The Synergistic Apoptotic Interaction of Indole-3-Carbinol and Genistein with TRAIL on Endometrial Cancer Cells

Bidur Parajuli,조치흠,신소진,권상훈,차순도,이현교,배인수 대한의학회 2013 Journal of Korean medical science Vol.28 No.4

Induction of apoptosis in target cells is a key mechanism by which chemotherapy promotes cell killing. The purpose of this study was to determine whether Indole-3-Carbinol (I3C)and Genistein in combination with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induce apoptosis in endometrial cancer cell (Ishikawa) and to assess apoptotic mechanism. The MTT assay and flow cytometry were performed to determine cell viability and cell cycle. The induction of apoptosis was measured by caspase-3 activity test, DNA fragmentation assay, annexin V binding assay and western blot analysis. There was no effect in cell growth inhibition and cell cycle progression alone or in two-combination. However, the treatment of I3C and Genistein followed by TRAIL showed significant cell death and marked increase in sub-G1 arrest. Three-combination treatment revealed elevated expression of DR4, DR5 and cleaved forms of caspase-3, caspase-8, PARP. The Flip was found down regulated. Moreover, increase in caspase-3 activity and DNA fragmentation indicated the induction of apoptosis. The results indicate that I3C and Genistein with TRAIL synergistically induced apoptosis via death receptor dependent pathway. Our findings might provide a new insight into the development of novel combination therapies against endometrial cancer.

The Protective Effect of Rutin against Ischemia/reperfusion-associated Hemodynamic Alteration through Antioxidant Activity

Bidur Bhandary,채한정,Cheng Shi Piao,김도성,이금화,채수완,김형룡 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.6

Reactive oxygen species exert toxic effects during ischemia-reperfusion (I/R) injury of various organs. This study was designed to evaluate the preventive effects of various isoflavonoids such as biochanin A, daidzein, genistein, rutin and quercetin. These compounds are wellknown naturally occurring compounds with beneficial health effects and antioxidant activity. Free radical scavenging activity was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay and superoxide dismutase (SOD) assay. Among the isoflavonoids tested, biochanine A, quercetin and rutin showed significant DPPH free radical scavenging activity. Similarly, treatment of biochanine A, genistein and rutin significantly increased SOD activity in neonant rat heart myocyte primary cells as well as in H9C2 cells. For ex vivo study, hearts from Sprague-Dawley rats were perfused in Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. Hearts were subjected to 20 min of pre-ischemia followed by 20 min of global ischemia, and then 50 min of reperfusion at 37oC. The test compounds were perfused 10 min before ischemia and during the entire reperfusion period. Among the isoflavonoids tested, only rutin significantly increased left ventricular developed pressure (LVDP) and increased maximum positive and negative dP/dt (+/- dP/dtmax). In left ventricular end diastolic pressure (LVEDP) analysis, rutin, daidzein and biochanin A were effective. Among the isoflavonoids, rutin had consistent protective effects in I/R injury by affecting cardiac dynamic factors as well as by enhancing SOD and DPPH activity.

Retrospective Study of Canine Cutaneous Tumors in Korea

( Bidur Pakhrin ),( Min Soo Kang ),( Il Hong Bae ),( Mi Sun Park ),( Hyang Jee ),( Mi Hyeon You ),( Dae Yong Kim ) 한국수의병리학회 2006 학술대회 Vol.10 No.-

An Involvement of Oxidative Stress in Endoplasmic Reticulum Stress and Its Associated Diseases

Bhandary, Bidur,Marahatta, Anu,Kim, Hyung-Ryong,Chae, Han-Jung MDPI 2013 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.14 No.1

<P>The endoplasmic reticulum (ER) is the major site of calcium storage and protein folding. It has a unique oxidizing-folding environment due to the predominant disulfide bond formation during the process of protein folding. Alterations in the oxidative environment of the ER and also intra-ER Ca<SUP>2+</SUP> cause the production of ER stress-induced reactive oxygen species (ROS). Protein disulfide isomerases, endoplasmic reticulum oxidoreductin-1, reduced glutathione and mitochondrial electron transport chain proteins also play crucial roles in ER stress-induced production of ROS. In this article, we discuss ER stress-associated ROS and related diseases, and the current understanding of the signaling transduction involved in ER stress.</P>

Mitochondria in relation to cancer metastasis.

