Abstract:
BACKGROUND:Uterine leiomyosarcoma is a rare and aggressive gynecologic malignancy originating in the myometrium of the uterine corpus that tends to recur even after complete surgical excision. Current therapeutic agents have only modest effects on uterine leiomyosarcoma. Although antibodies and antibody-drug conjugates have been recognized as useful targeted therapies for other cancers, no study has yet evaluated the effects of this approach on uterine leiomyosarcoma. OBJECTIVE:This study aimed to examine the activity of tumoral CD70 in uterine leiomyosarcoma and assess the antitumor activity of CD70-antibody-drug conjugate treatment in uterine leiomyosarcoma. STUDY DESIGN:Target membrane proteins were screened by profiling and comparing membrane protein expression in 3 uterine leiomyosarcoma cell lines (SK-UT-1, SK-LMS-1, and SKN) and normal uterine myometrium cells using the isobaric tags for relative and absolute quantitation labeling method. Western blotting, fluorescence-activated cell sorting analyses, and immunohistochemistry were used to examine CD70 expression in the membrane proteins in uterine leiomyosarcoma cell lines and clinical samples. We developed an antibody-drug conjugate with a monoclonal antibody of the target membrane protein linked to monomethyl auristatin F and investigated its antitumor effects against uterine leiomyosarcoma (in vitro, in vivo, and in patient-derived xenograft models). RESULTS:CD70 was identified as a specific antigen highly expressed in uterine leiomyosarcoma cell lines. Of the 3 uterine leiomyosarcoma cell lines, CD70 expression was confirmed in SK-LMS-1 cells by western blotting and fluorescence-activated cell sorting analysis. CD70 overexpression was observed in 19 of 21 (90.5%) tumor specimens from women with uterine leiomyosarcoma. To generate CD70-antibody-drug conjugate, anti-CD70 monoclonal antibody was conjugated with a novel derivative of monomethyl auristatin F. CD70-antibody-drug conjugate showed significant antitumor effects on SK-LMS-1 cells (half maximal inhibitory concentration, 0.120 nM) and no antitumor effects on CD70-negative uterine leiomyosarcoma cells. CD70-antibody-drug conjugate significantly inhibited tumor growth in the SK-LMS-1 xenograft mouse model (tumor volume, 129.8 vs 285.5 mm3; relative reduction, 54.5%; P<.001) and patient-derived xenograft mouse model (tumor volume, 128.1 vs 837.7 mm3; relative reduction, 84.7%; P<.001). CONCLUSION:Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-antibody-drug conjugate may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.
journal_name
Am J Obstet Gynecoljournal_title
American journal of obstetrics and gynecologyauthors
Nakae R,Matsuzaki S,Serada S,Matsuo K,Shiomi M,Sato K,Nagase Y,Matsuzaki S,Nakagawa S,Hiramatsu K,Okazawa A,Kimura T,Egawa-Takata T,Kobayashi E,Ueda Y,Yoshino K,Naka T,Kimura Tdoi
10.1016/j.ajog.2020.08.028subject
Has Abstractpub_date
2020-08-19 00:00:00eissn
0002-9378issn
1097-6868pii
S0002-9378(20)30856-5pub_type
杂志文章abstract:OBJECTIVE:This study was undertaken to determine (1) the methadone serum trough level adequate to prevent withdrawal symptoms in heroin-addicted pregnant women and (2) whether the methadone serum trough level in symptomatic women with withdrawal symptoms differs from that of asymptomatic women. STUDY DESIGN:Pregnant w...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2002.127132
更新日期:2002-11-01 00:00:00
abstract::The effects of intravenous cocaine on heart rate and blood pressure were studied in pregnant and oophorectomized nonpregnant ewes. In response to intravenous cocaine doses of 1.0 and 2.0 mg/kg, both pregnant and nonpregnant ewes demonstrated dose-dependent increases in systolic, diastolic, mean arterial, and pulse pre...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)90424-6
更新日期:1990-02-01 00:00:00
abstract:OBJECTIVE:We investigated self-reported occupational exposure to antineoplastic drugs, anesthetic gases, antiviral drugs, sterilizing agents (disinfectants), and X-rays and the risk of spontaneous abortion in US nurses. STUDY DESIGN:Pregnancy outcome and occupational exposures were collected retrospectively from 8461 ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2011.12.030
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVES:The study was undertaken to compare Hispanic birth outcomes with those of white and African American women in North Carolina and to examine variables associated with adverse birth outcomes among Hispanic women. STUDY DESIGN:Retrospective comparison of birth outcomes by ethnicity/race, from linked birth/infa...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2003.348
更新日期:2003-05-01 00:00:00
abstract::One of the largest nationally reported cases of carcinoma in situ in the teenage population of the United States is based on 1 year's computerized data from Cancer Screening Services. In 1981, 796,337 women were screened with an average age of 25.9. Of these, 18,589 (2.33%) had abnormal cytology. In 194,069 (24.3%) of...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(84)90555-6
更新日期:1984-03-15 00:00:00
