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1.
BMC Pregnancy Childbirth ; 24(1): 277, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622521

ABSTRACT

BACKGROUND: Transverse uterine fundal incision (TUFI) is a beneficial procedure for mothers and babies at risk due to placenta previa-accreta, and has been implemented worldwide. However, the risk of uterine rupture during a subsequent pregnancy remains unclear. We therefore evaluated the TUFI wound scar to determine the approval criteria for pregnancy after this surgery. METHODS: Between April 2012 and August 2022, we performed TUFI on 150 women. Among 132 of the 150 women whose uteruses were preserved after TUFI, 84 women wished to conceive again. The wound healing status, scar thickness, and resumption of blood flow were evaluated in these women by magnetic resonance imaging (MRI) and sonohysterogram at 12 months postoperatively. Furthermore, TUFI scars were directly observed during the Cesarean sections in women who subsequently conceived. RESULTS: Twelve women were lost to follow-up and one conceived before the evaluation, therefore 71 cases were analyzed. MRI scans revealed that the "scar thickness", the thinnest part of the scar compared with the normal surrounding area, was ≥ 50% in all cases. The TUFI scars were enhanced in dynamic contrast-enhanced MRI except for four women. However, the scar thickness in these four patients was greater than 80%. Twenty-three of the 71 women conceived after TUFI and delivered live babies without notable problems until August 2022. Their MRI scans before pregnancy revealed scar thicknesses of 50-69% in two cases and ≥ 70% in the remaining 21 cases. And resumption of blood flow was confirmed in all patients except two cases whose scar thickness ≥ 90%. No evidence of scar healing failure was detected at subsequent Cesarean sections, but partial thinning was found in two patients whose scar thicknesses were 50-69%. In one woman who conceived seven months after TUFI and before the evaluation, uterine rupture occurred at 26 weeks of gestation. CONCLUSIONS: Certain criteria, including an appropriate suture method, delayed conception for at least 12 months, evaluation of the TUFI scar at 12 months postoperatively, and cautious postoperative management, must all be met in order to approve a post-TUFI pregnancy. Possible scar condition criteria for permitting a subsequent pregnancy could include the scar thickness being ≥ 70% of the surrounding area on MRI scans, at least partially resumed blood flow, and no abnormalities on the sonohysterogram. TRIAL REGISTRATION: Retrospectively registered.


Subject(s)
Placenta Accreta , Surgical Wound , Uterine Rupture , Pregnancy , Female , Humans , Cicatrix/diagnostic imaging , Cicatrix/etiology , Retrospective Studies , Uterus/diagnostic imaging , Uterus/surgery , Cesarean Section/adverse effects , Cesarean Section/methods
2.
J Obstet Gynaecol Res ; 50(2): 190-195, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37986672

ABSTRACT

AIM: We have established a novel extraperitoneal cesarean section technique by supravesical approach. An advantage of this technique over the conventional paravesical approach is that the lower uterine segment is broadly exposed and that all operative procedures can be performed under direct vision. We present the details of this novel technique. METHODS: The bladder and the peritoneum are exposed by removing the transversalis and extraperitoneal fasciae. Subsequently, a triangular area between the median umbilical ligament, the peritoneum, and the bladder is exposed. The median umbilical ligament is dissected at this site. Bladder dissection from the peritoneum is also initiated from this area and proceeds toward the lower uterine segment. RESULTS: Operative times for pelvic fascia dissection and bladder removal from the peritoneal surface are currently around 15-25 min. During the process of development of this technique, there have been no bladder injuries in 501 patients that caused urine leakage. DISCUSSION: The supravesical approach has been considered difficult due to the strong adhesion between the perivesical fascia and the peritoneum at the bladder fundus. In this paper, we show how to safely remove the bladder fundus from the peritoneum. The bladder can then be easily lowered down toward the lower uterine segment. Although this technique allows the lower uterine segment to be broadly exposed and all operative procedures can be performed under direct vision, a disadvantage is the comparatively long time currently required to perform it. CONCLUSIONS: This technique could be a valuable option for extraperitoneal cesarean section, but disadvantages must also be considered.


