast cancer or prostate cancer. DOX causes muscle weakness and fatigue. We investigated the effects of treadmill exercise on DOX-induced apoptosis and mitochondrial dysfunction in relation to central fatigue. For this study, we used the rat model of DOX-induced muscle damage.
METHODS:
DOX (2 mg/kg) was intraperitoneally injected 1 time per week for 4 weeks. Treadmill running continued 5 days per week for 4 weeks. Muscle strength and fatigue index in the gastrocnemius were measured. Immunohistochemistry for the expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe was conducted. We used western blot analysis for the expressions of Bax, Bcl-2, and caspases-3 in the gastrocnemius. Mitochondrial function in the gastrocnemius was also evaluated.
RESULTS:
DOX treatment decreased muscle strength with increase of fatigue index in the gastrocnemius. Mitochondria function was deteriorated and apoptosis in the gastrocnemius was enhanced by DOX treatment. Expressions of TPH and 5-HT in the dorsal raphe were increased by DOX treatment. Treadmill exercise attenuated DOX-induced muscle fatigue and impairment of mitochondria function. Apoptosis in the gastrocnemius was inhibited and over-expression of TPH and 5-HT was suppressed by treadmill exercise.
CONCLUSIONS
Apoptosis was enhanced and mitochondria function was deteriorated by DOX treatment, resulting in muscle weakness and central fatigue. Treadmill exercise suppressed apoptosis and prevented deterioration of mitochondria function in muscle, resulting in alleviation of muscle weakness and central fatigue during DOX therapy.
2.Prognostic Implications of Primary Tumor Resection in Stage IVB Colorectal Cancer in Elderly Patients.
Heui June AHN ; Ho Suk OH ; Yongchel AHN ; Sang Jin LEE ; Hyun Joong KIM ; Moon Ho KIM ; Dae Woon EOM ; Jae Young KWAK ; Myoung Sik HAN ; Jae Seok SONG
Annals of Coloproctology 2014;30(4):175-181
PURPOSE: The aim of this study was to identify prognostic factors in stage IVB colorectal cancer in elderly patients, focusing on the influence of treatment modalities, including palliative chemotherapy and primary tumor resection. METHODS: A cohort of 64 patients aged over 65 years who presented with stage IVB colorectal cancer at the Gangneung Asan Hospital between July 1, 2001, and December 31, 2009, was analyzed. Demographics, tumor location, tumor grade, performance status, levels of carcinoembryonic antigen (CEA), level of aspartate aminotransferase (AST), and distant metastatic site at diagnosis were analyzed. Using the treatment histories, we analyzed the prognostic implications of palliative chemotherapy and surgical resection of the primary tumor retrospectively. RESULTS: The cohort consisted of 30 male (46.9%) and 34 female patients (53.1%); the median age was 76.5 years. Primary tumor resection was done on 28 patients (43.8%); 36 patients (56.2%) were categorized in the nonresection group. The median survival times were 12.43 months in the resection group and 3.58 months in the nonresection group (P < 0.001). Gender, level of CEA, level of AST, Eastern Cooperative Oncology Group performance status, tumor location, and presence of liver metastasis also showed significant differences in overall survival. On multivariate analysis, male gender, higher level of CEA, higher AST level, and no primary tumor resection were independent poor prognostic factors. In particular, nonresection of the primary tumor was the most potent/poor prognostic factor in the elderly-patient study group (P = 0.001; 95% confidence interval, 2.33 to 21.99; hazard ratio, 7.16). CONCLUSION: In stage IVB colorectal cancer in elderly patients, resection of the primary tumor may enhance survival.
Aged*
;
Aspartate Aminotransferases
;
Carcinoembryonic Antigen
;
Chungcheongnam-do
;
Cohort Studies
;
Colorectal Neoplasms*
;
Demography
;
Diagnosis
;
Drug Therapy
;
Female
;
Gangwon-do
;
Humans
;
Liver
;
Male
;
Multivariate Analysis
;
Neoplasm Metastasis
;
Palliative Care
;
Prognosis
;
Retrospective Studies
3.Low-grade Mucinous Cystic Tumor Associated with Endo-metriosis in the Cecum.
