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Sample records for reduced prostate size

  1. Inhibitors of urokinase reduce size of prostate cancer xenografts in severe combined immunodeficient mice.

    PubMed

    Jankun, J; Keck, R W; Skrzypczak-Jankun, E; Swiercz, R

    1997-02-15

    Proteolytic enzymes are required to mediate tumor cell invasion and metastasis. The urokinase plasminogen activator (uPA) is commonly overexpressed by many human cancers. Therefore, uPA is a logical target to inhibit cancer invasion and metastasis. However, uPA inhibitors also reduce tumor growth. We used a mutated form of plasminogen activator inhibitor type 1 to conform a correlation between the inactivation of uPA and tumor size; we have compared these results with the action of p-aminobenzamidine and amiloride, known inhibitors of uPA. Our results show that blocking uPA by uPA inhibitors reduces tumor size in experimental animals. Our molecular simulation of docking inhibitors to the urokinase reveals that all tested small molecule inhibitors bind in proximity of uPA's specificity pocket, a critical site for future search of novel anticancer uPA inhibitors. PMID:9044824

  2. Prostate MRI can reduce overdiagnosis and overtreatment of prostate cancer.

    PubMed

    Rosenkrantz, Andrew B; Taneja, Samir S

    2015-08-01

    The contemporary management of prostate cancer (PCa) has been criticized as fostering overdetection and overtreatment of indolent disease. In particular, the historical inability to identify those men with an elevated PSA who truly warrant biopsy, and, for those needing biopsy, to localize aggressive tumors within the prostate, has contributed to suboptimal diagnosis and treatment strategies. This article describes how modern multi-parametric MRI of the prostate addresses such challenges and reduces both overdiagnosis and overtreatment. The central role of diffusion-weighted imaging (DWI) in contributing to MRI's current impact is described. Prostate MRI incorporating DWI achieves higher sensitivity than standard systematic biopsy for intermediate-to-high risk tumor, while having lower sensitivity for low-grade tumors that are unlikely to impact longevity. Particular applications of prostate MRI that are explored include selection of a subset of men with clinical suspicion of PCa to undergo biopsy as well as reliable confirmation of only low-risk disease in active surveillance patients. Various challenges to redefining the standard of care to incorporate solely MRI-targeted cores, without concomitant standard systematic cores, are identified. These include needs for further technical optimization of current systems for performing MRI-targeted biopsies, enhanced education and expertise in prostate MRI among radiologists, greater standardization in prostate MRI reporting across centers, and recognition of the roles of pre-biopsy MRI and MRI-targeted biopsy by payers. Ultimately, it is hoped that the medical community in the United States will embrace prostate MRI and MRI-targeted biopsy, allowing all patients with known or suspected prostate cancer to benefit from this approach.

  3. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model.

    PubMed

    Davis, Paul A; Vasu, Vihas T; Gohil, Kishorchandra; Kim, Hyunsook; Khan, Imran H; Cross, Carroll E; Yokoyama, Wallace

    2012-11-28

    Prostate cancer (PCa) has been linked to fat intake, but the effects of both different dietary fat levels and types remain inconsistent and incompletely characterised. The effects on PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) cancer model of an elevated fat (20 % of energy as fat) diet containing 155 g of whole walnuts were compared to those of an elevated fat (20 % of energy as soyabean oil) diet with matched macronutrients, tocopherols as well as a low-fat (8 % of energy as soyabean oil) diet. Mice, starting at 8 weeks of age, consumed one of the three different diets ad libitum; and prostates, livers and blood were obtained after 9, 18 or 24 weeks of feeding. No differences were observed in whole animal growth rates in either high-fat (HF) diet group, but prostate tumour weight and growth rate were reduced in the walnut diet group. Walnut diet group prostate weight, plasma insulin-like growth factor 1, resistin and LDL were lower at 18 weeks, while no statistically significant prostate weight differences by diet were seen at 9 or 24 weeks. Multiple metabolites in the livers differed by diet at 9 and 18 weeks. The walnut diet's beneficial effects probably represent the effects of whole walnuts' multiple constituents and not via a specific fatty acid or tocopherols. Moreover, as the two HF diets had dissimilar effects on prostate tumour growth rate and size, and yet had the same total fat and tocopherol composition and content, this suggests that these are not strongly linked to PCa growth.

  4. Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

    SciTech Connect

    Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Adamovich, Edward; Wallner, Kent E.

    2012-10-01

    Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate size for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.

  5. Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model.

    PubMed

    Kazmierczak, Robert A; Gentry, Bettina; Mumm, Tyler; Schatten, Heide; Eisenstark, Abraham

    2016-01-01

    Attenuated Salmonella typhimurium injected in the circulatory system of mammals selectively targets tumors. Using weekly intraperitoneal injections of attenuated Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor development in the TRAMP prostate tumor mouse model, which utilizes SV40 early region expression for autochthonous formation of prostate tumors that progress into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent murine model. Thirteen weekly intraperitoneal administrations of 105-107 CFU CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice and histological analysis of TRAMP prostates at 22 weeks indicated that Salmonella monotherapy at administrated levels decrease visible tumor size (>29%) but did not significantly inhibit previously described SV40 expression-driven TRAMP tumor progression to undifferentiated carcinomas when histologically examined. In conclusion, this work demonstrates baseline results for CRC2631 Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in preparation for study of combination therapies that resolve autochthonously generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate tumor progression. PMID:27504973

  6. Salmonella Bacterial Monotherapy Reduces Autochthonous Prostate Tumor Burden in the TRAMP Mouse Model

    PubMed Central

    Kazmierczak, Robert A.; Gentry, Bettina; Mumm, Tyler; Schatten, Heide; Eisenstark, Abraham

    2016-01-01

    Attenuated Salmonella typhimurium injected in the circulatory system of mammals selectively targets tumors. Using weekly intraperitoneal injections of attenuated Salmonella strain CRC2631, we tested for regression and/or inhibition of tumor development in the TRAMP prostate tumor mouse model, which utilizes SV40 early region expression for autochthonous formation of prostate tumors that progress into metastatic, poorly differentiated prostatic carcinomas in an immunocompetent murine model. Thirteen weekly intraperitoneal administrations of 105–107 CFU CRC2631 into 10 week old mice were well tolerated by the TRAMP model. Sacrifice and histological analysis of TRAMP prostates at 22 weeks indicated that Salmonella monotherapy at administrated levels decrease visible tumor size (>29%) but did not significantly inhibit previously described SV40 expression-driven TRAMP tumor progression to undifferentiated carcinomas when histologically examined. In conclusion, this work demonstrates baseline results for CRC2631 Salmonella monotherapy using the immunocompetent TRAMP prostate tumor model in preparation for study of combination therapies that resolve autochthonously generated TRAMP prostate tumors, further reduce tumor size, or inhibit prostate tumor progression. PMID:27504973

  7. Finasteride Reduces the Risk of Low-Grade Prostate Cancer in Men 55 and Older

    MedlinePlus

    ... Genetics of Prostate Cancer Prostate Cancer Screening Research Finasteride Reduces the Risk of Low-Grade Prostate Cancer ... PCPT) continue to show that regular use of finasteride (Proscar®) for up to 7 years decreased the ...

  8. Statin Use Reduces Prostate Cancer All-Cause Mortality

    PubMed Central

    Sun, Li-Min; Lin, Ming-Chia; Lin, Cheng-Li; Chang, Shih-Ni; Liang, Ji-An; Lin, I-Ching; Kao, Chia-Hung

    2015-01-01

    Abstract Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60–0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose–response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose–response relationship may exist. PMID:26426656

  9. Reducing the Risk of Benign Prostatic Hyperplasia Progression

    PubMed Central

    Roehrborn, Claus G

    2002-01-01

    The incidence of benign prostatic hyperplasia increases with age; the probability of progression rises with age at diagnosis and with baseline symptom severity. Although it is not life-threatening, the condition and its complications have a serious impact on quality of life. Acute urinary retention (AUR), though no longer thought an indication for immediate surgery, still requires treatment, often including surgery. Drug therapy with α-adrenergic receptor blockers or 5-α-reductase inhibitors, such as finasteride, reduces the risk for AUR and the need for surgery, as well as symptoms and bother. Finasteride therapy also results in long-term reduction in prostate volume. PMID:16986063

  10. How surgical innovation reduced death and suffering from prostate cancer.

    PubMed

    Walsh, Patrick C

    2013-01-01

    Radical prostatectomy for the cure of prostate cancer never gained widespread popularity because of severe side effects: all men were impotent, many were totally incontinent, and when performed by the retropubic approach, bleeding was often life threatening. When I arrived at Johns Hopkins in 1974 as the new director of the Brady Urological Institute, I embarked upon a series of anatomic studies to determine the source of this morbidity. Using the operating room as an anatomy laboratory and performing dissections in stillborn male infants, it was possible to define important, previously unrecognized anatomic structures. Application of these discoveries to the surgical technique made it possible to preserve sexual function, reduce urinary continence to a minimum, and perform the procedure in a relative bloodless field. Armed with the ability to cure prostate cancer more safely with surgery and with fewer side effects, radical prostatectomy was rapidly adopted and in the following decade death from prostate cancer declined by 40%.

