SOX1 Functions as a Tumor Suppressor by Repressing HES1 in Lung Cancer.

The development of lung cancer is a complex process that involves many genetic and epigenetic changes. Sex-determining region Y (SRY)-box (SOX) genes encode a family of proteins that are involved in the regulation of embryonic development and cell fate determination. SOX1 is hypermethylated in human cancers. However, the role of SOX1 in the development of lung cancer is unclear. We used quantitative methylation-specific polymerase chain reaction (MSP), quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis, and web tools to confirm the frequent epigenetic silencing of SOX1 in lung cancer. Stable overexpression of SOX1 repressed cell proliferation, anchorage-independent growth, and invasion in vitro as well as cancer growth and metastasis in a xenograft mouse model. Knockdown of SOX1 by the withdrawal of doxycycline partly restored the malignant phenotype of inducible SOX1-expressing NSCLC cells. Next, we discovered the potential downstream pathways of SOX1 using RNA-seq analysis and identified HES1 as a direct target of SOX1 using chromatin immunoprecipitation (ChIP)-PCR. Furthermore, we performed phenotypic rescue experiments to prove that overexpression of HES1-FLAG in SOX1-expressing H1299 cells partly reversed the tumor-suppressive effect. Taken together, these data demonstrated that SOX1 acts as a tumor suppressor by directly inhibiting HES1 during the development of NSCLC.

Purification of Colon Carcinoma Cells from Primary Colon Tumor Using a Filtration Method via Porous Polymeric Filters.

Cancer stem cells (CSCs) or cancer-initiating cells (CICs) are key factors for tumor generation and metastasis. We investigated a filtration method to enhance CSCs (CICs) from colon carcinoma HT-29 cells and primary colon carcinoma cells derived from patient colon tumors using poly(lactide-co-glycolic acid)/silk screen (PLGA/SK) filters. The colon carcinoma cell solutions were permeated via porous filters to obtain a permeation solution. Then, the cell cultivation media were permeated via the filters to obtain the recovered solution, where the colon carcinoma cells that adhered to the filters were washed off into the recovered solution. Subsequently, the filters were incubated in the culture media to obtain the migrated cells via the filters. Colon carcinoma HT-29 cells with high tumorigenicity, which might be CSCs (CICs), were enhanced in the cells in the recovered solution and in the migrated cells based on the CSC (CIC) marker expression, colony-forming unit assay, and carcinoembryonic antigen (CEA) production. Although primary colon carcinoma cells isolated from colon tumor tissues contained fibroblast-like cells, the primary colon carcinoma cells were purified from fibroblast-like cells by filtration through PLGA/SK filters, indicating that the filtration method is effective in purifying primary colon carcinoma cells.

Enrichment of cancer-initiating cells from colon cancer cells through porous polymeric membranes by a membrane filtration method.

Cancer-initiating cells (CICs) or cancer stem cells (CSCs) are primarily responsible for tumor initiation, growth, and metastasis and represent a few percent of the total tumor cell population. We designed a membrane filtration protocol to enrich CICs (CSCs) from the LoVo colon cancer cell line via nylon mesh filter membranes with 11 and 20 µm pore sizes and poly(lactide-co-glycolic acid)/silk screen (PLGA/silk screen) porous membranes (pore sizes of 20-30 µm). The colon cancer cell solution was filtered through the membranes to obtain a permeate solution. Subsequently, the cell culture medium was filtered through the membranes to collect the recovery solution where the cells attached to the membranes were rinsed off into the recovery solution. Then, the membranes were cultivated in the cultivation medium to collect the migrated cells from the membranes. The cells migrated from any membrane had higher expression of the CSC surface markers CD44 and CD133, had higher colony formation levels, and produced more carcinoembryonic antigen (CEA) than the colon cancer cells cultivated on conventional tissue culture plates (control). We established a method to enrich the CICs (CSCs) of colon cancer cells from migrated cells through porous polymeric membranes by the membrane filtration protocol developed in this study.

Painless ovarian tumor mimics ovarian cancer with all ligaments spontaneously detached: A case report.

