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      • KCI등재

        Elucidation for modulation of death receptor (DR) 5 to strengthen apoptotic signals in cancer cells

        Kyoung-jin Min,Seon Min Woo,Sk Abrar Shahriyar,Taeg Kyu Kwon 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.1

        The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis via death receptor (DR) 4 or DR5 preferentially in cancer cells, and not in normal cells with relatively high decoy receptor expression. However, multiple mechanisms in cancer cells induce resistance to DRs-mediated apoptosis. Therefore, understanding of molecular mechanisms for resistance to DRs-mediated apoptosis can find the strategy to increase sensitivity. Although multiple proteins are involved in resistance to DRs-mediated apoptosis, we focus on modulation of DR5 to overcome resistance. Here, we discuss regulation of DR5 expression or activation by epigenetic modification, transcription factor at the transcriptional levels, micro RNA and RNA-binding proteins at the posttranscriptional levels, and ubiquitination and glycosylation at the post-translational levels. In addition, we also mention about relationship between localization of DR5 and death signaling activation. The purpose of this review is to help understand relationship between regulatory mechanisms of DR5 and resistance to TRAIL or DRs-targeted agonist monoclonal antibodies, and to develop innovative anticancer therapies through regulation of DR5 signaling.

      • KCI등재

        임신중 자궁근종의 임상적 의의

        이선경,진규섭,신진옥,박원식 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.6

        1983년 3월부터 1994년 2월까지 경희대학병원 산부인과에서 입원 치료받은 환자중 자궁근종 을 동반한 임산부 152예를 대상으로 하였으며, 같은 기간 동안에 본원에 내원하여 분만 및 유산된 임산부 18,146예를 대조군으로 두군 간의 임상적 특징을 비교분석하여 다음과 같은 결론을 얻었다. 1. 자궁근종을 동반한 임산부에서의 평균연령은 30.97세로 대조군의 27.36세에 비해 약 4세 가량 많았으며, 자궁근종 환자는 초산부(58.6%)가 다산부(41.4%)에 비해 많았다. 2. 대부분의 자궁근종(76.3%)은 임상적 진찰이나 초음파검사에 의하여 임신전 또는 산전에 진단되었으며, 산전에 발견되지 않은 환자들은 제왕절개 분만 중에 우연히 발견되었다. 3. 자궁근종은 장막하 근종이 가장 많았으며, 가장 많이 생긴곳은 자궁체부의 저부였으며, 장막하 근종중 육경을 가진 경우 발견 당시 난소종양으로 오인하는 경우 (3.3%)도 있었다. 4. 임상적 진찰이나 초음파 검사로 주로 직경 3cm이상의 자궁근종이 진단이 되었고, 직경 3cm미만의 작은 근종들은 그 대부분이 제왕절개분만시 우연히 발견되었다. 근종의 크기는 5-9.9cm 크기가 전체의 44.1%로 가장 많았고 2개 이하의 자궁근종들을 가진 경우 (85.5%)가 대부분이었다. 5. 임신의 결과로는 자궁근종을 동반한 임산부에서 대조군에 비해 제왕절개분만 (78.4%, 87/111)이 유의하게 증가하였으며, 그 적응증으로는 자궁근종(41.4%)가 가장 많았고, 그 다음으로 반복제왕절개술, 노령초산부, 골반협착 등의 순서였다. 또한 제왕절개 자궁적출술에서도 근종군에서 유의한 증가를 보였다. 6. 산과적 합병증으로는 근종을 동반한 군에서 절박유산과 자연유산이 유의한 증가를 보였으며 그외 태반 조기박리, 조기진통, 조기양막파수, 자궁내 태아 발육지연, 이상태위 등에서 유의성이 없었다. 절제된 자궁근종의 병리조직 검사의 이차적 변성은 41.3%에서 보였으며 제일 먼저 초자변 성, 적색변성, 기타 변성 및 낭성변화 그리고 석회화 등의 순서였다. In a retrospective review of 18,146 pregnancies(control group )from March 1983 to February 1994, at the Department of Obsterics and Gynecology, Kyunghee University Hospital and the uterine leiomyomas were documented by sonography and pelvic examination on the prior to pregnancy or during the antenatal care in 152(0.84%) myoma associated pregnancies at the same period. Clinical manifestation such as mode of diagnosis, size of myoma, outcome of pregnancy and complications were analysed between the myoma associated group and control group . The result were as follows; 1. Mean age of the patients in myoma associated group and control group were 30.97 and 27.36 years old respectively. And also myomas were more detected in primi(58.6%) than multi (41.4%). 2. Almost uterine myomas (76.3%) were detected by clinical examination and ultrasonogram prior to delivery, and the rest (23.7%) were detected incidentally during cesarean section. 3. The most common type of uterine myomas was subserosal and the most common location was uterine fundus. The some subserosal myomas with pedicle were mis-diagnosed as ovarian tumor in about 3.3% on first detetion. 4. In clinical examination and ultrasonogram, diameter 3 cm or more sized uterine myoma were detected , Small myomas less than 3cm in diameter were detected incidentally at cesarean delivery. The majority (44.1%) of myomas were 5-9.9cm sized , and the major number(85.8%) of myomas in one case is 2 or less. 5. In pregnancy outcomes, cesarean section was increased significantly in myoma group (78.4%, 87/111) than control . And the first indication of cesarean section in myoma group is uterine myoma(41.4%) then the other indications were repeat cesarean delivery. old primigravida, pelvic contracture, etc. orderly. Also cesarean hysterectomy rate was increased in myoma group . 6. In obsteric complications , threatened and spontaneous abortion were increased significantly in myoma group than control, but abruptio placentae, preterm labor ,IUGR, PROM, malpresentaion were not significant increased. Secondary pathologic changes in the myomectomy specimen were seen in 41.3% and the first was hyaline degeneraion and the next was red degeneraion.

