Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

(E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to β-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-κB activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-α (TNF-α) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-κB-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-κB and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

Chorioamniotic membrane separation caused by the seromucinous collection from a placental chorioangioma

Placental chorioangioma is a benign non-trophoblastic tumor of the placenta that can have various adverse effects on the mother and fetus depending on its size. Chorioamniotic membrane separation is rare condition of detachment between the amniotic membrane and chorionic membrane. Chorioamniotic membrane separation after the second trimester of pregnancy is usually occurs after invasive procedures or may occur spontaneously; it is mostly associated with fetal abnormalities. Here, we report a case of chorioamniotic membrane separation that might be occurred caused by the seromucinous secretion from a placental chorioangioma.

(E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone displays suppression of inflammatory responses via inhibition of Src, Syk, and NF-kappaB

(E)-3-(3-methoxyphenyl)-1-(2-pyrrolyl)-2-propenone (MPP) is an aldol condensation product resulting from pyrrole-2-carbaldehyde and m- and p- substituted acetophenones. However, its biological activity has not yet been evaluated. Since it has been reported that some propenone-type compounds display anti-inflammatory activity, we investigated whether MPP could negatively modulate inflammatory responses. To do this, we employed lipopolysaccharide (LPS)-stimulated macrophage-like RAW264.7 cells and examined the inhibitory levels of nitric oxide (NO) production and transcriptional activation, as well as the target proteins involved in the inflammatory signaling cascade. Interestingly, MPP was found to reduce the production of NO in LPS-treated RAW264.7 cells, without causing cytotoxicity. Moreover, this compound suppressed the mRNA levels of inflammatory genes, such as inducible NO synthase (iNOS) and tumor necrosis factor (TNF)-alpha. Using luciferase reporter gene assays performed in HEK293 cells and immunoblotting analysis with nuclear protein fractions, we determined that MPP reduced the transcriptional activation of nuclear factor (NF)-kappaB. Furthermore, the activation of a series of upstream signals for NF-kappaB activation, composed of Src, Syk, Akt, and IkappaBalpha, were also blocked by this compound. It was confirmed that MPP was able to suppress autophosphorylation of overexpressed Src and Syk in HEK293 cells. Therefore, these results suggest that MPP can function as an anti-inflammatory drug with NF-kappaB inhibitory properties via the suppression of Src and Syk.

Experience of laparoscopic-assisted radical vaginal trachelectomy for 2 patients with cervical cancer stage I / 대한산부인과내시경학회지

Because of the organized screening programs, incidence and mortality of cervical cancer has been decreased and cervical cancer is diagnosed in relatively young age women and early stages. Traditional treatments for early cervical cancer are radical hysterectomy or chemoradiation, which irreversibly destroy reproductive capacity. Radical vaginal trachelectomy could be an alternative option for young women with early cervical cancer wishing to preserve fertility. Here, we report 2 cases of our initial experiences with Laparoscopy-Assisted Radical Vaginal Trachelectomy (LARVT) for patients with cervical cancer stage I. Two cases of 29 and 31-year-old nulliparous women were diagnosed with cervical cancer IA1-IA2. They underwent LARVT with permanent cervicoisthmic cerclage with 3 cycles of adjuvant chemotherapy. LARVT can be the procedure of choice for women with early stage cervical cancer who desire a fertility preservation.

Two Case Review of Transvaginal Cervicoisthmic Cerclage / 대한주산의학회잡지

The conventional treatment of cervical incompetence is cerclage operation. In most cases, the classical surgical cerclage methods described by McDonald and Shirodkar are performed. The cervicoisthmic cerclage is beneficial for the treatment of patients who have short cervix due to conization, cervisectomy or congenital anatomical deformity of uterus. This procedure is different from the classical McDonald and Shirodkar cerclages in that the suture site is placed at the junction of the cervix and the isthmus of uterine body. There are two approaches in cervicoisthmic cerclages, transabdominal and transvaginal ones. The transvaginal cervicoisthmic cerclage is easier to perform and less dependent on uterine size compared with the transabdominal cerclage. In addition there is less chance of direct uterine handling associated with bladder laceraton or fetal loss in transvaginal cervicoisthmic cerclage. We report two cases of transvaginal cervicoisthmic cerclage for the first time in Korea, in which patients have delivered at full term by cesarean section.