OBJECTIVE: Ovarian tumor is a frequently encountered gynecological disease. The tumor is usually anchored by a pedicle. In rare cases, it may detach and derive nourishment from other abdominal structures to which it adheres. Even rarer is for the tumor to be freely mobile, with no ligamentous attachment. CASE REPORT: A 21-year-old woman with delayed menstruation and chronic low abdominal pain for months, had a well-defined cystic lesion of approximately 9 × 9 cm in the middle of the pelvis, identified on transabdominal sonography and abdominal computed tomography. During an exploratory laparotomy, we found an ovarian tumor on the left side of the pelvis, in which the pedicle had spontaneously detached; it was removed without dissection or resection. The tumor was well-encapsulated and suspended without any ligament attachments. CONCLUSION: Freely mobile ovarian tumors with all ligaments spontaneously detached may be misdiagnosed because there is no pain caused by torsion. The absence of blood flow leads to internal necrosis, easily mistaken for malignancy or other diseases. Also, the location may change from the time images are captured until surgery. Surgery is the best option, regardless of the final diagnosis.

Residual ovarian syndrome: A case report with classic symptoms, imaging and pathology findings, and treatment.

OBJECTIVE: Residual ovarian syndrome (ROS) occurs after a hysterectomy in which one or both ovaries have been preserved and cause chronic pelvic pain, an asymptomatic pelvic mass, or dyspareunia. We present a case with classic symptoms and imaging and pathology findings, and review the treatment of residual ovarian syndrome. CASE REPORT: A 35-year-old woman with a diagnosis of ROS. CONCLUSION: Based on previous literature, almost 50% of patients with ROS require surgery for their symptoms. Treatment of ROS with gonadotropin-releasing hormone analogs or high dose progestogens may be helpful. However, there are limited data supporting the efficacy of pharmacologic therapy. Patients receiving pharmacologic therapy should be counseled about the limited data supporting the efficacy of this approach, the lack of a histologic diagnosis, and the risk of ovarian cancer in residual tissue.

Knockdown of POLDIP2 suppresses tumor growth and invasion capacity and is linked to unfavorable transformation ability and metastatic feature in non-small cell lung cancer.

The main problem in the treatment of non-small cell lung cancer (NSCLC) is metastasis. Epithelial-mesenchymal transition (EMT) is known as the critical signaling in tumor progression, metastasis, and also the drug resistance. In this study, we reported a novel gene Polymerase delta-interacting protein 2 (POLDIP2) was downregulated in NSCLC tissues and first demonstrated that overexpression of POLDIP2 increased the anchorage-independent growth (AIG) and invasiveness of H1299 cells. In addition, we examined that knockdown of POLDIP2 in H1299 and A549 cells reduced tumorigenicity and metastatic capacity in vitro and also in vivo. Moreover, downregulation of the cell proliferation marker cyclin D1 and EMT markers CDH2, Slug, and Twist was showed in H1299 cells by POLDIP2 knockdown, suggesting that the inhibition of malignancy was affected by modulating key genes for tumor growth and invasiveness. Taken together, our study is the first study that demonstrated that POLDIP2 gene was function as an oncogene in NSCLC and implied the oncogenic ability might be through promoting cell proliferation or EMT.

The impact of prenatal group B streptococcus screening as a national health policy in Taiwan.

OBJECTIVE: There was no national data on group B streptococcus (GBS) infections in Taiwan. Until 2012, when prenatal GBS screening was introduced to obstetric practices as a national health policy aimed at reducing neonatal GBS infections. The purpose of this study was to examine the impact of this national health policy on the incidence of maternal GBS colonization and neonatal GBS infection rate. Relatedly, the clinical characteristics of neonatal GBS infection were investigated to determine the correlations between the incidence of maternal GBS colonization and the neonatal GBS infection rate. MATERIALS AND METHODS: This population-based nationwide study used data for 2012-2013 from the National Health Insurance Research Database of Taiwan. A total of 789 newly diagnosed pregnant women with genital GBS infection were recruited. RESULTS: The maternal GBS screening rate was 93.2%. The maternal colonization rate of GBS was around 8.2%, and the incidence of neonatal GBS infection was 22.6%. The data indicate that no sepsis was developed in any of the cases, while fever was found in 3 cases (3/179, 1.7%) and UTI was found in 1 case (1/179, 0.6%). CONCLUSIONS: We conclude that a policy calling for universal maternal rectovaginal cultures for GBS with intrapartum antibiotic prophylaxis is a good national policy for reducing morbidity due to GBS infections in neonates in Taiwan.

Dandy-Walker syndrome with duplex kidney abnormalities in trisomy 18 - A rare case report.

