ABSTRACT
Objective: To determine whether an antepartum educational leaflet distributed to parents before infant delivery affected the rate of infant car-seat (ICS) use 1 month after delivery, because to the best of our knowledge, only few reports have evaluated systematic attempts to improve the rate of always ICS use by mothers driving infantsMethods: A multicenter questionnaire survey targeting pregnant Japanese women seeking antenatal care at the outpatient clinics of eight hospitals was designed. Women enrolled during the first half of the study period did not receive leaflets describing ICS safety guidelines (control group). Women enrolled during the latter half of the study period received the leaflet between gestational week 35 and 37 (intervention group). All women were requested to anonymously respond to the questionnaires within 1 month postpartum. The rates of ICS use, position, and direction after delivery were compared between both groups.Results: Of the 3534 women who responded to the questionnaire survey (response rate, 81.9%), 1772 women (50.1%) were assigned to the intervention group and 1762 (49.9%) women to the control group. The rates of ICS attachments (86.8% vs. 82.4% in the intervention and control groups, respectively, p = 0.0003), always ICS use (80.5% vs. 76.2%, respectively, p = 0.0019), ICS placement on the rear seat (78.6% vs. 74.1%, respectively, p = 0.0020), and ICS placement in a rear-facing position (62.2% vs. 56.7%, respectively, p = 0.0008) were significantly higher in the intervention group than those in the control group. The motor vehicle accident (MVA) rates within 1 month postpartum were similar between the intervention and control groups (0.51% vs. 0.57%, respectively, p = 0.8229).Conclusions: Antepartum minimal intervention via the distribution of an educational leaflet recommending ICS safety guidelines was associated with increased rates of ICS attachments, always ICS use, and ICS placement on the rear seat and in rear-facing positions; however, it did not contribute to reduced MVA rates after delivery.
Subject(s)
Child Restraint Systems/statistics & numerical data , Pregnant Women/education , Prenatal Care , Accidents, Traffic/statistics & numerical data , Female , Humans , Infant , Japan , Pamphlets , Pregnancy , Prospective Studies , Surveys and QuestionnairesABSTRACT
OBJECTIVE: To determine whether an educational leaflet had any effect on seat belt use, seat preference and motor vehicle accidents rate during pregnancy in Japan. DESIGN: Prospective, non-randomised control trial with a questionnaire survey. SETTING: Eight obstetric hospitals in Sapporo, Japan. PARTICIPANTS: 2216 pregnant women, of whom 1105 received the leaflet (intervention group) and 1111 did not (control group). INTERVENTIONS: Distribution of an educational leaflet on seat belt use to women in the intervention group. PRIMARY OUTCOME MEASURES: The effect of an educational leaflet on seat belt use, each pregnant woman's seat preference and the women's rates of motor vehicle accidents rate during their pregnancies. To evaluate the effects, the intervention group's responses to the questionnaires were compared with those of the control group. RESULTS: The proportion of subjects who always used seat belts during pregnancy was significantly higher in the intervention group (91.3%) than in the control group (86.7%; p=0.0005). Among all subjects, the percentage of women who preferred the driver's seat was lower during pregnancy (27.0%) than before pregnancy (38.7%), and the percentage of women who preferred the rear seat was higher during pregnancy (28.8%) than before pregnancy (21.0%). These two rates did not differ between two groups. Seventy-one women (3.2%) reported experiencing a motor vehicle accident during pregnancy. The motor vehicle accident rate for the intervention group (3.3%) was similar to that for the control group (3.2%). CONCLUSIONS: An educational seat belt leaflet was effective in raising the rate of consistent seat belt use during pregnancy, but it did not decrease the rate of motor vehicle accidents. The wearing of seat belts should be promoted more extensively among pregnant women to decrease rates of pregnancy-related morbidity and mortality from motor vehicle accidents.