abstract::Perimenopause represents a transition period lasting about 5 years before the permanent cessation of spontaneous menses. During this transition, the emphasis of clinical care changes. Although women still need effective contraception during perimenopause, issues including loss of bone mineral density, menstrual cycle ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,评审
doi:10.1067/mob.2001.116525
更新日期:2001-08-01 00:00:00
abstract:OBJECTIVE:Oxidative stress plays a causative role in diabetic embryopathy. We tested whether mitigating oxidative stress, using superoxide dismutase 1 (SOD1) transgenic (Tg) mice, would block hyperglycemia-induced specific protein kinase C (PKC) isoform activation and its downstream cascade. STUDY DESIGN:Day 8.5 embry...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2011.02.071
更新日期:2011-07-01 00:00:00
abstract::Predictive tests for the identification of women at high risk of the development of preeclampsia are critical to allow the most appropriate preventive measures. Preeclampsia is a vasospastic condition of pregnancy characterized by early and enhanced vascular reactivity to endogenous pressor agents. Exercise tolerance ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)91077-p
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:Our purpose was to improve the accuracy of prenatal prognostication by directly correlating obstetric ultrasonographic measurements with neonatal survival. STUDY DESIGN:We studied 130 singleton live-born infants with birth weights between 500 and 1000 gm and who underwent complete ultrasonographic examinatio...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(93)90606-j
更新日期:1993-09-01 00:00:00
abstract:OBJECTIVE:Our purpose was to determine whether postterm patients with oligohydramnios differ in their fetal and umbilical blood flow distribution from those with a normal volume of amniotic fluid. STUDY DESIGN:Pulsed-wave Doppler imaging was used prospectively to determine the resistance index in the fetal middle cere...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(95)90276-7
更新日期:1995-08-01 00:00:00
abstract:OBJECTIVES:Our objectives were to determine in pregnancies complicated by diabetic nephropathy (1) if impedance to flow in the uterine and umbilical arteries is normal and (2) if these fetuses are hypoxemic and acidemic and if they have decreased fetal heart rate variation and Doppler blood flow redistribution. STUDY ...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(11)91704-9
更新日期:1992-11-01 00:00:00
abstract::Epidural analgesia in labor is generally accepted as safe and effective and therefore has become increasingly popular. However, little is known regarding the effect of epidural analgesia on the incidence of cesarean section for dystocia in nulliparous women. During the first 6 months of 1987 we studied 711 consecutive...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(89)90377-3
更新日期:1989-09-01 00:00:00
abstract:OBJECTIVE:Our purpose was to review the long-term (5 to 10 years) clinical and urodynamic outcome in patients with stress urinary incontinence after Burch colposuspension. STUDY DESIGN:A follow-up of 87 women with stress urinary incontinence who had a Burch colposuspension between 1979 and 1985 at the Department of Ob...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(94)90077-9
更新日期:1994-09-01 00:00:00
abstract:OBJECTIVE:Defecatory symptoms, such as a sense of incomplete emptying and straining with bowel movements, are paradoxically present in women with fecal incontinence. Treatments for fecal incontinence, such as loperamide and biofeedback, can worsen or improve defecatory symptoms, respectively. The primary aim of this st...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.ajog.2019.11.1256
更新日期:2020-06-01 00:00:00
abstract::Prospective pregnancy evaluation through the combined use of a radioimmunoassay (RIA) for the beta-subunit of human chorionic gonadotropin (beta-hCG) and ultrasound during the first 42 days of gestation after ovulation was performed on a population asymptomatic for first-trimester spontaneous abortion. One hundred for...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(83)90977-8
更新日期:1983-08-15 00:00:00
abstract::Multifetal gestation is associated with increased frequency of maternal complications and higher perinatal morbidity and mortality. The need for contemporary data on the outcome of multifetal gestations is further underscored when selective reduction is considered. The present study details the obstetric management, n...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)90407-x
更新日期:1990-02-01 00:00:00
abstract::Oral contraceptives (OCs) raise the plasma levels of some clotting factors, especially factor VII. Until recently, however, there has been no evidence for a relationship between high levels of clotting factor and the onset of clinically manifest vascular disease. It has not been established, on a preliminary basis, th...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(16)32484-x
更新日期:1982-03-15 00:00:00
abstract::Sacral neuromodulation with an implanted device is used in patients who experience urinary retention and malfunctioning overactive bladder where conservative treatment is not sufficient. The knowledge of its effect on pregnancy is not known. This article presents the case of a 34-year-old pregnant woman with an implan...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2014.04.015
