A selective cyclin-dependent kinase 4, 6 dual inhibitor, Ribociclib (LEE011) inhibits cell proliferation and induces apoptosis in aggressive thyroid cancer

Lee, Hyun Joo,Lee, Woo Kyung,Kang, Chan Woo,Ku, Cheol Ryong,Cho, Yoon Hee,Lee, Eun Jig Elsevier 2018 Cancer letters Vol.417 No.-

<P><B>Abstract</B></P> <P>The RB-E2F1 pathway is an important mechanism of cell-cycle control, and deregulation of this pathway is one of the key factors contributing to tumorigenesis. Cyclin-dependent kinases (CDKs) and Cyclin D have been known to increase in aggressive thyroid cancer. However, there has been no study to investigate effects of a selective CDK 4/6 inhibitor, Ribociclib (LEE011), in thyroid cancer. Performing Western blotting, we found that RB phosphorylation and the expression of Cyclin D are significantly higher in papillary thyroid cancer (PTC) cell lines as well as anaplastic thyroid cancer (ATC) cell lines, compared with normal thyroid cell line and follicular thyroid cancer cell line. LEE011 dose-dependently inhibited RB phosphorylation and also decreased the expressions of its target genes such as <I>FOXM1, Cyclin A1,</I> and <I>Myc</I> in ATC. Furthermore, LEE011 induced cell cycle arrest in G0-G1 phase and cell apoptosis, and inhibited cell proliferation in ATC. Consistently, oral administration of LEE011 to ATC xenograft models strongly inhibited tumor growth with decreased expressions of pRB, pAKT and Ki-67, and also significantly increased tumor cell apoptosis. Taken together, our data support the rationale for clinical development of the CDK4/6 inhibitor as a therapy for patients with aggressive thyroid cancer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> pRB and Cyclin D were expressed high in aggressive thyroid cancer. </LI> <LI> LEE011 suppressed pRB and also decreased the expressions of its target genes in ATC. </LI> <LI> LEE011 induced cell cycle G1 arrest and apoptosis, and inhibited cell proliferation. </LI> <LI> LEE011 inhibited in vivo tumor growth with decreased expressions of pRB and Ki-67. </LI> <LI> We could explain the anticancer effects with the RB-E2F pathway. </LI> </UL> </P>

심혈관계 질환으로 관상질환 집중치료실에 입원한 환자들의 혜후 측정을 위한 APACHEⅢ점수 체계의 임상적 유용성

이공섭,이창선,최현주,홍종서,강지향,김도형,이민영,오인균,김병엽,김상억,김학찬,한승혜,이재용,지영우,안경주 대한순환기학회 2000 Korean Circulation Journal Vol.30 No.8

비혈연간 동종골수이식에 의해 치료된 중증 재생불량성빈혈 1예

김현중,이홍기,이방훈,이창근,이종태,정현식,김원석,윤성수,강원기,박근칠,김대식,고영혜,박찬형 대한조혈모세포이식학회 1997 대한조혈모세포이식학회지 Vol.2 No.1

비혈연간 동종골수이식은 혈연간 동종골수이식이 불가능한 환자에서 기존의 면역역제요법으로 효과가 없었던 경우나 재발한 경우에 적응증이 될수 있다. 이식 거부와 이식편대숙주병의 발생이 골수 이식의 성공률을 감소시키므로, 보다 강력한 conditioning regimen의 사용과 T cell이 제거된 골수를 사용하는 것이 필요하다. 기존의 high dose corticosteroid나 cyclosporine에 대하여 불응성인 이식편대숙주병의 치료를 위해서 ATG와 Mycophenolate mofetil (Cellcept®) 의 사용이나 Tacrolimus, Methotrexate와 같은 다른 면역억제제치료를 고려해 볼 수 있다. It is known that allogenic bone marrow transplantation is the most effective treatment for aplastic anemia. However, this treatment is only applicable to a minority of patients because the proportion of patients who have HLA-matched siblings about 25% to 30% of all the aplastic anemia patients. In the case of the absence of HLA-matched donor, unrelated allogenic bone marrow transplantation is considered. However, (because of severe acute and chronic GVHD and graft failure) the success rate of this approach is only 20~30%. Recently, it was reported that increased immunosuppressive condition combined with T cell depletion of the marrow graft would result in greater success. There was no case of successfully treated aplastic anemia patient by unrelated allogenic bone marrow transplantation in Korea. Here, we report a case of severe aplastic anemia successfully treated with unrelated allogenic bone marrow transplantation.