Subject(s)
Cesarean Section , Urinary Bladder Diseases , Humans , Female , Pregnancy , Cesarean Section/methods , Urinary Bladder/surgery , Peritoneum/surgery , Uterus
4.
J Obstet Gynaecol Res ; 49(5): 1424-1428, 2023 May.
Article in English | MEDLINE | ID: mdl-36859653

ABSTRACT

AIM: Due to the U.S. Food and Drug Administration's order to cease the use of surgical mesh for transvaginal repair, an improvement of the native tissue repair (NTR) of pelvic organ prolapse (POP) could become important as one of the first-line operative methods. This study details the surgical technique of an NTR method we developed, with report of our 5 years of experience. METHODS: Operative technique: A new fibromuscular layer (FL) was constructed using a thick and elastic tissue continuous with and obscured behind the original FL of the vaginal wall. PATIENTS: Between April 2017 and March 2020, we performed our novel repair technique on 87 women with POP of either quantification stage III or IV. RESULTS: We followed up 80 of the 87 women for over 24 months up to 60 months (follow-up rate: 91.2%). POP recurred (defined as stage II or higher) in four patients (5.0%). Operation time was 49-70 min. The bleeding volume was 70-250 g. There were no intra- or postoperative complications that required further treatment. CONCLUSIONS: This procedure could potentially become one of the first-line operative methods for repairing POP.


Subject(s)
Elastic Tissue , Pelvic Organ Prolapse , Pregnancy , Humans , Female , Gynecologic Surgical Procedures/methods , Vagina/surgery , Pelvic Organ Prolapse/surgery , Colpotomy , Surgical Mesh , Treatment Outcome
5.
J Obstet Gynaecol Res ; 48(6): 1484-1488, 2022 Jun.
Article in English | MEDLINE | ID: mdl-35315176

ABSTRACT

Toxic shock syndrome can be caused by methicillin-resistant Staphylococcus aureus (MRSA). During puerperium this condition is rare, and proper treatment during this period has not been clarified. Two patients developed toxic shock syndrome caused by MRSA soon after cesarean section. Despite the administration of antibiotics, both developed severe conditions and one of them required hysterectomy. The dosage was adjusted in the same way as nonpregnancy, but the actual drug concentration was significantly different from expectation. When there is severe infection during the early postpartum period, maintaining drug concentration at optimal levels may be difficult, and this could be life-threatening. Better understanding of the pharmacokinetics and establishment of a method to determine the optimal drug dose during puerperium is required.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Shock, Septic , Staphylococcal Infections , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cesarean Section/adverse effects , Female , Humans , Postpartum Period , Pregnancy , Shock, Septic/drug therapy , Shock, Septic/etiology , Staphylococcal Infections/complications , Staphylococcal Infections/drug therapy
6.
J Obstet Gynaecol Res ; 47(3): 900-903, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33331020

ABSTRACT

AIM: Transverse uterine fundal incision (TUFI) was developed to avoid catastrophic hemorrhage associated with cesarean section of the placenta previa-accreta. Abdominal incisions extend as far as the upper abdomen in patients in the third trimester of pregnancy and require general anesthesia. Instead, we tried to aspirate amniotic fluid (AF) to reduce the uterine size. METHODS: TUFI was performed in 19 of our patients in the third trimester in whom placenta previa accreta could not be ruled out between June 2012 and August 2016. After the lower abdominal vertical incision, we attempted to exteriorize the uterine fundus. If this was impossible, we inserted an 18-gauge spinal needle into the amniotic space. We aspirated AF until the uterine fundus could be exteriorized. RESULTS: We exteriorized the uterine fundus without extending the incision to the upper abdomen by aspirating 250-670 mL of AF in 12 patients who were between the 33rd and 37th week of pregnancy, and TUFI was performed under spinal anesthesia. AF aspiration was not required in four patients who were in the 30th or 31st week of pregnancy and in two patients with oligohydramnios in the 35th week of pregnancy. In one case, the trial was canceled due to hemorrhagic AF aspiration. No serious complications were observed in mothers or neonates. CONCLUSION: TUFI could be made by abdominal incision to the left of the umbilicus under spinal anesthesia without anesthesia by reducing the uterine size through AF aspiration, even for patients in the third trimester of pregnancy.


