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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To date, all available therapies for prostate cancer are plagued by adverse effects. Chemotherapy is no exception. The mechanisms of activity of chemotherapy agents are not cancer-specific. Normal tissues, particularly those that require rapid cell proliferation, are vulnerable to the effects of growth inhibition by these cytotoxic agents. Furthermore, both predictable as well as idiosyncratic toxicities unrelated to the antineoplastic activity of these agents can occur. In some cases, the cause of adverse events may be linked to the vehicle required to suspend water-insoluble chemotherapy drugs. Patient-specific factors can also significantly contribute to the risk of chemotherapy side-effects. However, with optimal clinical care the toxicity of antineoplastic agents can be substantially reduced. Long before chemotherapy is contemplated, it is imperative to limit treatments that reduce patients' capacity to tolerate subsequent chemotherapy. Moreover, offering treatment before patients' performance status declines can significantly improve tolerance of treatment. Once chemotherapy is initiated, the incidence and severity of adverse effects can be reduced through individualized selection of chemotherapy regimens and appropriate use of adjunct medications. Finally, aggressive management of toxicities after they occur lessens their duration and severity. The common toxicities of current chemotherapy regimens for prostate cancer, as well as strategies to limit and manage these toxicities are reviewed.
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PMID:Complications of chemotherapy for prostate cancer. 1156 90

Although MR spectroscopic imaging (MRSI) of the prostate has demonstrated clinical utility for the staging and monitoring of cancer extent, current acquisition methods are often inadequate in several aspects. Conventional 180 degrees pulses can suffer from chemical shift misregistration, and have high peak-power requirements that can exceed hardware limits in many prostate MRSI studies. Optimal water and lipid suppression are also critical to obtain interpretable spectra. While complete suppression of the periprostatic lipid resonance is desired, controlled partial suppression of water can provide a valuable phase and frequency reference for data analysis and an assessment of experimental success in cases in which all other resonances are undetectable following treatment. In this study, new spectral-spatial RF pulses were developed to negate chemical shift misregistration errors and to provide dualband excitation with partial excitation of the water resonance and full excitation of the metabolites of interest. Optimal phase modulation was also included in the pulse design to provide 40% reduction in peak RF power. Patient studies using the new pulses demonstrated both feasibility and clear benefits in the reliability and applicability of prostate cancer MRSI.
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PMID:Dualband spectral-spatial RF pulses for prostate MR spectroscopic imaging. 1174 72

The authors used a new method of treatment of prostatic cancer--selective stereotactic puncture cryodestruction of the anteriod hypophysis lobe--which prevents water-electrolyte imbalance, relieves pain syndrome due to bone metastases, reduces androgenic stimulation of the prostate, improves quality of life for patients of clinical group IV. The operation is low-traumatic and is not accompanied with serious complications.
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PMID:[Cryodestruction of the anterior lobe of adenohypophysis in terminal patients with prostatic cancer]. 1178 75

For many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostate-specific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADC(w)) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy.
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PMID:Early response of prostate carcinoma xenografts to docetaxel chemotherapy monitored with diffusion MRI. 1198 45

Low-energy gamma-emitting isotopes encapsulated for permanent implant are routinely applied in brachytherapy, most notably for prostate cancer. Before clinical use of a new source design, a full dosimetric analysis and standardized calibration are essential. Results of experimental measurement and analysis are reported here for the I-Plant (Implant Sciences Corporation) 125I source, model 3500. Dose measurements were made using standard methods employing thermoluminscent dosimeters in a water equivalent plastic phantom. Precision machined bores in the phantom located dosimeters and source(s) in a reproducible fixed geometry providing for transverse-axis and angular dose profiles over a range of distances from 0.17 to 10 cm. The data were analyzed in terms of parameters recommended by AAPM TG-43. The dose-rate constant, delta = 1.01 cGy/h U (+/-6%) (1 U = 1 cGy cm2 h(-1)), was evaluated with reference to a TG-51 calibrated 60Co standard, accounting for dosimeter response differences between 60Co and 125I photons. The radial dose function, g(r), the anisotropy function, F(r, theta), the anisotropy factor, phi(an)(r), and the point-source approximation anisotropy constant, phi(an), were derived from one- and two-dimensional dose distribution data measured in the phantom, accounting for finite dosimeter volume and with attention to inter-chip effects. The results confirm prior dosimetric characterization of the model 3500, and indicate that the new source is comparable to the MED3631-A/M and 6702 source designs and may substitute for model 6711 in permanent implants for the treatment of prostate cancer.
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PMID:Model 3500 125I brachytherapy source dosimetric characterization. 1199 56