更新日期:2014-07-01 00:00:00
abstract:OBJECTIVE:Although the presence of psammoma bodies in cervical cytologic smears has been associated previously with gynecologic malignancies, the clinical significance of this finding in asymptomatic women who undergo routine cervical cytologic screening has not been well defined. STUDY DESIGN:For this retrospective c...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1067/mob.2003.392
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVE:We wanted to test whether the recently described method of using the transferrin receptor system for fluorescence-activated cell-sorter enrichment of nucleated red blood cells can be used for prenatal diagnosis from maternal blood. STUDY DESIGN:Instead of the laborious, expensive fluorescence-activated cell-...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(92)91603-8
更新日期:1992-05-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to determine whether introduction of laparoscopically assisted vaginal hysterectomy decreases the percentage of women requiring laparotomy for hysterectomy. STUDY DESIGN:A retrospective review of women undergoing hysterectomies from 1990 through 1992 was performed. Type of hys...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(94)70032-x
更新日期:1994-08-01 00:00:00
abstract::In order to examine the relationship between circadian rhythms in different steroids, cortisol (F), estrone E1), estradiol (E2), and estriol (E3) were measured by radioimmunoassay in maternal venous plasma taken at 30 to 60-minute intervals over 24 hours from 11 healthy women at 34 to 35 weeks' gestation. Maternal F w...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(79)90393-4
更新日期:1979-11-15 00:00:00
abstract:OBJECTIVE:The efficacy, safety, and antibiotic-related charges for once-daily gentamicin with twice-daily clindamycin were compared with those of thrice-daily dosing of these antibiotics. STUDY DESIGN:Patients with puerperal endometritis or with chorioamnionitis in labor assessed to be at risk for endometritis were ra...
journal_title:American journal of obstetrics and gynecology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/s0002-9378(97)70269-2
更新日期:1997-10-01 00:00:00
abstract::Ovulation induction with pulsatile gonadotropin-releasing hormone achieves high ovulatory and pregnancy rates in hypogonadotropic hypogonadism while limiting the occurrence of ovarian hyperstimulation and multiple pregnancy. However, this form of therapy is apparently less effective in polycystic ovary syndrome. The a...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(90)91438-i
更新日期:1990-11-01 00:00:00
abstract::In 39 pregnant and six nonpregnant dogs the abdominal aorta was exposed extraperitoneally through a left paralumbar incision, and a vascular occluder and a flow transducer were placed around it. The tubing of the occluder and the wiring of the flow transducer were slipped under the skin and advanced to the back of the...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(81)90512-3
更新日期:1981-03-01 00:00:00
abstract::Preterm birth remains a major cause of perinatal morbidity and mortality. A short cervix is strongly associated with spontaneous preterm birth. Professional organizations support cervical length screening for singleton gestations with a prior spontaneous preterm birth and second-trimester cervical length measurements ...
journal_title:American journal of obstetrics and gynecology
pub_type: 社论
doi:10.1016/j.ajog.2016.07.019
更新日期:2016-12-01 00:00:00
abstract::Intrauterine 17 beta-estradiol pellets can induce an up-regulation of guinea pig myometrial beta-adrenergic receptor density and l-isoproterenol-dependent adenylate cyclase activity. Does 17 beta-estradiol influence the ability of beta-adrenergic receptors to form a "high affinity" state with l-isoproterenol, which is...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/0002-9378(89)90939-3
更新日期:1989-12-01 00:00:00
abstract:OBJECTIVE:In a seroepidemiologic study the effects of pregnancy and other factors on humoral response to human papillomavirus type 16 infection were examined. STUDY DESIGN:Multiple serum samples were taken at 3-month intervals for 15 months from 77 pregnant and 85 nonpregnant women. Serologic response to human papillo...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(98)80026-4
更新日期:1998-02-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to assess the incidence, case fatality rates, and risk factors of peripartum hysterectomy and arterial embolization for major obstetric hemorrhage. STUDY DESIGN:This was a 2-year prospective nationwide population-based cohort study. All pregnant women in the Netherlands during t...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/j.ajog.2009.09.003
更新日期:2010-02-01 00:00:00
abstract:OBJECTIVE:Our purpose was to evaluate the efficacy and consequences of sacrospinous ligament suspension and pelvic reconstruction. STUDY DESIGN:Patients who underwent sacrospinous ligament suspension between 1978 and 1991 were evaluated from follow-up visits, telephone interviews, questionnaires, and chart reviews. Be...
journal_title:American journal of obstetrics and gynecology
pub_type: 杂志文章
doi:10.1016/s0002-9378(96)70085-6
更新日期:1996-12-01 00:00:00