  11. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary fat is linked to prostate cancer (PCa), the most commonly diagnosed male cancer, but the nature and strength of the relationships between total fat, n-6 and n-3 fatty acids and PCa remain incompletely understood. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (N=10-12 per grou...

  12. Reducing Class Size To Increase Student Involvement.

    ERIC Educational Resources Information Center

    Lottes, Christine R.

    Reducing class size was considered an important element in a revised health course at Gettysburg College (Pennsylvania). However, reducing class size to approximately 15 students per class would require 38 sections, more than the health faculty could handle. To recruit additional instructors, the course was marketed to faculty and administrators…

  13. Reducing Class Size: Promises and Perils

    ERIC Educational Resources Information Center

    Bascia, Nina; Fredua-Kwarteng, Eric

    2008-01-01

    Reducing class size, especially in primary grades, can have tremendous academic and social benefits for children--benefits that endure well beyond those first years of school. But smaller class sizes are not a cure-all. Beyond the hoopla of enthusiasm for this seemingly simple change in educational practice lie serious consequences for students…

  14. An Endorectal Balloon Reduces Intrafraction Prostate Motion During Radiotherapy

    SciTech Connect

    Smeenk, Robert Jan; Louwe, Robert J.W.; Langen, Katja M.; Shah, Amish P.; Kupelian, Patrick A.; Lin, Emile N.J.Th. van; Kaanders, Johannes H.A.M.

    2012-06-01

    Purpose: To investigate the effect of endorectal balloons (ERBs) on intrafraction and interfraction prostate motion during radiotherapy. Methods and Materials: Thirty patients were treated with intensity-modulated radiotherapy, to a total dose of 80 Gy in 40 fractions. In 15 patients, a daily-inserted air-filled ERB was applied. Prostate motion was tracked, in real-time, using an electromagnetic tracking system. Interfraction displacements, measured before each treatment, were quantified by calculating the systematic and random deviations of the center of mass of the implanted transponders. Intrafraction motion was analyzed in timeframes of 150 s, and displacements >1 mm, >3 mm, >5 mm, and >7 mm were determined in the anteroposterior, left-right, and superoinferior direction, and for the three-dimensional (3D) vector. Manual table corrections, made during treatment sessions, were retrospectively undone. Results: A total of 576 and 567 tracks have been analyzed in the no-ERB group and ERB group, respectively. Interfraction variation was not significantly different between both groups. After 600 s, 95% and 98% of the treatments were completed in the respective groups. Significantly fewer table corrections were performed during treatment fractions with ERB: 88 vs. 207 (p = 0.02). Intrafraction motion was significantly reduced with ERB. During the first 150 s, only negligible deviations were observed, but after 150 s, intrafraction deviations increased with time. This resulted in cumulative percentages of 3D-vector deviations >1 mm, >3 mm, >5 mm, and >7 mm that were 57.7%, 7.0%, 0.7%, and 0.3% in the ERB-group vs. 70.2%, 18.1%, 4.6%, and 1.4% in the no-ERB group after 600 s. The largest reductions in the ERB group were observed in the AP direction. These data suggest that a 5 mm CTV-to-PTV margin is sufficient to correct for intrafraction prostate movements when using an ERB. Conclusions: ERB significantly reduces intrafraction prostate motion, but not interfraction

  15. Phenylthiourea specifically reduces zebrafish eye size.

    PubMed

    Li, Zeran; Ptak, Devon; Zhang, Liyun; Walls, Elwood K; Zhong, Wenxuan; Leung, Yuk Fai

    2012-01-01

    Phenylthiourea (PTU) is commonly used for inhibiting melanization of zebrafish embryos. In this study, the standard treatment with 0.2 mM PTU was demonstrated to specifically reduce eye size in larval fish starting at three days post-fertilization. This effect is likely the result of a reduction in retinal and lens size of PTU-treated eyes and is not related to melanization inhibition. This is because the eye size of tyr, a genetic mutant of tyrosinase whose activity is inhibited in PTU treatment, was not reduced. As PTU contains a thiocarbamide group which is presented in many goitrogens, suppressing thyroid hormone production is a possible mechanism by which PTU treatment may reduce eye size. Despite the fact that thyroxine level was found to be reduced in PTU-treated larvae, thyroid hormone supplements did not rescue the eye size reduction. Instead, treating embryos with six goitrogens, including inhibitors of thyroid peroxidase (TPO) and sodium-iodide symporter (NIS), suggested an alternative possibility. Specifically, three TPO inhibitors, including those that do not possess thiocarbamide, specifically reduced eye size; whereas none of the NIS inhibitors could elicit this effect. These observations indicate that TPO inhibition rather than a general suppression of thyroid hormone synthesis is likely the underlying cause of PTU-induced eye size reduction. Furthermore, the tissue-specific effect of PTU treatment might be mediated by an eye-specific TPO expression. Compared with treatment with other tyrosinase inhibitors or bleaching to remove melanization, PTU treatment remains the most effective approach. Thus, one should use caution when interpreting results that are obtained from PTU-treated embryos.

  16. An observational Study of the Association between Androgenetic Alopecia and Size of the Prostate

    PubMed Central

    Ramsamy, Kanagaraj; Subramaniyan, Radhakrishnan; Patra, Anjan Kumar

    2016-01-01

    Introduction: Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicle, leading to vellus transformation of the terminal hair follicle. It is caused by interactions between androgens, several genes, and environmental factors with hair follicles. Benign prostatic hyperplasia (BPH) is highly prevalent among elderly men but infrequent in those younger than 40 years. Because both entities share a common pathogenesis and AGA manifests before the onset of BPH, there could be an association between AGA and BPH. Aim: To study the possible association between AGA and the size of prostate. Materials and Methods: Sixty-five consecutive male patients, 35–65 years of age with AGA of Hamilton–Norwood classification Grades 3–7, were included in the study. AGA of Grades 1 and 2 patients on treatment with minoxidil, finasteride, or other treatments for AGA with history of prostate cancer or prostate disease were excluded from the study. Prostate size was measured through transabdominal ultrasonography. Statistical analysis was done with SPSS software. Results: Of the 65 AGA patients, the mean age was 47.18 years. Grade 4 AGA was the most common grade seen in 19 patients (29.2%), out of which, most (47.4%) were in the 56–65 years age group. 52.3% patients had normal prostate volume, and 47.7% had an enlarged prostate. The percentage of patients with the normal and enlarged prostate in moderate Grade 3 AGA was 68.8% and 31.2%, and in severe Grade 6 AGA, it was 33.3% and 66.7%, respectively. Prostate enlargement was more likely to occur in severe AGA than in moderate AGA(odds ratio 3.311; P = 0.025, which is significant). Conclusion: This study revealed an increase in prostate size with increasing age, with higher prevalence of Grade 1 prostate enlargement in younger individuals, and with higher prevalence of Grade 3 prostate enlargement in elderly men. The study also found a positive correlation between AGA and prostate size, with higher grades of