      • KCI등재

        산전 초음파로 진단된 태변성 복막염

        이선경,진규섭,장미경,정재돈,신진옥,추민호 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.6

        최근 본원 산부인과에서 산전 초음파검사 결과 태변성 위낭종과 석회화, 양수과다증 등의 소견이 있었던 태변성 복막염 환자를 제왕절개만출술로 분만후 신생아는 2차에 걸친 장문합 수술로 현재 특이 사항없이 성장하고 있는 태변 복막염 1례를 경험하였기에, 문헌고찰과 함 께 보고하는 바이다. Meconium peritonitis is a chemical or foreign body reaction of the peritoneum resulted from the prenatal small bowel perforation associated with or without obstructive lesions and malformation. Extravasation of sterile meconium into the peritoneal cavity causes an intense peritoneal reaction resulting in characteristic calcification and ascites which might be observed by the prenatal ultrasonographic examination. Prenatal ultrasonographic detection of the meconium preitonitis allows the preparation for the proper management which should reduce the mortality and morbidity of the neonates. Recently, a case of prenatal meconium peritionitis diagnosed by ultrasonography at 38 gestational age weeks was experienced at our department. We represent this case with a brief review of literatures concerned.

      • KCI등재

        Arylquin 1, a potent Par‑4 secretagogue, induces lysosomal membrane permeabilization‑mediated non‑apoptotic cell death in cancer cells

        Kyoung‑jin Min,Sk Abrar Shahriyar,권택규 한국독성학회 2020 Toxicological Research Vol.36 No.2

        Arylquin 1, a small-molecule prostate-apoptosis-response-4 (Par-4) secretagogue, targets vimentin to induce Par-4 secretion. Secreted Par-4 binds to its receptor, 78-kDa glucose-regulated protein (GRP78), on the cancer cell surface and induces apoptosis. In the present study, we investigated the molecular mechanisms of arylquin 1 in cancer cell death. Arylquin 1 induces morphological changes (cell body shrinkage and cell detachment) and decreases cell viability in various cancer cells. Arylquin 1-induced cell death is not inhibited by apoptosis inhibitors (z-VAD-fmk, a pan-caspase inhibitor), necroptosis inhibitors (necrostatin-1), and paraptosis inhibitors. Furthermore, arylquin 1 significantly induces reactive oxygen species levels, but antioxidants [N-acetyl-l-cysteine and glutathione ethyl ester] do not inhibit arylquin 1-induced cell death. Furthermore, Par-4 knock-down by small interfering RNA confers no effect on cytotoxicity in arylquin 1-treated cells. Interestingly, arylquin 1 induces lysosomal membrane permeabilization (LMP), and cathepsin inhibitors and overexpression of 70-kDa heat shock protein (HSP70) markedly prevent arylquin 1-induced cell death. Therefore, our results suggest that arylquin 1 induces non-apoptotic cell death in cancer cells through the induction of LMP.

      • KCI등재

        자궁경부암 근치수술후 발생한 합병증에 관한 임상적 고찰

        이선경,김승보,이재현,진규섭,정재돈,추민호 대한산부인과학회 1995 Obstetrics & Gynecology Science Vol.38 No.8

