Dysregulated Expression of Long Noncoding RNAs in Endometriosis.

Endometriosis is a common debilitating gynecologic disease. Almost 10% of reproductive-age women are affected by this disease; they commonly suffer pelvic pain and/or infertility. Early diagnosis of this multifactorial disease remains difficult because its etiology is not clear and the early symptoms are nonspecific. In addition, many reproductive-age women are unwilling to undergo invasive laparoscopic surgery because of the possibility of decreasing fertility. Thus, identifying biomarkers for the early diagnosis of endometriosis a key focus of current research. Long noncoding RNAs (lncRNAs) are a class of noncoding transcripts that have length of > 200 nucleotides and lack protein-coding ability but still influence gene expression in various ways. With advances in genome-wide analysis, researchers have determined that lncRNAs play an important role in many human diseases, particularly tumors. Moreover, the role of lncRNAs in the pathogenesis of endometriosis has been continually recognized. In this review, we discuss the status of current research on dysregulated lncRNAs and their roles in the pathogenesis of endometriosis. We aim to stimulate new investigations toward the identification of lncRNAs as biomarkers for the early diagnosis and therapy of this long-term gynecological disease.

In vitro and in vivo anti-cancer activity of formononetin on human cervical cancer cell line HeLa.

Worldwide, cervical cancer (CC) is the third most common malignancy in women, and it remains a leading cause of cancer-related death of women. Genomic studies indicate that phosphoinositide 3-kinase (PI3K)/AKT signaling is one of the most frequently deregulated pathways in several human cancers, including CC. This signaling pathway has an important role in cancer cell proliferation, survival, motility, and metabolism, and therefore could be an attractive therapeutic target. In a previous study, we used a sensitive and high-speed homogeneous assay for the detection of kinase activity and for screening of PI3K/AKT signaling inhibitors in a high-throughput screening (HTS) format and then obtain formononetin, as an O-methylated isoflavone existed in a number of plants and herbs like Astragalus membranaceus. We showed that formononetin inhibited the phosphorylation of AKT and induced the apoptosis of CC cell line HeLa in a dose-dependent manner. Furthermore, formononetin suppressed xenograft tumor growth in nude mice. Our results indicated that formononetin may be used as an anti-cancer drug for cervical cancer in the future.

[Pro-apoptotic effects of curcumin associated with CIK cells against ovarian carcinoma cells].

OBJECTIVE: To observe the pro-apoptotic effects of Curcumin associated with CIK cells against SKOV3 cells of ovarian carcinoma and discusses the possible molecular mechanisms. METHODS: CIK cells were induced from umbilicus cord blood. The apoptotic morphology of SKOV3 cells was observed under electron microscope after treated with Cur, CIK cells and Cur associated with CIK cells. The levels of Fas protein on surface of ovarian cancer cells and FasL protein on surface of CIK cells after Curcumin treatment were determined by Western blot. The inhibition rates on proliferation of CIK cells and Cur associated with CIK cells after addition of FasL monoclonal antibody were detected by (thiazolyl blue tetrazolium bromide) MTT. RESULTS: The changes of apoptotic morphology in the group of Cur associated with CIK cells were most obvious compared with that in the group of Cur or CIK cells alone. Cur could promote the expression of Fas on surface of SKOV3 cells and FasL on membranes of CIK cells. The inhibition rates on proliferation in the group of CIK cells and Cur associated with CIK cells could be restrained obviously after an addition of anti-FasmAb. CONCLUSION: The pro-apoptotic effects of SKOV3 cells increase with the combined use of Cur and CIK cells. The mechanism may be that Cur can promote the expression of Fas protein on cell surface of SKOV3 cells and FasL protein on cell membrane of CIK cells so as to up-regulate the expression of Fas protein in SKOV3 cells and lead ultimately to the a higher expression of Caspase3.

[Inhibition of GRP78 expression reverses cisplatin resistance in human ovarian cancer].