  17. An observational Study of the Association between Androgenetic Alopecia and Size of the Prostate

    PubMed Central

    Ramsamy, Kanagaraj; Subramaniyan, Radhakrishnan; Patra, Anjan Kumar

    2016-01-01

    Introduction: Androgenetic alopecia (AGA) is characterized by miniaturization of the hair follicle, leading to vellus transformation of the terminal hair follicle. It is caused by interactions between androgens, several genes, and environmental factors with hair follicles. Benign prostatic hyperplasia (BPH) is highly prevalent among elderly men but infrequent in those younger than 40 years. Because both entities share a common pathogenesis and AGA manifests before the onset of BPH, there could be an association between AGA and BPH. Aim: To study the possible association between AGA and the size of prostate. Materials and Methods: Sixty-five consecutive male patients, 35–65 years of age with AGA of Hamilton–Norwood classification Grades 3–7, were included in the study. AGA of Grades 1 and 2 patients on treatment with minoxidil, finasteride, or other treatments for AGA with history of prostate cancer or prostate disease were excluded from the study. Prostate size was measured through transabdominal ultrasonography. Statistical analysis was done with SPSS software. Results: Of the 65 AGA patients, the mean age was 47.18 years. Grade 4 AGA was the most common grade seen in 19 patients (29.2%), out of which, most (47.4%) were in the 56–65 years age group. 52.3% patients had normal prostate volume, and 47.7% had an enlarged prostate. The percentage of patients with the normal and enlarged prostate in moderate Grade 3 AGA was 68.8% and 31.2%, and in severe Grade 6 AGA, it was 33.3% and 66.7%, respectively. Prostate enlargement was more likely to occur in severe AGA than in moderate AGA(odds ratio 3.311; P = 0.025, which is significant). Conclusion: This study revealed an increase in prostate size with increasing age, with higher prevalence of Grade 1 prostate enlargement in younger individuals, and with higher prevalence of Grade 3 prostate enlargement in elderly men. The study also found a positive correlation between AGA and prostate size, with higher grades of

  18. Dosimetry estimation on variations of patient size in prostate volumetric-modulated arc therapy

    SciTech Connect

    Chow, James C.L.; Jiang, Runqing

    2013-04-01

    This study investigated the dosimetric variations of the target and critical organs of patients who had weight loss associated with prostate volumetric-modulated arc therapy (VMAT). Five patients with prostate volumes ranging from 32–86.5 cm{sup 3} were selected from a group of 30 patients. Prostate VMAT plans were carried out on each patient using the 6-MV photon beam with a single 360° arc. Decrease of patient size as a result of weight loss was mimicked by contracting the patient's external contour in the anterior, left, and right directions with depths from 0.5–2 cm. Soft tissue excluded by the contracted external contour was replaced by air and the dose distribution was recalculated using the same beam geometry and dose prescription. Dose-volume histograms and dose-volume points such as D99% and D5% for the planning target volume (PTV), clinical target volume (CTV), rectum, bladder, and femoral heads were calculated with variations of reduced depth. In addition, the minimum, maximum, and mean doses for the target and critical organs were determined. PTV and CTV D99% were found to have increased 2.86 ± 0.30% per cm and 2.75 ± 0.38% per cm of reduced depth ranging from 0.5–2 cm. Moreover, the rectal and bladder D30% increased 2.20 ± 0.20% per cm and 2.31 ± 0.83% per cm, and the femoral head D5% increased 3.30 ± 0.11% per cm of reduced depth. Results from variations of the minimum, maximum, and mean doses of the PTV, CTV, rectum, bladder, and femoral heads showed that there was a >5% increase of dose when the reduced depth reached 2 cm. This study provided dosimetry estimation for radiation oncology staff to justify dose variations of the target and critical organs when patients' weight loss occurred in prostate VMAT. Dose variations >5% were seen when the patients' reduced depth was equal to 2 cm.

  19. The REDUCE trial: chemoprevention in prostate cancer using a dual 5alpha-reductase inhibitor, dutasteride.

    PubMed

    Musquera, Mireia; Fleshner, Neil E; Finelli, Antonio; Zlotta, Alexandre R

    2008-07-01

    Dutasteride, a dual 5alpha-reductase inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). It reduces serum prostate-specific antigen levels by approximately 50% at 6 months and total prostate volume by 25% after 2 years. Randomized placebo-controlled trials in BPH patients have shown the efficacy of dutasteride in symptomatic relief, improvements in quality of life and peak urinary flow rate. Side effects occurring with dutasteride are decreased libido, erectile dysfunction, ejaculation disorders and gynecomastia. Preliminary data from placebo-controlled BPH trials have shown a decrease in the detection of prostate cancer in patients treated with dutasteride, although these studies were not designed to look at this issue. Dutasteride differs from finasteride in that it inhibits both isoenzymes of 5alpha-reductase, type I and type II. The landmark Prostate Cancer Prevention Trial at the end of the 7-year study demonstrated a 24.8% reduction in the incidence of prostate cancer in the finasteride group compared with placebo. However, a 25.5% increase in the prevalence of high-grade Gleason tumors has been observed, the clinical significance of which has been debated. Preliminary data suggest a decrease in prostate cancer incidence in dutasteride-treated patients and demonstrate type I alphareductase enzyme expression in prostate cancer. As a result, dutasteride is being investigated for prostate cancer prevention in the ongoing Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which is discussed here. PMID:18588452

  20. A Walnut-Enriched Diet Reduces the Growth of LNCaP Human Prostate Cancer Xenografts in Nude Mice

    PubMed Central

    Tan, Dun-Xian; Manchester, Lucien C.; Korkmaz, Ahmet; Fuentes-Broto, Lorena; Hardman, W. Elaine; Rosales-Corral, Sergio A.; Qi, Wenbo

    2013-01-01

    It was investigated whether a standard mouse diet (AIN-76A) supplemented with walnuts reduced the establishment and growth of LNCaP human prostate cancer cells in nude (nu/nu) mice. The walnut-enriched diet reduced the number of tumors and the growth of the LNCaP xenografts; 3 of 16 (18.7%) of the walnut-fed mice developed tumors; conversely, 14 of 32 mice (44.0%) of the control diet-fed animals developed tumors. Similarly, the xenografts in the walnut-fed animals grew more slowly than those in the control diet mice. The final average tumor size in the walnut-diet animals was roughly one-fourth the average size of the prostate tumors in the mice that ate the control diet. PMID:23758186

  1. Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness

    PubMed Central

    Adamo, Hanibal Hani; Strömvall, Kerstin; Nilsson, Maria; Halin Bergström, Sofia; Bergh, Anders

    2015-01-01

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues. PMID:26536349

  2. Effect of long-acting gonadotropin-releasing hormone analog (leuprolide) therapy on prostatic size and symptoms in 15 men with benign prostatic hypertrophy.

    PubMed

    Gabrilove, J L; Levine, A C; Kirschenbaum, A; Droller, M

    1989-09-01

    To determine the effects of reversible medical castration on prostatic size and symptoms we treated 15 patients with benign prostatic hypertrophy with a long-acting GnRH analog, leuprolide (1 mg/day sc), for a minimum of 4 months. The men's serum testosterone, dihydrotestosterone, and estradiol concentrations fell to very low levels within 4-6 weeks after the initiation of treatment. Transrectal ultrasonography of the prostate demonstrated an average shrinkage of 40% after 4 months of treatment (n = 15) and 46% after 6 months of treatment (n = 11). All 15 men had improvement in urinary flow and, to a lesser extent, in nocturia and frequency. The side-effects of the therapy were decreased potency and flushing. The most dramatic improvement occurred in 4 of the 5 men who had complete urinary obstruction before treatment. One man had a suprapubic cystotomy tube removed during the fifth treatment month. Two other men who had Foley catheters before treatment are voiding well without catheters since their third treatment month. Another man who had a very large prostate (300 g) before treatment had one successful voiding trial, although he still has a suprapubic cystotomy tube. One man decided to stop treatment after 6 months. Two months later his hormone values and prostate size had returned to pretreatment levels. One man treated during the fourth and fifth months with fluoxymesterone in addition to leuprolide had regrowth of his prostate while receiving this androgen. We conclude that leuprolide treatment of men with benign prostatic hypertrophy results in shrinkage of prostatic size and concomitant improvement in the obstructive symptoms of prostatism. The prostatic shrinkage reverses when treatment is discontinued or combined with androgen. PMID:2474565

  3. Reduced risk of prostate cancer among patients with diabetes mellitus.

    PubMed

    Weiderpass, Elisabete; Ye, Weimin; Vainio, Harri; Kaaks, Rudolf; Adami, Hans-Olov

    2002-11-20

    Although diabetes mellitus is associated with an increased risk of several malignancies, a negative association with prostate cancer is biologically most plausible. The epidemiologic evidence is, however, inconsistent, limited and based mostly on small studies. We present results from a large, population-based cohort study in Sweden, where we assessed prostate cancer risk among patients hospitalized for diabetes mellitus. The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIRs), with 95% confidence interval (CI), were used as a measure of relative risk. After complete exclusion of the first year of follow-up (to avoid selection bias), 135,950 men remained in the cohort, contributing 827,099 years of follow-up to the study. A total of 2,455 incident cases of primary prostate cancer were identified during 1-31 years of follow-up, yielding an overall SIR of 0.91 (95% CI 0.87-0.94); this risk reduction was more pronounced among patients who have been hospitalized for diabetic complications (SIR = 0.82; 95% CI 0.74-0.91). We found no consistent trends in risk related to age at first hospitalization or to duration of follow-up. We did find a small, but significantly decreased risk of prostate cancer among men who had been hospitalized for diabetes mellitus.