The data presented herein, although highly supportive for a protective role of various nutrients against bladder cancer, are far from definitive. Many authorities question the validity of current recommendations for nutritional chemoprevention against bladder cancer. The reason for the wide variations reported in epidemiologic studies lies in the nature of observational studies. Dietary studies are limited in their conclusions because the protection afforded by the consumption of a particular nutrient may be multifactorial, with different components of the food exerting potential chemopreventive effects. Furthermore, measuring levels of nutrients in the food intake of populations is confounded by factors that might affect these levels and also the incidence of cancer. For example, vitamin A can come from animal or vegetarian sources. Because animal fat has been identified as a potential carcinogen in man, depending on the source of the vitamin, varying levels of protection might be deduced. In addition, chemoprevention studies using dietary supplements are expected to have mild effects, and large studies would be required to confirm statistical significance. Even with agents such as intravesical chemotherapy, only half the studies achieve statistical significance [29]. Prospective randomized trials with a large sample size, longer follow-up, and an extended duration of treatment are needed to clarify the association between micronutrients and cancer protection. With these caveats in mind, several recommendations can be made. Simple measures, such as drinking more fluids (especially water), can have a profound impact on the incidence of bladder cancer. Vitamins are being extensively studied in chemopreventive trials for different cancers. There is strong evidence for a chemoprotective effect of vitamin A in bladder cancer. The authors recommend 32,000 IU/day of vitamin A initially, with lower doses (24,000 IU) for persons less than 50 kg. Because liver toxicity is a possibility with long-term administration, the dose should be decreased to 16,000 IU after 3 years. High doses of beta-carotene should be avoided based on a large clinical trial reporting a 25% increase in the number of cases of prostate cancer and a statistically significant increase in the incidence of lung cancer. Vitamin B6 has been studied in several clinical trials in bladder cancer. The US-based Veterans Administration cooperative study found benefit for vitamin B6 when given as a single agent. Data for vitamins C and E are insufficient to recommend either agent as stand-alone treatment. Nonetheless, each of these vitamins is known to have beneficial effects, including improved function of the immune system. It is possible that only a small percentage of patients with bladder cancer respond to vitamins B6, C, or E, yet each is safe, nontoxic, and inexpensive. In an effort to pool the efficacy of individual agents and to increase the power of study, the authors evaluated the combination of vitamins A, B6, C, and E in a double-blind trial. The observed 50% 5-year reduction in tumor recurrence was highly significant and greater than would be expected for any of the individual ingredients and suggests that combinations of nutritional agents may be most appropriate. A large-volume study along similar lines is being conducted. Among the numerous other compounds and dietary substances purported to have chemopreventive effect, soybeans, garlic, and green tea stand out as having the greatest promise and can freely be recommended to patients. For synthetically synthesized agents such as celecoxib, piroxicam, or DFMO, recommendations must be deferred until the results of clinical trials are conclusively in favor of their use. Many of the dietary factors found to be protective against bladder cancer are being investigated in other cancers and are beneficial to general health. Although naturally occurring nutrients are ideal, especially because the delicate balance of various micronutrients might be impossible to synthesize in the laboratory, the general population finds it easier to take vitamin supplements. Unfortunately, dietary changes such as decreasing fat and increasing fruit and vegetable intake are more difficult to initiate. There is a mistaken notion that simply because an agent is naturally occurring, it cannot be as beneficial as taking a substance synthesized in the laboratory. Even in a high-risk group such as nuclear-bomb survivors in Japan, high consumption of vegetables and fruit is protective against bladder cancer [44]. Encouraging patients to follow an essentially healthy food habit lifestyle will be a significant contribution in the fight against cancer.
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PMID:Chemoprevention of bladder cancer. 1210 42

The recent popularity of permanent implants for treatment of prostate cancer has created a large demand for low energy seed sources. Vendors have introduced new source designs to meet this demand. The AAPM has recommended that all low energy interstitial brachytherapy seed sources be subjected to independent dosimetric evaluations, preferably using experimental measurements as well as Monte Carlo calculations. This work presents the results of Thermo-Luminescence Dosimeter (TLD) measurements of dosimetric parameters on the transverse axis of a new 125I seed source, the Source Tech Medical STM1251 125I seed. Experimental measurements were performed in a Solid Water phantom, with the results corrected to values for liquid water using Monte Carlo calculated correction factors. The parameters measured include the dose rate constant and values of the radial dose function at distances of 0.5 cm through 5 cm. The measured dose rate constant in liquid water for the STM1251 125I seed was 1.039 cGy/U-hr. Measured radial dose function values agreed with Monte Carlo calculated ones to within 10%. These measurements therefore confirm the modeling and simulation of Monte Carlo calculations for this 125I source design, within the statistical uncertainties of the calculation and measurement techniques.
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PMID:Measured transverse-axis dosimetric parameters of the model STM1251 125I interstitial source. 1213 42