OBJECTIVE: To explore the effects of GRP78 suppression on the sensitivity to cisplatin and elucidate the role and mechanism of GRP78 in ovarian cancer cisplatin resistance. METHODS: The GRP78 siRNA expression plasmid was constructed to suppress GRP78 expression. Cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. Endoplasmic reticulum stress-related apoptosis related protein expressions were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. And cell apoptosis was detected by flow cytometry. RESULTS: The expressions of GRP78, CHOP and cleaved-caspase 4 were induced significantly by cisplatin (6 mg/L) in SKOV3 cells. And the expression of GRP78 was induced significantly by cisplatin in SKOV3/DDP cells. But the expressions of CHOP and cleaved-caspase 4 showed no significant difference. Inhibition of GRP78 expression and cisplatin combined treatment significantly increased the expressions of cleaved-caspase 4 and cleaved-caspase 3 in SKOV3/DDP cells. Inhibition of GRP78 expression reduced the cisplatin-induced up-regulations of p-Akt and p-mTOR and induced XBP1 mRNA shear expression and CHOP mRNA expression. CONCLUSION: Inhibition of GRP78 expression reverses cisplatin resistance in SKOV3/DDP cells. The mechanism may be through the activity of Akt/mTOR signaling pathway, CHOP expression levels and caspase activity.

[Expression and role of glucose-regulated protein 78 in ovarian serous adenocarcinoma].

OBJECTIVE: To explore the expression and role of glucose-regulated protein 78 in ovarian serous adenocarcinoma. METHODS: The surgical specimens were collected from 126 cases of serous ovarian tumors and 30 cases of normal ovarian tissue. And the mRNA and protein expressions of GRP78 were detected by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. RESULTS: The results of immunohistochemistry showed that GRP78 positive cells in ovarian serous adenocarcinoma were significantly higher than those in normal ovarian and ovarian serous cystadenoma tissues (P < 0.05). In ovarian serous adenocarcinoma, GRP78 expression was not associated with pathological grade, age and clinical staging (P > 0.05). And the mRNA expressions of GRP78 in normal ovarian tissue, ovarian serous cystadenoma and ovarian serous cystadenocarcinoma were 0.134 ± 0.021, 0.121 ± 0.032 and 0.685 ± 0.085 respectively. Protein expressions of GRP78 in normal ovarian tissue, ovarian serous cystadenoma and ovarian serous cystadenocarcinoma were 0.211 ± 0.042, 0.193 ± 0.032 and 0.770 ± 0.074 respectively. GRP78 mRNA and protein expression had no difference between different pathological grades of ovarian serous cystadenocarcinoma (P > 0.05). CONCLUSION: GRP78 is highly expressed in ovarian serous adenocarcinoma. And its differential expression between ovarian benign and malignant tumors is significant and correlated with the occurrence and progression of ovarian cancer.

[Expression of vitronectin in placental basal plate and its relationship with the pathogenesis of severe preeclampsia].

OBJECTIVE: To investigate the expression of vitronectin (VN) in placental basal plate and its relationship with the pathogenesis of severe preeclampsia. METHODS: From March 2010 to December 2011, 17 patients with early-onset severe preeclampsia who delivered in the Second Hospital of Jilin University were recruited as the early-onset severe preeclampsia group; and 16 women were recruited as the late-onset severe preeclampsia group. Meanwhile, 15 healthy pregnant women who delivered before 34 weeks were defined as the early control group (termination of pregnancy was carried out because of fetal heart malformations), and 15 healthy pregnant women delivered after 34 weeks were defined as the late control group. Immunohistochemistry and semi-quantitative reverse transcription (RT)-PCR were used to investigate the expression of VN protein and mRNA in the placental infarct center and its surrounding tissue of placental basal plate. The levels of serum prothrombin time (PT), part thromboplastin time (APTT) and fibrinogen (FIb) were detected and the international normalized ratio (INR) was calculated. The correlation of abnormal coagulation markers and VN expression levels in the early-onset severe preeclampsia group and the early control group was studied. RESULTS: (1) VN protein was detected in all placental basal plate of the four groups. It was highly expressed in the necrotic tissue of placental infarct center and weakly expressed in the tissue far from the infarcted area. (2) The mean levels of VN protein expression in placental basal plate of the early-onset severe preeclampsia group, the late-onset severe preeclampsia group, the late control group and the early control group were 0.152 ± 0.019, 0.113 ± 0.023, 0.095 ± 0.014 and 0.055 ± 0.010, respectively. And the differences between the groups were statistically significant (P < 0.01). The VN protein expression in placental infarct center, infarct edge, peri-infarct tissue and tissue far from the infarcted area gradually reduced, and the differences were statistically significant (P < 0.01). Compared with the same areas of each group, the differences were not statistically significant (P > 0.05). (3) VN mRNA were detectable in infarct center, infarct edge, per-infarct tissue and tissue far from the infarcted area of placental basal plate. In the early-onset severe preeclampsia group and the early control group, it was statistically higher in infarct center than in tissue far from the infarcted area (P < 0.05). (4) PT of the early-onset severe preeclampsia group was (9.45 ± 0.63) s, significantly shorter than that of the early control group [(9.88 ± 0.17) s, P < 0.05]. While there was no statistically significant difference in APTT, FIB and INR among the four groups (P > 0.05). (5) In the early-onset severe preeclampsia group, VN expression level and PT were significantly negative correlated (r = -0.612, P < 0.05); while in the early control group there was no correlation (r = 0.489, P > 0.05). CONCLUSION: VN was highly expressed in placental basal plate of the early-onset severe preeclampsia group, which caused the imbalance of coagulation and fibrinolysis system and the pathogenesis of severe preeclampsia.