  4. Metformin use and risk of prostate cancer: results from the REDUCE study.

    PubMed

    Feng, Tom; Sun, Xizi; Howard, Lauren E; Vidal, Adriana C; Gaines, Alexis R; Moreira, Daniel M; Castro-Santamaria, Ramiro; Andriole, Gerald L; Freedland, Stephen J

    2015-11-01

    The role of metformin in prostate cancer chemoprevention remains unclear. REDUCE, which followed biopsy-negative men with protocol-dictated PSA-independent biopsies at 2- and 4-years, provides an opportunity to evaluate the link between metformin use and prostate cancer diagnosis with minimal confounding from screening biases. In diabetic men from REDUCE, we tested the association between metformin use, use of other antidiabetic medications, versus no antidiabetic medication use, and prostate cancer diagnosis as well as prostate cancer grade (low-grade Gleason 4-6 and high-grade Gleason 7-10) using logistic regression. Of the 540 diabetic men with complete data, 205 (38%) did not report use of any antidiabetic medications, 141 (26%) reported use of at least one antidiabetic medication other than metformin, and 194 (36%) reported use of metformin. During the 4-year study, 122 men (23%) were diagnosed with prostate cancer. After adjusting for various clinical and demographic characteristics, we found that metformin use was not significantly associated with total (OR, 1.19; P = 0.50), low- (OR, 1.01; P = 0.96), or high-grade (OR, 1.83; P = 0.19) prostate cancer diagnosis. Likewise, there was no significant association between the use of non-metformin antidiabetic medications and prostate cancer risk in both crude (OR, 1.02; P = 0.95) and multivariable analysis (OR, 0.85; P = 0.56). Furthermore, the interactions between antidiabetic medication use and BMI, geographic location, coronary artery disease, smoking, and treatment group were not significant (all P > 0.05). Among diabetic men with a negative prestudy biopsy who all underwent biopsies largely independent of PSA, metformin use was not associated with reduced risk of prostate cancer diagnosis.

  5. Reducing Class Size Leads to Individualized Instruction.

    ERIC Educational Resources Information Center

    Zahorik, John A.

    1999-01-01

    SAGE is a five-year class-size-reduction program being implemented in 80 Wisconsin schools. A longitudinal, evaluative study is being conducted in 30 SAGE schools. Small classes have three effects leading to increased individualization: fewer discipline problems, greater knowledge of students, and more teacher enthusiasm (using directive methods).…

  6. A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer

    PubMed Central

    Archibald, Monica; Pritchard, Tara; Nehoff, Hayley; Rosengren, Rhonda J; Greish, Khaled; Taurin, Sebastien

    2016-01-01

    Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles’ charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. PMID:26811677

  7. A combination of sorafenib and nilotinib reduces the growth of castrate-resistant prostate cancer.

    PubMed

    Archibald, Monica; Pritchard, Tara; Nehoff, Hayley; Rosengren, Rhonda J; Greish, Khaled; Taurin, Sebastien

    2016-01-01

    Castrate-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Several tyrosine kinases have been implicated in the development and growth of CRPC, as such targeting these kinases may offer an alternative therapeutic strategy. We established the combination of two tyrosine kinase inhibitors (TKIs), sorafenib and nilotinib, as the most cytotoxic. In addtion, to improve their bioavailability and reduce their metabolism, we encapsulated sorafenib and nilotinib into styrene-co-maleic acid micelles. The micelles' charge, size, and release rate were characterized. We assessed the effect of the combination on the cytotoxicity, cell cycle, apoptosis, protein expression, tumor spheroid integrity, migration, and invasion. The micelles exhibited a mean diameter of 100 nm, a neutral charge, and appeared highly stable. The micellar TKIs promoted greater cytotoxicity, decreased cell proliferation, and increased apoptosis relative to the free TKIs. In addition, the combination reduced the expression and activity of several tyrosine kinases and reduced tumor spheroid integrity and metastatic potential of CRPC cell lines more efficiently than the single treatments. The combination increased the therapeutic potential and demonstrated the relevance of a targeted combination therapy for the treatment of CRPC. In addition, the efficacy of the encapsulated drugs provides the basis for an in vivo preclinical testing. PMID:26811677

  8. A simple analysis of extinction spectra of cancerous and normal prostate tissues in near infrared range using a size discrete particle distribution and Mie scattering model

    NASA Astrophysics Data System (ADS)

    Zhou, Kenneth J.; Chen, Jun

    2015-03-01

    The extinction spectra and optical coefficients of human cancerous and normal prostate tissues were investigated in the spectral range of 750 nm - 860 nm. The scattering coefficient (μs) was determined from the extinction measurements on thin prostate tissue and Beer's law. The absorption coefficient (μa) and the reduced scattering coefficient (μs') were extracted from integrate sphere intensity measurements on prostate tissue of which the thickness is in the multiple scattering range. The anisotropy factor (g) was calculated using the extracted values of μs and μs'. A micro-optical model of soft biological tissue was introduced to simulate the numerical computation of the absolute magnitudes of its scattering coefficients from the refractive index and a particle distribution function based on the Mie theory. A key assumption of the model is that the refractive index variations caused by microscopic tissue elements can be treated as particles with sizes distributed according to a skewed log-normal distribution function. The particle distribution and mean particle size of the two types of tissues were then calculated. Results show that the mean diameter of the particle size of cancerous tissue is larger than that of the cancerous tissue, which is responsible for larger reduced scattering coefficient of normal tissue in comparison with cancerous tissue. The results can be explained the change of tissue during prostate cancer evolution defined by Gleason Grade. The difference of the particles distribution and optical coefficients of cancerous and normal prostate tissues may present a potential criterion for prostate cancer detection.

  9. Reduced Contractility and Motility of Prostatic Cancer-Associated Fibroblasts after Inhibition of Heat Shock Protein 90

    PubMed Central

    Henke, Alex; Franco, Omar E.; Stewart, Grant D.; Riddick, Antony C.P.; Katz, Elad; Hayward, Simon W.; Thomson, Axel A.

    2016-01-01

    Background: Prostate cancer-associated fibroblasts (CAF) can stimulate malignant progression and invasion of prostatic tumour cells via several mechanisms including those active in extracellular matrix; Methods: We isolated CAF from prostate cancer patients of Gleason Score 6–10 and confirmed their cancer-promoting activity using an in vivo tumour reconstitution assay comprised of CAF and BPH1 cells. We tested the effects of heat shock protein 90 (HSP90) inhibitors upon reconstituted tumour growth in vivo. Additionally, CAF contractility was measured in a 3D collagen contraction assay and migration was measured by scratch assay; Results: HSP90 inhibitors dipalmitoyl-radicicol and 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) reduced tumour size and proliferation in CAF/BPH1 reconstituted tumours in vivo. We observed that the most contractile CAF were derived from patients with lower Gleason Score and of younger age compared with the least contractile CAF. HSP90 inhibitors radicicol and 17-DMAG inhibited contractility and reduced the migration of CAF in scratch assays. Intracellular levels of HSP70 and HSP90 were upregulated upon treatment with HSP90 inhibitors. Inhibition of HSP90 also led to a specific increase in transforming growth factor beta 2 (TGFβ2) levels in CAF; Conclusions: We suggest that HSP90 inhibitors act not only upon tumour cells, but also on CAF in the tumour microenvironment. PMID:27563925

  10. Weight Management to Reduce Prostate Cancer Risk: A Survey of Men’s Needs and Interests

    PubMed Central

    Schleper, Amy; Sullivan, Debra K.; Thrasher, J. Brantley; Holzbeierlein, Jeffrey M.; Klemp, Jennifer; Befort, Christie; Hamilton-Reeves, Jill M.