Bhandary, Bidur,Marahatta, Anu,Kim, Hyung-Ryong,Chae, Han-Jung Plenum Press 2012 Journal of bioenergetics and biomembranes Vol.44 No.6

<P>Mitochondria, also known as 'Power House of cell,' are crucial organelles, regulating energy metabolism. Recently, an involvement of mitochondria in cancer occurrence and metastasis has been proposed. The roles of mitochondria in cancer progression/metastasis include alteration of glycolysis, regulation of ROS and suppression of intrinsic apoptosis. This mini-review explains the specific mitochondrial characteristics during cancer metastasis with past and recent findings. It may contribute to understanding mitochondria-related mechanisms of cancer metastasis.</P>

Retrospective study of canine cutaneous tumors in Korea

김대용,Bidur Pakhrin,Min-Soo Kang,배일홍,박미선,Hyang Jee,유미현,김재훈,윤병일,최양규 대한수의학회 2007 Journal of Veterinary Science Vol.8 No.3

Over the 42 month period from January 2003 to June 2006, a total of 2,952 canine biopsy specimens were received from the Veterinary Medical Teaching Hospital of Seoul National University and from veterinary practitioners across the nation. Out of these, 748 (25.34%) cases were diagnosed as canine cutaneous tumors in the Department of Veterinary Pathology, College of Veterinary Medicine, Seoul National University, Korea. Thirty-eight different types of cutaneous tumors were identified and categorized into epithelial and melanocytic tumors (56.95%), mesenchymal tumors (38.90%), and hematopoietic tumors (4.14%) located in the skin. Among these, 69.25% were benign and 30.74% were malignant. The top ten most frequently diagnosed cutaneous tumors were epidermal and follicular cysts (12.70%), lipoma (11.36%), mast cell tumors (8.82%), cutaneous histiocytoma (7.49%), basal cell tumors (6.82%), sebaceous gland adenoma (6.68%), sebaceous gland hyperplasia (5.08%), hepatoid gland adenoma (3.61%), apocrine adenocarcinoma (3.07%), and fibroma (2.81%), in order of prevalence. They comprised 68.45% of all cutaneous tumors. These top ten cutaneous tumors were distributed on the trunk (30.08%), head and neck (20.9%), extremities (19.14%), anal and perianal area (8.59%), and tail (3.91%). The age of the dogs with the ten most frequent tumors had a mean age of 8.3 years, with a range of 2 months to 19 years. When all types of tumors were considered together in the entire population, there was no difference in incidence according to sex.

Hepatocellular adenoma in a Eurasian otter (Lutra lutra)

김대용,배일홍,Bidur Pakhrin,Hyang Jee,신남식 대한수의학회 2007 Journal of Veterinary Science Vol.8 No.1

A 7-year-old female Eurasian otter (Lutra lutra) at the Seoul Grand Park, Korea, died after displaying depression, anorexia, weight loss and rough skin for several days. At necropsy, a solitary friable round mass, which was approximately 12 × 9 × 5 cm and mottled dark red and yellow, was found bulging from the right hepatic lobe. Microscopically, the nonencapsulated, poorly circumscribed mass was composed of solid sheets of neoplastic hepatocytes. In addition, numerous small tan foci, ranging from 0.5 to 1.0 cm in diameter, were evenly scattered throughout the pancreatic tissue. These foci were found to be nonencapsulated, well-demarcated hyperplastic nodules of the exocrine pancreatic gland. We observed neither intrahepatic nor extrahepatic metastases. Based on the gross and microscopic changes, we diagnosed the animal as having a hepatocellular adenoma accompanied by exocrine pancreatic nodular hyperplasia.

Genitourinary rhabdomyosarcoma with systemic metastasis in a young dog

( Il Hong Bae ),( Bidur Pakhrin ),( Mi Hyeon You ),( Hyang Jee ),( Chul Yong Hwang ),( Dae Yong Kim ) 한국수의병리학회 2006 학술대회 Vol.10 No.-

포도상구균의 유도형 Clindamycin 내성 검출을 위한 Vitek II 시스템 평가

이성현,장숙진,문대수,박영진,안균열,한호림,Bidur,정옥연 대한진단검사의학회 2005 Annals of Laboratory Medicine Vol.25 No.6

