Triphenylamine-Based Conjugated Polyelectrolyte as a Hole Transport Layer for Efficient and Scalable Perovskite Solar Cells.

π-Conjugated polyelectrolytes (CPEs) have been studied as interlayers on top of a separate hole transport layer (HTL) to improve the wetting, interfacial defect passivation, and crystal growth of perovskites. However, very few CPE-based HTLs have been reported without rational molecular design as ideal HTLs for perovskite solar cells (PeSCs). In this study, the authors synthesize a triphenylamine-based anionic CPE (TPAFS-TMA) as an HTL for p-i-n-type PeSCs. TPAFS-TMA has appropriate frontier molecular orbital (FMO) levels similar to those of the commonly used poly(bis(4-phenyl)-2,4,6-trimethylphenylamine) (PTAA) HTL. The ionic and semiconducting TPAFS-TMA shows high compatibility, high transmittance, appropriate FMO energy levels for hole extraction and electron blocking, as well as defect passivating properties, which are confirmed using various optical and electrical analyses. Thus, the PeSC with the TPAFS-TMA HTL exhibits the best power conversion efficiency (PCE) of 20.86%, which is better than that of the PTAA-based device (PCE of 19.97%). In addition, it exhibits negligible device-to-device variations in its photovoltaic performance, contrary to the device with PTAA. Finally, a large-area PeSC (1 cm2 ) and mini-module (3 cm2 ), showing PCEs of 19.46% and 18.41%, respectively, are successfully fabricated. The newly synthesized TPAFS-TMA may suggest its great potential as an HTL for large-area PeSCs.

Clinical impact of radioactive iodine dose selection based on the number of metastatic lymph nodes in patients with papillary thyroid carcinoma: A multicenter retrospective cohort study.

OBJECTIVE: The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS: A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS: Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p < .001). In the subgroup with ≤5 metastatic LNs, the presence of extrathyroidal extension was only associated with recurrence (odds ratio: 7.333, p = .024) in multivariate analysis. RAI dose was significantly associated with recurrence rate in which the patients with high-dose RAI (3.7 GBq or higher) had less incidence of recurrence than those with low-dose RAI (1.11 GBq) in the subgroup with more than five metastatic LNs (odds ratio: 6.533, p = .026). CONCLUSIONS: High-dose RAI (≥3.7 GBq) therapy significantly lowered the recurrence rate in patients with more than five metastatic LNs. Therefore, RAI dose should be determined based on the number of metastatic LNs as well as conventional risk factors.

The effect of desflurane on retinal angiogenesis in a mouse model of oxygen-induced retinopathy.

PURPOSE: Retinopathy of prematurity (ROP) is an ocular disorder that primarily occurs in premature infants and is the most common cause of vision impairment. This study examined the effect of desflurane on angiogenesis in a mouse model of oxygen-induced retinopathy (OIR). METHODS: Mice were randomly allocated to the control (C), ROP control (Rc), or ROP with desflurane exposure (Rd) group. To induce ROP, 7-day-old mice were exposed to 75% oxygen in a chamber for 5 days [postnatal days (P) 7-12], and thereafter returned to room air. Age-matched mice exposed to room air formed the C group. The Rd group was exposed to 8% desflurane for 2 h on P12, P13, and P14 with 40% oxygen. To observe changes in angiogenesis of the retina, mice were sacrificed at P16. RESULTS: The ratio of avascular area/total retinal area was not changed significantly in the Rd group, compared to the Rc group. The expression of endothelial growth factor A (VEGF-A) and hypoxia inducible factor-1α (HIF-1α) in the Rd group and Rc group was not significantly different. CONCLUSIONS: Desflurane does not have a significant influence on retinal angiogenesis via HIF-1α and VEGF-A expression in the OIR mouse model. However, these findings are not directly applicable to premature infants, and it is thus necessary to perform further studies to determine the effect of desflurane on angiogenesis.