    2016-01-01

    Obese men have a higher rate of prostate cancer-related death than non-obese men, and obesity increases the risk of prostate cancer progression and biochemical recurrence. The purpose of this study was to assess needs and interests of men for a technology-driven weight loss intervention to reduce prostate cancer risk. We distributed a survey collecting demographic characteristics, health history, exercise and eating habits (and perception of those habits), current and prior attempts of health behavior change, and technology use. Survey answers were summarized by count and percent of total respondents. Completed surveys (N = 109) described men with a family history of prostate cancer (25%), a history of elevated prostate specific antigen (26%), and prostate cancer survivors (22%). We compared body mass index (BMI) to perception of weight; overweight and obese men perceived their weight as more normal than their BMI category suggests. Most men reported their diet needed minor improvement (74%), and 65% of men reported they are either currently trying to lose weight or interested in weight loss. Most respondents access the internet (92%), while text messaging (60%) and smartphone application use (40%) are less frequent, especially in men over 60. Our results revealed a need and willingness for lifestyle modification and suggest a need for evidence-based weight loss strategies and for addressing the misperception of weight status. A male-tailored intervention that implements technology could improve energy balance, hold men accountable to healthy behavior change, and promote dietary patterns in order to reduce prostate cancer risk. PMID:27547287

  11. Does resectoscope size play a role in formation of urethral stricture following transurethral prostate resection?

    PubMed Central

    Günes, Mustafa; Keles, Muzaffer Oguz; Kaya, Cevdet; Koca, Orhan; Sertkaya, Zülfü; Akyüz, Mehmet; Altok, Muammer; Umul, Mehmet; Karaman, Muhammet Ihsan

    2015-01-01

    ABSTRACT Background and aims: To investigate the possible effect of resectoscope size on urethral stricture rate after monopolar TURP. Materials and Methods: A retrospective study of 71 men undergoing TURP was conducted at two centers’ from November 2009 to May 2013. The patients were divided into one of two groups according to the resectoscope diameter used for TURP. Resectoscope diameter was 24 F in group 1 (n=35) or 26 F in group 2 (n=36). Urethral catheter type, catheter removal time and energy type were kept constant for all patients. Urethral stricture formation in different localizations after TURP was compared between groups. Results: There was no significant difference between the two groups in terms of age, pre-operative prostate gland volume (PV), prostate-specific antigen (PSA), maximal urinary flow rates (Qmax), International Prostate Symptom Score (IPSS) and post-voiding residual urine volume (PVR). The resection time and weight of resected prostate tissue were similar for both groups (p>0.05). A statistically significant higher incidence of bulbar stricture was detected in group 2 compared to group1 (p=0.018). Conclusions: The use of small-diameter resectoscope shafts may cause a reduction in the incidence of uretral strictures in relation to urethral friction and mucosal damage. PMID:26401868

  12. Role of step size and max dwell time in anatomy based inverse optimization for prostate implants.

    PubMed

    Manikandan, Arjunan; Sarkar, Biplab; Rajendran, Vivek Thirupathur; King, Paul R; Sresty, N V Madhusudhana; Holla, Ragavendra; Kotur, Sachin; Nadendla, Sujatha

    2013-07-01

    In high dose rate (HDR) brachytherapy, the source dwell times and dwell positions are vital parameters in achieving a desirable implant dose distribution. Inverse treatment planning requires an optimal choice of these parameters to achieve the desired target coverage with the lowest achievable dose to the organs at risk (OAR). This study was designed to evaluate the optimum source step size and maximum source dwell time for prostate brachytherapy implants using an Ir-192 source. In total, one hundred inverse treatment plans were generated for the four patients included in this study. Twenty-five treatment plans were created for each patient by varying the step size and maximum source dwell time during anatomy-based, inverse-planned optimization. Other relevant treatment planning parameters were kept constant, including the dose constraints and source dwell positions. Each plan was evaluated for target coverage, urethral and rectal dose sparing, treatment time, relative target dose homogeneity, and nonuniformity ratio. The plans with 0.5 cm step size were seen to have clinically acceptable tumor coverage, minimal normal structure doses, and minimum treatment time as compared with the other step sizes. The target coverage for this step size is 87% of the prescription dose, while the urethral and maximum rectal doses were 107.3 and 68.7%, respectively. No appreciable difference in plan quality was observed with variation in maximum source dwell time. The step size plays a significant role in plan optimization for prostate implants. Our study supports use of a 0.5 cm step size for prostate implants.

  13. Cross-Linked Hyaluronan Gel Reduces the Acute Rectal Toxicity of Radiotherapy for Prostate Cancer

    SciTech Connect

    Wilder, Richard B.; Barme, Greg A.; Gilbert, Ronald F.; Holevas, Richard E.; Kobashi, Luis I.; Reed, Richard R.; Solomon, Ronald S.; Walter, Nancy L.; Chittenden, Lucy; Mesa, Albert V.; Agustin, Jeffrey; Lizarde, Jessica; Macedo, Jorge; Ravera, John; Tokita, Kenneth M.

    2010-07-01

    Purpose: To prospectively analyze whether cross-linked hyaluronan gel reduces the mean rectal dose and acute rectal toxicity of radiotherapy for prostate cancer. Methods and Materials: Between September 2008 and March 2009, we transperitoneally injected 9mL of cross-linked hyaluronan gel (Hylaform; Genzyme Corporation, Cambridge, MA) into the anterior perirectal fat of 10 early-stage prostate cancer patients to increase the separation between the prostate and rectum by 8 to 18mm at the start of radiotherapy. Patients then underwent high-dose rate brachytherapy to 2,200cGy followed by intensity-modulated radiation therapy to 5,040cGy. We assessed acute rectal toxicity using the National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grading scheme. Results: Median follow-up was 3 months. The anteroposterior dimensions of Hylaform at the start and end of radiotherapy were 13 {+-} 3mm (mean {+-} SD) and 10 {+-} 4mm, respectively. At the start of intensity-modulated radiation therapy, daily mean rectal doses were 73 {+-} 13cGy with Hylaform vs. 106 {+-} 20cGy without Hylaform (p = 0.005). There was a 0% incidence of National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 Grade 1, 2, or 3 acute diarrhea in 10 patients who received Hylaform vs. a 29.7% incidence (n = 71) in 239 historical controls who did not receive Hylaform (p = 0.04). Conclusions: By increasing the separation between the prostate and rectum, Hylaform decreased the mean rectal dose. This led to a significant reduction in the acute rectal toxicity of radiotherapy for prostate cancer.

  14. Screening Coverage Needed to Reduce Mortality from Prostate Cancer: A Living Systematic Review

    PubMed Central

    Badgett, Robert G.; Hoffman, Richard M.

    2016-01-01

    Introduction Screening for prostate cancer remains controversial because of conflicting results from the two major trials: The Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial and the European Randomized Study of Screening for Prostate Cancer (ERSPC). Objective Meta-analyze and meta-regress the available PSA screening trials. Methods We performed a living systematic review and meta-regression of the reduction in prostate cancer mortality as a function of the duration of screening provided in each trial. We searched PubMed, Web of Science, the Cochrane Registry, and references lists from previous meta-analyses to identify randomized trials of PSA screening. We followed PRISMA guidelines and qualified strength of evidence with a GRADE Profile. Results We found 6 trials, but excluded one that also screened with trans-rectal ultrasound. We considered each ERSPC center as a separate trial. When pooling together all 11 trials we found no significant benefit from screening; however, the heterogeneity was 28.2% (95% CI: 0% to 65%). Heterogeneity was explained by variations in the duration of serial screening (I2 0%; 95% CI: 0% to 52%). When we analyzed the subgroup of trials that added more than 3 years of screening (range 3.2 to 3.8) we found a significant benefit for screening with risk ratio 0.78 (95% CI 0.65–0.94; I2 = 0%; 95% CI: 0% to 69%) and a number needed to invite for screening of 1000. We downgraded the quality of evidence to moderate due to our retrospective identification of subgroups and limited data on control group screening. Conclusions Adequate duration of screening reduces mortality from prostate cancer. The benefit, while small, compares favorably with screening for other cancers. Our projections are limited by the moderate quality of evidence. PMID:27070904

  15. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study.