A study on clinicopathological characteristics of ovarian masses / 대한산부인과학회지

OBJECTIVE: The aim of this study was to know the clinicopathological characteristics that help to make a decision about diagnosis and treatment of ovarian masses in Korean women. METHODS: Women who were undergone operations and histopathologically confirmed as ovarian masses at Inje University Busan Paik Hospital and Donrae Paik Hospital from January of 1997 to June of 2009 were enrolled in this study. Distribution according to histopathological types and ages were analyzed. RESULTS: Of the 2875 cases, there were 1078 cases (37.5%) of non neoplastic masses and 1797 cases (62.5%) of neoplastic masses. In the neoplatic masses, there were 1286 cases (44.7%) of benign tumors, 140 cases (4.9%) of borderline tumors and 371 cases (12.9%) of malignant tumors. Endometriomas were most common tumors (644 cases, 59.7%) among non-neoplastic masses. Mature cystic teratomas were the most common tumors (598 cases, 46.5%) among benign tumors. Mucinous cystadenomas were the most common types (105 cases, 75.0%) among borderline tumors. Epithelial ovarian cancers were the most common types (267 cases, 72.0%) among malignant tumors. As the result of age distribution, mature cystic teratomas were the most common types of the women of the first and second decade, endometriomas were the most common types of the women of the third and fourth decade, and benign epithelial tumors were the most common types of the women of fifth and after sixth decade. CONCLUSION: Taken as a whole, neoplastic ovarian masses were more common than non-neoplastic masses, but most common ovarian mass was endometrioma which is non-neoplastic mass.

Inhibition of cell growth and apoptosis in CaSki, cervical cancer cell line by arsenic compounds / 대한산부인과학회지

OBJECTIVE: To compare inhibition of cell growth and apoptosis in human cervical cancer cell lines (CaSki) by paclitaxel, cisplatin, arsenic trioxide and tetraarsenic oxide. METHODS: Inhibition of cell growth was determined by the water-soluble tetrazolium salts (WSTs) -1 assay. For apoptosis analysis in CaSki cell line treated with single or combination of two agents, CaSki cell line treated with each agent was stained with annexin-V/PI and flow cytometry was performed. RESULTS: Progression of apoptosis in CaSki cell line treated with paclitaxel, cisplatin, arsenic trioxide, and tetraarsenic oxide was time dependent. Inhibition of cell growth in CaSki cell line by paclitaxel, cisplatin, arsenic trioxide, and tetraarsenic oxide was dose and time dependent. Especially, tetraarsenic oxide was more effective in inhibition of CaSki cell growth compared to arsenic trioxide. Group treated with combination of cisplatin and tetraarsenic oxide showed more progressive apoptosis compared to other combination group. CONCLUSION: Tetraarsenic oxide has more potent anti-tumor effects than other agents on CaSki cell line. We need to consider further study about antitumor effect of tetraarsenic oxide through clinical study.

