- Structure of human telomere G-quadruplex in the presence of a model drug along the thermal unfolding pathway. [Journal Article]
- NANucleic Acids Res 2018 Nov 08
- A multi-technique approach, combining circular dichroism spectroscopy, ultraviolet resonance Raman spectroscopy and small angle scattering techniques, has been deployed to elucidate how the structura...
A multi-technique approach, combining circular dichroism spectroscopy, ultraviolet resonance Raman spectroscopy and small angle scattering techniques, has been deployed to elucidate how the structural features of the human telomeric G-quadruplex d[A(GGGTTA)3GGG] (Tel22) change upon thermal unfolding. The system is studied both in the free form and when it is bound to Actinomycin D (ActD), an anticancer ligand with remarkable conformational flexibility. We find that at room temperature binding of Tel22 with ActD involves end-stacking upon the terminal G-tetrad. Structural evidence for drug-driven dimerization of a significant fraction of the G-quadruplexes is provided. When the temperature is raised, both free and bound Tel22 undergo melting through a multi-state process. We show that in the intermediate states of Tel22 the conformational equilibrium is shifted toward the (3+1) hybrid-type, while a parallel structure is promoted in the complex. The unfolded state of the free Tel22 is consistent with a self-avoiding random-coil conformation, whereas the high-temperature state of the complex is observed to assume a quite compact form. Such an unprecedented high-temperature arrangement is caused by the persistent interaction between Tel22 and ActD, which stabilizes compact conformations even in the presence of large thermal structural fluctuations.
- Identification and expression analysis of type II and type III Pi transporters in the opossum kidney cell line. [Journal Article]
- EPExp Physiol 2018 Oct 31
- What is the central question of this study? The Opossum Kidney (OK) cell line is the main in vitro model of proximal tubular Pi transport, but it is incomplete because only the NaPiIIa Pi transporter...
What is the central question of this study? The Opossum Kidney (OK) cell line is the main in vitro model of proximal tubular Pi transport, but it is incomplete because only the NaPiIIa Pi transporter has been identified. What is the main finding and its importance? We have cloned and characterized the Pi transporters NaPiIIc, PiT1 and PiT2 from OK cells and have analysed the relevance of the four transporters in Pi transport. All four transporters are involved in the up-regulated Pi transport of cells incubated using a low Pi medium, and only PiT1 is not involved in basal transport.
- Biological Drivers of Wilms Tumor Prognosis and Treatment. [Review]
- CChildren (Basel) 2018 Oct 26; 5(11)
- Prior to the 1950s, survival from Wilms tumor (WT) was less than 10%. Today, a child diagnosed with WT has a greater than 90% chance of survival. These gains in survival rates from WT are attributed ...
Prior to the 1950s, survival from Wilms tumor (WT) was less than 10%. Today, a child diagnosed with WT has a greater than 90% chance of survival. These gains in survival rates from WT are attributed largely to improvements in multimodal therapy: Enhanced surgical techniques leading to decreased operative mortality, optimization of more effective chemotherapy regimens (specifically, dactinomycin and vincristine), and inclusion of radiation therapy in treatment protocols. More recent improvements in survival, however, can be attributed to a growing understanding of the molecular landscape of Wilms tumor. Particularly, identification of biologic markers portending poor prognosis has facilitated risk stratification to tailor therapy that achieves the best possible outcome with the least possible toxicity. The aim of this review is to (1) outline the specific biologic markers that have been associated with prognosis in WT and (2) provide an overview of the current use of biologic and other factors to stratify risk and assign treatment accordingly.
- Shogaol but not gingerol has a neuroprotective effect on hemorrhagic brain injury: Contribution of the α, β-unsaturated carbonyl to heme oxygenase-1 expression. [Journal Article]
- EJEur J Pharmacol 2018 Oct 23; 842:33-39
- We investigated the effects of shogaol, which has an α, β-unsaturated carbonyl group, and gingerol, which does not, on primary-cultured microglia to understand how the α, β-unsaturated carbonyl inter...
We investigated the effects of shogaol, which has an α, β-unsaturated carbonyl group, and gingerol, which does not, on primary-cultured microglia to understand how the α, β-unsaturated carbonyl interacts with Kelch-like ECH-associated protein (Keap)1. Shogaol (1 μM) but not the same concentration of gingerol significantly increased heme oxygenase (HO)-1 protein levels in cultured microglia without cytotoxicity. In addition, shogaol suppressed the release of the inflammation marker nitric oxide induced by 30 U/ml thrombin treatment. A docking simulation suggested that the α, β-unsaturated carbonyl of shogaol but not gingerol interacts with Keap1. Nuclear import of nuclear factor E2-related factor 2 and increased binding of the HO-1 E2 enhancer support the docking-simulation prediction. The transcription inhibitor actinomycin D (0.1 μg/ml) markedly blocked the increase of HO-1 mRNA levels by shogaol. To evaluate whether the α, β-unsaturated carbonyl can be used for intracerebral hemorrhage (ICH) therapy, we investigated the effect of shogaol on an in vivo mouse ICH model. Intracerebroventricular injection of 0.2 nmol shogaol increased striatal HO-1 protein levels and rescued ICH-induced neuron loss. Thus, the α, β-unsaturated carbonyl is necessary for the interaction of compounds, such as shogaol, with Keap1, and these findings may be useful for screening novel ICH therapeutic agents that increase HO-1 expression.
