Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proton beam radiotherapy exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic second cancer. The aim of this study was to explore strategies to reduce stray radiation dose to a patient receiving a 76 Gy proton beam treatment for cancer of the prostate. The whole-body effective dose from stray radiation, E, was estimated using detailed Monte Carlo simulations of a passively scattered proton treatment unit and an anthropomorphic phantom. The predicted value of E was 567 mSv, of which 320 mSv was attributed to leakage from the treatment unit; the remainder arose from scattered radiation that originated within the patient. Modest modifications of the treatment unit reduced E by 212 mSv. Surprisingly, E from a modified passive-scattering device was only slightly higher (109 mSv) than from a nozzle with no leakage, e.g., that which may be approached with a spot-scanning technique. These results add to the body of evidence supporting the suitability of passively scattered proton beams for the treatment of prostate cancer, confirm that the effective dose from stray radiation was not excessive, and, importantly, show that it can be substantially reduced by modest enhancements to the treatment unit.
 ...
PMID:Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer. 1836 78

Treatment planning calculations for proton therapy require an accurate knowledge of radiological path length, or range, to the distal edge of the target volume. In most cases, the range may be calculated with sufficient accuracy using kilovoltage (kV) computed tomography (CT) images. However, metal implants such as hip prostheses can cause severe streak artifacts that lead to large uncertainties in proton range. The purposes of this study were to quantify streak-related range errors and to determine if they could be avoided by using artifact-free megavoltage (MV) CT images in treatment planning. Proton treatment plans were prepared for a rigid, heterogeneous phantom and for a prostate cancer patient with a metal hip prosthesis using corrected and uncorrected kVCT images alone, uncorrected MVCT images and a combination of registered MVCT and kVCT images (the hybrid approach). Streak-induced range errors of 5-12 mm were present in the uncorrected kVCT-based patient plan. Correcting the streaks by manually assigning estimated true Hounsfield units improved the range accuracy. In a rigid heterogeneous phantom, the implant-related range uncertainty was estimated at <3 mm for both the corrected kVCT-based plan and the uncorrected MVCT-based plan. The hybrid planning approach yielded the best overall result. In this approach, the kVCT images provided good delineation of soft tissues due to high-contrast resolution, and the streak-free MVCT images provided smaller range uncertainties because they did not require artifact correction.
 ...
PMID:Can megavoltage computed tomography reduce proton range uncertainties in treatment plans for patients with large metal implants? 1842 Nov 22

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1 polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20-0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis.
 ...
PMID:Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk. 1856 16

Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2 sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells to apoptosis induction through genotoxic stress imposed by sub-lethal concentration of hydrogen peroxide. Together, our findings suggest a potential autocrine pathway of p53 activation by transcriptional regulation, and a new approach to reactivate p53 for cancer therapy.
 ...
PMID:The autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) induces senescence or quiescence of prostate, breast and liver cancer cells via transcriptional activation of p53. 1863 75

Green tea and black tea (BT) contain gallated [(-)-epigallocatechin-3-gallate (EGCG), (-)-epicatechin-3-gallate] and nongallated [(-)-epicatechin, (-)-epigallocatechin (EGC)] tea polyphenols (PP). During BT production, PP undergo oxidation and form larger polymers such as theaflavins (THE) and thearubigins, which contribute to the health benefit of BT. This article gives an overview of the role of chemical characteristics and endogenous metabolism of tea PP and their bioavailability in humans and describes attempts to increase their bioavailability. At pH close to neutral, EGCG and EGC form homo- and heterodimers generating hydrogen peroxide. To confirm the pH instability of EGCG, EGC, and THE in cell culture medium, their antiproliferative activity was determined in the presence and absence of catalase. The antiproliferative activity in LNCaP prostate cancer cells was decreased when incubated with catalase prior to EGCG, EGC, and THE treatment. In addition, new findings demonstrated that the formation of methyl-EGC increased the stability at neutral pH compared with EGC. Approaches to increase the bioavailability of flavan-3-ols are reviewed, which include the administration of tea in combination with fruit juices, coadministration with piperine, and peracetylation of EGCG. Future intervention studies will need to focus on the bioactivity not only of green tea and BT PP but also of their metabolites and biotransformation products.
 ...
PMID:Nongallated compared with gallated flavan-3-ols in green and black tea are more bioavailable. 1864 Dec 2

As a clinical application of an exciting scientific breakthrough, a compact and cost-efficient proton therapy unit using high-power laser acceleration is being developed at Fox Chase Cancer Center. The significance of this application depends on whether or not it can yield dosimetric superiority over intensity-modulated radiation therapy (IMRT). The goal of this study is to show how laser-accelerated proton beams with broad energy spreads can be optimally used for proton therapy including intensity-modulated proton therapy (IMPT) and achieve dosimetric superiority over IMRT for prostate cancer. Desired energies and spreads with a varying deltaE/E were selected with the particle selection device and used to generate spread-out Bragg peaks (SOBPs). Proton plans were generated on an in-house Monte Carlo-based inverse-planning system. Fifteen prostate IMRT plans previously used for patient treatment have been included for comparison. Identical dose prescriptions, beam arrangement and consistent dose constrains were used for IMRT and IMPT plans to show the dosimetric differences that were caused only by the different physical characteristics of proton and photon beams. Different optimization constrains and beam arrangements were also used to find optimal IMPT. The results show that conventional proton therapy (CPT) plans without intensity modulation were not superior to IMRT, but IMPT can generate better proton plans if appropriate beam setup and optimization are used. Compared to IMRT, IMPT can reduce the target dose heterogeneity ((D5-D95)/D95) by up to 56%. The volume receiving 65 Gy and higher (V65) for the bladder and the rectum can be reduced by up to 45% and 88%, respectively, while the volume receiving 40 Gy and higher (V40) for the bladder and the rectum can be reduced by up to 49% and 68%, respectively. IMPT can also reduce the whole body non-target tissue dose by up to 61% or a factor 2.5. This study has shown that the laser accelerator under development has a potential to generate high-quality proton beams for cancer treatment. Significant improvement in target dose uniformity and normal tissue sparing as well as in reduction of whole body dose can be achieved by IMPT with appropriate optimization and beam setup.
 ...
PMID:Dosimetric advantages of IMPT over IMRT for laser-accelerated proton beams. 1903 41