Production of steviol from steviol glucosides using ß-glucosidase from a commercial pectinase, Sumizyme PX.

OBJECTIVE: To purify and characterize a specific enzyme from a commercial pectinase for the production of steviol from stevioside (Ste) without adding organic solvent and to improve steviol production. RESULTS: Commercial Sumizyme PX converted Ste to steviol with a yield of 98%. ß-Glucosidase from Sumizyme PX (ßglyPX) was purified in three steps with 12.5-fold purification and 51% yield. The specific activity of the purified ßglyPX was 141 U/mg. The molecular weight of ßglyPX was ~ 116 kDa on SDS-PAGE. Its optimum activity was at pH 3.5 and 65 °C. It was stable for 12 h up to 55 °C and for 24 h at pH 2-9.5. K m values of ßglyPX for pNPGal, oNPGlc, lactose, and Ste were 2.4, 0.7, 18, and 7.8 mM, respectively. The optimum conditions for steviol production were 55 °C, 900 U/ml, 80 mg Ste/ml, 12 h. CONCLUSION: ßglyPX contains great potential for industrial steviol production from Ste.

The effect of sevoflurane on retinal angiogenesis in a mouse model of oxygen-induced retinopathy.

BACKGROUND: Sevoflurane is commonly used in general anesthesia for premature neonates. The main mechanism of retinopathy of prematurity (ROP) is increased levels of vascular endothelial growth factor (VEGF). For the investigation of sevoflurane's effect on angiogenesis, the angiogenesis and VEGF expression in the retina were measured after administering sevoflurane in an oxygen-induced retinopathy mice model. MATERIALS AND METHODS: The mice were divided into the normoxic group (Nc and Ns group; n = 6) and the ROP group (C, Rc, and Rs group; n = 6). Rc group were exposed to 75% oxygen for 5 days beginning on postnatal day (P) 7, and then returned to room air. Age-matched mice in the C group were exposed to room air. To observe angiogenesis of the retina, the mice were sacrificed on P16. The Rs group was exposed to 2 vol% sevoflurane for 2 h on P12, P13, and P14 with 40% oxygen. RESULTS: The angiogenic area and the spreading distance of vessels on P4 were statistically decreased in the Ns group, compared to the Nc group. The avascular area on P16 was significantly increased and the expression of VEGF was suppressed in the Rs group compared to the Rc group. CONCLUSIONS: Sevoflurane can inhibit retinal angiogenesis via suppressing VEGF expression in an OIR mice model with exposure to relative hypoxia. Nevertheless, it is still difficult to apply the results of this study immediately to humans because of the heterogeneity of responses to sevoflurane.

Transcript Levels of Androgen Receptor Variant 7 and Ubiquitin-Conjugating Enzyme 2C in Hormone Sensitive Prostate Cancer and Castration-Resistant Prostate Cancer.

PURPOSE: This study is designed to identify the androgen receptor variant 7 (AR-V7) status, clinical significance of AR-V7 in hormone sensitive prostate cancer (HSPC). Then, we evaluated AR-V7 and changes of its target gene, ubiquitin-conjugating enzyme E2C (UBE2C) which is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin-conjugating enzyme, in castration-resistant prostate cancer (CRPC) in serial tumor biopsies from patients receiving androgen deprivation therapy. METHODS: We used RT-PCR and Q-PCR assay to evaluate AR-V7, androgen receptor full length (AR-FL), and UBE2C in tumor biopsies from patients with HSPC and CRPC. We examined associations between mRNA expression of AR-V7 and clinicopathologic factors. Furthermore, to identify other potential genes involved in the development of CRPC, RNA sequencing was conducted, using paired prostate cancer (PCa) tissues obtained immediately prior to treatment and at the time of therapeutic resistance. RESULTS: A total of 13 HSPC patients and three CRPC patients were enrolled. Neither a high Gleason score (score of 8 and 9) nor a high risk of PCa (a high risk of locally advanced PCa according to NCCN guidelines) was correlated with mRNA expression of AR-V7 in HSPC (P = 0.153 and P = 0.215). The mRNA expression of AR-FL, but not AR-V7, was significantly associated with the mRNA expression of UBE2C level in HSPC (P = 0.007). However, increased expression of AR-V7, not AR-FL, paralleled increased expression of UBE2C in the CRPC specimens (P = 0.03). AR-V7 expression status before ADT was likely related to shorter CRPC development in patients treating ADT. The result of the RNA-sequencing analysis using serial samples from the same patient before and after castration demonstrated an increased level of the PI3K regulatory subunit 1 (P = 0.018). CONCLUSION: Our study revealed the role of UBE2C as a marker of the androgen signaling pathway in PCa. Differential gene expression analysis using serial samples from the same patient before and after castration revealed potential genes and pathways involved in development of CRPC. Further studies are needed to determine whether these genes and pathways are potential therapeutic target for CRPC. Prostate 77:60-71, 2017. © 2016 Wiley Periodicals, Inc.

