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.

Laminin-511 and recombinant vitronectin supplementation enables human pluripotent stem cell culture and differentiation on conventional tissue culture polystyrene surfaces in xeno-free conditions.

Human pluripotent stem cells (hPSCs) are typically cultivated on extracellular matrix (ECM) protein-coated dishes in xeno-free culture conditions. We supplemented mixed ECM proteins (laminin-511 and recombinant vitronectin, rVT) in culture medium for hPSC culture on conventional polystyrene dishes. Three hPSC cell lines were successfully cultivated on uncoated polystyrene dishes in medium supplemented with optimal conditions of laminin-511 and rVT. Excellent colony shape and colony size as well as high expansion fold of hPSCs were found under these conditions, whereas the colony size was small and poor expansion fold was found solely on L-511-coated dishes. A small portion of L-511 in the culture medium supported hPSC adhesion and prevented the adhesion from being too strong on the uncoated dishes, and rVT in the culture medium further supported adhesion of hPSCs on the dishes by maintaining their pluripotency. Having the optimal composition of L-511 and rVT in the culture medium was important for generating good hPSC colony shapes and sizes as well as a high expansion fold. After long-term culture of hPSCs on uncoated dishes supplemented with the mixed proteins, the hPSCs successfully showed pluripotent markers and could differentiate into a specific lineage of cells, cardiomyocytes, with high efficiency.

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.

Culture and differentiation of purified human adipose-derived stem cells by membrane filtration via nylon mesh filters.

Human adipose-derived stem cells (hASCs) cultured for 5 passages were filtered through nylon (NY) mesh filter membranes coated with and without extracellular matrix proteins to obtain the permeation solution. Subsequently, the culture media were filtered via the membranes to obtain the recovery solution. Then, the membranes were cultured in cell culture medium to obtain the migrated cells from the membranes. The hASCs in the permeation solution, through any type of NY mesh filter membrane having 11 and 20 µm pore sizes, had lower osteogenic differentiation ability than conventional hASCs cultured on tissue culture polystyrene (TCP) dishes for passage 5, whereas the hASCs purified by the membrane migration method through NY mesh filter membranes coated with recombinant vitronectin, which have 11 and 20 µm pore sizes, showed a higher proliferation speed as well as higher osteogenic differentiation potential than the conventional hASCs cultured on TCP dishes for passage 5. The membrane filtration and migration methods would be useful for cell sorting for specific cells, such as hASCs with high proliferation and high osteogenic differentiation ability, which do not need antibody binding or genetic modification of the cells for the specific isolation of the cells.

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.

Flow mediated dilatation of Taiwanese women with normal singleton pregnancies.

OBJECTIVE: To determine the normal values of flow mediated dilatation (FMD) in Taiwanese women with normal singleton pregnancies for the early detection of preeclampsia. MATERIALS AND METHODS: Data of women with normal singleton pregnancies seen at the Tri-Service General Hospital and Taiji Clinic between January 2014 and December 2015 were collected and analyzed. FMD was measured using high-resolution ultrasonography of the brachial artery for the assessment of endothelial function at the first and second trimester. The relationship between the FMD values and maternal gestational age was analyzed. RESULTS: A total of 122 pregnant women were included in the study. Systole FMD values first and second trimester were 9.05 ± 3.72 and 10.93 ± 3.74, respectively; and the diastole were 9.24 ± 3.64 and 11.18 ± 3.93, respectively. FMD and gestational age were positively correlated (systole, p = 0.0175; diastole, p = 0.0149). CONCLUSION: The normal values of FMD in Taiwanese women with normal singleton pregnancies were established, and data suggests that both systolic and diastolic FMD increase with gestational age. Because of the high failure rate, measurement of FMD may not be suitable as a routine clinical examination.

Asymptomatic uterine incarceration at term: Successful management of a rare complication in pregnancy.

OBJECTIVE: Incarcerated gravid uterus is a rare complication of pregnancy and can become a critical condition during delivery. For extremely uncommon cases that persist to the third trimester, correct diagnosis before delivery and appropriate management of the associated complications are important. CASE REPORT: This was the first case of a full-term pregnancy with incarcerated gravid uterus, reported at a medical center. The condition was not diagnosed during pregnancy, which led to serious complications during the cesarean delivery; however, the prognosis was favorable because of the timely management. CONCLUSION: Based on the previous case reports and clinical presentation of this case, early diagnosis with ultrasound and pelvic examination is the key to successful treatment. Vertical and more cephalad uterine incision reduces the risk of bladder perforation and injury to the cervix and vagina. A successful teamwork of obstetricians, gynecologists, urologists, and anesthesiologists can ensure favorable outcomes for both mother and fetus.

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.

Pregnancy and childbirth in a patient with multiple sclerosis: A case report of successful management.

OBJECTIVE: Multiple sclerosis (MS) preferentially affects females of reproductive age, making reproduction an important issue for women with MS. An increased incidence of poor labor progress often results in assisted vaginal delivery or a cesarean section. However, with good pre-pregnancy counseling and management, women with MS can conceive and give birth safely. Here, we present a case of pregnancy with MS, which was carried to term uneventfully and ended with unassisted vaginal delivery. CASE REPORT: A 36-year-old woman was treated for MS for three years before she conceived. Because of her mild clinical presentation, medication was discontinued when her pregnancy was confirmed. Counseling was completed, and she had a smooth pregnancy course and gave birth vaginally at 38 weeks and two days. CONCLUSION: Based on this case report, women with mild clinical presentation of MS before pregnancy can conceive and carry successfully to term with no or improved disease presentation.

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.

The climate impact on female acute pyelonephritis in Taiwan: A population-based study.