Dae Woon EOM ; Gil Hyun KANG ; Sang Wook YI ; Seung Mun JUNG ; Jin Ho KWAK ; Hyuk Jai JANG ; Kun Moo CHOI ; Myung Shick HAN
Journal of the Korean Surgical Society 2007;73(1):72-76
We report here on an unusual case of mucinous cystic tumor that was associated with endometriosis in the cecum. A 45-year-old woman was admitted to the hospital due to her 5 day history of right lower quadrant abdominal pain with a mild fever. A laparotomy was performed under the clinical impression of the tubo-ovarian abscess. A relatively well defined a multi-locular cystic mass (8.0x8.0x7.0 cm) filled with white-to-yellow thick mucoid material was found in the wall of the cecum. The right ovary and fallopian tube showed marked fibrous adhesion to the external surface of the cecal mass. A right hemicolectomy and salpingo-oophorectomy were performed. Histologically, the tumor was similar to those of ovarian borderline mucinous tumor, the intestinal type, and the mucinous epithelium of the tumor was merged with the endometriotic epithelium and stroma. On immunostaining, the CK20 positive mucinous epithelium was well demarcated from the CK7 endometriotic epithelium. This is the first case of low-grade mucinous cystic tumor intimately associated with intestinal endometriosis in the cecum.
Abdominal Pain
;
Abscess
;
Cecum*
;
Endometriosis
;
Epithelium
;
Fallopian Tubes
;
Female
;
Fever
;
Humans
;
Laparotomy
;
Middle Aged
;
Mucins*
;
Ovary
4.Experience of a Korean Disaster Medical Assistance Team in Sri Lanka after the South Asia Tsunami.
Young Ho KWAK ; Sang Do SHIN ; Kyu Seok KIM ; Woon Yong KWON ; Gil Joon SUH
Journal of Korean Medical Science 2006;21(1):143-150
On 26 December 2004, a huge tsunami struck the coasts of South Asian countries and it resulted in 29,729 deaths and 16,665 injuries in Sri Lanka. This study characterizes the epidemiology, clinical data and time course of the medical problems seen by a Korean disaster medical assistance team (DMAT) during its deployment in Sri Lanka, from 2 to 8 January 2005. The team consisting of 20 surgical and medical personnel began to provide care 7 days after tsunami in the southern part of Sri Lanka, the Matara and Hambantota districts. During this period, a total of 2,807 patients visited our field clinics with 3,186 chief complaints. Using the triage and refer system, we performed 3,231 clinical examinations and made 3,259 diagnoses. The majority of victims had medical problems (82.4%) rather than injuries (17.6%), and most conditions (92.1%) were mild enough to be discharged after simple management. There were also substantial needs of surgical managements even in the second week following the tsunami. Our study also suggests that effective triage system, self-sufficient preparedness, and close collaboration with local authorities may be the critical points for the foreign DMAT activity.
Adolescent
;
Adult
;
Aged
;
Asia, Southeastern
;
Child
;
Child, Preschool
;
Emergency Medical Services/organization & administration/statistics & numerical data
;
Female
;
Geography
;
Humans
;
Infant
;
Infant, Newborn
;
International Cooperation
;
Korea
;
Male
;
*Medical Assistance
;
Middle Aged
;
*Natural Disasters
;
Patients/classification/*statistics & numerical data
;
*Relief Work
;
Retrospective Studies
;
Sri Lanka
5.Evidence for Cyclooxygenase-2 Association with Caveolin-3 in Primary Cultured Rat Chondrocytes.
Jin Oh KWAK ; Woon Kyu LEE ; Hyun Woo KIM ; Sun Mi JUNG ; Kwang Jin OH ; Sang Yong JUNG ; Yang Hoon HUH ; Seok Ho CHA
Journal of Korean Medical Science 2006;21(1):100-106
The purpose of this study was to demonstrate the cellular localization of cyclooxygenase-2 (COX-2) and caveolin-3 (Cav-3) in primarily cultured rat chondrocytes. In normal rat chondrocytes, we observed relatively high levels of Cav-3 and a very low level of COX-2 mRNA and protein. Upon treating the chondrocytes with 5 microM of CdCl2 (Cd) for 6 hr, the expressions of COX-2 mRNA and protein were increased with the decreased Cav-3 mRNA and protein expressions. The detergent insoluble caveolae-rich membranous fractions that were isolated from the rat chondrocytes and treated with Cd contained the both proteins of both COX-2 and Cav-3 in a same fraction. The immuno-precipitation experiments showed complex formation between the COX-2 and Cav-3 in the rat chondrocytes. Purified COX-2 with glutathione S-transferase-fused COX-2 also showed complex formation with Cav-3. Confocal and electron microscopy also demonstrated the co-localization of COX-2 and Cav-3 in the plasma membrane. The results from our current study show that COX-2 and Cav-3 are co-localized in the caveolae of the plasma membrane, and they form a protein-protein complex. The co-localization of COX-2 with Cav-3 in the caveolae suggests that the caveolins might play an important role for regulating the function of COX-2.