Subject(s)
Placenta Accreta , Placenta Previa , Amniotic Fluid , Cesarean Section , Female , Humans , Infant, Newborn , Pregnancy , Uterus/surgery
7.
J Obstet Gynaecol Res ; 46(8): 1456-1459, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32363698

ABSTRACT

Uterine ruptures typically occur suddenly, have obvious symptoms, and may require urgent treatment. We experienced a case of complete rupture of an unscarred uterus that was undetected for 9 days. We report the clinical course and possible factors that led to it. Nine days after delivery, complete rupture of the posterior uterine wall was diagnosed by magnetic resonance imaging. The colon and ovaries were tightly adhered to the posterior uterine body. When this adhesive lesion was detached, 7 cm horizontal defects of the muscular layer were revealed. The ruptured wound was repaired. Magnetic resonance imaging 1 year postoperatively showed no thinning of the repaired lesion and suggested successful reperfusion. Mild clinical course despite complete uterine rupture was presumably because of adhesion of the ovaries and intestines to the rupture site.


Subject(s)
Uterine Rupture , Female , Humans , Pregnancy , Uterine Rupture/etiology , Uterine Rupture/surgery , Uterus/diagnostic imaging , Uterus/surgery
8.
Int J Gynecol Pathol ; 39(1): 79-83, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31815893

ABSTRACT

Primary ovarian lymphomas are rare, but can potentially evoke diagnostic problems. We present a case of ovarian lymphoma, in which an ambiguous intraoperative pathologic report led to overtreatment (unnecessary surgery). A 73-yr-old woman with fatigue and low-grade fever was diagnosed as having a left ovarian tumor by imaging modalities. Exploratory laparotomy was carried out to confirm the diagnosis. The frozen tissue sections of the ovarian tumor showed condensed proliferation of atypical round cells accompanied with a few small lymphocytes. The pathologists could not determine whether this tumor was a lymphoma or another malignancy (eg, dysgerminoma). Hence, they reported it to gynecologists who operated as simply a malignant tumor in order to evade misdiagnosis. On the basis of the inconclusive pathologic report, the gynecologists decided to change the planned laparotomy to total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. A postoperative paraffin section-based pathologic diagnosis was diffuse large B-cell lymphoma of the ovary, which basically does not require surgical treatments. Subsequently, chemotherapy for B-cell lymphoma was initiated, and no lymphoma recurrence has been reported to date. A more robust preoperative discussion between the gynecologists and the pathologists might have avoided the overtreatment.


Subject(s)
Intraoperative Care , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/surgery , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/surgery , Aged , Female , Frozen Sections , Humans , Hysterectomy , Lymph Node Excision , Lymphoma, Large B-Cell, Diffuse/pathology , Magnetic Resonance Imaging , Medical Overuse , Neoplasm Recurrence, Local , Ovarian Neoplasms/pathology , Pelvis/surgery , Referral and Consultation , Salpingo-oophorectomy , Treatment Outcome
9.
J Obstet Gynaecol Res ; 46(1): 173-175, 2020 Jan.
Article in English | MEDLINE | ID: mdl-31646709

ABSTRACT

Cesarean section en caul could cause neonatal anemia, but the mechanism remains unknown. We demonstrate an association between neonatal anemia and velamentous insertion of the umbilical cord in cesarean section en caul, and suggest a way to make this procedure safer. We performed cesarean section en caul, but the placenta and the membrane sac were delivered separately. The neonate was severely anemic. The umbilical cord was attached to the membrane and the blood vessel connecting the umbilical cord and placenta was torn. The amniotic membrane covering the placental surface had peeled away. Velamentous insertion of the umbilical cord could be a cause of neonatal anemia associated with cesarean section en caul.