부신피질 자극호르몬 단독결핍 1례

박경식,이승현,최석영,박태규,이동화,이찬우,정성복,이인규 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.3

부신피질 자극호르몬 단독결핍은 국내에서 7례만이 보고된 희귀 질환이며 병인 및 경과 등 아직 불분명한 측면이 많다. 이는 질환지체의 희귀성도 있지만 치료후 자연경과에 대한 장기적인 추적검사가 이루어진 경우가 드물기 때문이기도 하다. 저자들은 비특이적인 전신증상을 주소로 내원한 폐경기후의 56세 여자 환자에서 자가면역질환의 증거없이 고프로릭틴혈증을 보인 부신피질 자극호르몬 단독결핍 1례를 경험하고 1년간의 부신피질호르몬 대치요법후 추적검사를 실시하였기에 문헌 고찰과 함께 보고하는 바이다. Isolated ACTH deficiency is a rare disorder which shows secondary adrenal insufficiency with normal states of other pituitary hormones. A 56-year-old postmenopausal woman complaining general weakness and intermittent mental confusion presented negligible serum cortisol and ACTH level with hyperprolactinemia and mild hyponatremia. Rapid ACTH stimulation test did not show significant increase of serum cortisol level. Combined pituitary stimulation test showed negligible response of cortisol and ACTH, and slightly decreased response of prolactin and gonadotropin. But the responses of TSH and GH were normal. There was no evidence of organic pituitary of hypothalamic lesion in brain MRI and antithyroid autoantibody was not detected in serum. After receiving 12 months of glucocorticoid replacement therapy, she skipped the medicine for 3 weeks and we performed follow-up endocrinologic tests. Serum ACTH and cortisol level was also negligible and prolonged ACTH simulation test showed normal response of serum cortisol. CRF stimulation test showed no response of serum ACTH. Basal prolactin level was decreased to near normal and combined pituitary stimulation test showed normal response of prolactin with slightly blunted response of TSH and GH. We concluded that the case was nonautoimmune origined isolated ACTH deficiency which was accompanied by hyperprolactinemia and resultant deficiency of gonadotropin, so we report this case with review of literatures.

머리염색이 인체에 미치는 영향

윤형식,황성호,이현륭,김수호,박연석,권낙현,정호진,김동훈,노현주,홍성호,박병찬,이관,정해관 東國大學校醫學硏究所 2002 東國醫學 Vol.9 No.1

일상생활에서 모발염색은 흔히 접할 수 있는 미용의 한 종류로 특히 젊은층을 중심으로 폭발적으로 유행하고 있다. 염색을 위항 사용하는 약제는 표백제와 발색제 등 각종 화학약품이 사용되고 있으나 이로 인한 건강장해에 대한 연구는 그리 많지 않다. 저자들은 염색이 인체의 모발건강에 미치는 영향을 파악하기 위하여 염색과 관련된 주관적 증상과 모발의 변화에 대한 실험적 연구를 시행하였다. 동국대학교 경주 캠퍼스 재학생 80명을 대상으로 설문조사를 시행하여 염색 유 ·무 및 염색 후에 경험한 증상에 대해 설문 조사하였고, 의과대학 재학생 46명을 대상으로 피부 반응 테스트를 실시하였다. 또한 염색 전후의 모발 탄성도를 측정하였고 모발의 상태를 파악하기 위해 전자 현미경검사를 실시하였다. 설문조사 결과 염색 전에 비하여 염색 후 안구혼탁, 안구건조, 시력저하, 발진 및 접촉성 피부염, 모발손상, 모근손상 등의 증상을 더 많이 경험한다고 호소하였다(p<0.05). 모발손상과 모근손상은 헤어드라이어 사용 빈도에 따라 증가하는 것으로 조사되었다(p<0.05). 피부반응검사에서 가려움증이 가장 많은 증상이었으며 이는 여성보다는 남성에서 높은 것으로 조사되었다. 염색 전후의 모발장력은 염색 전 134.5±10.37g, 염색 128.0±30.69g, 염색 이틀 후 112.5±19.69g으로 나타났다. 염색 전후의 모발의 전자현미경 케라틴 층이 현저히 감소하고 모발이 가늘어지는 차이를 보였다. 염색은 모발손상, 모발 케라틴 손상 및 모근 손상, 발진 및 접촉성 피부반응, 안구혼탁, 안구건조, 시력 저하를 유발한다. 따라서 염색약으로 인한 손상에 대한 주의와 예방이 필요하다고 생각한다. 예방대책으로 염색 전 피부테스트를 통한 적합성 여부를 판단하는 것이 필요하며 가급적 염색을 피하는 것이 좋을 것이다. 염색약에 발암물질이 포함되어있다는 보고도 있어 염색 제조사의 철저한 실험과 염색 물질의 선별이 염색으로 인한 부작용을 최소화하는데 중요한 역할을 할 것이다. Hair coloring has became one of the most popular cosmetic activities to younger generations during last decade. However, there are few studies on the health effect of widespread use of chemical dyes. This study was conducted to study the effects of hair coloring dye on hair and other systems. We conducted a questionnaire survey of 80 persons in Kyongju campus, Dongguk University. We have done open patch skin test on 46 medical students. We also conducted scanning electron microscopy to examine the hair strength and structure before and after hair coloring process. Injury of hair and hair bulb, contact dermatitis, turbid eyes, xerophthalmia, and poor visual acuity were the main symptoms complained after hair coloring (p<0.05). Injury of hair and hair bulb were increased by frequency of hair-dryer use(p<0.05). In open patch test, pruritus was complanined by more than half of the subjects. Mean strength of hairs before and after hair coloring was as follows; 134.5 (SD 10.37)g before hair coloring, 128.0 (SD 30.69)g immediately after hair coloring, and 112.5 (SD 19.69)g after two days. The scanning electron microscopic findings of hair surface before and after hair coloring showed decreased keratin layer and thinning of the hair. Hair coloring induces injury to hair, its keratin layer, and hair bulb as well as contact dermatitis, turbid eyes, xerophthalmia, and poor visual acuity. Therefore, we think that precaution is needed in use of hair coloring dye. To prevent complications induced by hair coloring dye, it is necessary, especially to those with allergy or skin disorders, to perform skin test before action and avoid hair coloring whenever possible. Longterm health effects of hairdye should be studied and manufacturing companies should try to minimize complications induced by hair coloring dye.

