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

During the past 10 years, numerous phase I-II studies were conducted and provided clinical experience with combined radiation therapy and hyperthermia treatments. Among the rare complications reported in these combined radiation therapy-hyperthermia trials were myonecrosis and peripheral neuropathy which were felt, mainly on a clinical basis, to be caused by local heat damage. Recently, such complications were noted in two patients with recurrent prostatic cancer treated in our department with radiation therapy combined with deep regional hyperthermia delivered by the Sigma-60 applicator of the BSD 2000 hyperthermia system (Salt Lake City, UT, USA). Analysis of the results of three-dimensional modelling of the SAR (specific absorption rate, W/kg) pattern in these patients indicated high SAR at the sites of the complications. Pretreatment three-dimensional modelling or other methods of predicting potential areas of high power deposition may have a role for future hyperthermia treatment planning aiding in the prevention of possible local heat damage and providing improved delivery of heat to the target volume.
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PMID:Peripheral neuropathy and myonecrosis following hyperthermia and radiation therapy for recurrent prostatic cancer: correlation of damage with predicted SAR pattern. 131 65

Interstitial microwave therapy is an experimental treatment for prostate cancer. The objective of this work was to measure the power deposition (specific absorption rate, SAR) patterns of helical microwave antennae both individually and in array patterns that would be useful for clinical treatment protocols. Commercial helical antenna 3D SAR patterns were measured in muscle equivalent phantoms using a thermographic technique. Two array patterns were tested: a 'square' and a 'crescent' array, both surrounding the urethra. To assess the feasibility of pre-treatment planning, the measured SAR patterns were input to a treatment planning computer simulation program based on a series of trans-rectal ultrasound images from a prostate cancer patient. The simulation solved the Pennes linear bioheat heat transfer equation in prostate tissue, with the aim of achieving a target of 55 degrees C at the prostate periphery while not allowing normal surrounding tissues (bladder, urethra, rectum) to rise above 42 C. These criteria could not be met with the square array but they could be met with the crescent array, provided that the prostate was first dissected away from the rectum. This can be done with a procedure such as 'hydrodissection', where sterile saline is injected to separate the prostate and rectum. The results of these SAR measurements and heat transfer simulations indicate that arrays of helical antennae could be used for safe and effective thermal therapy for prostate cancer.
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PMID:Helical antenna arrays for interstitial microwave thermal therapy for prostate cancer: tissue phantom testing and simulations for treatment. 1147 33

We describe herein synthesis, SAR, and biological evaluation of a novel series of cytotoxic serine amide phosphates (SAPs) for prostate cancer. These compounds were tested for their cytotoxicity in five human prostate cancer cell lines (DU-145, PC-3, LNCaP, PPC-1, and TSU), and in CHO and RH7777 cells (negative controls). Comparison of anticancer effects of these compounds with a standard chemotherapeutic agent 5-fluorouracil shows that they are very effective in killing prostate cancer cells with low micromolar cytotoxicity and provide us a new lead for the development of drugs for prostate cancer.
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PMID:Synthesis and biological evaluation of novel cytotoxic phospholipids for prostate cancer. 1534 52

We have previously described serine amide phosphates (SAPs) as a novel class of cytotoxic agents for prostate cancer. Several of them showed potent cytotoxicity against human prostate cancer cell lines, but were not selective in non-tumor cells. To improve the selectivity and further enhance the potency, we designed a new series of 2-aryl-4-oxo-thiazolidin-3-yl amides. The current work describes synthesis, SAR, and biological evaluation of these compounds for their ability to inhibit the growth of prostate cancer cells. The antiproliferative effects of synthesized compounds were examined in five human prostate cancer cell lines (DU-145, PC-3, LNCaP, PPC-1, and TSU), and in RH7777 cells (negative controls). From this study, three potent compounds (8, 20, and 21) have been detected, which are effective in killing prostate cancer cells with improved selectivity compared to SAPs.
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PMID:Synthesis and antiproliferative activity of 2-aryl-4-oxo-thiazolidin-3-yl-amides for prostate cancer. 1545 13

The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.
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PMID:New COX-2/5-LOX inhibitors: apoptosis-inducing agents potentially useful in prostate cancer chemotherapy. 1556 90