This paper describes a new method for scanning the conductivity of a tissue or an organ using a multielectrode impedance probe placed at the center of the region of interest. The long-term objective of the study is the evaluation, using an urethral impedance probe, of the lesion produced by ultrasound ablathermy of localized prostate cancer. The probe consists of electrodes placed at the surface of an insulating cylinder. The injected current passes around the cylinder and spreads in the medium surrounding the probe. This paper presents the theoretical bases of this method, the calculated sensitivity distributions of electrode configurations involving a pair of diametrically opposed electrodes and an application in vitro. The experimental set-up consisted of a water tank and a 16-electrode prototype probe 50 mm in diameter. Data sets were collected in the presence of conductivity perturbations produced by small size insulators or conductors and a 7.5% constant perturbation model. The presented images, although reconstructed using a simple retro-projection algorithm, demonstrate the feasibility of the method. Improvements in data collection and image reconstruction are possible.
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PMID:Electrical impedance endo-tomography: imaging tissue from inside. 1216 51

Interest in exploiting traditional medicines for prevention or treatment of cancer is increasing. Extracts from the herb Tripterygium wilfordii hook F have been used in China for centuries to treat immune-related disorders. Recently it was reported that triptolide (PG490), a purified compound from Tripterygium, possessed antitumor properties and induced apoptosis by p53-independent mechanisms in a variety of malignant cell lines. This property of triptolide attracted our attention because we have found that primary cultures of human prostatic epithelial cells derived from normal tissues and adenocarcinomas are in general extremely resistant to apoptosis. Furthermore, the function of wild-type p53 is impaired in these cells such that drugs that require p53 activity to induce cell death are ineffective. Therefore, the properties of triptolide and the recent approval of its water-soluble form (PG490-88) for entry into Phase I clinical trials suggested that this drug was a promising candidate to test for antitumor activity against prostate cells. Experiments presented here demonstrated that triptolide had dose-dependent effects on both normal and cancer-derived primary cultures of human prostatic epithelial cells. Low concentrations of triptolide inhibited cell proliferation and induced a senescence-like phenotype. Higher concentrations of triptolide induced apoptosis that was unexpectedly associated with nuclear accumulation of p53. Paradoxically, levels of the p53 target genes, p21(WAF1/CIP1) and hdm-2, were reduced, as was bcl-2. Our preclinical studies suggest that triptolide might be an effective preventive as well as therapeutic agent against prostate cancer and that triptolide may activate a functional p53 pathway in prostate cells.
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PMID:Antiproliferative and proapoptotic activities of triptolide (PG490), a natural product entering clinical trials, on primary cultures of human prostatic epithelial cells. 1217 99

The development of novel strategies for the treatment of malignancies by successful intervention in advanced stage disease is a major challenge in oncology. We tested the hypothesis that this can be achieved by the rational design of taxoid onium salts modified at C-7 and C-2' positions. The characterization of these molecules revealed a dramatically improved water solubility and prodrug behavior in plasma. Specifically, all compounds released parental paclitaxel with half-lives ranging from 0.9 to 180 min. In the absence of plasma, only the 2'-(N-methylpyridinium acetate) derivative of paclitaxel (2'-MPA-paclitaxel) revealed a complete abrogation of paclitaxel specific microtubule assembly disassembly dynamics and a 3 log reduction in cellular binding, indicating that reversible blockage of the C-2' position by methylpyridinium acetate yields a true paclitaxel prodrug. Structure/activity profiles of all compounds in tissue culture revealed cytotoxicity effective at picomolar concentrations with a panel of 16 cancer cell lines in contrast to 4 nonmalignant cell lines. Importantly, the decisive cytotoxic potential observed in vitro for all compounds correlated only with in vivo findings for 2'-MPA-paclitaxel. Specifically, the 2'-MPA-paclitaxel prodrug induced regression of primary tumors in three xenograft models of nonsmall cell lung carcinoma, ovarian carcinoma and prostate cancer, in contrast to ineffective C-7 derivatives and parental paclitaxel. At the same time, a reduced systemic toxicity of 2'-MPA-paclitaxel was observed in contrast to a far more toxic parental paclitaxel. Taken together, these findings demonstrate that the 2'-MPA-paclitaxel prodrug is a promising new candidate for cancer therapy.
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PMID:A novel 2'-(N-methylpyridinium acetate) prodrug of paclitaxel induces superior antitumor responses in preclinical cancer models. 1223 91


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