CAR-T Cells in the Treatment of Ovarian Cancer: A Promising Cell Therapy.

Ovarian cancer (OC) is among the most common gynecologic malignancies with a poor prognosis and a high mortality rate. Most patients are diagnosed at an advanced stage (stage III or IV), with 5-year survival rates ranging from 25% to 47% worldwide. Surgical resection and first-line chemotherapy are the main treatment modalities for OC. However, patients usually relapse within a few years of initial treatment due to resistance to chemotherapy. Cell-based therapies, particularly adoptive T-cell therapy and chimeric antigen receptor T (CAR-T) cell therapy, represent an alternative immunotherapy approach with great potential for hematologic malignancies. However, the use of CAR-T-cell therapy for the treatment of OC is still associated with several difficulties. In this review, we comprehensively discuss recent innovations in CAR-T-cell engineering to improve clinical efficacy, as well as strategies to overcome the limitations of CAR-T-cell therapy in OC.

MutL homolog 1 germline mutation c.(453+1_454-1)_(545+1_546-1)del identified in lynch syndrome: A case report and review of literature.

BACKGROUND: Lynch syndrome (LS) is an autosomal dominant hereditary disorder because of germline mutations in DNA mismatch repair genes, such as MutL homolog 1 (MLH1), PMS1 homolog 2, MutS homolog 2, and MutS homolog 6. Gene mutations could make individuals and their families more susceptible to experiencing various malignant tumors. In Chinese, MLH1 germline mutation c.(453+1_454-1)_(545+1_546-1)del-related LS has been infrequently reported. Therefore, we report a rare LS patient with colorectal and endometrioid adenocarcinoma and describe her pedigree characteristics. CASE SUMMARY: A 57-year-old female patient complained of irregular postmenopausal vaginal bleeding for 6 mo. She was diagnosed with LS, colonic malignancy, endometrioid adenocarcinoma, secondary fallopian tube malignancy, and intermyometrial leiomyomas. Then, she was treated by abdominal hysterectomy, bilateral oviduct oophorectomy, and sentinel lymph node resection. Genetic testing was performed using next-generation sequencing technology to detect the causative genetic mutations. Moreover, all her family members were offered a free genetic test, but no one accepted it. CONCLUSION: No tumor relapse or metastasis was found in the patient during the 30-mo follow-up period. The genetic panel sequencing showed a novel pathogenic germline mutation in MLH1, c.(453+1_454-1)_(545+1_546-1)del, for LS. Moreover, cancer genetic counseling and testing are still in the initial development state in China, and maybe face numerous challenges in the further.

Disseminated ovarian granulosa cell tumor after laparoscopic surgery: Two case reports.