Subject(s)
Anemia, Neonatal/etiology , Cesarean Section/adverse effects , Umbilical Cord/abnormalities , Adult , Amnion/surgery , Cesarean Section/methods , Female , Humans , Infant, Newborn , Pregnancy , Risk Factors , Umbilical Cord/surgery
11.
Reprod Med Biol ; 16(3): 268-275, 2017 07.
Article in English | MEDLINE | ID: mdl-29259477

ABSTRACT

Aim: To determine the effectiveness of a formula diet in weight reduction and the recovery of menstruation in obese patients with ovulatory disorders. Methods: After the enrollment of 39 obese women with ovulatory disorders, they replaced one or two of their three normal meals with a microdiet (MD) (240 kcal/meal) for 24 weeks. Physical, endocrinological, and biochemical tests were conducted before and at 12 and 24 weeks of the study. Of the 39 women enrolled, 26 were not taking clomiphene. They were divided into three groups according to their body weight outcomes and then analyzed for menstruation recovery. Results: A weight reduction of ≥5% was observed in 31 (81.5%) of the 39 women. There were significant decreases in the body weight and Body Mass Index during the study. Menstruation returned in 18 (69%) of the 26 patients without clomiphene treatment, with the recovery being significantly more prevalent in the groups (totally 81.0%) that exhibited a 5%-10% weight reduction and ≥10% weight reduction, compared to the group with a <5% weight reduction. Conclusion: The use of a formula diet effectively reduced the patients' body weight and led to the recovery of menstruation in these obese patients with ovulatory disorders.

12.
J Obstet Gynaecol Res ; 43(4): 779-782, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28109122

ABSTRACT

Uterine perforation, a complication of dilation and curettage, is typically recognized immediately after the procedure by clinical symptoms of peritoneal irritation resulting from intraperitoneal bleeding. Our patient complained of having an uncomfortable feeling, slight dizziness, palpitation in the sitting position and abdominal discomfort but did not show signs of peritoneal irritation 24 h after dilation and curettage. However, she suddenly complained of abdominal pain. Tenderness and rebound tenderness were detected at the lower abdominal wall. Ultrasonography and magnetic resonance imaging suggested uterine perforation. When the abdominal cavity was opened, a hematoma under the broad ligament of the uterus, laceration of the side wall of the uterine cervix and a small amount of bloody ascites and small clots in the abdominal cavity were observed. The uterine cervical wall was sutured. Physicians should postpone discharge and observe the clinical course carefully when a patient complains of inexplicable discomfort after dilation and curettage.


Subject(s)
Abortion, Missed/surgery , Dilatation and Curettage/adverse effects , Uterine Perforation/diagnostic imaging , Adult , Female , Humans , Uterine Perforation/etiology , Uterine Perforation/surgery
13.
J Matern Fetal Neonatal Med ; 30(15): 1809-1812, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27580274

ABSTRACT

OBJECTIVE: Key considerations for managing an umbilical artery aneurysm (UAA) are a timely termination and the prevention of rupture of the UAA during delivery. Herein, we propose a treatment strategy based on our experience of UAA complicated by a fetal cardiac anomaly. CASE: A case of UAA was referred to our hospital at 23 weeks of gestation. The UAA increased its size to 6 cm. The blood reservoir within the UAA was presumed to be equivalent to the circulating blood volume of the fetus. At 28 weeks, small echogenic components suspected to be hematomas appeared in the umbilical vein, and the umbilical interstitial substance became edematous. An improvement in the fetus' condition could not be expected unless the UAA size was smaller. Thus, a cesarean delivery was performed at 30 weeks during which the UAA ruptured. The baby was anemic, disseminated intravascular coagulation (DIC) and later died. CONCLUSION: We present an assessment of a large blood reservoir within an UAA that may indicate the likelihood of high-output cardiac failure of the fetus. Either a classical cesarean section or a transverse uterine fundal incision should be performed when the UAA size is greater than 5 cm to prevent rupture of the UAA.