OBJECTIVE: Trisomy 18 is one of the major numerical chromosomal disorders. The incidence of trisomy 18 is approximately one in 6000 live births. Dandy-Walker malformation (DWM) is the most common congenital malformation of the cerebellum, with an incidence of about one in 5000 live births. The incidence of trisomy 18 associated with DWM is rare and long-term survival rate is very low. CASE REPORT: A case involving a 39-year-old pregnant female with a case of trisomy 18 associated with DWM. CONCLUSION: The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition. We report a case involving a 39-year-old pregnant female with a case of trisomy 18 associated with Dandy-Walker malformation (DWM). Fetal ultrasonography showed hypoplasia of the cerebellar vermis and dilatation of the fourth ventricle and was characterized by an enlarged posterior fossa. Fetal magnetic resonance imaging showed inferior vermian hypoplasia and a large posterior fossa cyst communicating with the fourth ventricle causing high insertion of the torcular herophili, which was compatible with DWM. Furthermore, the karyotyping report revealed trisomy 18. The incidence of trisomy 18 associated with DWM is rare, and our report presents an unusual case that supplements our knowledge of this condition.

Pregnancy in a noncommunicating rudimentary horn of a unicornuate uterus: Prerupture diagnosis and management.

OBJECTIVE: The estimated incidence of rudimentary horn pregnancy is one in 76,000. It is a life-threatening entity with a 50% risk of uterine rupture. With advances in prenatal ultrasound in recent decades, there may be an opportunity to detect rudimentary horn pregnancy earlier, resulting in a lower incidence of maternal morbidity and mortality. Management is typically resection of the rudimentary horn and the ipsilateral fallopian tube by either laparotomy or laparoscopy. CASE REPORT: Here, we present the case of a 22-year-old woman with a suspected ectopic pregnancy of 12 weeks' gestation. Ultrasound and magnetic resonance imaging were performed as preoperative evaluations. A definitive diagnosis was made during laparotomy, and resection of the rudimentary horn pregnancy was performed. CONCLUSION: Diagnosis and management of rudimentary horn pregnancy remain a challenge. We should be alert to prenatal ultrasound with the intention of making an earlier diagnosis, thereby resulting in decreased maternal morbidity and mortality.

Gestational choriocarcinoma with renal and pulmonary metastases lacking a primary uterine origin.

OBJECTIVE: We describe a case of gestational choriocarcinoma metastasized to the kidney and lung, which presented initially as refractory hematuria after a term pregnancy 5 years earlier. CASE REPORT: A 35-year-old woman, G2P1, with a previous history of full-term pregnancy in 2009, presented to the emergency department complaining of intermittent gross hematuria for 2 months. Abdominal computed tomography showed a suspicious arteriovenous malformation in the right kidney and a thrombus within the right renal vein. Transarterial embolization was performed twice to treat the refractory hematuria but was unsuccessful, and radical nephrectomy of the right kidney was performed. The diagnosis was gestational metastatic choriocarcinoma of the kidney based on morphological, immunohistochemical, and DNA studies. Lung metastases were found by computed tomography of the chest. Pelvic ultrasound was performed but showed no primary tumor in the uterine cavity. After surgical intervention, adjuvant chemotherapy involving first single-agent chemotherapy with methotrexate followed by multiagent chemotherapy (EMACO regimen) failed. CONCLUSION: In women of reproductive age, unexplained hematuria should raise concerns about possible choriocarcinoma, either metastatic gestational or primary nongestational choriocarcinoma of the kidney.

Quantitative DNA methylation analysis of selected genes in endometrial carcinogenesis.