Clinicopathological characteristics including BRAF V600E mutation status and PET/CT findings in papillary thyroid carcinoma.

OBJECTIVE: We assessed the associations between FDG uptake in primary papillary thyroid carcinomas (PTCs) and clinicopathological features, including the BRAF V600E mutation, using quantitative and qualitative analyses of preoperative PET/CT data. DESIGN AND PATIENTS: This was a retrospective review of 106 patients with PTC who underwent PET/CT scans between February 2009 and January 2011 before undergoing total thyroidectomy. Data collected from surgical specimens were compared with FDG uptake in the primary tumour using quantitative and qualitative analyses of preoperative PET/CT data. Clinicopathological data included the primary tumour size, subtype, capsular invasion, extrathyroid extension, multifocality, BRAF V600E mutation status, lymph node metastasis and distant metastasis. RESULTS: The SUVmax of the primary tumour was significantly higher in patients with a primary tumour >1 cm, extrathyroid extension or the BRAF V600E mutation than in patients without these features (P<.001, .049 and <.001). Univariate analyses showed that primary tumour size, extrathyroid extension and BRAF V600E mutation status were associated with the SUVmax of the PTC. Multivariate analysis indicated that primary tumour size and the BRAF V600E mutation were associated with the SUVmax of the PTC. In a visual assessment, the primary tumour size was larger in FDG-avid than in non-FDG-avid PTCs (P<.001). There was no significant difference in the presence of multifocality, thyroid capsular invasion, extrathyroid extension, BRAF V600E mutation, lymph node metastasis or distant metastasis between FDG-avid and non-FDG-avid PTCs. CONCLUSIONS: Primary tumour size and the BRAF V600E mutation are significant factors associated with the SUVmax on preoperative PET/CT in patients with PTC.

Regulation of vascular smooth muscle phenotype by cross-regulation of krüppel-like factors.

Regulation of vascular smooth muscle cell (VSMC) phenotype plays an essential role in many cardiovascular diseases. In the present study, we provide evidence that krüppel-like factor 8 (KLF8) is essential for tumor necrosis factor α (TNFα)-induced phenotypic conversion of VSMC obtained from thoracic aorta from 4-week-old SD rats. Stimulation of the contractile phenotype of VSMCs with TNFα significantly reduced the VSMC marker gene expression and KLF8. The gene expression of KLF8 was blocked by TNFα stimulation in an ERK-dependent manner. The promoter region of KLF8 contained putative Sp1, KLF4, and NFκB binding sites. Myocardin significantly enhanced the promoter activity of KLF4 and KLF8. The ectopic expression of KLF4 strongly enhanced the promoter activity of KLF8. Moreover, silencing of Akt1 significantly attenuated the promoter activity of KLF8; conversely, the overexpression of Akt1 significantly enhanced the promoter activity of KLF8. The promoter activity of SMA, SM22α, and KLF8 was significantly elevated in the contractile phenotype of VSMCs. The ectopic expression of KLF8 markedly enhanced the expression of SMA and SM22α concomitant with morphological changes. The overexpression of KLF8 stimulated the promoter activity of SMA. Stimulation of VSMCs with TNFα enhanced the expression of KLF5, and the promoter activity of KLF5 was markedly suppressed by KLF8 ectopic expression. Finally, the overexpression of KLF5 suppressed the promoter activity of SMA and SM22α, thereby reduced the contractility in response to the stimulation of angiotensin II. These results suggest that cross-regulation of KLF family of transcription factors plays an essential role in the VSMC phenotype.

