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.

[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].

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.

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.

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.

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.

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.

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.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

Phosphorylation of STAT3 at Tyr705 regulates MMP-9 production in epithelial ovarian cancer.

Ovarian cancer's poor progression is closely associated with overexpression of matrix metalloproteinase 9 (MMP-9), which belongs to the class of enzymes believed to be involved in the degradation of extracellular matrix. However, the mechanisms underlying regulation of MMP-9 are not completely understood. STAT (signal transducer and activator of transcription) family of transcription factors is well known to be engaged in diverse cellular functions. Activation of STAT3 has been observed in a number of cancers, promoting tumorigenesis and metastasis via transcriptional activation of its target genes. In this study, we tested our hypothesis that STAT3 regulates MMP-9 gene expression in epithelial ovarian cancer. Using epithelial ovarian cancer cell lines as in vitro model, we show an abundance of phosphorylated STAT3 at Tyr705 (p-STAT3) in SKOV3 cell line. We further show that MMP-9 gene promoter was significantly enriched by p-STAT3, and IL-6 treatment led to a significant increase of MMP-9 at mRNA and protein levels, in addition to an association of p-STAT3 with MMP-9 gene. By using luciferase reporter assay, we determined that the STAT3 DNA responsive element of MMP-9 was sufficient to regulate transcriptional activity of a heterologous promoter. These results suggest that the phosphorylation of STAT3 regulates MMP-9 production in ovarian cancer, which might be responsible for its invasiveness and metastasis.

A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro.

Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid ß-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings.

Aberrantly elevated redox sensing factor Nrf2 promotes cancer stem cell survival via enhanced transcriptional regulation of ABCG2 and Bcl-2/Bmi-1 genes.

The presence of cancer stem cells in cervical cancer stem cells (CSCs) is important in the prevention of therapy failure and tumor recurrence. Upregulation of transcriptional regulation of redox sensing factor Nrf2 leads to the overexpression of drug efflux proteins such as ABCG2 in cancer stem cells and thus results in cancer treatment failure and cancer relapse. In the present study, we purified approximately 3.1% of cervical CSCs, which exhibited aberrant upregulation of Nrf2 in conjunction with an elevated transcriptional regulation of ABCG2, Bcl-2 and Bmi-1. Consequently, CSCs possess prolonged cell survival, infinite cell proliferation and highly resistant apoptosis. Following silencing of the function of Nrf2 the cervical CSCs became more sensitive to DNA targeting drugs and apoptosis. Our results suggested that Nrf2-mediated drug and apoptosis resistance are important in cancer therapies and tumor recurrence. Therefore, designing anticancer drugs targeting Nrf2 may be crucial to prevent CSC-mediated tumorigenesis.

Low expression of phosphatase and tensin homolog in clear­cell renal cell carcinoma contributes to chemoresistance through activating the Akt/HDM2 signaling pathway.

Clear-cell renal cell carcinoma (CCRCC) is the most frequent primary malignancy in the adult kidney. Most patients with advanced CCRCC have poor prognosis as CCRCC remains resistant to chemotherapy. The present study explored the possible mechanism underlying CCRCC resistance to chemotherapy and found that loss of PTEN in CCRCC may be involved. Knockdown of PTEN in the CCRCC cell line ACHN blocked etoposide-induced apoptosis and etoposide-impaired cell proliferation was also inhibited. It has been demonstrated that most chemotherapy drugs exert their anti-cancer effects via p53-mediated apoptosis, and in accordance, with this, the present study showed that treatment with etoposide significantly increased p53 levels. Silencing of PTEN in ACHN inhibited the Akt/HDM2 signaling cascade and depressed p53 expression, and the interaction between HDM2 and p53 was also enhanced. This was further verified in CCRCC tissue specimens from patients The results of the present study suggested that loss of PTEN, which deactivated Akt/HDM2 signaling followed by degradation of p53, may contribute to the development of etoposide resistance in CCRCC.

Effects of cyclooxygenase-2 gene silencing on the biological behavior of SKOV3 ovarian cancer cells.

The aim of the present study was to investigate the effects of plasmid-mediated RNA interference targeting of cyclooxygenase-2 (COX-2) on the biological behaviors of SKOV3 human ovarian cancer cells and to analyze the function of COX-2 in carcinogenesis and development of ovarian cancer. A COX-2 small hairpin (sh)RNA sequence was designed and synthesized and pGPU6-COX-2-shRNA plasmids were constructed. The recombinant vector plasmids were stably transfected into SKOV3 cells. The mRNA and protein expression of COX-2 was subsequently analyzed by quantitative polymerase chain reaction and western blot analysis, respectively. MTT and colony formation assays were used to detect the cellular proliferation ability and flow cytometry was performed to detect phase changes in the cell cycle. Finally, a Transwell assay was used to detect cell invasion. The SKOV3 cells, transfected with recombinant vector plasmids, and control cells, were injected into nude mice and the tumor emergence time, volume and weight were measured. The impact of COX-2 gene silencing on the growth of xenograft tumors in nude mice was analyzed. Following transfection of the pGPU6-COX-2-shRNA plasmid, in vitro analyses indicated that the shRNA efficiently suppressed the mRNA and protein expression of COX-2. COX-2 gene silencing significantly inhibited the proliferation and invasion ability of SKOV3 cells, leading to cell cycle arrest in G1. The tumor formation time in the interference group was significantly prolonged, and the tumor volume and weight were significantly decreased, as compared with the control group. Plasmid-mediated shRNA was shown to effectively silence COX-2 expression in SKOV3 ovarian cancer cells. It was identified that COX-2 functioned in regulating proliferation, cell cycle and invasion of ovarian cancer cells. These findings provided a theoretical basis for determining the function of COX-2 in the development of ovarian cancer and suggested that COX-2 may be an effective target for gene therapy and clinical applications.

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.

[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 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.

[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.