    PubMed

    Möller, Elisabeth; Wilson, Kathryn M; Batista, Julie L; Mucci, Lorelei A; Bälter, Katarina; Giovannucci, Edward

    2016-02-15

    Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI ≥ 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI ≥ 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men ≤ 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations

  16. Body size across the life course and prostate cancer in the Health Professionals Follow-up Study.

    PubMed

    Möller, Elisabeth; Wilson, Kathryn M; Batista, Julie L; Mucci, Lorelei A; Bälter, Katarina; Giovannucci, Edward

    2016-02-15

    Current evidence of an association between body size and prostate cancer is conflicting, possibly due to differential effects of body size across the lifespan and the heterogeneity of the disease. We therefore examined childhood and adult body size in relation to total incident prostate cancer and prognostic subtypes in a prospective cohort of 47,491 US men in the Health Professionals Follow-up Study. We assessed adult height, body mass index (BMI) in early and middle-to-late adulthood, adult waist circumference, and body shape at age 10. With follow-up from 1986 to 2010, we estimated the relative risk (RR) of prostate cancer using Cox proportional hazards models. We identified 6,183 incident cases. Tallness was associated with increased risk of advanced-stage tumors, particularly fatal disease (RR = 1.66, 95% CI 1.23-2.23, highest vs. lowest quintile, ptrend < 0.001). High BMI at age 21 was inversely associated with total prostate cancer (RR = 0.89, 95% CI 0.80-0.98, BMI ≥ 26 vs. 20-21.9, ptrend = 0.01) and with fatal and advanced disease. The association for late adult BMI differed by age (pinteraction < 0.001); high BMI was inversely associated with total prostate cancer (RR = 0.64, 95% CI 0.51-0.78, BMI ≥ 30 vs. 21-22.9, ptrend <0.001) and with non-advanced and less aggressive tumors among men ≤ 65 years, whereas no association was seen among men >65 years. Adult waist circumference was weakly inversely associated with less aggressive disease. Childhood obesity was unclearly related to risk. Our study confirms tall men to be at increased risk of fatal and advanced prostate cancer. The influence of adiposity varies by prognostic disease subtype and by age. The relationship between body size and prostate cancer is complex. Body size changes progressively throughout life and consequent effects on prostate cancer risk may be associated with related changes in hormonal and metabolic pathways. This large prospective study examined potential associations

  17. Risk of All-Cause and Prostate Cancer-Specific Mortality After Brachytherapy in Men With Small Prostate Size

    SciTech Connect

    Nguyen, Paul L.; Chen, Ming H.; Choueiri, Toni K.; Hoffman, Karen E.; Hu, Jim C.; Martin, Neil E.; Beard, Clair J.; Dosoretz, Daniel E.; Moran, Brian J.; Katin, Michael J.; Braccioforte, Michelle H.; Ross, Rudi; Salenius, Sharon A.; Kantoff, Philip W.; D'Amico, Anthony V.

    2011-04-01

    Background: Brachytherapy for prostate cancer can be technically challenging in men with small prostates ({<=}20 cc), but it is unknown whether their outcomes are different than those of men with larger prostates. Methods and Materials: We studied 6,416 men treated with brachytherapy in one of 21 community-based practices. Cox regression and Fine and Gray's regression were used to determine whether volume {<=}20 cc was associated with a higher risk of all-cause mortality (ACM) or prostate cancer-specific mortality (PCSM), respectively, after adjustment for other known prognostic factors. Results: 443 patients (6.9%) had a prostate volume {<=}20 cc. After a median follow-up of 2.91 years (interquartile range, 1.06-4.79), volume {<=}20 cc was associated with a significantly higher risk of ACM (adjusted hazard ratio = 1.33 [95% CI 1.08-1.65], p = 0.0085) with 3-year estimates of ACM for {<=}20 cc vs. >20 cc of 13.0% vs. 6.9% (p = 0.028). Only 23 men (0.36%) have died of prostate cancer, and no difference was seen in PCSM by volume (p = 0.4). Conclusion: Men with small prostates at the time of implant had a 33% higher risk of ACM, and the underlying cause of this remains uncertain. No increase in PCSM was observed in men with volume {<=}20cc, suggesting that a small prostate should not in itself be a contraindication for brachytherapy, but inasmuch as absolute rates of PCSM were small, further follow-up will be needed to confirm this finding.

  18. Does the size matter?: Prostate weight does not predict PSA recurrence after radical prostatectomy.

    PubMed

    Davidson, Darrell D; Koch, Michael O; Lin, Haiqun; Jones, Timothy D; Biermann, Katharina; Cheng, Liang

    2010-04-01

    Previous studies suggest that low prostate weight is a significant negative prognostic factor for prostate cancer. In the current study, the data for 431 men who underwent radical retropubic prostatectomy between 1990 and 1998 were analyzed for association between prostate weight and various clinical and pathologic parameters. These included age, preoperative prostate-specific antigen (PSA) level, PSA recurrence, pathologic stage, Gleason grade, extraprostatic extension, positive surgical margins, tumor volume, associated high-grade prostatic intraepithelial neoplasia, perineural invasion, and lymph node metastasis. Potential associations were probed by using Cox regression model analysis. A significant positive correlation was found between prostate weight and increasing patient age or increasing preoperative PSA level. There was no significant independent association between prostate weight and any of the other variables examined. No association was found between prostate weight and PSA recurrence. Although increasing prostate weight correlates with increased patient age and higher preoperative PSA level, it does not independently predict postoperative cancer recurrence.

  19. A Double-Blind Placebo-Controlled Randomized Clinical Trial With Magnesium Oxide to Reduce Intrafraction Prostate Motion for Prostate Cancer Radiotherapy

    SciTech Connect

    Lips, Irene M.; Gils, Carla H. van; Kotte, Alexis N.T.J.; Leerdam, Monique E. van; Franken, Stefan P.G.; Heide, Uulke A. van der; Vulpen, Marco van

    2012-06-01

    Purpose: To investigate whether magnesium oxide during external-beam radiotherapy for prostate cancer reduces intrafraction prostate motion in a double-blind, placebo-controlled randomized trial. Methods and Materials: At the Department of Radiotherapy, prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. The primary outcome was the proportion of patients with clinically relevant intrafraction prostate motion, defined as the proportion of patients who demonstrated in {>=}50% of the fractions an intrafraction motion outside a range of 2 mm. Secondary outcome measures included quality of life and acute toxicity. Results: In total, 46 patients per treatment arm were enrolled. The primary endpoint did not show a statistically significant difference between the treatment arms with a percentage of patients with clinically relevant intrafraction motion of 83% in the magnesium oxide arm as compared with 80% in the placebo arm (p = 1.00). Concerning the secondary endpoints, exploratory analyses demonstrated a trend towards worsened quality of life and slightly more toxicity in the magnesium oxide arm than in the placebo arm; however, these differences were not statistically significant. Conclusions: Magnesium oxide is not effective in reducing the intrafraction prostate motion during external-beam radiotherapy, and therefore there is no indication to use it in clinical practice for this purpose.

  20. Use of Individual Fraction Size Data from 3756 Patients to Directly Determine the {alpha}/{beta} Ratio of Prostate Cancer

    SciTech Connect

    Williams, Scott G. . E-mail: scott.williams@petermac.org; Taylor, Jeremy M.G.; Liu Ning; Tra, Yolande; Duchesne, Gillian M.; Kestin, Larry L.; Martinez, Alvaro; Pratt, Gary R.; Sandler, Howard

    2007-05-01

    Purpose: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. Methods and Materials: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The {alpha}/{beta} ratios were estimated via a proportional hazards model stratified by risk severity and institution. Results: The {alpha}/{beta} ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, {infinity} Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; {alpha}/{beta} ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. Conclusions: This study supports the concept that the {alpha}/{beta} ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.

  1. Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells.

    PubMed

    Choi, Kyong-Hoon; Nam, Ki Chang; Malkinski, Leszek; Choi, Eun Ha; Jung, Jin-Seung; Park, Bong Joo

    2016-01-01

    In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe₂O₄-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe₂O₄) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe₂O₄ particles were finely adjusted by controlling the size of the primary CoFe₂O₄ nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe₂O₄-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe₂O₄-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe₂O₄-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism. PMID:27607999

  2. Size-Dependent Photodynamic Anticancer Activity of Biocompatible Multifunctional Magnetic Submicron Particles in Prostate Cancer Cells.

    PubMed

    Choi, Kyong-Hoon; Nam, Ki Chang; Malkinski, Leszek; Choi, Eun Ha; Jung, Jin-Seung; Park, Bong Joo

    2016-09-06

    In this study, newly designed biocompatible multifunctional magnetic submicron particles (CoFe₂O₄-HPs-FAs) of well-defined sizes (60, 133, 245, and 335 nm) were fabricated for application as a photosensitizer delivery agent for photodynamic therapy in cancer cells. To provide selective targeting of cancer cells and destruction of cancer cell functionality, basic cobalt ferrite (CoFe₂O₄) particles were covalently bonded with a photosensitizer (PS), which comprises hematoporphyrin (HP), and folic acid (FA) molecules. The magnetic properties of the CoFe₂O₄ particles were finely adjusted by controlling the size of the primary CoFe₂O₄ nanograins, and secondary superstructured composite particles were formed by aggregation of the nanograins. The prepared CoFe₂O₄-HP-FA exhibited high water solubility, good MR-imaging capacity, and biocompatibility without any in vitro cytotoxicity. In particular, our CoFe₂O₄-HP-FA exhibited remarkable photodynamic anticancer efficiency via induction of apoptotic death in PC-3 prostate cancer cells in a particle size- and concentration-dependent manner. This size-dependent effect was determined by the specific surface area of the particles because the number of HP molecules increased with decreasing size and increasing surface area. These results indicate that our CoFe₂O₄-HP-FA may be applicable for photodynamic therapy (PDT) as a PS delivery material and a therapeutic agent for MR-imaging based PDT owing to their high saturation value for magnetization and superparamagnetism.