OBJECTIVE: Most endometrial carcinomas appear to develop from precursors (e.g., endometrial hyperplasia) that progress for several years. Patients who are ultimately diagnosed with carcinoma often present clinically with complaints of abnormal vaginal bleeding years before diagnosis, which offers an opportunity for early diagnosis and curative treatment. The analysis of DNA methylation may be used as a method for detecting endometrial cancer (EC). To test the potential clinical application of this method, we used quantitative methylation analysis of five genes in a full spectrum of endometrial lesions. MATERIALS AND METHODS: This hospital-based, prospective, case-controlled study was conducted on 68 patients, which included patients who had a normal endometrium (n = 18), hyperplasia of the endometrium (n = 24), and EC (n = 26). Methylation levels of the following genes were determined by using real-time methylation-specific polymerase chain reaction (PCR) amplification: zinc finger protein 177 (ZNF177), collagen type XIV α1 (COL14A1), dihydropyrimidinase-like 4 (DPYSL4), homeobox A9 (HOXA9), transmembrane protein with epidermal growth factor-like and two follistatin-like domains 2 (TMEFF2). The methylation index (MI) cutoff values for the different diagnoses were determined to test the sensitivity and specificity of the method and to generate the receiver operating characteristic (ROC) curves. The Mann-Whitney U test was used to test between-group differences in the MI. RESULTS: The MI of the five genes was significantly higher in EC than the MIs in specimens of hyperplasia of endometrium and normal appearance (p < 0.001). The ROC analysis demonstrated that the sensitivity, specificity, and accuracy for detecting EC were 92.3%, 94.4%, and 95.1%, respectively, for ZNF177; 92.3%, 94.4%, and 95.7%, respectively, for COL14A1; 80.8%, 94.4%, and 81.4%, respectively, for HOXA9; 65.4%, 94.4%, and 89.5%, respectively, for TMEFF2; and 61.5%, 94.4%, and 63.3%, respectively, for DPYSL4. The combined testing of ZNF177 and COL14A1 had the best specificity (100%), but compromised sensitivity (88.5%). CONCLUSION: Promoter methylation of ZNF177, COL14A1, HOXA9, DPYSL4, and TMEFF2 genes is a frequent epigenetic event in EC. Furthermore, the epigenetic hypermethylation of TMEFF2 may be a valuable marker for identifying undetected EC within endometrial hyperplasia.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients.

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening.

Methylation of IRAK3 is a novel prognostic marker in hepatocellular carcinoma.

AIM: To examine the methylation levels of interleukin-1 receptor-associated kinase 3 (IRAK3) and GLOXD1 and their potential clinical applications in hepatocellular carcinoma (HCC). METHODS: mRNA expression and promoter methylation of IRAK3 and GLOXD1 in HCC cells were analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and methylation-specific PCR (MSP), respectively. Using pyrosequencing results, we further established a quantitative MSP (Q-MSP) system for the evaluation of IRAK3 and GLOXD1 methylation in 29 normal controls and 160 paired HCC tissues and their adjacent nontumor tissues. We also calculated Kaplan-Meier survival curves to determine the applications of gene methylation in the prognosis of HCC. RESULTS: IRAK3 and GLOXD1 expression was partially restored in several HCC cell lines after treatment with 5-aza-2'-deoxycytidine (DNA methyltransferase inhibitor; 5DAC). A partial decrease in the methylated band was also observed in the HCC cell lines after 5DAC treatment. Using GLOXD1 as an example, we found a significant correlation between the data obtained from the methylation array and from pyrosequencing. The methylation frequency of IRAK3 and GLOXD1 in HCC tissues was 46.9% and 63.8%, respectively. Methylation of IRAK3 was statistically associated with tumor stage. Moreover, HCC patients with IRAK3 methylation had a trend toward poor 3-year disease-free survival (P < 0.05). CONCLUSION: IRAK3 and GLOXD1 were frequently methylated in HCC tissues compared to normal controls and nontumor tissues. IRAK3 methylation was associated with tumor stage and poor prognosis of patients. These data suggest that IRAK3 methylation is a novel prognostic marker in HCC.

Arterial blood and end-tidal concentrations of sevoflurane during the emergence from anesthesia in gynecologic patients

OBJECTIVE: The end-tidal concentration of inhalation anesthetics is a clinical indicator for predicting the emergence from anesthesia. This study was conducted to assess the relationship between arterial blood and end-tidal sevoflurane concentrations during emergence. METHODS: Thirty-two female American Society of Anesthesiologists physical status I-II patients receiving general anesthesia for elective gynecologic surgery were included. A fixed dose of 3.5% inspiratory sevoflurane in 6 L min-1 oxygen was maintained until the end of surgery. At 20 and 10 minutes before and 0, 5, 10, 15, and 20 minutes after discontinuing sevoflurane, as well as at the time of eye opening by verbal command, defined as awakening, 1 ml arterial blood was obtained to measure its sevoflurane concentration by gas chromatography. Simultaneous inspiratory and end-tidal concentrations of sevoflurane were detected by an infrared analyzer and tested by Bland-Altman agreement analysis. RESULTS: The arterial blood concentrations of sevoflurane were similar to the simultaneous end-tidal concentrations during emergence: 0.36% (0.10) and 0.36% (0.08) sevoflurane at awakening, respectively. The mean time from discontinuing sevoflurane to eye opening was 15.8 minutes (SD 2.9, range 10-26) and was significantly correlated with the duration of anesthesia (52-192 minutes) (P = 0.006) but not with the body mass index or total fentanyl dose. CONCLUSION: The mean awakening arterial blood concentration of sevoflurane was 0.36%. The time to awakening was prolonged in accordance with the anesthetic duration within 3 hours. With well-assisted ventilation during emergence, the sevoflurane end-tidal concentration was nearly equal to its arterial blood concentration, which could be a feasible predictor for awakening. .