Reduced Mitochondrial Properties in Putative Progenitor/Stem Cells of Human Keratinocytes

BACKGROUND: The characterization of progenitor/keratinocyte stem cells (KSC) remains an unachieved goal. A previous study showed that rapid adhering cells to collagen IV had the characteristics of putative progenitor/KSCs. OBJECTIVE: The purpose of this study was to investigate the genetic expression of rapid adhering cells compared to non adhering cells to determine the characteristic of KSCs. METHODS: We isolated rapid adhering cells representative of KSCs from non adhering cells representative of transient amplifying cells. In addition, we differentiated cells from human tonsilar keratinocytes utilizing the adhering capability of the KSCs to collagen IV. Annealing control primer based differentially displayed polymerase chain reaction (PCR) was performed as well as Western blot analysis. RESULTS: The levels of mitochondria-related gene expression were low in the rapid adhering cells compared to the non adhering cells. Mitochondrial complex I, COX IV, peroxiredoxins (I, II and IV) and mitochondrial membrane potential were all low in the rapid adhering cells compared to the non adhering cells. CONCLUSION: Using an adhesion method on human collagen IV-coated plates, our results suggest that reduced mitochondrial function may be an important characteristic of KSCs.

Maternal and Perinatal Outcomes of Early- and Late-onset Preeclampsia / 대한주산의학회잡지

PURPOSE: Early-onset preeclampsia is thought to be associated with fetal mortality and maternal complications. We compared maternal clinical characteristics, complications, and perinatal outcome between early- and late-onset preeclampsia. METHODS: We analysed retrospectively 212 pregnant women with preeclampsia between 2004 and 2008 at a tertiary university hospital. We divided preeclamptic women as early-onset (n=58), with an onset before 32 weeks gestation, and late-onset (n=154), with an onset after 32 weeks gestation. We compared maternal characteristics, maternal complications, and neonatal outcomes between the two groups. RESULTS: There were no significant differences in maternal age, parity, BMI, previous history of preeclampsia, hypertension, and DM between early- and late-onset preeclampsia. Among the maternal complications, maternal blood pressure was higher in early-onset preeclampsia without any statistical significance, but the amount of 24 hours urine protein was significantly higher in early-onset preeclampsia than late-onset (P=0.003). There were significantly higher rate of visual disturbance, elevated liver enzyme, pulmonary edema and severe disease in early-onset preeclampsia (all P<0.05). Comparing neonatal outcome, there were higher rate of fetal death in uterus (FDIU) (P=0.0001), low Apgar score (P<0.0001), and perinatal death (P<0.0001) in early-onset preeclampsia. Fetal birth weight and onset of preeclampsia were significant covariate factors for perinatal mortality. CONCLUSION: Early-onset preeclampsia was related to poor perinatal and materanl outcomes, but there was no difference in maternal characteristics. Further studies are necessary for prediction, pathogenesis, and therapy of early-onset preeclampsia.

Analysis of residual tumor based on pathologic severity and site of positive margin after cold-knife conization of the uterine cervix / 대한산부인과학회지

OBJECTIVE: To evaluate correlation of sites of positive margin and residual tumor and to establish management after conization. METHODS: Of 599 cold-knife conizations [15 (2.6%) with cervical intraepithelial neoplasia (CIN) I, 37 (6.1%) with CIN II, 450 (75.1%) with CIN III, 97 (16.2%) with microinvasion] performed at our institution from January, 1993 to June, 2006, 144 patients (24.0%) had positive margins and 113 patients were included in the retrospective study excluding 31 cases that were not followed more than 12 months. Correlation of conization pathology and residual tumor according to sites of positive margin were evaluated. RESULTS: The prevalence rates of positive margins were 6.7% (1/15) in CIN I, 21.6% (8/37) in CIN II, 21.1% (95/450) in CIN III, and 41.2% (40/97) in microinvasion. The prevalence rate of positive margin increased with severity of conization pathology (P=0.0001). Of 113 patients followed more than 12 months, 27.4% (31/113) had residual tumor [0.0% (0/1) in CIN I, 12.5% (1/8) in CIN II, 18.9% (14/74) in CIN III, and 53.3% (16/30) in microinvasion]. The prevalence rate of residual tumor increased with severity of conization pathology (P=0.0028). Residual tumor was more common in patients in whom both endocervical and exocervical margins or in whom only the endocervical margin were involved than in those in whom only exocervical margin was involved [87.5% (7/8) or 35.3% (24/68) versus 0% (0/37), respectively]. CONCLUSIONS: Expectant management is reasonable for patients with positive margin after conization. However, careful follow-up of these patients is essential, particularly in endocervical involvement.

