The increase in number of cesarean section (CS) operations has resulted in an increase in cases of isthmocele development. The objective of this study is to determine the risk factors for isthmocele ...development after CS.
Isthmocele measurements were taken for 404 women with a history of at least one low transverse CS. The following potential risk factors were investigated: patient's age at CS, cause of CS, weeks of gestation at CS, premature rupture of membrane (PROM), phase of labor, type suture (single/double layer), operation time, uterine flexion (anteversion/retroversion), and blood transfusion during operation. A transvaginal ultrasound was carried out to examine the isthmocele in the uterus after CS, including the shape of the isthmocele, residual myometrial thickness, depth and width of isthmocele, cervical thickness, location of the isthmocele, and clinical characteristics.
In our study population, the isthmocele had a prevalence of 73.8%. Most isthmocele had a triangular (65.4%) or semicircular shape (10.4%). The presence of an isthmocele was significantly associated with repeat CS, premature rupture of membrane (PROM), short operation time, and extent of cervix dilatation at CS. The risk of isthmocele was low in women who had placenta previa totalis (PPT), twin, a long operation time, or a transfusion during the operation.
In our study, isthmocele development was significantly associated with repeat CS, PROM, a short operation time, and the extent of cervix dilatation at CS. Therefore, PROM prevention and a more careful uterine closure are needed to reduce the risk of developing an isthmocele after CS.
Androgen ablation is the first-line therapy for patients with metastatic prostate cancer (CaP). However, castration resistance will eventually emerge. In the present study, we have investigated the ...role of bone morphogenetic protein-6 (BMP-6) in the development of castration-resistant prostate cancer (CRPC) in the context of bone metastases.
We initially investigated the clinical course of 158 men with advanced CaP who were treated with primary androgen deprivation therapy. To elucidate the underlying mechanism of CRPC in the context of bone metastases, we examined the impact of bone stromal cells on CaP in the absence of androgens using a co-culture model.
In the 158 patients, we found that the median time to prostate-specific antigen progression was significantly shorter when bone metastases were present (14 months (95% CI, 10.2-17.8 months) vs 57 months (95% CI, 19.4-94.6 months)). These results suggest that bone-tumour interactions may accelerate castration resistance. Consistent with this hypothesis, in vitro co-cultures demonstrated that CaP cells proliferated under an androgen-depleted condition when incubated with bone stromal cells. Mechanistically, gene expression analysis using quantitative polymerase chain reaction arrays showed a dramatic induction of BMP-6 by CaP cell lines in the presence of bone stromal cells. Further studies revealed that WNT5A derived from bone stromal cells induced the expression of BMP-6 by CaP cells; BMP-6 in turn stimulated cellular proliferation of CaP cells in an androgen-deprived media via a physical interaction between Smad5 and β-catenin. Intracellularly, WNT5A increased BMP-6 expression via protein kinase C/NF-κB pathway in CaP cell lines.
These observations suggest that bone-CaP interaction leads to castration resistance via WNT5A/BMP-6 loop.
The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player ...in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-l-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.
Summary
What is known and objective
Higher rate of statin‐related hepatotoxicity has been reported for Koreans than for Westerners. Moreover, statin‐related aminotransferase elevation for those who ...show borderline levels of aspartate transaminase (AST) and alanine transaminase (ALT) (≤×3 of UNL) at baseline has not been fully investigated.
Methods
Post‐statin changes AST/ALT levels during the first year for 21 233 Korean outpatients at two large academic teaching hospitals from January 2009 to December 2013 were analysed using electronic health record data. The date of the first statin prescription was set as baseline. We also performed a comparative analysis of statin‐related AST/ALT elevations according to the type of statin, followed by an analysis of clinical risk factors.
Results and discussion
The progression rate to abnormal AST/ALT values >×3 the upper normal limit (UNL) was significantly higher (2·4–16% vs. 0·3–1·7%, P < 0·001) in subjects with borderline (>×1, but ≤×3 of UNL) compared with normal AST/ALT values at baseline. Those with normal baseline AST/ALT did not show significantly different progression rate between different statin medications (P = 0·801). However, patients taking pitavastatin (HR = 0·76, P = 0·657) were least likely to develop abnormal AST/ALT, whereas those taking fluvastatin (HR = 2·96, P = 0·029) were the most likely to develop abnormal AST/ALT compared with atorvastatin for patients who were with baseline borderline AST/ALT. However, given the small sample sizes and the observational nature of our study, these need further study.
What is new and conclusion
It is advisable to regularly monitor AST/ALT levels even in patients with AST/ALT increases >×1. Future studies should aim to determine the possible risk factors for each specific statin type by analysing various confounding variables.
The progression rate to abnormal AST/ALT values (>×3 the UNL) was significantly higher in subjects with borderline (>×1, but ≤ ×3 of UNL) compared to normal AST/ALT values at baseline. It is advisable to regularly monitor AST/ALT levels in patients with AST/ALT increases >×1, but ≤×3 of UNL.
The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine ...diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms.