Subject(s)
Aneurysm/therapy , Fetal Diseases , Heart Defects, Congenital/complications , Umbilical Arteries , Adult , Anemia/complications , Anemia/diagnosis , Aneurysm, Ruptured/therapy , Cesarean Section , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/diagnosis , Encephalocele/complications , Encephalocele/embryology , Fatal Outcome , Female , Fetal Diseases/diagnosis , Fetal Diseases/physiopathology , Gestational Age , Heart Defects, Congenital/diagnosis , Heart Defects, Congenital/embryology , Humans , Infant, Premature, Diseases/diagnosis , Pregnancy , Ultrasonography, Prenatal , Umbilical Veins
14.
Hypertens Pregnancy ; 35(1): 82-90, 2016.
Article in English | MEDLINE | ID: mdl-26909470

ABSTRACT

OBJECTIVE: The aim of this study was to reduce the rate of cesarean section (CS) in severe pregnancy-induced hypertension (PIH) by introducing a set of indicative criteria for CS. METHODS: Labor induction was attempted in Japanese patients (n = 41) with severe PIH after 34 weeks of gestation. Vital signs and symptoms that may increase the risk of serious complications were defined. Following the appearance of one or more signs or symptoms, labor induction was suspended and CS was performed. The impact of using specific indicative criteria was evaluated by comparing the CS rate among patients who delivered before and after the criteria were introduced. RESULTS: Labor induction was attempted in 36 of 41 patients. Among the 36 patients in whom vaginal delivery was started, 12 patients required CS, and the remaining 24 patients succeeded in vaginal delivery. The introduction of specific indicative criteria for CS was associated with a significant reduction in the CS rate, from 95% (43/45) to 41% (17/41). CONCLUSIONS: Unnecessary CS may be avoided by defining the limits of safe labor induction.


Subject(s)
Cesarean Section , Delivery, Obstetric , Hypertension, Pregnancy-Induced/therapy , Labor, Induced , Adult , Female , Gestational Age , Humans , Pregnancy , Pregnancy Trimester, Third , Prospective Studies
16.
J Obstet Gynaecol Res ; 40(3): 826-8, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24738125

ABSTRACT

We present a case of cardiac tamponade that occurred during the course of treatment for severe pre-eclampsia. A 37-year-old woman who underwent cesarean section for severe pre-eclampsia developed cardiac tamponade after delivery. While percutaneous pericardiocentesis temporarily improved her condition, pericardial effusion, dyspnea and tachycardia reappeared 5 days after delivery. A continuous drainage tube placed in the pericardial cavity for 5 days was required to maintain maternal cardiac function. Her clinical course was uneventful after continuous drainage and she was discharged 20 days after delivery. No such causes of symptomatic pericardial effusion were detected in the present case. Physicians should be aware of this complication when dyspnea is accompanied by tachycardia and enlargement of the cardiac silhouette with hypolucent lungs on chest X-ray. Immediate pericardiocentesis is also required to prevent life-threatening cardiac tamponade in such cases.