RATIONALE: Granulosa cell tumors (GCT) have an incidence of 0.6 to 0.8/100,000. Short-term relapsed ovarian GCT is extremely rare. Herein, this report aims to present 2 rare cases of disseminated ovarian GCT and analyze the causes of recurrence. PATIENT CONCERNS: The 2 patients presented with abdominal pain. DIAGNOSIS: Both the patients were diagnosed with relapsed ovarian GCT (IIIc stage) in the adult type. INTERVENTIONS: The 2 patients had a medical history of surgery for ovarian GCT by using laparoscopic with power morcellators (LPM). They experienced relapsed ovarian GCT postoperatively. Subsequently, they received a repeated operation through a laparotomy approach. Numerous malignant metastasis neoplasms were detected at the port-sites. Then, tumor resection was performed. OUTCOMES: The postoperative pathologies of both case 1 and case 2 reported ovarian GCT (IIIc stage) in adult type. The 2 patients presented disease-free survival for more than 33 months follow-up period. LESSONS: The application of LPM may be a risk factor of disseminated ovarian GCT. However, laparoscopic surgery is still an optimal treatment strategy for ovarian tumors. Besides, gynecologists should comply with the tumor-free principle during surgery.

[Retracted] Effects of cyclooxygenase­2 gene silencing on the biological behavior of SKOV3 ovarian cancer cells.

Following the publication of the above article, the authors have requested that it be retracted. They alerted the Editorial Office to the fact that the same data, albeit with a different view, had been selected to show the 'CON' and 'NC' experiments for the colony­formation assays featured in Fig. 6. The Editor has agreed to the authors' request that the paper be retracted. All the authors agree to this retraction, and apologize for any inconvenience caused. [the original article was published in Molecular Medicine Reports 11: 59­66, 2015; DOI: 10.3892/mmr.2014.2732].

[Choose which method for the chemotherapy of epithelial ovarian carcinoma: a meta-analysis].

OBJECTIVE: To evaluate the differences of clinical efficacy between intraperitoneal and intravenous chemotherapy. METHODS: The literature database was extensively searched to retrieve the randomized controlled trials with a relevance of study goal. The strict inclusion and exclusion criteria were formulated. And the original studies were selected. After a quality evaluation, the data were extracted. The Cochrane collaboration Revman 4.2 version software was used for meta-analysis. RESULTS: Five clinical studies were included and there were a total of 1 229 eligible patients. Intraperitoneal chemotherapy and intravenous chemotherapy groups were compared: (1) 2 and 3-year progression-free survival (PFS) increased, 2, 3 and 5-year overall survival (OS) increased. The difference was significant enough so that definite conclusions could be drawn; (2) Among the six indicators of unpleasant chemotherapeutic effects (leucopenia, anemia, thrombopenia, GI tract reactions, neurotoxicity and fever), the occurrence of gastrointestinal reaction increased. The difference was significant enough so that definite conclusions could be drawn. And the remaining five indicators had no statistical significance so that definite conclusions could not be drawn. CONCLUSIONS: For patients with epithelial ovarian cancer (Stages FIGOII-IV) undergoing previously a satisfactory tumor reduction surgery (postoperative residual lesions < 1 to 2 cm), intraperitoneal chemotherapy can improve their 2 and 3-year PFS rates and the 2, 3 and 5-year OS rates; Intraperitoneal chemotherapy has not reduced the side effects. But there is an elevated occurrence of gastrointestinal reactions.

Primary ovarian carcinoid: Two cases report and review of literature.

INTRODUCTION: Carcinoid tumor is one of the most frequent neuroendocrine tumors, and the majority of which are usually observed in the lungs and gastrointestinal tract. The prevalence of ovarian carcinoids is merely 0.1% in ovarian neoplasms and 1% in carcinoid tumors. We described 2 rare cases in our hospital of primary ovarian carcinoid (POC), causing carcinoid syndrome (CS) of the diarrhea, constipation, and carcinoid heart disease. Besides, we also reviewed related literatures about its origin, variant, clinical manifestation, diagnosis methods, pathological features, treatment strategies and prognosis from 2009 to 2019. PATIENT CONCERNS: Case 1 was a 61-year-old postmenopausal woman and presented with diarrhea, abdominal pain, enlargement, bloating and dizziness. Case 2 was a 49-year-old patient who complained of constipation, abdominal pain, bloating, and headache. DIAGNOSIS: Both patients were diagnosed as primary ovarian carcinoid, insular type. INTERVENTIONS: Total abdominal hysterectomy (TAH), bilateral salpingo-oophorectomy (BSO), omentectomy, pelvic lymphadenectomy, and appendectomy without chemotherapy were performed in case 1. Cervix resection, right salpingo-oophorectomy, appendectomy, and pelvic lesion resection with chemotherapy was conducted in case 2. OUTCOMES: Both patients achieved satisfactory treatment effects. The follow-up period was 18 and 17 months in case 1 and case 2, respectively. Case 1 encountered carcinoid heart disease and received percutaneous transluminal coronary angioplasty (PTCA) postoperatively. Case 2 suffered multiple metastases postoperatively. However, after effective treatment, both patients were in good condition during follow-up duration. CONCLUSION: POC is an extraordinarily rare disease, and commonly with a satisfactory outcome. TAH+BSO with or without postoperative chemotherapy has been considered as an acceptable treatment strategy for POC patients.