  3. Prostate Diseases

    MedlinePlus

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine away from ... and out of the body. A young man's prostate is about the size of a walnut. It ...

  4. Investigation of the PSF-choice method for reduced lipid contamination in prostate MR spectroscopic imaging.

    PubMed

    Panych, Lawrence P; Roebuck, Joseph R; Chen, Nan-kuei; Tang, Yi; Madore, Bruno; Tempany, Clare M; Mulkern, Robert V

    2012-11-01

    The purpose of this work was to evaluate a previously proposed approach that aims to improve the point spread function (PSF) of MR spectroscopic imaging (MRSI) to avoid corruption by lipid signal arising from neighboring voxels. Retrospective spatial filtering can be used to alter the PSF; however, this either reduces spatial resolution or requires extending the acquisition in k-space at the cost of increased imaging time. Alternatively, the method evaluated here, PSF-choice, can modify the PSF localization to reduce the contamination from adjacent lipids by conforming the signal response more closely to the desired MRSI voxel grid. This is done without increasing scan time or degrading SNR of important metabolites. PSF-choice achieves improvements in spatial localization through modifications to the radiofrequency excitation pulses. An implementation of this method is reported for MRSI of the prostate, where it is demonstrated that, in 13 of 16 pilot prostate MRSI scans, intravoxel spectral contamination from lipid was significantly reduced when using PSF-choice. Phantom studies were also performed that demonstrate, compared with MRSI with standard Fourier phase encoding, out-of-voxel signal contamination of spectra was significantly reduced in MRSI with PSF-choice.

  5. Reducing stray radiation dose to patients receiving passively scattered proton radiotherapy for prostate cancer

    PubMed Central

    Taddei, Phillip J; Fontenot, Jonas D; Zheng, Yuanshui; Mirkovic, Dragan; Lee, Andrew K; Titt, Uwe; Newhauser, Wayne D

    2014-01-01

    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:18369278

  6. Visual Space: Adaptation to Texture Density Reduces Perceived Object Size.

    PubMed

    Kingdom, Frederick A A

    2016-07-25

    A recent study shows that visual adaptation to dense textures, while causing an increase in the perceived sparseness of a subsequently viewed less-dense texture, paradoxically reduces the perceived size of an object, revealing a dissociation between the internal spatial representations of textures and objects.

  7. Reducing myocardial infarct size: challenges and future opportunities.

    PubMed

    Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J

    2016-03-01

    Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is 'myocardial reperfusion injury', a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies-however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury.

  8. Reducing myocardial infarct size: challenges and future opportunities

    PubMed Central

    Bulluck, Heerajnarain; Yellon, Derek M; Hausenloy, Derek J

    2016-01-01

    Despite prompt reperfusion by primary percutaneous coronary intervention (PPCI), the mortality and morbidity of patients presenting with an acute ST-segment elevation myocardial infarction (STEMI) remain significant with 9% death and 10% heart failure at 1 year. In these patients, one important neglected therapeutic target is ‘myocardial reperfusion injury’, a term given to the cardiomyocyte death and microvascular dysfunction which occurs on reperfusing ischaemic myocardium. A number of cardioprotective therapies (both mechanical and pharmacological), which are known to target myocardial reperfusion injury, have been shown to reduce myocardial infarct (MI) size in small proof-of-concept clinical studies—however, being able to demonstrate improved clinical outcomes has been elusive. In this article, we review the challenges facing clinical cardioprotection research, and highlight future therapies for reducing MI size and preventing heart failure in patients presenting with STEMI at risk of myocardial reperfusion injury. PMID:26674987

  9. DuraSeal as a spacer to reduce rectal doses in low-dose rate brachytherapy for prostate cancer.

    PubMed

    Heikkilä, Vesa-Pekka; Kärnä, Aarno; Vaarala, Markku H

    2014-08-01

    The purpose of this study was to evaluate the utility of off-label use of DuraSeal polyethylene glycol (PEG) gel in low-dose rate (LDR) prostate brachytherapy seed implantation to reduce rectal doses. Diluted DuraSeal was easy to use and, in spite of a clearance effect, useful in decreasing D₂cc rectal doses. PMID:25201125

  10. Prostate biopsy

    MedlinePlus

    ... prostate biopsy; Fine needle biopsy of the prostate; Core biopsy of the prostate; Targeted prostate biopsy; Prostate biopsy - transrectal ultrasound (TRUS); Stereotactic transperineal prostate biopsy (STPB)

  11. Trefoil factor 3 (TFF3) enhances the oncogenic characteristics of prostate carcinoma cells and reduces sensitivity to ionising radiation.

    PubMed

    Perera, Omesha; Evans, Angharad; Pertziger, Mikhail; MacDonald, Christa; Chen, Helen; Liu, Dong-Xu; Lobie, Peter E; Perry, Jo K

    2015-05-28

    Trefoil factor 3 (TFF3) is a secreted protein which functions in mucosal repair of the gastrointestinal tract. This is achieved through the combined stimulation of cell migration and prevention of apoptosis and anoikis, thus facilitating repair. Deregulated TFF3 expression at the gene and protein level is implicated in numerous cancers. In prostate cancer TFF3 has previously been reported as a potential biomarker, overexpressed in a subset of primary and metastatic cases. Here we investigated the effect of increased TFF3 expression on prostate cancer cell behaviour. Oncomine analysis demonstrated that TFF3 mRNA expression was upregulated in prostate cancer compared to normal tissue. Forced-expression models were established in the prostate cancer cell lines, DU145 and PC3, by stable transfection of an expression vector containing the TFF3 cDNA. Forced expression of TFF3 significantly increased total cell number and cell viability, cell proliferation and cell survival. In addition, TFF3 enhanced anchorage independent growth, 3-dimensional colony formation, wound healing and cell migration compared to control transfected cell lines. We also observed reduced sensitivity to ionising radiation in stably transfected cell lines. In dose response experiments, forced expression of TFF3 significantly enhanced the regrowth of PC3 cells following ionising radiation compared with control transfected cells. In addition, TFF3 enhanced clonogenic survival of DU145 and PC3 cells. These studies indicate that targeting TFF3 for the treatment of prostate cancer warrants further investigation.

  12. Lycopene and apo-12'-lycopenal reduce cell proliferation and alter cell cycle progression in human prostate cancer cells.

    PubMed

    Ford, Nikki A; Elsen, Amy C; Zuniga, Krystle; Lindshield, Brian L; Erdman, John W

    2011-01-01

    Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8'-lycopenal, or apo-12'-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12'-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12'-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression. PMID:21207319

  13. Smoking Is Associated with Acute and Chronic Prostatic Inflammation: Results from the REDUCE Study.

    PubMed

    Moreira, Daniel M; Nickel, J Curtis; Gerber, Leah; Muller, Roberto L; Andriole, Gerald L; Castro-Santamaria, Ramiro; Freedland, Stephen J

    2015-04-01

    Both anti- and proinflammatory effects of cigarette smoking have been described. As prostate inflammation is common, we hypothesized smoking could contribute to prostate inflammation. Thus, we evaluated the association of smoking status with acute and chronic inflammation within the prostate of men undergoing prostate biopsy. We retrospectively analyzed 8,190 men ages 50 to 75 years with PSA levels between 2.5 and 10 ng/mL enrolled in the Reduction by Dutasteride of Prostate Cancer Events study. Smoking status was self-defined as never, former, or current. Prostate inflammation was assessed by systematic central review blinded to smoking status. The association of smoking with inflammation in the baseline, 2-year, and 4-year biopsies was evaluated with univariable and multivariable logistic regressions. At study enrollment, 1,233 (15%), 3,203 (39%), and 3,754 (46%) men were current, former, and never smokers, respectively. Current smokers were significantly younger and had smaller prostates than former and never smokers (all P < 0.05). Former smokers were significantly heavier than current and never smokers (P < 0.001). Acute and chronic prostate inflammations were identified in 1,261 (15%) and 6,352 (78%) baseline biopsies, respectively. In univariable analysis, current smokers were more likely to have acute inflammation than former (OR, 1.35; P, 0.001) and never smokers (OR, 1.36; P, 0.001). The results were unchanged at 2- and 4-year biopsies. In contrast, current smoking was linked with chronic inflammation in the baseline biopsy, but not at 2- and 4-year biopsies. In conclusion, among men undergoing prostate biopsy, current smoking was independently associated with acute and possibly chronic prostate inflammations. PMID:25644151

  14. NPM1 Silencing Reduces Tumour Growth and MAPK Signalling in Prostate Cancer Cells

    PubMed Central

    Loubeau, Gaëlle; Boudra, Rafik; Maquaire, Sabrina; Lours-Calet, Corinne; Beaudoin, Claude; Verrelle, Pierre; Morel, Laurent

    2014-01-01

    The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration. PMID:24796332

  15. [Changes in prostatic circulation in response to laser therapy and magnetic therapy in patients with benign prostatic hyperplasia].