Flavisolibacter tropicus sp. nov., isolated from tropical soil.

A Gram-stain-negative, non-motile, deep yellow, rod-shaped bacterium, designated strain LCS9T, was isolated from a soil sample at the tropical zone within the Ecorium of the National Institute of Ecology in Seocheon, central-western Korea. 16S rRNA gene sequence analysis showed that strain LCS9T clustered with members of the genus Flavisolibacter of the family Chitinophagaceae, phylum Bacteroidetes. Sequence similarities between strain LCS9T and the type strains of the genus Flavisolibacter ranged from 94.6 to 94.9 %. Strain LCS9T grew at 10-37 °C (optimum, 25 °C) and at pH 6.0-10.0 (optimum, pH 7); was positive for catalase and oxidase; and negative for nitrate reduction and production of indole. Cells showed pigment absorbance peaks at 451 and 479 nm, and had 0.03 % survival following exposure to 3 kGy gamma radiation. Strain LCS9T had the following chemotaxonomic characteristics: the major quinone was menaquinone-7 (MK-7); the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH; polar lipids included phosphoatidylethanolamine, an unidentified aminophospholipid, unidentified aminolipidsand unidentified lipids. The DNA G+C content was 39.4 mol%. Based on polyphasic analysis, the type strain LCS9T (=KCTC 42070T=JCM 19972T) represents a novel species for which the name Flavisolibacter tropicus sp. nov. is proposed. Radiation resistance in the genus Flavisolibacter has not been reported to date, and so this is the first report of low-level radiation resistance of a member of the genus.

Regulation of retinal angiogenesis by endothelial nitric oxide synthase signaling pathway.

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

Insulin regulates monocyte trans-endothelial migration through surface expression of macrophage-1 antigen.

During the pathogenesis of atherosclerosis, adhesion of monocytes to vascular endothelium and subsequent migration across the endothelium has been recognized as a key process in the chronic inflammatory response in atherosclerosis. As type 2 diabetes is closely associated with the pathogenesis of atherosclerosis, we investigated whether monocyte adhesion and migration were affected by insulin. We found that insulin activated Akt and induced subsequent migration in THP-1. However, glucose and insulin-like growth factor-1, which is a growth factor that is structurally similar to insulin, were not effective. Insulin-dependent migration of THP-1 was blocked by inhibition of PI3K or Akt and by silencing of Akt1. Insulin-dependent migration of bone marrow-derived monocytic cells (BDMCs) was attenuated by inhibition of PI3K and Akt. In addition, BDMCs from Akt1(-/-) mice showed defects in insulin-dependent migration. Stimulation of THP-1 with insulin caused adhesion with human vein endothelial cells (HUVECs) that was blocked by silencing of Akt1. However, stimulation of HUVECs did not cause adhesion with THP-1. Moreover, BDMCs from Akt1(-/-) mice showed defects in insulin-dependent adhesion with HUVECs. Insulin induced surface expression of Mac-1, and neutralization of Mac-1 blocked insulin-induced adhesion of THP-1 as well as BDMCs. Surface expression of Mac-1 was blocked in THP-1 with silenced Akt1, and in BDMCs isolated from mice lacking Akt1. Finally, trans-endothelial migration of THP-1 and BDMCs was blocked by Mac-1-neutralizing antibody, in THP-1 with silenced Akt1 and in BDMCs from Akt1(-/-) mice. These results suggest that insulin stimulates monocyte trans-endothelial migration through Akt-dependent surface expression of Mac-1, which may be part of the atherogenesis in type 2 diabetes.