OBJECTIVE: Urinary tract infection (UTI) is the main reason of community-acquired infection which causes large losses in social economy. The individual as well as climate factors make changes on the incidence. Acute pyelonephritis (APN) is one of the most serious UTI in female. The object of our study is to analyze whether climate factors will have effect on the incidence of female APN in Taiwan. MATERIALS AND METHODS: This study consisted of 14,568 female patients with APN from 2001 to 2013 in Taiwan and patients with repeated APN were excluded. The monthly climate data was collected from the Central Weather Bureau. The available monthly climate data included highest, lowest, and average level of temperatures, humidity, rainfall, total rain days, and sunshine hours. RESULTS: The total incidence of female APN was 23.44 each 10,000 populations. The incidence of APN was positively correlated with temperature (r = 0.66), sunshine hours (r = 0.45), rainfall (r = 0.42), rain days (r = 0.29), and humidity (r = 0.23) per month. There is the strongest correlation between the average monthly temperature and the incidence of APN (ß = 0.54). The correlation with the incidence of APN was also followed by rain days (ß = 0.28) and humidity (ß = 0.27). CONCLUSION: There is a significant expression on the incidence of female APN affected by seasonality and climate parameters. The monthly average temperature has the strongest correlation with female APN. The results of this research may facilitate the potential preventive strategies on female APN.

Successful treatment with granulocyte-colony stimulating factor for ritodrine-induced neutropenia in a twin pregnancy.

OBJECTIVE: Neutropenia developed after continuous intravenous infusion of ritodrine hydrochloride (Yutopar) for preterm uterine contractions in a twin pregnancy. We successfully returned the low neutrophil count to the normal range after discontinuation of infusion of ritodrine and treatment with granulocyte colony stimulating factor (G-CSF). CASE REPORT: A 34-year-old woman with twin pregnancy was treated with ritodrine for preterm uterine contractions at 27 weeks and 6 days gestation. Neutropenia developed after continuous intravenous infusion of ritodrine for about 4 weeks. We ceased the ritodrine infusion immediately and treated the neutropenia with G-CSF. A cesarean delivery was performed the day after cessation of the ritodrine infusion because of uncontrolled preterm labor. There were no adverse side effects or infectious complications in the mother or the newborns. The maternal neutrophil count recovered to the normal range 4 days after administration of G-CSF. CONCLUSION: Based on prior case reports and the clinical presentation of our case, G-CSF may be a useful treatment for pregnant women with ritodrine-induced neutropenia. However, more clinical studies are required to confirm the safety and efficacy of this treatment.

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.

Short-term starvation with a near-fatal asthma attack induced ketoacidosis in a nondiabetic pregnant woman: A case report.

Life-threatening refractory metabolic acidosis due to starvation ketoacidosis is rarely reported, even among nondiabetic pregnant women, and may be overlooked. Furthermore, stressful situations may increase the acidosis severity.In the present case, a nondiabetic multiparous woman was admitted for a near-fatal asthma attack and vomiting during the third trimester of pregnancy. She was intubated and rapidly developed high anion gap metabolic acidosis. We diagnosed the patient with starvation ketoacidosis based on vomiting with concomitant periods of stress during pregnancy and the absence of other causes of high anion gap metabolic acidosis. She responded poorly to standard treatment, although the ketoacidosis and asthma promptly resolved after an emergency caesarean section. The patient and her baby were safely discharged.Short-term starvation, if it occurs during periods of stress and medication, can result in life-threatening ketoacidosis, even among nondiabetic women during the third trimester of pregnancy. Awareness of this condition may facilitate prompt recognition and proactive treatment for dietary and stress control, and emergent interventions may also improve outcomes.

Myocardial infarction and ischemic hepatitis complicated by postpartum hemorrhage.

OBJECTIVE: To present a rare case of life-threatening postpartum hemorrhage due to uterine atony complicated by acute myocardial infarction and ischemic hepatitis. CASE REPORT: A 37-year-old parturient, gravida 1 para 0, presented with symptoms and signs of shock due to postpartum hemorrhage after delivery. Ischemic hepatitis, pulmonary edema, and adult respiratory distress syndrome developed the following morning. On the 7(th) postpartum day, she developed chest pain and was subsequently diagnosed with acute inferior myocardial infarction based on serial changes on the electrocardiogram (ECG) and myocardial enzymes. The clinical condition improved after a series of resuscitative efforts and percutaneous transluminal coronary angioplasty. CONCLUSION: The presented case demonstrated that when hypovolemic shock develops with complications of pulmonary edema or ischemic hepatitis, the possibility of cardiovascular disease should be immediately investigated and preventive measures initiated.

Cardiac arrest during emergency cesarean section for severe pre-eclampsia and peripartum cardiomyopathy.

OBJECTIVE: To present the correlation between severe pre-eclampsia and peripartum cardiomyopathy in pregnancy. CASE REPORT: A 41-year-old parturient, gravida 3, para 1, at 34 4/7 weeks' gestation, was diagnosed with severe pre-eclampsia. At the time of admission, a plain chest film disclosed bilateral pleural effusions. An emergent cesarean section was planned because of decreased fetal movement, heavy daily protein loss, and bilateral pleural effusions. During the cesarean section, she developed shock with acute respiratory failure. She underwent advanced cardiac life support and intubation with mechanical ventilator support. Peripartum cardiomyopathy was subsequently diagnosed by echocardiography. CONCLUSION: The presented case demonstrates that routine echocardiography is highly recommended for suspected peripartum cardiomyopathy in gravidas with severe pre-eclampsia and symptoms or signs of heart failure.