Subject(s)
Accidents, Traffic/statistics & numerical data , Health Education , Seat Belts/statistics & numerical data , Adolescent , Adult , Female , Health Education/methods , Humans , Japan , Pregnancy , Prospective Studies , Young AdultABSTRACT
BACKGROUND: We have performed 36 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer and experienced 10 deliveries. Pregnancy after RT has far higher risks of prematurity and complications such as preterm premature rupture of the membrane (pPROM) and chorioamnionitis. We report the significance of transabdominal cerclage in the follow-up of pregnancy after vaginal RT. METHODS: Our operative procedure is based on that of Dargent et al. We amputated the cervix approximately 10 mm below the isthmus. For the removal of the parametrium, we cut at the level of type II hysterectomy. A nylon suture is also placed around the residual cervix. Pregnancy courses after vaginal RT were studied in 9 patients (10 pregnancies) with respect to cervical length and several infectious signs. RESULTS: Obstetric prognosis after RT was improved with our follow-up modality. Four patients who were followed up with this modality were able to continue their pregnancies until late in the third trimester. However, it was not effective for four patients who showed cervical incompetence due to slack cerclage. They suffered from pPROM without any infectious signs and uterine contraction. Though we performed transabdominal uterine cervical cerclage for one patient in her 19th week of pregnancy, it was unsuccessful. CONCLUSIONS: Cervical cerclage placed at the time of RT played an important role in preventing dilatation of the uterine cervix and the subsequent occurrence of pPROM. Transabdominal cervical cerclage should be performed earlier in pregnancy or before pregnancy in patients who have experienced problems with cervical cerclage.
Subject(s)
Cervix Uteri/surgery , Pregnancy Complications, Neoplastic , Uterine Cervical Neoplasms/surgery , Vagina/surgery , Adult , Cerclage, Cervical/methods , Cervix Uteri/pathology , Chorioamnionitis/pathology , Female , Fetal Membranes, Premature Rupture/pathology , Humans , Infant, Newborn , Pregnancy , Uterine Cervical Neoplasms/complications , Uterine Cervical Neoplasms/pathology , Vagina/pathologyABSTRACT
The purpose of this study was to clarify the risk factors and outcomes of placental polyp. This retrospective study was conducted on 1645 patients delivered or aborted in Sapporo Medical University from 2007 through 2011. Transvaginal color Doppler ultrasonography, hysteroscopy, contrast-enhanced MRI or 3D-CT angiography were performed. There were 1532 deliveries and 113 abortions. Seventy-one (4.3%) were ART-conceived and the remaining 1574 (95.7%) were non-ART pregnancies. Fifteen (0.91%) cases were confirmed as having placental polyp. Nine cases of placental polyp were identified among the 1574 (0.57%) as non-ART-related pregnancies, and 6 were identified among the 71 (8.5%) as ART-related pregnancies. Thus, pregnancies achieved through ART showed 20x greater incidence of complicating placental polyp than pregnancies achieved through without ART (p = 9.02 × 10(-6); odds ratio, 19.59; 95% confidence interval, 5.27-72.84, logistic regression analysis). Evaluation of blood flow within the polyp showed that in five of seven patients with low blood flow, the polyps spontaneously dropped off 79-115 days postpartum. Thus, ART-related pregnancies may be a risk factor of placental polyp, and spontaneous drop-off of the polyp is often observed in cases with low blood flow within the mass.
Subject(s)
Placenta Diseases/epidemiology , Polyps/epidemiology , Reproductive Techniques, Assisted/adverse effects , Abortion, Induced/adverse effects , Abortion, Induced/statistics & numerical data , Abortion, Spontaneous/epidemiology , Adult , Female , Humans , Placenta Accreta/epidemiology , Placenta Diseases/diagnostic imaging , Polyps/diagnostic imaging , Pregnancy , Pregnancy Complications/epidemiology , Pregnancy Complications/etiology , Pregnancy Outcome/epidemiology , Retrospective Studies , Risk Factors , UltrasonographyABSTRACT
AIM: MicroRNA-34a (miR-34a) is associated with invasion and metastasis of various cancers. The trophoblastic cells of placenta accreta invade into the myometrium in a similar way to the invasion of cancers. We studied the roles of miR-34a in the pathogenesis of placenta accreta. METHODS: The human choriocarcinoma cell line JAR was used for in vitro experiments as a model of trophoblasts, and placental tissues from the operative specimen of patients with or without placenta accreta were used for experiments in vivo. Morpholino antisense oligomer against miR-34a (miR-34a Morpho/AS) was added to JAR, and the expression of miR-34a and plasminogen activator inhibitor-1 (PAI-1) was determined by real time PCR. The effects of antisense, interleukin (IL)-6 and IL-8 in the process of invasion were studied with an invasion assay. Expression of miR-34a in vivo was studied with the use of fluorescent in situ hybridization (FISH). RESULTS: Expression of miR-34a was inhibited by 65% with the administration of antisense, and a slight increase in miR-34a expression was observed with the addition of IL-6 and IL-8. PAI-1 expression decreased with the addition of IL-6 and IL-8, and increased with the administration of antisense. There was an increase in invasive capacity through the inhibition of miR-34a expression. Strong FISH expression of miR-34a was observed in trophoblast cells of non-placenta accreta, and a clear decrease in miR-34a expression was observed in those of placenta accreta. CONCLUSIONS: Expression of miR-34a was downregulated in placenta accreta. In vitro experiments also showed that the invasive potential of JAR increased by suppressing miR-34a, probably through the expression of PAI-1.