Akt1 isoform modulates phenotypic conversion of vascular smooth muscle cells.

In this study, we investigated the role of Akt1 isoform in phenotypic change of vascular smooth muscle cells (VSMCs) and neointima formation. Laminin-induced conversion of synthetic VSMCs into contractile VSMCs was measured by expression of marker proteins for contractile VSMCs and collagen gel contraction assay. Culture of synthetic VSMCs on laminin-coated plates induced expression of marker proteins for contractile VSMCs and showed contraction in response to angiotensin II (AngII) stimulation. Silencing integrin-linked kinase attenuated activation of Akt and blocked phenotypic conversion of VSMCs resulting in the loss of AngII-dependent contraction. Laminin-induced phenotypic conversion of VSMCs was abrogated by phosphatidylinositol 3-kinase inhibitor or in cells silencing Akt1 but not Akt2. Proliferation of contractile VSMCs on laminin-coated plate was enhanced in cells silencing Akt1 whereas silencing Akt2 did not affect. Promoter activity of myocardin and SM22α was enhanced in contractile phenotype and overexpression of myocardin stimulated promoter activity of SM22α in synthetic phenotype. Promoter activity of myocardin and SM22α was reduced in cells silencing Akt1 and promoter activity of SM22α was restored by overexpression of myocardin in cells silencing Akt1. However, silencing of Akt2 affected neither promoter activity of myocardin nor SM22α. Finally, neointima formation in carotid artery ligation and high fat-diet-induced atherosclerosis was facilitated in mice lacking Akt1. This study demonstrates that Akt1 isoform stimulates laminin-induced phenotypic conversion of synthetic VSMCs by regulating the expression of myocardin. VSMCs become susceptible to shifting from contractile to synthetic phenotype by the loss of Akt1 in pathological conditions.

Structural insights into the efficient CO2-reducing activity of an NAD-dependent formate dehydrogenase from Thiobacillus sp. KNK65MA.

CO2 fixation is thought to be one of the key factors in mitigating global warming. Of the various methods for removing CO2, the NAD-dependent formate dehydrogenase from Candida boidinii (CbFDH) has been widely used in various biological CO2-reduction systems; however, practical applications of CbFDH have often been impeded owing to its low CO2-reducing activity. It has recently been demonstrated that the NAD-dependent formate dehydrogenase from Thiobacillus sp. KNK65MA (TsFDH) has a higher CO2-reducing activity compared with CbFDH. The crystal structure of TsFDH revealed that the biological unit in the asymmetric unit has two conformations, i.e. open (NAD(+)-unbound) and closed (NAD(+)-bound) forms. Three major differences are observed in the crystal structures of TsFDH and CbFDH. Firstly, hole 2 in TsFDH is blocked by helix α20, whereas it is not blocked in CbFDH. Secondly, the sizes of holes 1 and 2 are larger in TsFDH than in CbFDH. Thirdly, Lys287 in TsFDH, which is crucial for the capture of formate and its subsequent delivery to the active site, is an alanine in CbFDH. A computational simulation suggested that the higher CO2-reducing activity of TsFDH is owing to its lower free-energy barrier to CO2 reduction than in CbFDH.

Platelet-derived growth factor regulates vascular smooth muscle phenotype via mammalian target of rapamycin complex 1.