Animals
;
Animals, Newborn
;
Blotting, Western
;
Cadmium Chloride/pharmacology
;
Caveolae/drug effects/metabolism/ultrastructure
;
Caveolin 3/*genetics/metabolism
;
Cell Membrane/drug effects/metabolism
;
Cells, Cultured
;
Chondrocytes/cytology/drug effects/*metabolism
;
Cyclooxygenase 2/*genetics/metabolism
;
Gene Expression
;
Immunoprecipitation
;
Microscopy, Confocal
;
Microscopy, Electron
;
RNA, Messenger/genetics/metabolism
;
Rats
;
Reverse Transcriptase Polymerase Chain Reaction
6.Primary ovarian hepatoid carcinoma: Case report with review of the literature.
Seung Chul LIM ; Jae Wook KIM ; Young Tae KIM ; Jae Hoon KIM ; Sang Woon KIM ; Bo Sung YOON ; Dong Wook KWAK ; Nam Hoon CHO ; Joo Hyuk SON ; Sunghoon KIM
Korean Journal of Gynecologic Oncology 2006;17(1):84-88
Hepatoid carcinoma is histologically similar to hepatocelluar carcinoma and produce alfa-fetoprotein. Ovarian hepatoid carcinoma is extremely rare whether primary or metastatic. We experienced one case of primary ovarian hepatoid carcinoma. In this case report, we present histologic findings, therapeutic modalities of primary hepatoid carcinoma with review of literatures.
alpha-Fetoproteins
;
Female
;
Ovary
7.Identification of a novel murine organic anion transporter like protein 1 (OATLP1) expressed in the kidney.
Sun Mi JUNG ; Woon Kyu LEE ; Jin Oh KWAK ; Sang Yong JUNG ; Jinyoung PARK ; Wan Young KIM ; Jin KIM ; Seok Ho CHA
Experimental & Molecular Medicine 2006;38(5):485-493
The organic anion transporters (OATs) are expressed in various tissues, primarily in the kidney and liver, but they are also expressed in the placenta, small intestine, and the choroid plexus, which are all epithelial tissues that transport xenobiotics. Six isoforms of OATs are currently known. Considering the variety of organic anionic compounds, other OATs isoforms can be assumed. In this connection, we have searched for a new isoform in the expressed sequence tag (EST) database. We found the new candidate clone AK052752 in the mouse kidney cDNA library and we named it mouse organic anion transporter like protein 1 (mOATLP1). The mOATLP1 cDNA consisted of 2221 base pairs that encoded a 552 amino acid residue protein with 12 putative transmembrane domains. The deduced amino acid sequence of mOATLP1 showed 37 to 63% identity to other members of the OAT family. According to the tissue distribution based on Northern blot analysis, 2.7 kb and 2.9 kb mOATLP1 transcripts (approximate sizes) were observed in the kidney and liver. An 85-kDa band (approximate) was detected using Western blot analysis of mouse kidney performed with a synthesized oligopeptide-induced mOATLP1 antibody. Immunohistochemical results showed mOATLP1 was stained in the blood vessels, glomeruli (the parietal epithelial cells and podocytes), distal convoluted tubules, connecting tubules, and inner medullary collecting tubules. mOATLP1 appears to be a novel candidate for an organic anion transporter isoform identified in the kidney.
Tissue Distribution
;
Sequence Homology, Amino Acid
;
Rabbits
;
Protein Structure, Tertiary
;
Protein Isoforms/isolation & purification
;
Phylogeny
;
Organic Anion Transporters/*isolation & purification/*metabolism
;
Oligopeptides/immunology
;
Multigene Family
;
Molecular Sequence Data
;
Mice
;
Kidney/*metabolism
;
Immunohistochemistry
;
Cloning, Molecular
;
Blotting, Western
;
Animals
;
Amino Acid Sequence
8.Heparin Resistance during Cardiopulmonary Bypass in Infective Endocarditis Patients: A case report.