        저자들은 1986년 3월 1일부터 1993년 12월 31일까지 경희대학교 의과대학 산부인과학교실에 서 자궁경부암 stage Ib와 stage IIa로 근치적 자궁적출술을 시행한 125명을 대상으로 하였다. 결과는 다음과 같다. 1. 수술당시 사망한 환자는 없었고, 근치적 자궁적출술시 평균 수혈량은 6.7pint 이었다. 수혈 양과 열성 유병율 사이에는 유의한 상관관계가 없었다. 또한 수혈량과 침윤암의 재발사이에도 유의한 상관관계가 없었다. 2. 요관질루가 1예(0.8%) 방광질루가 3예(2.4%), 직장질루가 3예 있었다. (2.4%) 3. 수술후 요로감염으로 치료받은 환자는 23명(18.4%)이었는데 요배양 검사결과 E. coli가 7 명(30.4%)으로 가장 많았다. 근치적 자궁적출술 후 기능성 방광장애등으로 총 도뇨관 삽입기 관이 증가할수록 요로감염도 증가하는 양상을 보였고 됴뇨관 삽입기관과 열성 유병율과의 관계는 유의성이 없었다. 4. 근치적 자궁적출술을 받은 125명의 환자중 3명이 장폐쇄를 보였고 (2.4%) 폐렴이 1예 (0.8%), 요료감염이 23예(18.4%) 창상 감염이 6예(4.8%), 골반내 혈종 혹은 붕소염이 2예 (1.6%) 이었다. 5. 일시적인 간기능 장애는 21명의 환자에서 보였는데 (16.8%) 수술시간과 일시적인 간기능 장애 사이에는 상관관계는 없었으나 10pints 이상의 다량의 수혈과 일시적인 간기능장애 사 이에는 어느정도 유의성이 있는 것으로 생각되었다. 6. 55명의 환자(44.0%) 가 기능성 방광장애를 경험하였는데 환자의 나이와 기능성 방광장애 사이에는 유의한 상관관계를 관찰할 수 없었다. 7. 임파낭 형성은 8명의 환자(6.4%)에서 보였으며 hemovac제거 시시와 임파낭 형성사이에 별다른 상관관계를 보이지 않았다. 8. 수술후 만선 합병증중에서 방광감각 소실은 15명의 환자에서 발생하였으며 (12.0%) 신우 신염은 7명의 환자 (5.6%)에서 하지 혹은 외음부 부종은 12명(9.6%) 수술후 헤르니아는 4명 (3.2%)에서 발생하였다. Since Wertheim developed surgical technique of the radical hysterectomy with pelvic lymphadenectomy about 1900, this procedure has been the first effective method available for the cure of cervical carcinoma. Although many retrospective stuides have been published with varied results between radical hysterectomy and radiotherapy, the operation allows preservation of ovarian function as well as better vaginal integrity and health. We had executed 125 cases of radical hysterectomy of the patients of cervical cancer stage Ib and IIa who were hospitalized in the Department of Obsterics and Gyunecology, School of Medicine, Kyunghee University, during the term of from March 1. 1986 to December 31. 1993. The purpose of this study was to analyze the postoperative complications and correlations associated with other factors. The results were as follows; 1. There was no operative death. The mean blood transfusion in radical hysterectomy was 6.7 pints of blood (whole blood, packed RBC and fresh frozen plasma). there was no significant correlation between the amount of blood transfusion and febrile morbidity(p=0.18999). Also there was no significant correlation between the amount of blood transfusion and recurrence of invasive cervix cancer (p=0.91644). 2. There was one case of ureterovaginal fistula(0.8%), 3 cases of vesicovaginal fistula(2.4%) and 3 cases of rectovaginal fistula(2.4%). 3. Three of the 125 patients treated with radical hysterectomy experienced small bowel obstruction (2.4%) 4. There were one cases pneumonia(0.8%), 23 cases of UTI(18.4%), 6 cases of wound disruption or abscess(4.8%) and 2 cases of pelvic hematoma or cellultitis (1.6%) There was no significant correlation between the duration of indwelling foley catheter and febrile morbidity (p=0.44538). 5. Twenty one patients experinced transient hepatic dysfuction after radical hysterectomy(16.8%). There was no correlation between operative time and transient hepatic dysfunction (p=0.85291). But there was some significant difference between large amount of blood transfusion (10 or more pints) and transient hepatic dysfunction(p=0.05284). 6. 55 patients experinced functional vesical disturbance(44.0%) there was no correlation between age of patients and functional vesical disturbance (p=0.96241) 7. Lymphocyst formation occured in 8patients (6.4%) there was no correlation between time for removal of hemovac and lymphocyst formation(p=0.79487). 8. Of chronic postoperative complications, loss of bladder sensation (hypotony, atony) occured in 15 patients (12.0%) the pyelonephritis occured in 7 patients (5.6%) the leg or vulva edema occured in 12 patients (9.6%) and four patients experienced postoperative ventral hernia(3.2%)

      • Cepharanthine Enhances TRAIL-Mediated Apoptosis Through STAMBPL1-Mediated Downregulation of Survivin Expression in Renal Carcinoma Cells

        Shahriyar, Sk Abrar,Woo, Seon Min,Seo, Seung Un,Min, Kyoung-jin,Kwon, Taeg Kyu MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.10

        <P>Cepharanthine (CEP) is a natural plant alkaloid, and has anti-inflammatory, antineoplastic, antioxidative and anticancer properties. In this study, we investigated whether CEP could sensitize renal carcinoma Caki cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. CEP alone and TRAIL alone had no effect on apoptosis. However, combined CEP and TRAIL treatment markedly enhanced apoptotic cell death in cancer cells, but not in normal cells. CEP induced downregulation of survivin and cellular-FLICE inhibitory protein (c-FLIP) expression at post-translational levels. Ectopic expression of survivin blocked apoptosis by combined treatment with CEP plus TRAIL, but not in c-FLIP overexpression. Interestingly, CEP induced survivin downregulation through downregulation of deubiquitin protein of STAM-binding protein-like 1 (STAMBPL1). Overexpression of STAMBPL1 markedly recovered CEP-mediated survivin downregulation. Taken together, our study suggests that CEP sensitizes TRAIL-mediated apoptosis through downregulation of survivin expression at the post-translational levels in renal carcinoma cells.</P>

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