Pregnancy with giant ovarian dysgerminoma: A case report and literature review.

RATIONALE: Dysgerminoma is an extraordinarily rare neoplasm arising from the malignant germ cells of the ovary. Early antenatal diagnosis and proper management of the neoplasm to improve maternal-neonatal results are the considerable challenges facing the gyne-oncologist. We summarize the clinical features and discuss treatment strategies of the ovary dysgerminoma (OD). Besides, we also review the literature on OD in PubMed, Web of Science Core Collection, Library of Congress, and LISTA from 1939 to 2019 to evaluate its clinical characteristics, feto-maternal compromise, management, and fertility outcome. PATIENT CONCERNS: A 25-year-old pregnant woman reported lower abdominal pain and vomiting. DIAGNOSIS: The patient was diagnosed as right OD. INTERVENTIONS: She received a cesarean section due to severe abdominal pain, delivered a healthy girl at 38 C 4 weeks of gestation, and accepted fertility-preserving surgery. However, the patient refused chemotherapy postoperatively. OUTCOMES: The patient was followed up 42 days, 3 months, and 6 months after surgery, and no tumor recurrence was observed. LESSONS: OD has non-specificity characteristics, including age, symptoms, image date, and tumor marks. However, these abnormal indicators may provide some evidence for accurate antenatal diagnosis. The management strategies should be considered comprehensively on an individual basis, and fertility-preserving surgery should be carried out in the second trimester if further pregnancy is desired. Adjuvant chemotherapy needs to be applied to the treatment of OD patients with The International Federation of Gynecology and Obstetrics (FIGO) stages II, III, and IV and timely chemotherapy is suggested if there are several weeks before the expected date of delivery. The overall prognosis of OD patients is excellent.

Spontaneous rupture of an unscarred uterus with an intact amniotic sac extrusion and fetal leg entrapment at 28 gestational weeks: a case report.

The spontaneous rupture of an unscarred uterus at 28 gestational weeks is an extremely rare event, particularly when associated with an intact amniotic sac extrusion and fetal leg entrapment, which has not been previously reported. A 27-year-old primigravid woman was referred to our department, due to perpetual abdominal pain, at 28 weeks and 5 days of gestation. The patient, G3p0, had previously undergone two induced abortions. At the time of admission, abdominal ultrasonography suggested a defect in the left uterine horn. An emergency laparotomy was subsequently performed and revealed an intact amniotic sac extrusion and fetal leg entrapment. Considering the risk of placental abruption, and the possibility of a secondary rupture if the gestation was not terminated, an emergency Cesarean section was recommended. Uterine rupture may be suspected whenever a patient complains of durative abdominal pain at 28 weeks and 5 days of gestation, even in the absence of an intra-abdominal hemorrhage or vaginal bleeding.

PMS2 germline mutation c.1577delA (p.Asp526Alafs*69)-induced Lynch syndrome-associated endometrial cancer: A case report.