Major risk factors for stillbirth in different trimesters of pregnancy--a systematic review.

Stillbirth remains an event that has an important impact on global health issues. Different levels of health care between countries suggest that the stillbirth rate may be one of the indicators of the quality of a country's medical system. In this review, major risk factors for stillbirth will be discussed, especially in different trimesters of pregnancy. Early identification of risk factors for stillbirth and appropriate antenatal management may reduce preventable stillbirths and improve general outcomes of pregnancy.

Rare case of a paratubal cystadenoma with bilateral hydrosalpinges in an infertile woman.

OBJECTIVE: Serous tumors can occur on the surface of the ovaries and-rarely-as primary tumors on the peritoneal surface. However, the origin of extraovarian serous tumors is unknown. An unusual case of a serous tumor is presented here. CASE REPORT: A 34-year-old nulligravid woman presented for evaluation of her primary infertility, with acute abdominal pain. At laparoscopy, a paratubal cyst, independent of the ovaries, was found to be associated with bilateral hydrosalpinges. The final pathology diagnosis was of a benign paratubal serous cystadenoma. CONCLUSION: We present an unusual case of a paratubal serous cystadenoma with bilateral hydrosalpinges in an infertile woman, which was resected laparoscopically..

The accuracy of magnetic resonance imaging for preoperative deep myometrium assessment in endometrial cancer.

OBJECTIVE: To evaluate the accuracy of preoperative magnetic resonance imaging (MRI) to detect deep myometrial invasion in patients with endometrial cancer. MATERIALS AND METHODS: We retrospectively reviewed 66 cases of women with endometrial cancer, who underwent preoperative MRI assessment and surgical staging between January 2006 and October 2010. The MRI findings were then compared with the pathology results. The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI in detecting deep myometrium invasion were evaluated. RESULTS: The sensitivity, specificity, accuracy, PPV, and NPV results of MRI for the detection of deep myometrium invasion were 92.52%, 74.35%, 81.81%,71.42%, and 93.54%, respectively, with a kappa of 0.64. In the postmenopausal group, the values were 100%, 55.5%, 74.19%, 61.9%, and 100%. In the premenopausal women, they improved to 85.7%, 90.47%, 88.57%, 88.71%, and 90.47%. The sensitivity (100%) was better than the specificity (55.56%) in the postmenopausal women. The predictive value was markedly higher in the premenopausal women than the postmenopausal women (85.7% vs. 61.9%). CONCLUSION: In patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.

Analysis of intrauterine fetal demise--a hospital-based study in Taiwan over a decade.

OBJECTIVE: To identify timing-specified risk factors for stillbirth, in order to help physicians to reduce preventable factors and stillbirths, and improve general outcomes of pregnancy. MATERIALS AND METHODS: A retrospective analysis was performed of births registered in our hospital, a medical center in Taiwan, between September 1, 1999 and December 31, 2011. We collected basic characteristics from the medical records, including maternal and fetal conditions. All stillbirths were divided into two groups according to gestational age: the second trimester group and the third trimester group. Comparisons were made between these groups. RESULTS: There were a total of 12,290 births and 121 stillbirths during our study period. The 121 stillbirths were divided into two groups: 67/121 (55.4%) were in the second trimester group and 54/121 (44.6%) were in the third trimester group. The overall incidence for intrauterine fetal demise was 0.98% (121/12,290). The increased risks in the third trimester stillbirths, as compared with the second trimester group, were significantly associated with males born, increased maternal body mass index (BMI) at delivery, habitual cigarette smoking, previous history of intrauterine fetal demise, and diabetic or hypertensive pregnancies. Unexplained causes (29.85%) were the most common causes of second trimester intrauterine fetal demise and the most common cause of third trimester intrauterine fetal demise was umbilical cord pathology (33.33%). CONCLUSION: Management of any pregnant patient remains a challenge. Identifying upstream and cost-effective solutions will improve these pregnancy outcomes.