Subject(s)
Cardiac Tamponade/etiology , Cesarean Section/adverse effects , Postoperative Complications/etiology , Pre-Eclampsia/physiopathology , Adult , Cardiac Tamponade/surgery , Cardiac Tamponade/therapy , Drainage , Female , Humans , Pericardiocentesis , Postoperative Complications/surgery , Postoperative Complications/therapy , Pre-Eclampsia/surgery , Pregnancy , Recurrence , Severity of Illness Index , Treatment Outcome
17.
Endocrinology ; 154(8): 2870-80, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23709086

ABSTRACT

Several clinical studies have shown a correlation of hypersecretion of LH and polycystic ovary syndrome (PCOS), infertility, and miscarriage in women, suggesting that chronically elevated LH impairs fertility. Growth arrest of small antral follicles in PCOS is also assumed to be associated with an abnormal endocrine environment involving increased LH stimulation, a hyperandrogenic milieu, and subsequent dysregulated FSH action in the ovarian follicles. In this study, we examined whether and how LH modulates follicular development and steroid production during preantral-early antral follicle transition by using a rat preantral follicle culture system. LH augments testosterone and estradiol production in preantral follicles via up-regulating mRNA abundance of CYP17A1 and CYP19A1. LH promotes rat preantral follicle growth, and the follicular size reaches that of early antral follicles in vitro, a response attenuated by the specific androgen receptor antagonist and a targeted disruption of androgen receptor gene. Sustained follicle stimulation by LH, but not by androgen, decreases FSH receptor mRNA levels and FSH receptor signaling and inhibits FSH-induced follicular growth. The data suggest that LH promotes preantral-early antral transition via the increased synthesis and growth-promoting action of androgen. However, chronic LH stimulation impairs FSH-dependent antral follicle growth by suppressing granulosa cell FSHR expression via the modulation of intraovarian regulators, including LH-induced thecal factors.


Subject(s)
Follicle Stimulating Hormone/pharmacology , Luteinizing Hormone/pharmacology , Ovarian Follicle/drug effects , Androgens/pharmacology , Animals , Aromatase/genetics , Aromatase/metabolism , Cattle , Dose-Response Relationship, Drug , Estradiol/metabolism , Female , Gene Expression/drug effects , Gene Expression Profiling , Granulosa Cells/drug effects , Granulosa Cells/metabolism , Humans , Oligonucleotide Array Sequence Analysis , Ovarian Follicle/metabolism , Ovarian Follicle/physiology , Rats , Receptors, FSH/genetics , Receptors, FSH/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Steroid 17-alpha-Hydroxylase/genetics , Steroid 17-alpha-Hydroxylase/metabolism , Testosterone/metabolism , Theca Cells/drug effects , Theca Cells/metabolism , Tissue Culture Techniques
18.
Am J Physiol Lung Cell Mol Physiol ; 303(3): L208-14, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22637154

ABSTRACT

Although vernix caseosa is known to be a natural biofilm at birth, human pulmonary surfactant commences to remove the vernix from fetal skin into the amniotic fluid at gestational week 34, i.e., well before delivery. To explain this paradox, we first produced two types of fluorescently labeled liposomes displaying morphology similar to that of pulmonary surfactant and vernix caseosa complexes. We then continuously administered these liposomes into the amniotic fluid space of pregnant rabbits. In addition, we produced pulmonary surfactant and vernix caseosa complexes and administered them into the amniotic fluid space of pregnant rabbits. The intra-amniotic infused fluorescently labeled liposomes were absorbed into the fetal intestinal epithelium. However, the liposomes were not transported to the livers of fetal rabbits. We also revealed that continuous administration of micelles derived from pulmonary surfactants and vernix caseosa protected the small intestine of the rabbit fetus from damage due to surgical intervention. Our results indicate that pulmonary surfactant and vernix caseosa complexes in swallowed amniotic fluid might locally influence fetal intestinal enterocytes. Although the present studies are primarily observational and further studies are needed, our findings elucidate the physiological interactions among pulmonary, dermal-epidermal, and gastrointestinal developmental processes.