Patients with previously untreated MGC received S-1 40 mg/m2 b.i.d. on days 1–14 and irinotecan 150 mg/m2 plus oxaliplatin 85 mg/m2 on day 1 every 3 weeks.
Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6).
The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.
Most of the p53 target genes, all except MDM2, COP1 and PIRH2, perform functions in apoptosis, differentiation and cell cycle arrest. The aforementioned oncogenes downregulate p53 through a negative ...feedback mechanism, and thus contribute to tumor development. In this study, we report a new p53 target, PRL-1, which is believed to be a significant regulator in the development and metastasis of a variety of cancer types. Phosphatase of regenerating liver 1 (PRL-1) overexpression reduced the levels of endogenous and exogenous p53 proteins, and inhibited p53-mediated apoptosis. On the other hand, the ablation of PRL-1 by small interfering RNA (siRNA) increased p53 protein levels. The p53 downregulation was mediated by p53 ubiquitination and subsequent proteasomal degradation. Furthermore, p53 ubiquitination by PRL-1 was achieved through two independent pathways, by inducing PIRH2 transcription and by inducing MDM2 phosphorylation through Akt signaling. In addition, we showed that the PRL-1 gene harbors a p53 response element in the first intron, and its transcription is regulated by the p53 protein. These findings imply that the new oncogenic p53 target, PRL-1, may contribute to tumor development by the downregulation of p53 by a negative feedback mechanism.
A new, pH dependent and water-soluble, conjugated oligomer (amino, trimethylammonium oligophenylene vinylene,
) was synthesized with a quaternary ammonium salt and an aromatic amine at the two ends ...of a π-conjugated oligomer, thus creating a strong dipole across the molecule. A unique white light LED is successfully fabricated from a stimuli responsive organic molecule whose emission properties are dominated by the pH value of the solution through controlled intermolecular charge transfer.
1, 5, 10, 11 Collectively, more than 20 case control studies have shown either a significant or equivocal inverse relationship that was not statistically significant, that became non-significant ...after adjustment, or that could not be distinguished from other factors in their relation to risk between folate status (assessed by dietary folate intake or by measurement of blood folate levels) and the risk of CRC or its precursor, adenoma, in the general population and in individuals with chronic ulcerative colitis. 1, 5, 10, 11 Several large prospective studies also suggest a 40% reduction in the risk of CRC and adenomas in those with the highest intake of folate compared with those with the lowest intake. 11 Two recent meta-analyses of epidemiological studies have confirmed a significant inverse association between folate intake and the risk of CRC, with a 20-25% reduction in the risk of CRC in subjects with the highest folate intake compared with those with the lowest intake. 12 Some epidemiological studies have shown a beneficial effect of multivitamin supplements containing = or >, slanted400 μg folic acid for = or >, slanted15 years on CRC risk and mortality. 13, 14 In addition, several small clinical trials have demonstrated that folic acid supplementation can improve or reverse surrogate endpoint biomarkers of CRC. 1, 5, 15 There exist several biologically plausible mechanisms by which folate deficiency increases, whereas folate supplementation reduces, the risk of CRC in normal colorectal epithelial cells. 5, 6, 15, 16 As an essential cofactor for the de novo biosynthesis of purines and thymidylate, folate plays an important role in DNA synthesis, stability and integrity, and repair, aberrations of which have been implicated in colorectal carcinogenesis. 5, 6, 16 Folate may also modulate DNA methylation, which is an important epigenetic determinant in gene expression, in the maintenance of DNA integrity and stability, in chromosomal modifications, and in the development of mutations. 5, 6, 15 A growing body of evidence from in vitro, animal, and human studies indicates that folate deficiency is associated with DNA strand breaks, impaired DNA repair, increased mutations, and aberrant DNA methylation, and that folate supplementation can correct some of these defects induced by folate deficiency. 5, 6, 15 Folate therefore appears to be an ideal nutritional factor for CRC prevention.
We present statistical characteristics of 1578 delta Scuti stars including nearby field stars and cluster member stars within the Milky Way. We obtained 46% of these stars (718 stars) from work by ...Rodriguez and collected the remaining 54% of stars (860 stars) from other literature. We updated the entries with the latest information of sky coordinates, color, rotational velocity, spectral type, period, amplitude, and binarity. The majority of our sample is well characterized in terms of typical period range (0.02-0.25 days), pulsation amplitudes (<0.5 mag), and spectral types (A-F type). Given this list of delta Scuti stars, we examined relations between their physical properties (i.e., periods, amplitudes, spectral types, and rotational velocities) for field stars and cluster members, and confirmed that the correlations of properties are not significantly different from those reported in Rodriguez's work. All the delta Scuti stars are cross-matched with several X-ray and UV catalogs, resulting in 27 X-ray and 41 UV-only counterparts. These counterparts are interesting targets for further study because of their uniqueness in showing delta Scuti-type variability and X-ray/UV emission at the same time. The compiled catalog can be accessed through the Web interface http://stardb.yonsei.ac.kr/DeltaScuti.
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