As placenta barrier controls material exchanges between mother and fetus during pregnancy, studies on the placental transport mechanism of drugs is of great importance to analyze the efficacy, safety and toxicity of drugs. BeWo cells are derived from human choriocarcinomas, which can form monolayer trophoblast cells to offers an efficient placenta barrier in vitro for estimating nutrient and drug intake, efflux and transport. This essay focuses on the establishment and characteristics of BeWo cell model, and the advance on studies on nutrient and drug intake, efflux and transport mechanism by applying the model.
Biological Transport ; Choriocarcinoma ; metabolism ; Female ; Humans ; Placenta ; metabolism ; Pregnancy ; Tumor Cells, Cultured ; metabolism ; Uterine Neoplasms ; metabolism

OBJECTIVETo investigate the feature of histomorphology and biology of uterine bizarre leiomyoma from the clinical, pathological features as well as the immunohistochemical expression.

METHODSTotally 25 cases of leiomyomas were studied. Among them, immuno-histochemical staining (SP and ABC methods) for smooth muscle actin (SMA), proliferative cell nucleus antigen (PCNA), estrogen receptors (ER), and progesterone receptors (PR) were performed in 20 cases. The clinical features and follow-up records were analyzed.

RESULTSThe main clinical findings were irregular vaginal bleeding, pain and pelvic tumor. One case was with immense amount of ascitis and the other two were with pregnancy. All the cases had no history of taking pregestine. Light microscopy showed that part of all the cell nuclei were bizarre, accompanying with double or multiple nuclei in which rather big and reddish staining inclusion bodies were obtained (D = 7 - 26 micro m), and the mitotic figures were 0 - 2/10 HPF. Among 20 cases with immunohistochemical staining, markers indicating muscle cells in origin were positive in the bizarre cells, 15 of which (75%) with negative or weak positive PCNA, and 18 of which (90%) with negative ER. There were significant difference between the studied and control groups (P = 0.027, P < 0.005 respectively) and in addition, PR was positive in both these two groups. A majority of the nucleus inclusion bodies was SMA positive. Follow-up records demonstrated so far no recurrence cases obtained.

CONCLUSIONSUterine atypical leiomyoma belongs to benign tumor, although its shape is bizarre. In this group, the morphology changes are correlated with pregnancy, but not with pregestine. The expression of immunohistochemistry shows certain features, and is important to identify uterine bizarre leiomyoma with leiomyosarcoma and STUMP in pathological diagnosis.

Adult ; Female ; Humans ; Immunohistochemistry ; Leiomyoma ; metabolism ; pathology ; Middle Aged ; Pregnancy ; Uterine Neoplasms ; metabolism ; pathology

OBJECTIVETo observe the cell binding characteristics of SonoVue microbubbles targeting choriocarcinoma cells and provide evidence for clinical ultrasonic localization of the tumor utilizing the microbubbles.

METHODSThe targeted microbubbles were prepared by conjugating anti-HCG antibody with the SonoVue microbubbles and added in choriocarcinoma cells or endometrial stromal cells to compare the cell binding rate of the agents under optical microscope and with flow cytometry.

RESULTSFlow cytometry demonstrated a binding rate of 77.6% between the SonoVue microbubbles and anti-HCG antibody. Light microscopy showed that the total rosette formation rate of the choriocarcinoma cells exposed to the targeted microbubble bearing anti-HCG antibody reached (87.8-/+6.3)%, significantly higher than that of the endometrial stromal cells [(9.4-/+1.7)%, P<0.05]. The binding rate of the targeted microbubbles with the choriocarcinoma cells before and after PBS washing were (85.4-/+4.7)% and (83.1-/+3.8)% (P>0.05), respectively, suggesting strong stability of the binding. The binding rate was 81.0% according to the results of flow cytometry.

CONCLUSIONThe targeted microbubbles as a contrast agent can efficiently bind to the choriocarcinoma cells in vitro with a stability sufficient to resist the blood flow.