RATIONALE: Lynch syndrome (LS) is an autosomal dominant cancer predisposition condition caused by germline heterozygous mutations in mismatch repair (MMR) genes. However, as one of the MMR genes, PMS2 mutation-induced LS-associated endometrial cancer (LSAEC) was rarely reported. PATIENT CONCERNS: A 26-year-old female patient suffered from prolonged menstrual period and increased menstrual flow for 2 months. DIAGNOSES: The patient was diagnosed with cervix CIN III, endometrial cancer (EC), anemia, and LS. INTERVENTIONS: Total hysterectomy, bilateral salpingectomy, pelvic lymphadenectomy were performed for treating EC, while ovariectomy was refused by the patient. The patient underwent postoperative chemotherapy with paclitaxel combined with carboplatin for 6 courses of treatment. Laparoscopic partial enterectomy was applied for treating colon cancer 5 years later after the surgery treatment for EC. Besides, Sanger sequencing and high-throughput genome sequencing were employed to detect the genetic status of the family that included two generations with four members. Immunohistochemistry (IHC) staining was used to identify the function of PMS2 mutation. OUTCOMES: The 26-year-old Chinese patient suffered from LSAEC and recovered well after surgery. A PMS2 germline heterozygous mutation (c.1577delA) was confirmed by gene sequencing 5 years later. In addition, PMS2 mutation was verified by IHC. The patient was followed up for 7 years. LESSONS: Carrying PMS2 germline mutation (c.1577delA) confers an extremely high susceptibility of suffering from LS-associated cancers. Thus, close clinical monitoring and prophylactic surgery are highly recommended to reduce the morbidity and mortality of LS-associated cancers.

TRP14 promotes resistance to cisplatin by inducing autophagy in ovarian cancer.

Cisplatin is a common chemotherapeutic agent against ovarian cancer; however, drug resistance is a major limiting factor for its use in clinical treatment. The underlying mechanisms of cisplatin resistance in ovarian cancer have not yet been fully elucidated. Thus, this study aimed to elucidate some of the mechanisms responsible for resistance to cisplatin in ovarian cancer. The results demonstrated that the cisplatin­resistant human ovarian cancer cell lines, SKOV3/DDP and A2780/DDP, exhibited higher autophagy levels than the control ovarian cancer cell lines, SKOV3 and A2780. Moreover, autophagy inhibition by 3­methyladenine or shRNA against autophagy­related gene (ATG)5 potentiated the cytotoxicity induced by cisplatin, whereas autophagy induction by rapamycin (Rapa) increased cell survival. Exposure to cisplatin induced an upregulation in the expression of thioredoxin­related protein of 14 kDa (TRP14). Furthermore, TRP14 knockdown or overexpression decreased or increased the autophagy response and cisplatin resistance, and this effect was reversed by treatment with Rapa or ATG5 knockdown. The findings of this study also suggested that TRP14 induced autophagy and chemoresistance via the 5'AMP­activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. Importantly, the data from a tissue array revealed a positive association between TRP14 and Beclin1 in human ovarian cancer and marginal tissues. These findings have identified, for the first time, to the best of our knowledge, that TRP14 induces autophagy and consequently cisplatin resistance in ovarian cancer cells via the AMPK/mTOR/p70S6K signaling pathway. This in turn renders TRP14 as a potential predictor or target in ovarian cancer therapy.

Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis.

BACKGROUND: Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism. METHODS: The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 (MMP-9) in SKOV-3 cells. RESULTS: In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3. CONCLUSIONS: Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced angiogenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.

[Microarray analysis of differentially expressed genes in peripheral leucocytes derived from severe preeclampsia and normotensive pregnancies].

OBJECTIVE: To investigate genes involved in the mechanisms underlying the progression of severe preeclampsia. METHODS: We conducted a multiregional gene expression analysis using peripheral leucocytes from patients with preeclampsia and normal controls. Total RNA was extracted from peripheral blood of six severe preeclampsia and five normotensive pregnancies. We performed genome-wide expression profiling using Affymetrix HG_U133 plus 2.0 chips to screen out differentially expressed genes of 2 fold or more and q_value < 5.4%. Using Gene Ontology we identified the function of differentially expressed genes after cluster analysis. RESULTS: Among the 47 000 genes that were screened in the microarray, 140 genes were found to be differentially expressed between normal and preeclamptic pregnancies. Eighty six up-regulated candidate genes were mainly involved in cysteine metabolism urea cycle and metabolism of amiogroups, proteasome, TGF-beta signaling pathway, and the ratio of calponin2 (CNN2), matrix metallopeptidase 8 (MMP8), V-set and immunoglobulin domain containing 4 (VSIG4), proteasome 26S subunit ATPase 5 (PSMC5) was evidently increased in preeclampsia patients. Among 54 down-regulated candidates, natural killer cell mediated cytotoxicity, antigen processing and presentation, metabolism of xenobiotics by cytochrome P450 were the main pathways. KIR3DL2, AKR1C3, CHURC1 and SLC25A13 were obviously decreased in preeclampsia patients. CONCLUSIONS: The gene expression of peripheral leucocytes in preeclampsia patients is significantly different from that of uncomplicated pregnancies. CNN2, MMP8, VSIG4, PSMC5, KIR3DL2, AKR1C3, CHURC1 and SLC25A13 may be involved in the molecular mechanisms underlying the progression of severe preeclampsia.