Comparisons of clinicopathologic characteristics and prognostic factors between squamous cell carcinoma and adenocarcinoma of the uterine cervical cancer patients underwent radical hysterectomy and pelvic lymphadenectomy / 부인종양

OBJECTIVE: To compare clinicopathologic characteristics and prognostic factors between squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the uterine cervix. METHODS: We reviewed medical records and pathologic reports of 568 patients with SCC and 78 patients with AC who underwent radical hysterectomy and pelvic lymphadenectomy from January 1988 to December 2004. We analyzed clinicopathologic factors and 5-years survival rate (5-YSR), and than compared 5-YSR between SCC and AC according to clinicopathologic factors. RESULTS: At the stage I, the incidence of AC (82.0%) was more than SCC (69.6%) and at the stage II, the incidence of SCC (30.4%) was higher than AC (18.0%). The rate of lymph-vascular space invasion was higher in SCC (28.2%) than AC (15.4%). The 5-YSR was not different between SCC (85.7%) and AC (86.9%). In multivariate analysis, depth of invasion, resection margin, pelvic lymph node metastasis were independent prognostic factors in SCC and FIGO stage, pelvic lymph node metastasis were independent prognostic factors in AC significantly. At the 5-YSR between SCC and AC, the prognosis of AC (50.0%) was poorer than SCC (78.0%) in the case of the one pelvic lymph node metastasis (p=0.0632). CONCLUSION: The FIGO stage and lymph-vascular space invasion were significant different in clinicopathologic characteristics between SCC and AC. The prognosis of AC was poorer than SCC in the case of the one pelvic lymph node metastasis (p=0.0632). But, the overall 5-YSR was not different between SCC and AC.

The spectrum of 5p deletion in Korean 20 patients with Cri du chat syndrome

PURPOSE: Cri-du-Chat syndrome (CdCs) is a rare but clinically recongnizable condition with an estimated incidence of 1:50,000 live births. The clinical characteristics of the syndrome include severe psychomotor and mental retardation, microcephaly, hypertelorism, hypotonia, and slow growth. Also the size of the chromosome 5p deletion ranges were known from the region 5p13 to the terminal region. In this study, we report the spectrum of 5p deletion in Korean 20 pts. with CdCs and genotype-phenotype associations in CdCs. METHODS: In order to delineate genotype-phenotype correlation, molecular cytogenetic studies including GTG banding and clinical characterization were performed on Korean 20 pts with CdCs including parents. CGH array and Fluorescence in situ hybridization (FISH) analysis were used to confirm a terminal deletion karyotype and map more precisely the location of the deletion breakpoint. RESULTS: Molecular analysis of the spectrum of 5p deletion revealed 9 pts (45%) with a del (5)(p14), 7 pts. (35%) a del (5)(p13), 3 pts. (15%) a del (5)(p15.1) and 1 pt. (5%) a del (5)(p15.2) in 20 pts with CdCs. 4(20%)pts were identified to have additional chromosome abnormalites of deficiency and duplication involving chromosomes of 6, 8, 18, & 22. Parental study identified 3 familial case (2 paternal and 1 maternal origin) showing parents being a balanced translocation carrier. And the comparison study of the deletion break points among these 20 pts. with their phenotype has showed the varying clinical pheno-types in the CdCs critical region. CONCLUSION: The characterization of 5p deletion including parental study may help to delineate the genotypephenotype correlation in CdCs. Also these molecular cytogenetic analyses will be able to offer better information for accurate genetic diagnosis in CdCs and further make possible useful genetic counseling in pts. and family.