Choriocarcinoma ; pathology ; Contrast Media ; metabolism ; Female ; Humans ; Microbubbles ; Phospholipids ; metabolism ; Pregnancy ; Sulfur Hexafluoride ; metabolism ; Uterine Neoplasms ; metabolism

OBJECTIVETo investigate the clinicopathologic significance of pin1 and PR in patients with endometrial adenocarcinoma.

METHODSThe expression of pin1 and PR were investigated by immunohistochemistry in a total of 50 endometrial adenocarcinoma specimens.

RESULTSPin1 was over expressed in 66% (33/50) of the cases. The expression rate decreased gradually with tumor differentiation(P<0.05). In addition, pin1 expression was negatively correlated with lymph node metastasis and invasive depth of myometrium. Moreover, pin1 was positively correlated with PR expression.

CONCLUSIONOur results suggest that pin1 may play important roles in the tumorigenesis and migration of endometrial cancer. Pin1 expression may be considered as a prognostic marker as PR in patients with endometrial cancer.

Adult ; Biomarkers, Tumor ; metabolism ; Endometrial Neoplasms ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Middle Aged ; NIMA-Interacting Peptidylprolyl Isomerase ; Peptidylprolyl Isomerase ; metabolism ; Receptors, Progesterone ; metabolism ; Uterine Neoplasms ; metabolism ; pathology

OBJECTIVE: To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism. METHODS: Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L). RESULTS: DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells. CONCLUSION CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.
Female ; Humans ; Cell Line, Tumor ; HeLa Cells ; Neoplastic Stem Cells/metabolism* ; RNA, Small Interfering/metabolism* ; Uterine Cervical Neoplasms/metabolism*

BACKGROUNDAdenomyosis (AM) has impaired contraction. This study aimed to explore the expression of potassium channels related to contraction in myometrial smooth muscle cells (MSMCs) of AM.

METHODSUterine tissue samples from 22 patients (cases) with histologically confirmed AM and 12 (controls) with cervical intraepithelial neoplasia were collected for both immunohistochemistry and real-time polymerase chain reaction to detect the expression of large conductance calcium- and voltage-sensitive K + channel (BKCa)-α/β subunits, voltage-gated potassium channel (Kv) 4.2, and Kv4.3. Student's t-test was used to compare the expression.

RESULTSThe BKCa-α/β subunits, Kv4.2, and Kv4.3 were located in smooth muscle cells, glandular epithelium, and stromal cells. However, BKCa-β subunit expression in endometrial glands of the controls was weak, and Kv4.3 was almost undetectable in the controls. The expression of BKCa-α messenger RNA (mRNA) (0.62 ± 0.19-fold decrease, P < 0.05) and Kv4.3 mRNA (0.67 ± 0.20-fold decrease, P < 0.05) decreased significantly in the MSMCs of the control group compared with the AM group. However, there were no significant differences in BKCa-β subunit mRNA or Kv4.2 mRNA.

CONCLUSIONSThe BKCa-α mRNA and the Kv4.3 mRNA are expressed significantly higher in AM than those in the control group, that might cause the abnormal uterus smooth muscle contractility, change the microcirculation of uterus to accumulate the inflammatory factors, impair the endometrium further, and aggravate the pain.

Adenomyosis ; metabolism ; Adult ; Female ; Humans ; Immunohistochemistry ; Large-Conductance Calcium-Activated Potassium Channels ; metabolism ; Male ; Myocytes, Smooth Muscle ; metabolism ; Potassium Channels, Voltage-Gated ; metabolism ; Real-Time Polymerase Chain Reaction ; Shal Potassium Channels ; metabolism ; Uterine Contraction ; physiology ; Uterine Neoplasms ; metabolism ; Uterus ; metabolism

Adult ; Carcinoma, Small Cell ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Leukosialin ; metabolism ; Lymphoma ; metabolism ; pathology ; Peroxidase ; metabolism ; Sarcoma, Myeloid ; metabolism ; pathology ; surgery ; Uterine Cervical Neoplasms ; metabolism ; pathology ; surgery ; Uterine Cervicitis ; metabolism ; pathology