- Outcome of First-Line Hysterectomy for Gestational Trophoblastic Neoplasia in Patients No Longer Wishing to Conceive and Considered With Isolated Lung Metastases: A Series of 30 Patients. [Journal Article]
- IJInt J Gynecol Cancer 2018; 28(9):1766-1771
- CONCLUSIONS: For GTN patients no longer wishing to conceive with lung metastases discovered postoperatively, treated by hysterectomy, and whose hCG is decreasing, it is reasonable to expect and to inform patients that approximately 27% will require salvage chemotherapy. However, in patients with lung metastases discovered preoperatively, evidence to recommend first-line hysterectomy is insufficient and these patients should receive first-line chemotherapy.
- The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy is feasible but does not improve outcome for patients with metastatic rhabdomyosarcoma: A report from the Children's Oncology Group. [Journal Article]
- CCancer 2018 Oct 23
- CONCLUSIONS: The addition of cixutumumab or temozolomide to intensive multiagent chemotherapy for metastatic RMS was safe and feasible. Neither agent improved outcome compared with the same chemotherapy that was used on ARST0431.
- Choriocarcinoma with brain metastasis after term pregnancy: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(42):e12904
- CONCLUSIONS: Timely diagnosis of postpartum choriocarcinoma can significantly improve its prognosis. A stratified treatment should be administered according to the International Federation of Gynecology and Obstetrics staging and World Health Organization prognostic scoring systems. Blood β-HCG is a sensitive marker for evaluating therapeutic efficacy and follow-up after remission.
- Maintenance chemotherapy to reduce the risk of a metachronous Wilms tumor in children with bilateral nephroblastomatosis. [Journal Article]
- PBPediatr Blood Cancer 2018 Oct 18; :e27500
- From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vinc...
From 2009 to 2018, 10 consecutive patients with Wilms tumors and bilateral nephroblastomatosis, who had completed standard therapy, were provided a maintenance chemotherapy regimen consisting of vincristine and dactinomycin every 3 months for 12 months in order to prevent an early metachronous Wilms tumor. One patient (10%) with Beckwith-Wiedemann syndrome developed a new tumor, without anaplasia. There were no significant toxicities reported during maintenance. All patients are currently alive with no evidence of disease. Further investigations are recommended to determine the utility of this approach.
- Maternally inherited rRNA triggers de novo nucleolus formation in porcine embryos. [Journal Article]
- ZZygote 2018 Oct 12; :1-8
- SummaryThe present study examines the role of RNA polymerase I (RPI)-mediated transcription, maternally inherited rRNA and nucleolar proteins in the resumption of fibrillogranular nucleoli during emb...
SummaryThe present study examines the role of RNA polymerase I (RPI)-mediated transcription, maternally inherited rRNA and nucleolar proteins in the resumption of fibrillogranular nucleoli during embryonic genome activation (EGA) in porcine embryos. Late 4-cell embryos were incubated in the absence (control) or presence of actinomycin D (AD) (0.2 μg/ml for inhibition of RPI; 2.0 μg/ml for inhibition of total transcription) and late 2-cell embryos were cultured to the late 4-cell stage with 0.2 μg/ml AD to block EGA. Embryos were then processed for reverse-transcriptase polymerase chain reaction (RT-PCR), and for autoradiography (ARG), transmission electron microscopy (TEM), fluorescence in situ hybridization (FISH), silver staining and immunofluorescence (for RPI). Embryos in the control group displayed extranucleolar and intranucleolar ARG labelling, and exhibited de novo synthesis of rRNA and reticulated functional nucleoli. Nucleolar proteins were located in large foci. After RPI inhibition, nucleolar precursors transformed into segregated fibrillogranular structures, however no fibrillar centres were observed. The localization of rDNA and clusters of rRNA were detected in 57.1% immunoprecipitated (IP) analyzed nucleoli and dispersed RPI; 30.5% of nuclei showed large deposits of nucleolar proteins. Embryos from the AD-2.0 group did not display any transcriptional activity. Nucleolar formation was completely blocked, however 39.4% of nuclei showed rRNA clusters; 85.7% of nuclei were co-localized with nucleolar proteins. Long-term transcriptional inhibition resulted in the lack of ARG and RPI labelling; 40% of analyzed nuclei displayed the accumulation of rRNA molecules into large foci. In conclusion, maternally inherited rRNA co-localized with rDNA and nucleolar proteins can initiate a partial nucleolar assembly, resulting in the formation of fibrilogranular structures independently on activation of RPI-mediated transcription.
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- Comparison of hypocrellin B-mediated sonodynamic responsiveness between sensitive and multidrug-resistant human gastric cancer cell lines. [Journal Article]
- JMJ Med Ultrason (2001) 2018 Oct 11
- CONCLUSIONS: These results suggest that HB-SDT could induce apoptosis in SGC7901 and SGC7901/ADR cells via production of ROS. SGC7901/ADR was found to be more sensitive to HB-SDT than SGC7901 cells under the same experimental condition. Meanwhile, a noteworthy difference in cell membrane injury between SGC7901 and SGC7901/ADR cells was detected. The decreased membrane fluidity in SGC7901/ADR cells may be one of the reasons for its increased membrane damage.