Low-density lipoprotein receptors play an important role in the inhibition of prostate cancer cell proliferation by statins

AbstractBackgroundThere are some reports about the antitumor effects of statins in these days. Statins decrease the level of cholesterol in the blood by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Inhibition of this enzyme decreases intracellular cholesterol synthesis. Thus, the expression of low-density lipoprotein receptor (LDLr) is increased to import more cholesterol from the bloodstream. In this study, we assessed the effects of statins on the proliferation of prostate cancer cells, and studied the relationship between the expression of LDLr and the effects of statins.MethodsSimvastatin was used in the experiments. We studied the effect of simvastatin on PC-3 and LNCaP cell proliferation using the MTS assay, and evaluated the expression of LDLr after administration of simvastatin by quantitative polymerase chain reaction and Western blotting. Intracellular cholesterol levels in the prostate cancer cells were measured after administration of simvastatin. Furthermore, small interfering RNA (siRNA) was used to knockdown the gene expression of LDLr.ResultsIn PC-3 cells, simvastatin inhibited cell proliferation. In LNCaP cells, only a high concentration of simvastatin (100μM) inhibited cell proliferation. In LNCaP cells, the protein level of LDLr was increased by simvastatin. In PC-3 cells, the protein levels of LDLr were unregulated. In PC-3 cells, but not in LNCaP cells, intracellular cholesterol levels were significantly decreased by simvastatin. After knocking down LDLr expression by siRNA, intracellular cholesterol levels were decreased, and cell proliferation was inhibited by simvastatin in LNCaP cells.ConclusionSimvastatin inhibited prostate cancer cell growth by decreasing cellular cholesterol and could be more effective in androgen-independent prostate cancer, where there is loss of regulation of LDLr expression. LDLr was shown to play an important role in the statin-induced inhibition of prostate cancer cell proliferation. These results suggest that future studies evaluating the cholesterol-lowering effects of statin may lead to new approaches to the prevention and treatment of prostate cancer

Dietary counseling for hyperuricemia

In Japan, hyperuricemia is on the rise. The guideline for the management of hyperuricemia and gout recommends lifestyle changes before beginning drug therapy. This study aimed to evaluate the effectiveness of dietary counseling following the guideline. Thirty-three subjects (24 men and 9 women) with asymptomatic hyperuricemia underwent dietary counseling for 6 months based on the following recommendations : (1) prevent excessive purine intake, (2) prevent excessive fructose intake, (3) limit alcohol drinking, and (4) drink sufficient water. Obese subjects were counseled on adequate energy intake. Blood sampling, anthropometric measurements, dietary surveys, and 24-h urine collection were performed at baseline and at 6 months. Serum uric acid (S-UA) levels were significantly lower at 6 months compared to baseline. Water intake and urine volume were considerably higher at 6 months than at baseline. When compared to baseline, urine UA (U-UA) levels were significantly lower, and renal fractional excretion of UA (FEUA) was significantly higher at 6 months. Changes in renal function (serum creatinine, estimated glomerular filtration rate, and FEUA) were significantly associated with ΔS-UA level. In this study, S-UA level was significantly decreased by dietary counseling in line with the guideline. This study illustrates the effectiveness of dietary counseling for asymptomatic hyperuricemia

Chemokine and Free Fatty Acid Levels in Insulin-Resistant State of Successful Pregnancy: A Preliminary Observation

Increased insulin resistance and inflammatory action are observed in pregnancy-induced hypertension (PIH), but similar insulin resistance is observed also in successful pregnancy. To estimate insulin resistance and inflammatory activity in normal pregnancy and PIH, serum concentrations of free fatty acids (FFA; corrected with albumin to estimate unbound FFA), monocyte chemoattractant protein (MCP)-1, and high-molecular weight (HMW) adiponectin were measured in severe PIH patients with a BMI less than 25 kg/m2 and were measured 3 times during the course of pregnancy in women with normal pregnancies. FFA/albumin, MCP-1, and HMW adiponectin concentrations were significantly higher in PIH patients than in women with normal pregnancies. The 3 measurements of FFA/albumin showed a significant increase through the course of uncomplicated pregnancies. In contrast, MCP-1 and HMW adiponectin were significantly decreased during the course of pregnancy. These results suggest that the reduced MCP-1 concentration in normal pregnancy may be a pathway to inhibit the induction of pathological features from physiological insulin resistance and homeostatic inflammation

Proposal of a Simple Method to Estimate Neutrino Oscillation Probability and CP Violation in Matter

We study neutrino oscillation within the framework of three generations in matter. We propose a simple method to approximate the coefficients A, B and C which do not depend on the CP phase \delta in the oscillation probability P(\nu_e \to \nu_{\mu})=A\cos \delta + B\sin \delta +C. An advantage of our method is that an approximate formula of the coefficients A, B and C in arbitrary matter {\it without the usual first order perturbative calculations} of the small parameter \Delta m_{21}^2/\Delta m_{31}^2 or \sin \theta_{13} can be derived. Furthermore we show that all the approximate formulas for low, intermediate and high energy regions given by other authors in constant matter can be easily derived from our formula. It means that our formula is applicable over a wide energy region.Comment: 15 pages, 9 figures, accepted version in PL

Removal of accidentally ingested large foreign object via the anus after watchful waiting