Subject(s)
Amnion/drug effects , Enterocytes/metabolism , Intestinal Mucosa/metabolism , Liposomes/administration & dosage , Pulmonary Surfactants/pharmacology , Vernix Caseosa/physiology , Animals , Enterocytes/cytology , Female , Fetus , Fluorescence , Humans , Injections , Intestines/cytology , Palmitic Acid , Porphobilinogen/analogs & derivatives , Pregnancy , Rabbits , Survival Rate
19.
J Obstet Gynaecol Res ; 38(2): 466-70, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22229846

ABSTRACT

Primary leiomyosarcomas arising from the ovarian vein are extremely rare and are associated with high morbidity. A 49-year-old nulliparous woman presented with a left lower abdominal mass. Although extremely rare, the radiological appearance is able to preoperatively identify malignant retroperitoneal masses, such as leiomyosarcomas originating from the ovarian vein; thus, the patient underwent a simple total excision of the mass-adjacent organs, as well as complete resection of the uterus, bilateral adnexae and the left ovarian vein. Adjuvant postoperative combination chemotherapy with gemcitabine and docetaxel was administered. At 22 months, she had no recurrence or metastasis. Delayed diagnosis and high metastatic potentiality are associated with the high morbidity of vascular leiomyosarcomas. The preoperative radiological appearance is useful for early diagnosis, and radical treatment with adjuvant chemotherapy consisting of gemcitabine and docetaxel may improve the poor prognosis of patients with leiomyosarcoma arising from the ovarian vein.


Subject(s)
Leiomyosarcoma/surgery , Ovary/blood supply , Vascular Neoplasms/surgery , Female , Humans , Leiomyosarcoma/diagnosis , Leiomyosarcoma/pathology , Magnetic Resonance Imaging , Middle Aged , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray Computed , Vascular Neoplasms/diagnosis , Vascular Neoplasms/pathology
20.
Int J Oncol ; 39(6): 1359-64, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21935568

ABSTRACT

Cisplatin is one of the most potent antitumor agents for ovarian cancer, but has also been implicated in normal tissue cytotoxicity. We examined the effect of cisplatin alone and in combination with C16Y, a newly-identified anti-angiogenic peptide from the NH2-terminal domains of the γ-chain of laminin-1, on the modulation of Bcl-2/Bax expression and induction of apoptosis in ovarian cancer cells (OVACAR3). C16Y did not elicit cell death of human umbilical vein endothelial cells (HUVECs). Cisplatin exerted a lethal effect with an EC50 of 10 µM in OVACAR3s. In the presence of 25 or 50 µg/ml of C16Y (a range which has no effect against HUVECs), the EC50 for cisplatin in OVACAR3s decreased to 3.5 and 2.0 µM, respectively. Using fluorescence-activated cell sorting (FACS) analysis of DNA stained OVACAR3s and terminal deoxynucleotide tranferase-mediated dUTP nick end-labeling (TUNEL), we found that even at concentrations of 1 and 3 µM cisplatin, C16Y at 10 and 25 µg/ml increased the incidence of apoptosis in OVACAR3s by 3-5-fold. Each drug had some measurable effect on Bax protein expression. Furthermore, Bcl-2 protein expression levels were markedly reduced by C16Y alone and cisplatin alone in a dose-dependent manner. The combination of C16Y and cisplatin resulted in a further dramatic reduction in Bcl-2, underscoring the pronounced synergy produced by cisplatin and C16Y together. On the other hand, C16Y did not activate any other signal transduction pathways that usually culminate in the activation of apoptosis, such as the p53, p21waf1, p73, ERK1/2 or PI3-AKT pathways. These observations suggest that the suppression of the Bcl-2/Bax ratio may play an important role in mediating the synergistic effect of cisplatin and C16Y on the induction of apoptosis in OVACAR3 cells.


Subject(s)
Angiogenesis Inhibitors/pharmacology , Apoptosis/drug effects , Cisplatin/pharmacology , Oligopeptides/pharmacology , Ovarian Neoplasms/metabolism , Peptides/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolism , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/genetics , Cell Proliferation/drug effects , Down-Regulation/drug effects , Drug Synergism , Endothelial Cells/drug effects , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , NIH 3T3 Cells , Ovarian Neoplasms/genetics , Signal Transduction/drug effects
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