[Correlation between killer cell immunoglobulin-like receptors genes and pre-eclampsia].

OBJECTIVE: To analyze the killer cell immunoglobulin-like receptors (KIR) gene polymorphism of pre-eclampsia patients and approach the correlation between KIR genes and pre-eclampsia. METHODS: The KIR gene polymorphisms of 71 pre-eclampsia patients and 100 healthy pregnant women were detected by PCR-SSP. The KIR2DL4 mRNA level in placentas from pre-eclampsia and gestational normal pregnancies were quantified by real time RT-PCR. Forty pre-eclampsia patients and 38 healthy pregnant women were detected for single nucleotide polymorphisms (SNP) in the gene coding and joint areas between introns and extrons by directly sequencing techniques of KIR2DL4 genomic DNA. Finally, all alleles and genotypes of KIR2DL4 gene were case-control studied. RESULT: Distributions of some relatively activating KIR genotypes shewed a significant association with pre-eclampsia. Real-time RT-PCR showed that KIR2DL4 mRNA can be measured both in placenta of women with pre-eclampsia being of pre-eclampsia was significantly lower than that of normal pregnancy, only as much as 0.276 times that of controls. We identified 18 polymorphisms, of which, 7 were first reported. But no significant differences in genotype distributions or allele frequencies were observed in these SNPs between cases and controls. CONCLUSION: The distributions of some relatively activating KIR genotypes showed a significant association with pre-eclampsia, which indicates that the polymorphism of KIR genes may be associated with the genetic predisposition to pre-eclampsia. And because the expression of KIR2DL4 mRNA in the placentas of cases was significantly lower than control group, it is speculated that the decrease of KIR2DL4 expression in placenta may participate in the pathogenesis of pre-eclampsia.

Inhibitory effect of ginsenoside Rg3 combined with cyclophosphamide on growth and angiogenesis of ovarian cancer.

BACKGROUND: Ginsenoside Rg3, the main component isolated from ginseng, inhibits some kinds of tumour growth and angiogenesis. The combination of low dose chemotherapy and antiangiogenesis inhibitors suppresses growth of experimental tumours more effectively than conventional therapy. The effect of this combination on ovarian cancer remains to be evaluated. Therefore, we investigated the synergism of ginsenoside Rg3 and cyclophosphamide (CTX) on growth and angiogenesis of human ovarian cancer. METHODS: Twenty-eight female athymic mice were divided randomly into 4 groups of 7: ginsenoside Rg3, CTX, ginsenoside Rg3 and CTX combination and control, after being transplanted with ovarian cancer cells (SKOV-3). The mice were given intraperitoneal injection of ginsenoside Rg3 and CTX for the 10 days following inoculation of SKOV-3 cells. The life quality and number of living days of mice were recorded. The size of tumour, tumour inhibitive rate, life elongation rate, proliferating cell nuclear antigen labelling index (PCNALI), expression of vascular endothelial cell growth factor (VEGF) and microvessel density (MVD) of the tumour tissues were estimated. RESULTS: Life quality of mice in ginsenoside Rg3 and combined treatment groups were better and number of living days longer than control. Average tumour weights of each treated group were less than control and there was no significant difference among the treated groups. PCNALI of treated groups was lower than control. The MVD value and VEGF expression in treated groups were significantly lower than control and the MVD values of ginsenoside Rg3 and combined treatment groups were lower than that of CTX group. CONCLUSIONS: Ginsenoside Rg3 significantly inhibited growth and angiogenesis of ovarian cancer when used alone or combined with CTX. Ginsenoside Rg3 and CTX combination reinforced the antitumour effect each other and improved the living quality and survival time of mice with tumour.