One of the commonest complaints, for which a patient arrives in hospitals, is the presence of foreign body. It could be due to accidental ingestion or any other cause which leads to presences of a foreign body in the gastrointestinal tract. It is believed that foreign objects larger than 5–6 cm in size are unlikely to pass through the duodenum. Here, we describe a case wherein the patient accidentally swallowed a 7-cm-sized mouthguard that could not be removed by emergency upper gastrointestinal endoscopy but was subsequently removed via the anus after a period of watchful waiting

Overall Feature of CP dependence for Neutrino Oscillation Probability in Arbitrary Matter Profile

We study the CP dependence of neutrino oscillation probability for all channels in arbitrary matter profile within three generations. We show that an oscillation probability for \nu_e \to \nu_\mu can be written in the form P(\nu_e \to \nu_\mu) =A_{e\mu} cos \delta + B_{e\mu} sin \delta + C_{e\mu} without any approximation using the CP phase \delta. This result holds not only in constant matter but also in arbitrary matter. Another probability for \nu_\mu \to \nu_\tau can be written in the form P(\nu_\mu \to \nu_\tau)= A_{\mu\tau} cos \delta + B_{\mu\tau} sin \delta + C_{\mu\tau} + D_{\mu\tau} cos 2\delta + E_{\mu\tau} sin 2\delta. The term which is proportional to sin 2\delta disappear, namely E_{\mu\tau}=0, in symmetric matter. It means that the probability reduces to the same form as in constant matter. As for other channels, probabilities in arbitrary matter are at most the quadratic polynomials of sin \delta and cos \delta as in the above two channels. In symmetric matter, the oscillation probability for each channel reduces to the same form with respect to \delta as that in constant matter.Comment: 11 pages, no figures, LaTeX2e, a few misprints have been correcte

Enhancement of CP Violating terms for Neutrino Oscillation in Earth Matter

We investigate the $\nu_e \to \nu_{\mu}$ oscillation in the framework of three generations when neutrinos pass through the earth. The oscillation probability is represented by the form, $P(\nu_e \to \nu_\mu)=A\cos \delta+B\sin \delta+C$ in arbitrary matter profile by using the leptonic CP phase $\delta$. We compare our approximate formula in the previous paper with the formula which includes second order terms of $\alpha=\Delta m_{21}^2/\Delta m_{31}^2$ and $s_{13}=\sin \theta_{13}$. Non-perturbative effects of $\alpha$ and $s_{13}$ can be taken into account in our formula and the precision of the formula is rather improved around the MSW resonance region. Furthermore, we compare the earth matter effect of $A$ and $B$ with that of $C$ studied by other authors. We show that the magnitude of $A$ and $B$ can reach a few ten % of $C$ around the main three peaks of $C$ in the region $E>1$ GeV by numerical calculation. We give the qualitative understanding of this result by using our approximate formula. The mantle-core effect, which is different from the usual MSW effect, appears not only in $C$ but also in $A$ and $B$, although the effect is weakened.Comment: 16 pages, 5 figure

Exact Formulas and Simple CP dependence of Neutrino Oscillation Probabilities in Matter with Constant Density

We investigate neutrino oscillations in constant matter within the context of the standard three neutrino scenario. We derive an exact and simple formula for the oscillation probability applicable to all channels. In the standard parametrization, the probability for $\nu_e$ $\to$ $\nu_{\mu}$ transition can be written in the form $P(\nu_e \to \nu_{\mu})=A_{e\mu}\cos\delta+B_{e\mu}\sin\delta+C_{e\mu}$ without any approximation using CP phase $\delta$. For $\nu_{\mu}$ $\to$ $\nu_{\tau}$ transition, the linear term of $\cos 2\delta$ is added and the probability can be written in the form $P(\nu_{\mu} \to \nu_{\tau})=A_{\mu\tau}\cos\delta+B_{\mu\tau} \sin\delta+C_{\mu\tau}+D_{\mu\tau}\cos 2\delta$. We give the CP dependences of the probability for other channels. We show that the probability for each channel in matter has the same form with respect to $\delta$ as in vacuum. It means that matter effects just modify the coefficients $A$, $B$, $C$ and $D$. We also give the exact expression of the coefficients for each channel. Furthermore, we show that our results with respect to CP dependences are reproduced from the effective mixing angles and the effective CP phase calculated by Zaglauer and Schwarzer. Through the calculation, a new identity is obtained by dividing the Naumov-Harrison-Scott identity by the Toshev identity.Comment: 12 pages, RevTeX4 style, changed title, minor correction

SAHG, a comprehensive database of predicted structures of all human proteins

Most proteins from higher organisms are known to be multi-domain proteins and contain substantial numbers of intrinsically disordered (ID) regions. To analyse such protein sequences, those from human for instance, we developed a special protein-structure-prediction pipeline and accumulated the products in the Structure Atlas of Human Genome (SAHG) database at http://bird.cbrc.jp/sahg. With the pipeline, human proteins were examined by local alignment methods (BLAST, PSI-BLAST and Smith–Waterman profile–profile alignment), global–local alignment methods (FORTE) and prediction tools for ID regions (POODLE-S) and homology modeling (MODELLER). Conformational changes of protein models upon ligand-binding were predicted by simultaneous modeling using templates of apo and holo forms. When there were no suitable templates for holo forms and the apo models were accurate, we prepared holo models using prediction methods for ligand-binding (eF-seek) and conformational change (the elastic network model and the linear response theory). Models are displayed as animated images. As of July 2010, SAHG contains 42 581 protein-domain models in approximately 24 900 unique human protein sequences from the RefSeq database. Annotation of models with functional information and links to other databases such as EzCatDB, InterPro or HPRD are also provided to facilitate understanding the protein structure-function relationships