Mammalian target of rapamycin complex (mTORC) regulates various cellular processes including proliferation, growth, migration and differentiation. In this study, we showed that mTORC1 regulates platelet-derived growth factor (PDGF)-induced phenotypic conversion of vascular smooth muscle cells (VSMCs). Stimulation of contractile VSMCs with PDGF significantly reduced the expression of contractile marker proteins in a time- and dose-dependent manner. In addition, angiotensin II (AngII)-induced contraction of VSMCs was completely blocked by the stimulation of VSMCs with PDGF. PDGF-dependent suppression of VSMC marker gene expression was significantly blocked by inhibition of phosphatidylinositol 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), and mTOR whereas inhibition of p38 MAPK had no effect. In particular, inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked the PDGF-dependent phenotypic change of VSMCs whereas silencing of Rictor had no effect. In addition, loss of AngII-dependent contraction by PDGF was significantly retained by silencing of Raptor. Inhibition of mTORC1 by rapamycin or by silencing of Raptor significantly blocked PDGF-induced proliferation of VSMCs. Taken together, we suggest that mTORC1 plays an essential role in PDGF-dependent phenotypic changes of VSMCs.

Essential role of krüppel-like factor 5 during tumor necrosis factor α-induced phenotypic conversion of vascular smooth muscle cells.

Tumor necrosis factor α (TNFα) plays an essential role in the regulation of vascular smooth muscle cell (VSMC) phenotype. In the present study, we provide evidence that krüppel-like factor 5 (KLF5) plays an essential role in TNFα-induced phenotypic conversion of VSMCs. Ectopic expression of KLF5 completely blocked phenotypic conversion of VSMCs from synthetic to contractile type. In addition, stimulation of VSMCs with TNFα facilitated expression of KLF5, whereas expression of smooth muscle marker genes such as SM22α and smooth muscle actin (SMA) was significantly down-regulated. TNFα significantly enhanced the promoter activity of KLF5 as well as mRNA level, which is significantly suppressed by the inhibition of the MAPK pathway. Silencing of KLF5 suppressed TNFα-induced phenotypic conversion of VSMCs, whereas overexpression of KLF5 stimulated phenotypic conversion of VSMCs and facilitated the loss of angiotensin II (AngII)-dependent contraction. Finally, overexpression of KLF5 significantly attenuated the promoter activity of SM22α and SMA. Therefore, we suggest that TNFα-dependent induction of KLF5 may play an essential role in phenotypic modulation of VSMCs.

Oncogenic Role of BOLL in Colorectal Cancer.

BACKGROUND: Boule-like RNA-binding protein (BOLL protein) is the progenitor of the Deleted in Azoospermia (DAZ) gene family. To date, previous studies have focused on the reproductive function of BOLL. While we were identifying new DNA methylation biomarkers for colorectal cancer (CRC), we found that BOLL protein was overexpressed in CRC. AIM: The aim of this study was to determine the role of BOLL in CRC by epigenetic and functional studies in vivo and in vitro. METHODS: BOLL promoter methylation and expression were determined by MethyLight, RT-PCR, Western blot, and immunohistochemistry. The functional role of BOLL in CRC was evaluated by cell proliferation, colony formation, migration and invasion, cell cycle status, and tumor growth in a xenograft model. RESULTS: BOLL promoter methylation was enhanced in CRC tissues compared with normal colorectal tissues [97/124 (78 %) vs. 2/124 (2 %)]. However, the mean immunoreactivity score of CRC tissues and paired adjacent normal tissues was 8.15 ± 0.18 (SD) and 3.35 ± 0.19 (SD), respectively (p < 0.01). No significant association was observed between immunoreactivity score and clinicopathological parameters, including age, gender, tumor size, tumor differentiation, and tumor node metastasis stage. Expression of BOLL in CRC cell lines significantly enhanced cell proliferation (p < 0.01), colony formation (p < 0.01), and migration (p < 0.01). In BOLL-expressing cells, the percentage of cells in S-phase of the cell cycle was significantly increased. Tumor volume in BOLL xenografted mice was significantly enhanced after subcutaneous implantation (p < 0.01). CONCLUSIONS: Our study demonstrated an oncogenic role of BOLL in CRC despite tumor-specific promoter hypermethylation.