The Effects of Body Mass Index on Baseline Hormonal Status and Glucose Metabolism in Women with Chronic Anovulation / 대한불임학회지

OBJECTIVE: To assess the difference of baseline hormonal status and pathophysiology, and confirm the risk factors for long term complication according to Body Mass Index in women with polycystic ovary syndrome. MATERIALS AND METHODS: Serum level of LH, FSH, Estradiol, Prolactin, Testosterone, DHEA-S, fasting insulin were measured and 100 gm oral glucose tolerance test and endometrial biopsy were performed in total 75 chronic anovulation patients and 20 normal cycling infertility patients. 95 evaluated patients were divided into 3 groups including patients with chronic anovulation having BMI below 25, BMI beyond 25.1, normal cycling infertility patients, Group 1 (n=39), Group 2 (n=36), Group 3 (n=20), respectively. Statistical analysis was performed respect to relationship between BMI and measured hormone level, sum of glucose level during 100 gm OGTT, insulin resistance using t-test, ANOVA test, Post Hoc test, Mann-Whitney test. p<0.05 was considered as statistically significant. RESULTS: Serum LH level and LH/FSH ratio was significantly higher in Group 1, compared than Group 2 or 3 (p<0.05), BMI and LH, LH/FSH ratio was negatively correlated (r=-0.351, r=-0.318). There was no significant difference according to BMI in FSH, testosterone, estradiol, prolactin, DHEA-S level. Fasting insulin and sum of glucose level during 100 gm OGTT were significantly higher in Group 2 compared than Group 1 or Group 3 (p<0.05), there was no significant difference between Group 1 and Group 3. Insulin resistance was more frequently identified in Group 2 compared than Group 1 (p=0.001). CONCLUSIONS: BMI and LH, LH/FSH ratio were negatively correlated, so clinical significance of LH, LH/FSH ratio in diagnosis of PCOS may be attenuated by increasing body weight. Overweight patients with chronic anovulation may be the risk group for developing insulin resistance, hyperinsulinemia, glucose intolerance, later type 2 DM. Hyperinsulinemia may operate mainly in overweight chronic anovulation patients in development of hyperandrogenism.

Expression of p53 and c-erbB-2 Proteins as a Prognostic Factor in Patients with Gastric Carcinomas

Gastric cancer is not only one of the most common cancers in the world but also one of the most important malignant tumors in terms of incidence in Korea. In spite of it's clinical significance, the mechanism of malignant transformation in the stomach has not yet been well characterized. Recent studies disclosed enormous data suggesting that the p53 protein and the c-erbB-2 proto-oncogene have a critical role in the tumorogenesis of gastric cancer. More recently, the expression of the p53 protein has been associated with increased proliferative activity, but serves as a poor prognostic indicator in the case of patients for whom aggressive adjuvant therapy is required. Amplification of the c-erbB-2 oncogene has also been reported in gastric cancer. In the case of breast cancer, it has been demonstrated that no close correlation exists between the c-erbB-2 expression and the prognosis. However, no reports describe the relation between c-erbB-2 expression, p53 expression, PCNA expression and the prognosis for patients with gastric cancer. So this study was done to evaluate the expression of the p53 and c-erbB-2 and to assess the prognostic value in patients eith gastric cancer. The results are as follows: 1) The overall expression rates for p53 and c-erbB-2 were 38% and 20%, respectively. 2) There was no close relation between the expression rate of p53 and the tumor size, the Borrmann type, the nodal involvement, distant metastasis, Ming's classification, or Lauren's classification. The expression rate of p53 was closely related the tumor stage. 3) The expression rate of p53 in tumors which expressed PCNA was higher than that in tumors which did not express PCNA (p5 cm) was higher than that in small tumors(0.05). 6) The overall cumulative 5-year survival rate in the positive expression group for c-erbB-2 was lower than that in the negative group and the difference was statistically significant(p<0.05). In conclusion, it is suggested that p53 expression can not used as a prognostic factor for gastric cancer, but c-erbB-2 may be such a prognostic factor.