ATHB12, an ABA-lnducible Homeodomain-Leucine Zipper (HD-Zip) Protein of Arabidopsis, Negatively Regulates the Growth of the Inflorescence Stem by Decreasing the Expression of a Gibberellin 20-Oxidase Gene

Ora Son,허윤선,김윤경,이현정,김성한,김미란,남경희,이명석,김부용,박종범,박정안,이석찬,Atsushi Hanada,Shinjiro Yamaguchi,이인정,김승기,윤대진,Eva So¨derman,천충일 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

ATHB12, an ABA-lnducible Homeodomain-Leucine Zipper (HD-Zip) Protein of Arabidopsis, Negatively Regulates the Growth of the Inflorescence Stem by Decreasing the Expression of a Gibberellin 20-Oxidase Gene

Ora Son,허윤선,김윤경,이현정,김성한,김미란,남경희,이명석,김부용,박종범,박정안,이석찬,Atsushi Hanada,Shinjiro Yamaguchi,이인정,김승기,윤대진,Eva So¨derman,천충일 Sookmyung Women's University Research Institute of 2010 여성과 건강 Vol.6 No.1

유방암의 위와 대장전이

유현아,김은영,서민지,정은,조민정,오현진,장지혜,박지찬,이정의,박석영 이화여자대학교 의과학연구소 2014 EMJ (Ewha medical journal) Vol.37 No.2

Gastric metastasis from breast cancer is rare and only six cases have been reported in Korea. Colon metastasis is more rare than gastric metastasis. We report a 63-year-old woman with gastric and colon metastases of invasive lobular carcinoma of breast. She was diagnosed as right breast cancer, received right modified radical mastectomy 10 years ago and has been treated with chemotherapy and hormone therapy. Investigating for melena and a small caliber of stool, we found gastric and colon metastases. The diagnosis of metastatic breast cancer was made through gross pathologic and immunohistochemistry staining. We report a case with gastric and colon metastases from breast cancer and a review of the associated six case reports in Korea.

대구지역 가로수잎의 중금속

이찬형,윤현숙,박연준,권종대,노기철,장성환 한국환경과학회 2002 한국환경과학회지 Vol.11 No.12

This study was conducted to determine the contents of heavy metals in leaves of roadside trees according to different growth stages in Daegu city. The orders of heavy metal contents in leaves of roadside tree and soil were Fe〉Mn〉Zn〉Pb〉Cu〉Cr〉Cd and Fe〉Mn〉Zn〉Cu〉Pb〉Cr〉Cd, respectively. The contents of heavy metals in leaves of roadside trees and soil showed an increasing tendency as the levels of traffic volume increased. The contents of heavy metals in leaves on October were higher than those on May.

기존 트랙터 로터리날의 운동분석

이현동,김기대,김찬수,김성환 충남대학교 농업과학연구소 2004 농업과학연구 Vol.31 No.1

In this study, motion characteristics and power requirement of rotary tilling according to shape of conventional rotary blade were measured This study was performed to establish factors which needed to develop energy saving rotary blade. Starting point of edged curve of imported rotary blade was faster than that of domestic rotary blade after measuring and analyzing edged curve of rotary blade. So domestic rotary blade tills much soil than imported rotary blade. In analyzing motion of rotary blade, Rotary blade of A, D type was begun to contact at part 3. Analyzing back surface of rotary blade which contact to soil at critical λ results in contacting at e-f part. In measuring power requirement of rotary blade, specific torque and specific work of rotary blade are 160~170 kgf·m/m², 3,700 kgf·m/m³. It shows power requirement of rotary blade according to shape of rotary blade are very different.