Subject(s)
Down-Regulation/physiology , MicroRNAs/metabolism , Placenta Accreta/etiology , Placenta/metabolism , Cell Line, Tumor , Female , Humans , Interleukin-6/pharmacology , Interleukin-8/pharmacology , MicroRNAs/genetics , Placenta/drug effects , Placenta Accreta/genetics , Placenta Accreta/metabolism , Plasminogen Activator Inhibitor 1/genetics , Plasminogen Activator Inhibitor 1/metabolism , Pregnancy , Trophoblasts/drug effects , Trophoblasts/metabolismABSTRACT
BACKGROUND: We have performed 26 vaginal radical trachelectomies (RTs) for patients with early invasive uterine cervical cancer since 2003 and, to date, have experienced 8 deliveries. The procedure has a high risk for preterm labor and the subsequent occurrence of preterm premature rupture of membranes (pPROM). We report the present situation and the limits of follow-up of pregnancy after vaginal RT. METHODS: Our operative procedure is based on that of Dargent et al. We usually amputate the cervix approximately 10 mm below the isthmus. To remove the parametrium, we cut at the level of type II hysterectomy. Pregnancy courses after vaginal RT were studied in 8 patients with respect to symptoms, cervical length, and several infectious signs. RESULTS: We recommended that patients enter hospital early in their second trimester, and prophylactic daily vaginal disinfection with povidone-iodine and an ulinastatin vaginal suppository were administered. Careful checking for vaginal infectious signs, as well as cervical length and abdominal tension of patients was also performed. Four patients followed up with this modality were able to continue their pregnancies until late in the third trimester. However, this follow-up modality was not effective for patients who showed cervical incompetence due to slack cervical cerclage. They suffered from pPROM at 26 and 19 weeks of gestation. CONCLUSION: We need a new approach for the management of pregnant patients after vaginal RT with cervical incompetence due to slack cervical cerclage to prevent cervical infection.
Subject(s)
Pregnancy Complications, Neoplastic/surgery , Uterine Cervical Neoplasms/surgery , Vagina/surgery , Adult , Female , Fetal Membranes, Premature Rupture/pathology , Humans , Hysterectomy , Infant, Newborn , Lymph Node Excision , Pregnancy , Pregnancy Complications, Neoplastic/pathology , Uterine Cervical Neoplasms/pathology , Vagina/pathologyABSTRACT
This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient's serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient's serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism.
ABSTRACT
A diagnosis of cervical cancer during pregnancy poses difficult management and ethical problems. Survival of the patient is the foremost concern, but fetal viability and well-being must also be addressed. Radical trachelectomy (RT) has recently begun to be performed as a possible treatment modality for early stage invasive uterine cervical cancer in pregnant patients who would like to continue their pregnancy. A 32-year-old Japanese woman visited a local hospital for prenatal care, and was diagnosed with a FIGO I B1 adenocarcinoma of the uterine cervix. She had a strong desire to avoid pregnancy termination, so she was admitted to our hospital for fertility-preserving surgery. After extensive counseling, vaginal radical trachelectomy with abdominal pelvic lymphadenectomy was performed in the 16th gestational week. The excised uterine cervix and lymph nodes were pathologically negative for cancer. To maintain her pregnancy, daily vaginal disinfection with povidone iodine, bed rest, and administration of ritodrine and an ulinastatin vaginal suppository were continued until the delivery. At 34 weeks' gestation, an emergency cesarean section was performed because of sudden premature rupture of the membranes. A baby girl was born weighing 2112 g, with Apgar score of 8/9. The mother remains without evidence of recurrence at the time of this report. This is the first case of successful pregnancy and delivery in Japan after vaginal RT.