Sungwon NA ; Sang Boem NAM ; Young Joon OH ; Jong Hwa LEE ; So Woon AHN ; Young Lan KWAK
Korean Journal of Anesthesiology 2005;49(6):868-871
Appropriate anticoagulation is essential for safe cardiopulmonary bypass (CPB). Two patients with infective endocarditis were scheduled for valve replacement. After an intravenous heparin injection for the CPB, the increases in the activated clotting time (ACT) in both patients were less than expected. Subsequent additional heparin administration failed to maintain a sufficient ACT for the CPB, and antithrombin III (AT III) tests during the CPB revealed low activities in both patients. Heparin resistance, due to consumption of circulating AT III as a result of infective endocarditis or prior heparinization, was postulated. While fresh frozen plasma (FFP) could not be timely administered in the first patient, ACT was successfully prolonged after the administration of FFP in the second. It is strongly suggested that adequate management of heparin resistance should be prepared for patients with infective endocarditis who require CPB.
Antithrombin III
;
Antithrombin III Deficiency
;
Cardiopulmonary Bypass*
;
Endocarditis*
;
Heparin*
;
Humans
;
Plasma
9.Heparin Resistance during Cardiopulmonary Bypass in Infective Endocarditis Patients: A case report.
Sungwon NA ; Sang Boem NAM ; Young Joon OH ; Jong Hwa LEE ; So Woon AHN ; Young Lan KWAK
Korean Journal of Anesthesiology 2005;49(6):868-871
Appropriate anticoagulation is essential for safe cardiopulmonary bypass (CPB). Two patients with infective endocarditis were scheduled for valve replacement. After an intravenous heparin injection for the CPB, the increases in the activated clotting time (ACT) in both patients were less than expected. Subsequent additional heparin administration failed to maintain a sufficient ACT for the CPB, and antithrombin III (AT III) tests during the CPB revealed low activities in both patients. Heparin resistance, due to consumption of circulating AT III as a result of infective endocarditis or prior heparinization, was postulated. While fresh frozen plasma (FFP) could not be timely administered in the first patient, ACT was successfully prolonged after the administration of FFP in the second. It is strongly suggested that adequate management of heparin resistance should be prepared for patients with infective endocarditis who require CPB.
Antithrombin III
;
Antithrombin III Deficiency
;
Cardiopulmonary Bypass*
;
Endocarditis*
;
Heparin*
;
Humans
;
Plasma
10.DNA Hypermethylation of Tumor-Related Genes in Gastric Carcinoma.
Su Hyung HONG ; Ho Gak KIM ; Woon Bok CHUNG ; Eun Young KIM ; Jong Young LEE ; Sang Mo YOON ; Joong Goo KWON ; Yoon Kyung SOHN ; Eun Kyung KWAK ; Jung Wan KIM
Journal of Korean Medical Science 2005;20(2):236-241
The hypermethylation of the CpG islands is a common mechanism for the inactivation of tumor-related genes. In the present study, we analyzed the methylation status of genes for cell repair such as hMLH1, MGMT, and GSTP1, and a gastric cancer-specifically methylated DNA fragment, MINT 25 in gastric cancer cases and control groups. The study population consisted of 100 gastric cancer patients (50 distal and 50 proximal carcinomas), and 238 healthy controls. All genes showed more frequent hypermethylation in the cases than in the control group (p<0.0001). We investigated the association between promoter hypermethylation and relevant parameters including age, gender, alcohol consumption, smoking, and family history. There was a common hypermethylation of hMLH1 (p=0.008), MGMT (p= 0.0001), and GSTP1 (p=0.0003) in females. This study also demonstrates that hypermethylation was strongly associated with non-drinkers (MGMT, p=0.046 and MINT 25, p=0.049) and non-smokers (hMLH1, p=0.044; MGMT, p=0.0003; MINT 25, p=0.029). Moreover, the frequency of MINT 25 hypermethylation increased with age (p=0.037), and MGMT methylation was frequently detected in distal gastric cancer than in proximal type (p=0.038). Our study suggested that promoter hypermethylation of the genes involved in cell repair system and MINT 25 is associated strongly with some subgroups of primary gastric carcinoma.
Adult
;
Aged
;
*DNA Methylation
;
Female
;
Glutathione Transferase/genetics
;
Humans
;
Isoenzymes/genetics
;
Male
;
Middle Aged
;
Neoplasm Proteins/genetics
;
Nuclear Proteins/genetics
;
O(6)-Methylguanine-DNA Methyltransferase/genetics
;
Promoter Regions (Genetics)
;
Research Support, Non-U.S. Gov't
;
Stomach Neoplasms/*genetics

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