PRUNE2 plays an important role in regulating tumor cell differentiation, proliferation, and invasiveness in neuroblastoma. Our previous study revealed that PRUNE2/OBSCN two-gene relative expression classifer accurately differentiated leiomyosarcoma from gastrointestinal stromal tumor. However, the association between PRUNE2 expression and prognosis in leiomyosarcoma is poorly understood. In this study, we evaluated the prognostic role of PRUNE2 in leiomyosarcoma. PRUNE2 expression was detected using immunohistochemistry in 30 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from MD Anderson Cancer Center, and high expression was detected in 36.7% (11/30) of the samples. To validate these results, immunohistochemistry was performed on another cohort of 45 formalin-fixed, paraffin-embedded leiomyosarcoma tissues from Tianjin Medical University Cancer Institute & Hospital, and high PRUNE2 protein expression was detected in 37.8% (17/45) of the samples. Moreover, elevated PRUNE2 expression was significantly associated with tumor size (P = 0.03) and hemorrhage/cyst (P = 0.014), and was an independent favorable prognostic factor for overall survival in leiomyosarcoma patients from Tianjin Medical University Cancer Institute & Hospital (P < 0.05). These data suggest that increased PRUNE2 protein expression may serve as a favorable prognostic marker in human leiomyosarcoma.
Biomarkers, Tumor ; metabolism ; Female ; Gastrointestinal Neoplasms ; metabolism ; mortality ; Humans ; Immunohistochemistry ; Leiomyosarcoma ; metabolism ; mortality ; Male ; Middle Aged ; Neoplasm Proteins ; metabolism ; Retroperitoneal Neoplasms ; metabolism ; mortality ; Skin Neoplasms ; metabolism ; mortality ; Survival Rate ; Uterine Neoplasms ; metabolism ; mortality

AIMTo investigate the expressions of main subtypes of heat shock protein (HSP) in cervical cancer and precancerosis tissues.

METHODSAccording to the pathological diagnosis, 478 cases of cervical biopsy specimen were divided into invasive carcinoma of cervix group (63 cases), cervical intraepithelial neoplasia group (CIN, 106 cases), chronic cervicitis group (293 cases) and normal uterine cervix (16 cases).The expression levels of HSP70, HSP90a and HSP90beta3 mRNA were detected by quantitative RT-PCR with specific complex cRNA as internal control.

RESULTS(1) The expressions of HSP70, HSP90a and HSP90beta mRNA were significantly down-trended stepwise in invasive carcinoma of cervix, CIN, chronic cervicitis and normal cervix tissue (P < 0.01, respectively). (2) In the invasive carcinoma of cervix group, the expression level of HSP90beta mRNA was higher in advanced stage (FIGO II b) compared with incipient(FIGO-II a) carcinoma of the cervix (P < 0.05). (3) The expressions of HSP70 and HSP90 mRNA were each higher in poorly differentiated tumor than in well-differentiated tumor (P < 0.05, respectively). (4) The expression levels of all three HSP mRNA had no significant differences, it was observed with different histological types of cervical cancer (P > 0.05).

CONCLUSIONHeat shock protein may play some important roles in malignant transformation of cervix cell and aggravation of cervix cancer. HSP70 and HSP90alpha may promote cancer cell transition and proliferation, and HSP90beta may participate in cell differentiation.

Carcinoma ; metabolism ; pathology ; Female ; HSP70 Heat-Shock Proteins ; metabolism ; HSP90 Heat-Shock Proteins ; metabolism ; Humans ; Precancerous Conditions ; metabolism ; pathology ; Tumor Cells, Cultured ; Uterine Cervical Neoplasms ; metabolism ; pathology ; Uterine Cervicitis ; metabolism ; pathology

Adult ; Aged ; Capsid Proteins ; metabolism ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cervical Intraepithelial Neoplasia ; metabolism ; pathology ; Diagnosis, Differential ; Female ; Humans ; Middle Aged ; Oncogene Proteins, Viral ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; pathology ; Uterine Cervicitis ; metabolism ; pathology ; Young Adult