Subject(s)
Adenocarcinoma/surgery , Pregnancy Complications, Neoplastic/surgery , Uterine Cervical Neoplasms/surgery , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adult , Cesarean Section , Female , Gynecologic Surgical Procedures , Humans , Hysterectomy , Infant, Newborn , Japan , Lymph Node Excision , Neoplasm Staging , Pregnancy , Pregnancy Complications, Neoplastic/pathology , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. METHODS: Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. RESULTS: New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. CONCLUSION: Ligation and cutting of several supplying arteries by RT induces new arterial vascularization and it does not seem to affect fetal growth and placental function.
Subject(s)
Gynecologic Surgical Procedures/methods , Uterine Cervical Neoplasms/surgery , Adult , Female , Humans , Pregnancy , Treatment OutcomeABSTRACT
BACKGROUND: Pregnancy with invasive gynecologic cancer is a rare condition. It is still unclear whether we can choose planned delay in treatment until maturation of the fetus as a treatment modality for this condition. If there are no adverse effects from the cancer and there is improvement of neonatal outcomes, this treatment modality might be an option for patients with this condition. METHODS: Eight pregnant patients were diagnosed as having invasive gynecologic cancer between January 1998 and December 2007. Five of them, (four with invasive uterine cervical cancer and one with ovarian cancer) chose planned delay in treatment. The pregnancy courses and prognoses of these patients were studied. RESULTS: The period of planned delay in treatment varied from 2 weeks to 19 weeks. The period was shorter for patients who had complications. The pain caused by the cancer was the main obstacle to this treatment modality in two patients (one with advanced ovarian cancer and one with uterine cervical cancer). No apparent tumor growth, elevation of tumor markers, or complications induced by the cancer itself were detected in the remaining three patients. Only the patient with advanced ovarian cancer died of the primary disease after the delivery. Fetal outcome was uniformly good for the delayed-treatment group. All the babies are growing well, and no fetal deaths or neonatal deaths occurred. CONCLUSION: Planned delay in treatment to allow for fetal maturity is acceptable in pregnant patients with certain types of invasive gynecologic cancers.
Subject(s)
Cesarean Section , Hysterectomy , Live Birth , Ovarian Neoplasms/surgery , Ovariectomy , Patient Care Planning , Pregnancy Complications, Neoplastic/therapy , Uterine Cervical Neoplasms/surgery , Abortion, Therapeutic , Adult , Chemotherapy, Adjuvant , Female , Gestational Age , Humans , Lymph Node Excision , Neoplasm Invasiveness , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Patient Selection , Pregnancy , Pregnancy Complications, Neoplastic/mortality , Pregnancy Complications, Neoplastic/surgery , Radiotherapy, Adjuvant , Time Factors , Uterine Cervical Neoplasms/mortality , Uterine Cervical Neoplasms/pathologyABSTRACT
BACKGROUND: Pregnancy-related complications after vaginal radical trachelectomy (RT) for early-stage invasive uterine cervical cancer were studied in comparison with those occurring after laser conization. The strategy to reduce vaginal RT-related complications during pregnancy is also discussed. METHODS: Pregnancy courses after vaginal RT in two patients and those after laser conization in five patients, whose operations were performed during the same period, were studied with respect to symptoms, cervical length, and infectious signs. RESULTS: The cervix shortened progressively both in patients with laser conization and in those with RT. However, throughout the pregnancy, the remaining cervix after the operation was longer in patients who had undergone conization than in those who had undergone vaginal RT. After laser conization, two of the five patients suffered from preterm rupture of the membrane (PROM) at 36 weeks of gestation, and both patients who had undergone vaginal RT had premature PROM (pPROM), at 32 and 24 weeks of gestation, respectively. CONCLUSION: Prevention of preterm labor and the following occurrence of pPROM is a significant task to be resolved in order to improve pregnancy outcome after vaginal RT for early-stage invasive uterine cervical cancer. Daily vaginal disinfection with povidone iodine and the administration of a ulinastatin vaginal suppository, bed rest, and the use of ritodrine would be the best approach, and a more conservative approach for stage Ia2 also might be taken into consideration.