Urea-based, low molecular weight ligands of glutamate carboxypeptidase II (GCPII) have demonstrated efficacy in various models of neurological disorders and can serve as imaging agents for prostate cancer. To enhance further development of such compounds, we determined X-ray structures of four complexes between human GCPII and urea-based inhibitors at high resolution. All ligands demonstrate an invariant glutarate moiety within the S1' pocket of the enzyme. The ureido linkage between P1 and P1' inhibitor sites interacts with the active-site Zn(1)(2+) ion and the side chains of Tyr552 and His553. Interactions within the S1 pocket are defined primarily by a network of hydrogen bonds between the P1 carboxylate group of the inhibitors and the side chains of Arg534, Arg536, and Asn519. Importantly, we have identified a hydrophobic pocket accessory to the S1 site that can be exploited for structure-based design of novel GCPII inhibitors with increased lipophilicity.
 ...
PMID:Interactions between human glutamate carboxypeptidase II and urea-based inhibitors: structural characterization. 1905 59

Pleiotrophin (PTN) is a secreted growth factor involved in angiogenesis and tumor growth. We have recently shown that low concentrations of hydrogen peroxide (HP) stimulate PTN expression, through activation of the transcription factor AP-1. In the present work, we studied the possible involvement of endothelial nitric oxide synthase (eNOS) and the role of nitric oxide (NO) in the regulation of PTN expression, as well as involvement of the latter in the NO-induced human endothelial and prostate cancer cell migration. Inhibition of eNOS or the downstream effector soluble guanylate cyclase (sGC) completely suppressed HP-induced AP-1 activities that lead to PTN expression and cell migration. The NO donor sodium nitroprusside (SNP) through activation of sGC significantly and concentration-dependently increased expression of PTN, through transcriptional activation of the corresponding gene. Moreover, SNP had no effect on the migration of stably transfected prostate cancer cells that do not express PTN and knockdown of PTN receptor protein tyrosine phosphatase beta/zeta (RPTPbeta/zeta) completely abolished SNP-induced cell migration. NO added exogenously or produced endogenously by low concentrations of HP through stimulation of sGC activates extracellular signal-regulated kinase[1/2] (ERK[1/2]) and leads to PTN expression and cell migration. On the other hand, p38, which also intervenes in the up-regulation of PTN expression by low concentrations of HP, seems to act upstream of eNOS and does not intervene in the SNP-induced PTN expression and cell migration. The above data suggest that PTN through its receptor RPTPbeta/zeta is a mediator of the stimulatory effects of eNOS/NO on human endothelial and prostate cancer cell migration.
 ...
PMID:Nitric oxide stimulates migration of human endothelial and prostate cancer cells through up-regulation of pleiotrophin expression and its receptor protein tyrosine phosphatase beta/zeta. 1905 21

Proton magnetic resonance spectroscopic imaging (MRSI) of the prostate has been described at 1.5 T and 3 T as a means of localizing prostate cancers with high sensitivity and specificity. This technique could be improved by increasing the field strength further; however, it has not been described in detail above 3 T. To address the increase in B1 and SAR at high field strengths, a new protocol is described for reduced power STEAM MRSI of the prostate at 4.0 Tesla, using a pelvic surface coil array for RF transmission and reception, and a solid, reusable endorectal coil for reception only. The optimal STEAM sequence timing parameters for observation of the strongly coupled citrate spin system were determined through simulation to be echo time (TE) = 27 ms and mixing time (TM) = 27 ms, and the results were verified in vitro. Power reduction was achieved by applying the VERSE method to each of the three slice selective pulses in the STEAM sequence, and the B(1)max and SAR were reduced by 43% and 36%, respectively. Finally, in vivo spectroscopic imaging data were acquired from a prostate cancer patient, demonstrating the detection of citrate, choline, and creatine with 0.37 cc nominal resolution in a 10 minute scan.
 ...
PMID:Reduced power magnetic resonance spectroscopic imaging of the prostate at 4.0 Tesla. 1916 76

Proton therapy (PT) is becoming a more widely available treatment option on the world stage and there is some interest in investment in this treatment option in Australia. The benefit of PT has been shown for a number of tumour sites, particularly for paediatric patients. The workload from these patients may not completely fill the maximum yearly workload of a machine. This work aims to ascertain if prostate cancer would be a suitable candidate to fill the rest of the workload at an Australian PT facility. Passive and intensity modulated proton therapy (IMPT) plans were generated for a prostate patient. These were compared to 7 field sliding window and step and shoot IMRT plans. All plans used a prescription dose of 78 CGE. IMRT and IMPT plans used inverse planning for optimisation. Homogeneity in the PTV was best for the IMPT plan. IMPT also gave the best rectal sparing. The bladder and femoral heads were exposed to less dose in both proton plans. Proton plans exposed normal tissue outside the PTV to less than 50% of the dose given by the IMRT plans. PT, particularly IMPT, is a suitable treatment option for the prostate cancer patient presented here.
 ...
PMID:A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy. 1923 59


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>