Influence of the molecular structure of macrocyclic pyridinophanes, their analogues and some other compounds on anticancer activity (Leukemia, central nervous system (CNS) cancer, prostate cancer, breast cancer, melanoma, non-small cell lung cancer, colon cancer, ovarian cancer, renal cancer) was investigated by means of a new 4D-QSAR approach based on the simplex representation of molecular structures (SiRMS). For all the investigated molecules, the 3D structural models were first created and the set of conformers (fourth dimension) was used. Each conformer was represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). Statistic characteristics of the QSAR partial least squares (PLS) models were satisfactory (correlation coefficient r=0.990-0.861; cross-validation coefficient CVR=0.914-0.633). The molecular fragments increasing and decreasing anticancer activity were defined. This information may be useful for the design and direct synthesis of novel anticancer agents.
SAR QSAR Environ Res 2005 Jun
PMID:Investigation of anticancer activity of macrocyclic Schiff bases by means of 4D-QSAR based on simplex representation of molecular structure. 1580 10

In our continuing efforts to develop novel chemotherapeutic agents for prostate cancer, recently we reported the discovery of 2-arylthiazolidine-4-carboxylic acid amides (ATCAAs) as a new class of cytotoxic agents. Several of them were very effective in killing specific human prostate cancer cell lines with low/sub-micromolar cytotoxicity and high selectivity against control cells in our sulforhodamine B assay. Encouraged with these preliminary results, we decided to further optimize this new scaffold to enhance the potency and selectivity. Current work describes the synthesis, SAR, and biological evaluation of new compounds for their ability to inhibit the growth of five human prostate cancer cell lines. The cytotoxicity data demonstrated that ATCAAs are sensitive to simple modifications or changes, which allowed us to understand the minimum structural requirements of this class of compounds to exhibit potent and selective anticancer activity against prostate cancer cells.
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PMID:SAR studies of 2-arylthiazolidine-4-carboxylic acid amides: a novel class of cytotoxic agents for prostate cancer. 1600 17

4-Ethoxycarbonylethyl curcumin (ECECur) (3) is a current drug candidate for the treatment of prostate cancer. Due to problems inherent in the tautomerism of ECECur, 4-fluoro-4-ethoxycarbonylethyl curcumin (4) and 4-ethoxycarbonylethylenyl curcumin (5) were designed and synthesized. These two target compounds and their synthetic intermediates (4-9) were evaluated for their inhibitory activity against androgen receptor transcription in LNCaP and PC-3 prostate cancer cell lines. While the enol-keto analogs showed varying anti-androgen potencies, the di-keto analogs showed no activity. Tetrahydropyranylation of the phenoxy groups had a positive impact on the anti-AR activity of 4-ethoxycarbonylethylenyl curcumin, but a negative impact on the activity of ECECur. With potent anti-AR activity, di-tetrapyranylated 4-ethoxycarbonylethylenyl curcumin (9), which exists in only one form, is a good drug lead for further structural modification. Based on the SAR information obtained from the above study, five new compounds were designed and subsequently synthesized. Among them, compound 10 was found to be the most potent anti-AR agent and is considered to be a promising drug candidate for the treatment of prostate cancer.
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PMID:Antitumor agents 247. New 4-ethoxycarbonylethyl curcumin analogs as potential antiandrogenic agents. 1642 89

Through an in vivo screening model, we developed the in vivo SAR of beta-alkylthio indolyl carbinols. Through these efforts we identified a compound with potent oral in vivo efficacy in both immature and mature rat prostate weight reduction models and in a murine xenograft prostate cancer model.
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PMID:beta-Alkylthio indolyl carbinols: potent nonsteroidal antiandrogens with oral efficacy in a prostate cancer model. 1733 85

Using a live cell, high-throughput caspase-3 activator assay, we have identified a novel series of 4-anilinoquinazolines as inducers of apoptosis. In this report, we discuss the discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine, compound 2b (EP128265, MPI-0441138) as a highly active inducer of apoptosis (EC50 for caspase activation of 2 nM) and as a potent inhibitor of cell proliferation (GI50 of 2 nM) in T47D cells. Compound 2b inhibited tubulin polymerization, was effective in cells overexpressing ABC transporter Pgp-1, and was efficacious in the MX-1 human breast and PC-3 prostate cancer mouse models. In contrast to the SAR of 4-anilinoquinazolines as EGFR kinase inhibitors, the methyl group on the nitrogen linker was essential for the apoptosis-inducing activity of 4-anilinoquinazolines and substitution in the 6- and 7-positions of the quinazoline core structure decreased potency.
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PMID:Discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (EP128265, MPI-0441138) as a potent inducer of apoptosis with high in vivo activity. 1865 28


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