Background : While broth based antimicrobial susceptibility test methods work well for the detection of the majority of antimicrobial resistance mechanisms, antimicrobial resistance mechanism in some microorganisms may not be detected by these methods. The purpose of this study was to compare Vitek II system with a standard method for the ability to detect inducible clindamycin resistance in Staphylococcus aureus. Methods : Of 200 clinical isolates of S. aureus tested, 183 were methicillin resistant (MRSA) and 17 were methicillin susceptible (MSSA). A disk approximation test (Clinical Laboratory Standards Institute; CLSI, Wayne, PA, USA) was performed as the standard method by placing standard erythromycin and clindamycin disks in adjacent positions. Vitek II ID-GPI (bioMerieux, Durham, NC, USA) was used for identification and Vitek AST-P536 (bioMerieux, Durham, NC, USA) for antimicrobial susceptibility tests. Results : Clindamycin resistance rates of S. aureus tested by disk diffusion and Vitek II system were 89% and 56%, respectively. All but one inducible clindamycin resistant MRSA isolates were susceptible to clindamycin by Vitek II system. Five inducible clindmycin resistant MSSA isolates were all susceptible to clindamycin by Vitek II system. Vitek II system did not detect the inducible clindamycin resistance in S. aureus. Conclusions : Our results showed that Vitek II system was unacceptable for the detection of inducible clindamycin resistance in S. aureus. We suggests that the disk approximation test should be used to detect the inducible clindamycin resistance in S. aureus 배경 : 많은 미생물 검사실은 자동화 장비를 이용하여 신속하게 항생제 감수성 검사를 실시하고 있다. 자동화된 액체배지 희석법은 대부분의 항생제 내성기전을 찾아낼 수 있으나 몇몇 미생물에서는 찾아내지 못하는 것으로 보고되고 있다. 본 연구에서는clindamycin 유도형 내성S. aureus의 검출에 있어 디스크 인접법과 자동화 액체배지희석법인 Vitek II 시스템을 비교해보고자하였다.방법 : Methicillin resistant Staphylococcus aureus (MRSA)183주와 methicillin susceptible Staphylococcus aureus (MSSA)17주로 구성된 총 20주의 S. aureus 임상분리주를 대상으로 검사를 실시하였다. 표준검사법으로 미국 Clinical and LaboratoryStandards Institute (CLSI)에서 추천하는 디스크 인접법을 시행했으며, Vitek II ID-GPI (bioMerieux, Durham, NC, USA)와 Vitek AST-P536 (bioMerieux, Durham, NC, USA)을 이용하여 균의 동정과 항균제감수성시험을 실시하였다. 결과 : 디스크 인접법과 Vitek II로 검사하였을 때S. aureus의 clindamycin의 내성률은 각각 89%와 56%로 나타났다. MRSA에서 유도형 내성을 보인 60주중 1주만이 Vitek II에서 clinda-mycin에 대해 내성을 보였으며, 나머지는 모두 감수성 결과를 보였다. 또한, MSSA에서 Vitek II는 유도형 내성 5주 모두 clinda-mycin 감수성으로 보고하여 유도형 clindamycin 내성S. aureus를 찾지 못하였다. 결론 : S. aureus에 대한 유도형 clindamycin 내성을 찾기 위한 방법으로 Vitek II 시스템은 부적절하며 CLSI에서 추천하는 디스크 인접법을 사용해야 할 것이다.

Multilobular tumor of the mandible in a Pekingese dog

김대용,배일홍,Hyang Jee,Min-Soo Kang,Bidur Pakhrin 대한수의학회 2006 JOURNAL OF VETERINARY SCIENCE Vol.7 No.3

Multilobular tumor of bone detected in a 2.5-year-old male Pekingese dog is reported. Grossly, the neoplasm consisted of multiple, variably sized, gritty, grayish-white to yellow nodules separated by thick collagenous septa. Histologically, these nodules contained multiple lobules of irregularly shaped and sized islands of well-differentiated osteoid and cartilage, separated by anastomosing fibrovascular septa. Chondrocytes and osteocytes were observed in the lacunae and in more osseous islands in the lobule, respectively. These lobules were surrounded by mesenchymal spindle cells. Mitotic figures were not evident. The neoplastic pattern was consistent with that of a multilobular bone tumor. Diagnosis was based on gross and light microscopic findings. The cause of this neoplasm was not determined.