Subject(s)
Gynecologic Surgical Procedures/methods , Pregnancy Complications, Neoplastic , Uterine Cervical Neoplasms/surgery , Adult , Conization , Female , Humans , Laparoscopy , Laser Therapy , Neoplasm Invasiveness , Pregnancy , Pregnancy Outcome , Uterine Cervical Neoplasms/pathologyABSTRACT
We report a rare case of advanced ovarian mucinous adenocarcinoma in a pregnant woman. A 28-year-old pregnant Japanese woman was diagnosed with an ovarian tumor 8 cm in diameter at a local hospital. She was sent to a private hospital at 25 weeks of gestation because of the growing ovarian tumor. Advanced ovarian carcinoma with widespread intraabdominal dissemination was detected by laparotomy at the hospital and she was referred to our hospital for further management. At 27 weeks of gestation, she underwent cesarean section, followed by abdominal total hysterectomy, and bilateral salpingo-oophorectomy. A girl weighing 879 g was delivered, with Apgar scores of 4 and 6 at 1 and 5 min, respectively. The pathological diagnosis of the tumor was mucinous cystadenocarcinoma grade 2. Although chemotherapy was not effective for her and she died of the disease 4 months after the surgery, her baby grew well and weighed 3750 g 3 months after delivery. For the treatment of such patients, we believe we should choose operative therapy as early as possible after the maturation of the fetus, although there are several reports of successful treatment with the administration of chemotherapy during pregnancy. To determine a better approach for such patients, multidisciplinary staff meetings, including gynecological oncologists, obstetricians, neonatologists, psychologists, and the patient are important.
Subject(s)
Cystadenocarcinoma, Mucinous/pathology , Ovarian Neoplasms/pathology , Pregnancy Complications, Neoplastic , Adult , Cystadenocarcinoma, Mucinous/secondary , Cystadenocarcinoma, Mucinous/surgery , Female , Humans , Hysterectomy , Infant, Newborn , Ovarian Neoplasms/secondary , Ovarian Neoplasms/surgery , Ovariectomy , PregnancyABSTRACT
A 32-year-old Japanese woman was diagnosed as having stage Ib1 adenocarcinoma by diagnostic laser conization at a local hospital. She was admitted to our hospital for fertility-sparing treatment. A radical trachelectomy (RT) was performed using the laparoscopic vaginal procedure. The procedure was started with a laparoscopic pelvic lymphadenectomy. As the lymph nodes were tumor free, RT was carried out transvaginally. The excised uterine cervix and lymph nodes were pathologically negative for cancer. Eight months after the operation, the patient became pregnant without any artificial reproduction techniques. At 17 weeks of gestation, she was admitted to our hospital again for a threatened abortion. Continuous tocolytic treatment with ritodrine and daily administration of a granulocyte elastase inhibitor vaginal suppository were given. At 32 weeks of gestation, she underwent emergency cesarean section because of sudden premature rupture of the membranes. A girl weighing 1991 g was delivered, with Apgar scores of 7 and 8 at 1 and 5 min, respectively. Both the mother and the baby were discharged without trouble. This is the first successful case in Japan of delivery after vaginal RT for invasive uterine cervical cancer.
Subject(s)
Pregnancy Outcome , Uterine Cervical Neoplasms/surgery , Adult , Cesarean Section , Female , Fetal Membranes, Premature Rupture/surgery , Gynecologic Surgical Procedures/methods , Humans , Laparoscopy , PregnancyABSTRACT
Preeclampsia is often accompanied by hypoxia of the placenta and this condition induces apoptosis in trophoblastic cells. The aim of this study was to characterize global changes of apoptosis-related proteins induced by hypoxia in trophoblastic cells so as to clarify the mechanism of hypoxia-induced apoptosis by using the PoweBlot, an antibody-based Western array. Human choriocarcinoma cell line JAR was cultured for 24 hours under aerobic and hypoxic conditions. Hypoxia induced apoptosis accompanied by increased expression of Bcl-x, Caspase-3 and -9, Hsp70, PTEN, and Bag-1. Bad, pan-JNK/SAPK-1, Bcl-2, Bid, and Caspase-8 showed decreased expression. Hypoxia-induced apoptosis was increased with the transfection of a bag-1 antisense oligonucleotide. The bag-1 antisense oligonucleotide affected the expression of Bid, Bad, Bcl-2, JNK, and phosphorylated JNK, although expression of PTEN and Bcl-X did not change. Bag-1 may inhibit apoptosis by suppressing the expression of Bid and Bad. It may also enhance apoptosis by inhibiting the expression of Bcl-2 and by modulating phosphorylation of JNK. Both mitochondrial and stress-activated apoptosis pathways played important roles in the hypoxia induced cell death of trophoblastic cells. These findings will contribute to establish new approach to detect hypoxic stress of the placenta, which leads to preeclampsia and other hypoxia-related obstetrics complications.