Androgen Receptor-dependent Expression of Low-density Lipoprotein Receptor-related Protein 6 is Necessary for Prostate Cancer Cell Proliferation.

Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation. Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation. Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells. Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6. However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells. Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.

Hepatitis B virus reactivation during anti-cancer chemotherapy in patients with past hepatitis B virus infection.

BACKGROUND/AIMS: The necessity of preemptive antiviral therapy in patients with past HBV infection is uncertain. We evaluated the incidence and risk factors of HBV reactivation in cancer patients with past HBV infection who received anti-cancer chemotherapy. METHODOLOGY: Between Jan. 2009 and Dec. 2011, we reviewed 675 HBsAg negative and anti-HBc positive patients who had solid cancers or hematologic malignancies that were treated with intravenous cytotoxic chemotherapy. RESULTS: Among 675 patients, 321 (47.6%) patients had solid cancer and 354 (52.4%) had hematologic malignancy. HBV reactivation was observed in 13 patients (1.9%). In solid cancer patients, 1 (0.3%) patient had HBV reactivation, whereas 12 out of 365 (3.3%) patients with hematologic malignancy experienced HBV reactivation. Among the 12 HBV-reactivated patients with hematologic malignancy, 11 patients had lymphoma. Lymphoma carried a significantly higher risk for HBV reactivation than solid cancer in patients with past HBV infection (OR, 24.134; 95% CI, 3.027-192.406; P = 0.003). Among HBV-reactivated lymphoma patients, 2 patients experienced fulminant liver failure. The absence of anti- HBs was identified as a risk factor for HBV reactivation (OR, 22.446; 95% CI, 4.816-104.609; P < 0.001). CONCLUSIONS: Preemptive antiviral therapy should be considered in lymphoma patients with past HBV infection before starting anti-cancer chemotherapy

Acute myocardial infarction after radiofrequency catheter ablation of typical atrial flutter.

A 53-yr-old man underwent radiofrequency ablation to treat persistent atrial flutter. After the procedure, the chest pain was getting worse, and the electrocardiogram showed ST-segment elevation in inferior leads with reciprocal changes. Immediate coronary angiography showed total occlusion with thrombi at the distal portion of the right coronary artery, which was very close to the ablation site. Intervention with thrombus aspiration and balloon dilatation was successful, and the patient recovered without any kind of sequelae. Although the exact mechanism is obscure, the most likely explanation is a thermal injury to the vascular wall that ruptured into the lumen and formed thrombus. Vasospasm and thromboembolism can also be other possibilities. This case raise the alarm to cardiologists who perform radiofrequency ablation to treat various kinds of cardiac arrhythmias, in that myocardial infarction has been rarely considered one of the complications.

Modified RCTU Score: A Semi-Quantitative, Visual Tool for Predicting Alzheimer's Conversion from aMCI.

This research evaluated the modified RCTU score, derived from amyloid PET scans, for predicting the progression from amnestic Mild Cognitive Impairment (aMCI) to Alzheimer's Disease (AD). aMCI patients underwent baseline evaluations, including amyloid PET. AD conversion was identified through neuropsychological tests after observation. The RCTU was modified by segmenting frontal, parietal, and temporal lobes into left and right, resulting in seven areas. Scores from both modified and conventional RCTU were analyzed and compared. Among 45 patients, 12 progressed to AD (over 17.8 ± 6.8 months). AD converters showed higher scores in modified RCTU scores. Modified RCTU score had strong correlations with amyloid SUVR (r > 0.7). Modified RCTU sum score was the significant covariate of AD conversion. Modified RCTU could determine the asymmetry of amyloid deposits. We demonstrated that symmetric deposits of amyloid showed a higher risk for AD conversion when analyzed using modified RCTU. The modified RCTU score is a promising method for predicting AD conversion, correlating strongly with amyloid SUVR.