Subject(s)
Apoptosis , Cell Hypoxia , Proteomics , Trophoblasts/pathology , Cell Line, Tumor , DNA-Binding Proteins/analysis , DNA-Binding Proteins/physiology , Female , Humans , Mitogen-Activated Protein Kinase 8/metabolism , PTEN Phosphohydrolase/metabolism , Phosphorylation , Pregnancy , Proto-Oncogene Proteins c-bcl-2/analysis , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors/analysis , Transcription Factors/physiology , Trophoblasts/metabolismABSTRACT
Ultrastructural characteristics of benign, low-malignant potential (LMP), and malignant ovarian tumors were investigated, considering the aspects of histologic subtypes and histologic grading. In addition, the histogenesis of ovarian cancer was histologically investigated in an attempt to elucidate whether malignant tumor was generated from benign or LMP tumor, or whether it was generated de novo from normal tissues. Although all the benign, LMP, and malignant tumors appeared to be derived from Mullerian duct in serous tumors, the origin of endometrioid or mucinous tumor could not be ultrastructurally clarified. However, there was ultrastructural similarity between benign and malignant tumors among serous, endometrioid, and mucinous tumors, and it was suggested that benign adenoma may be the developmental origin of malignant tumors regardless of the histologic subtype. In addition, the investigation of endometrioid tumors revealed that the differences of histologic grading in malignant tumors reflected the ultrastructural differences, and that G1 tumor had an ultrastructure that was more similar to that of benign and LMP tumors than to that of G2 tumor.
Subject(s)
Ovarian Neoplasms/pathology , Ovarian Neoplasms/ultrastructure , Animals , Cystadenoma, Mucinous/pathology , Cystadenoma, Mucinous/ultrastructure , Endometrial Neoplasms/pathology , Endometrial Neoplasms/ultrastructure , Female , Humans , Microscopy, Electron , Mitochondria/ultrastructureABSTRACT
BACKGROUND: To understand the complicated network of paclitaxel (PTX)-induced apoptosis pathways and to elucidate mechanisms of drug resistance in ovarian cancer, we looked at PTX-induced apoptosis by using cDNA microarray. We also quantitated the changes in apoptosis-related proteins in the process of apoptosis. METHODS: An ovarian cancer cell line KF, and its PTX-resistant clone KFTX, were treated with PTX or carboplatin (CBDCA). After exposure to PTX or CBDCA, the induction of apoptosis was examined by internucleosomal DNA fragmentation. Changes in mRNA expression after 12 h of exposure to PTX were studied using cDNA microarray and RT-PCR. Changes in P53 and Bcl-2 levels were also measured over 24 h by ELISA. RESULTS: With increased doses of PTX or CBDCA, an increase in apoptosis was noted in both cell lines. cDNA microarray revealed that PTX treatment upregulated expression of caspase 1, 2, 3, 4, 6, 9, 10, their activator apaf-1, and stress reaction-related genes, gadd34, gadd153 in KF, although most of them were unchanged or downregulated in KFTX. bag-1 and hsc70 were markedly upregulated in KFTX. p53 and bcl-2 were not upregulated in either cell line. Results from protein studies also supported the cDNA microarray data. CONCLUSIONS: p53-independent mitochondrial pathways and stress-reaction-induced pathways play critical roles in PTX-induced apoptosis in ovarian cancer cells. Suppression of those pathways and upregulation of bag-1 and hsp-70 played an important role in acquiring resistance to PTX.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Ovarian Neoplasms/drug therapy , Paclitaxel/pharmacology , Carrier Proteins/metabolism , Cell Line, Tumor , Clone Cells/drug effects , DNA, Complementary/drug effects , DNA, Neoplasm/drug effects , DNA-Binding Proteins , Drug Resistance, Neoplasm , Enzyme-Linked Immunosorbent Assay , Female , Gene Expression Regulation, Neoplastic , Humans , Oligonucleotide Array Sequence Analysis , Ovarian Neoplasms/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Transcription Factors , Tumor Suppressor Protein p53/metabolism , Up-RegulationABSTRACT
Single nucleotide polymorphism (SNP) of the promoter region of MMP-1 (at -1607 bp) creates Ets binding sites, and correlations between this SNP and cancer susceptibility have been reported for various cancers. In this study, we genotyped the SNP in 23 cervical intraepithelial neoplasias (CIN) and 86 cervical cancer specimens. We found a correlation between promoter polymorphism and MMP-1 expression, and that this SNP was correlated with the clinical stage of cervical cancer. These findings suggested that SNP of MMP-1 promoter might influence the ability in cervical cancer invasion via transcriptional activity of this gene.
Subject(s)
Matrix Metalloproteinase 1/genetics , Polymorphism, Single Nucleotide , Uterine Cervical Dysplasia/genetics , Uterine Cervical Neoplasms/genetics , Base Sequence , Female , Gene Frequency , Genotype , Humans , Immunohistochemistry , Matrix Metalloproteinase 1/analysis , Promoter Regions, Genetic , Tumor Cells, Cultured , Uterine Cervical Neoplasms/pathology , Uterine Cervical Dysplasia/pathologyABSTRACT
OBJECTIVE: The aim of this study was to compare the usefulness of a new universal grading system for ovarian cancer proposed by Shimizu et al. (Cancer 82 (1998), 893; Gynecol. Oncol. 70 (1998), 2) with that of the FIGO grading system as a prognostic factor of ovarian cancer. METHODS: We reviewed all paraffin-embedded tissues of epithelial ovarian cancer obtained from 130 women who underwent initial treatment including primary surgery in our hospital between January 1990 and December 2000. The scores of the specimens were obtained according to both the universal grading system and the FIGO grading system. RESULTS: Both the FIGO grading system and the universal grading system worked as significant prognostic indicators. Patients with Grades 1 and 3 of the universal grading system had high and low 5-year survival rates, respectively, compared to those of the FIGO grading system. Inconsistencies in histologic grade between the FIGO and universal grading systems were observed in 22 patients. The positive rate of lymph node metastasis in patients with Grade 3 of the universal grading system was significantly high compared to those of the FIGO grading system (P = 0.03). Patients with Grade 3 of the universal grading system with residual tumor of not less than 2 cm in diameter were observed more frequently than those of the FIGO grading system. C4ONCLUSION: The universal grading system was superior to the FIGO grading system in terms of the prediction of malignancies such as the potential of lymph node metastasis and invasion and the adaptability to clear cell cancer.
Subject(s)
Ovarian Neoplasms/pathology , Adenocarcinoma, Clear Cell/pathology , Carcinoma, Endometrioid/pathology , Cystadenocarcinoma, Mucinous/pathology , Cystadenocarcinoma, Serous/pathology , Female , Humans , Multivariate Analysis , Neoplasm Staging , Observer Variation , Paraffin Embedding , Reproducibility of ResultsABSTRACT
OBJECTIVE: To better control both acute and delayed emesis resulting from cisplatin(CDDP)-based chemotherapy for gynecological malignancies, we designed a 'cocktail therapy' (CCT) using granisetron (GRN) in combination with methylprednisolone (MPD) plus droperidol (DRP). METHODS: Two crossover clinical trials were carried out to compare the efficacy and safety of (a) GRN alone (3 mg/patient) with that of GRN, MPD (250 mg/patient) and DRP (0.5 ml/patient) in 42 patients (CCT group) and (b) GRN and MPD (CMB group) with that of the CCT group in 27 patients during the first 7 days of chemotherapy, independent of the weight/body surface of the patients. One of these regimens was administered intravenously for the first 3 days of chemotherapy, in case of failure for a maximum of 5 days. RESULTS: For acute emesis, complete protection from nausea and vomiting by the end of the 1st day was achieved in 64.3% receiving GRN and in 92.9% receiving CCT (p < 0.01). For delayed emesis, complete protection was best achieved in CCT on days 2-3, showing statistical significance compared to GRN treatment (p < 0.01). Comparing the three kinds of treatment during 7 days, the lowest protection was 38.1% in the GRN group, 51.9% in the CMB group and 72.5% in the CCT group, especially on days 2 or 3. CONCLUSIONS: The CCT combination is useful for the control of delayed and/or anticipatory emesis resulting from CDDP-based chemotherapy for women with gynecological malignancies.