    PubMed

    2005-01-01

    The results of preoperative preparation were analysed in 59 patients with prostatic benign hyperplasia (PBH) subjected to TUR. Treatment outcomes were assessed by transrectal ultrasound (color Doppler mapping) in two groups of patients. Group 1 received combined therapy including transrectal laser radiation of the prostate, group 2--transrectal magnetotherapy. The analysis showed that laser radiation reduced insignificantly the size of the prostate and adenomatous node, improved microcirculation and circulation in the prostate. This resulted in relief of inflammation and reduction of the number of postoperative inflammatory complications. Transrectal magnetotherapy has a positive effect on vascularization and hemodynamics of the prostate, local immunity, contamination of the tissues with pathogenic flora. PMID:16419474

  16. 6 Common Cancers - Prostate Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

  17. Reduced incidence of bone metastases in irradiated areas after external radiation therapy of prostatic carcinoma

    SciTech Connect

    Jacobsson, H.; Naeslund, I. )

    1991-06-01

    Fourteen males, out of 380 patients, treated with radiation to the central pelvis and lumbar spine for poorly differentiated prostatic carcinoma were analyzed in retrospect. The dose of radiation to the bones of the target area was 5,000 cGy. The patients showed no signs of metastases at bone scintigraphy performed in connection with the treatment. In an average of 34 months after finishing radiotherapy, the patients developed metastases at bone scintigraphy. The pattern was similar in all patients. The treated target area appeared as a cold zone surrounded by more or less homogenously and strongly increased activity of the axial skeleton, characteristic of bone metastases. Radiography, which was performed in 11 patients, confirmed widespread metastatic disease sparing the target area. This was interpretated as bone metastasis being precluded by the irradiation. The most probable explanation of this finding is eradication in situ of distant micrometastases already present in the bone marrow at the time of treatment. An alternate explanation is a reduced implantation of later seeded blood-born metastases as an effect of the irradiation. The characteristic pattern of this phenomenon must be recognized at bone scintigraphy.

  18. Tunable Reduced Size Planar Folded Slot Antenna Utilizing Varactor Diodes

    NASA Technical Reports Server (NTRS)

    Scardelletti, Maximilian C.; Ponchak, George E.; Jordan, Jennifer L.; Jastram, Nathan; Mahaffey, Joshua V.

    2010-01-01

    A tunable folded slot antenna that utilizes varactor diodes is presented. The antenna is fabricated on Rogers 6006 Duriod with a dielectric constant and thickness of 6.15 and 635 m, respectively. A copper cladding layer of 17 m defines the antenna on the top side (no ground on backside). The antenna is fed with a CPW 50 (Omega) feed line, has a center frequency of 3 GHz, and incorporates Micrometrics microwave hyper-abrupt 500MHV varactors to tune the resonant frequency. The varactors have a capacitance range of 2.52 pF at 0 V to 0.4 pF at 20 V; they are placed across the radiating slot of the antenna. The tunable 10 dB bandwidth of the 3 GHz antenna is 150 MHz. The varactors also reduce the size of the antenna by 30% by capacitively loading the resonating slot line. At the center frequency, 3 GHz, the antenna has a measured return loss of 44 dB and a gain of 1.6 dBi. Full-wave electromagnetic simulations using HFSS are presented that validate the measured data. Index Terms capacitive loading, Duriod, folded slot antenna, varactor.

  19. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Cancer.gov

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  20. A Cinematic Magnetic Resonance Imaging Study of Milk of Magnesia Laxative and an Antiflatulent Diet to Reduce Intrafraction Prostate Motion

    SciTech Connect

    Nichol, Alan M.; Warde, Padraig R.; Lockwood, Gina A.

    2010-07-15

    Purpose: To determine the reduction of prostate motion during a typical radiotherapy (RT) fraction from a bowel regimen comprising an antiflatulent diet and daily milk of magnesia. Methods and Materials: Forty-two patients with T1c-T2c prostate cancer voided the bladder and rectum before three cinematic magnetic resonance imaging scans obtained every 9 s for 9 min in a vacuum immobilization device. The MRIs were at baseline without bowel regimen (MRI-BL), before CT planning with bowel regimen (MRI-CT), and before a randomly assigned RT fraction (1-42) with bowel regimen (MRI-RT). A single observer tracked displacement of the posterior midpoint (PM) of the prostate. The primary endpoints were comparisons of the proportion of time that the PM was displaced >3 mm (PTPM3) from its initial position, and the secondary endpoints were comparisons of the reduction of initial rectal area, with and without the bowel regimen. Results: The mean rectal area was: 13.5 cm{sup 2} at MRI-BL, 12.7 cm{sup 2} at MRI-CT, and 12.3 cm{sup 2} at MRI-RT (MRI-BL vs. MRI-CT, p = 0.11; MRI-BL vs. MRI-CT, p = 0.07). Moving rectal gas alone (56%) and moving gas and stool (18%) caused 74% of intrafraction prostate motion. The PTPM3 was 11.3% at MRI-BL, 4.8% at MRI-CT, and 12.0% at MRI-RT (MRI-BL vs. MRI-CT, p = 0.12; MRI-BL vs. MRI-RT, p = 0.89). Conclusion: For subjects voiding their rectum before imaging, an antiflatulent diet and milk of magnesia laxative did not significantly reduce initial rectal area or intrafraction prostate motion.

  1. The Relationship between Prostate Inflammation and Lower Urinary Tract Symptoms: Examination of Baseline Data from the REDUCE Trial

    PubMed Central

    Nickel, J. Curtis; Roehrborn, Claus G.; O'Leary, Michael P.; Bostwick, David G.; Somerville, Matthew C.; Rittmaster, Roger S.

    2008-01-01

    Objective The ongoing REDUCE trial is a 4-yr, phase 3, placebo-controlled study to determine if daily dutasteride 0.5 mg reduces the risk of biopsy detectable prostate cancer. Prostate biopsies performed in all men prior to entry were centrally reviewed, thus allowing an examination of the relationship between inflammatory changes and lower urinary tract symptoms (LUTS). Methods Eligible men were aged 50–75 yr, with serum prostate-specific antigen ≥2.5 ng/ml and ≤10 ng/ml (50–60 yr), or ≥3.0 ng/ml and ≤10 ng/ml (>60 yr) and an International Prostate Symptom Score (IPSS) <25 (or <20 if already on alpha-blocker therapy). Acute prostatitis was an exclusion criterion. For a given individual, inflammation was assessed across all cores and the amount of inflammation scored as none (0), mild (1), moderate (2), or marked (3). LUTS was assessed with the use of the IPSS. The relationship between inflammation scores (averaged over all cores) and total IPSS; grouped IPSS (0–3, 4–7, 8–11, 12–15, 16–19, ≥20); and irritative, obstructive, and nocturia subscores was determined by Spearman rank correlations. The relative contribution of inflammation, age, and body mass index was then examined with the use of linear regression analyses. Results Data were available for 8224 men. Statistically significant but relatively weak correlations were found between average and maximum chronic inflammation and IPSS variables (correlation coefficients, 0.057 and 0.036, respectively; p < 0.001 for total IPSS). Both age and average chronic inflammation were significant in the linear regression after adjustment for other covariates; for both variables, more severe inflammation was associated with higher IPSS scores. Conclusions In the REDUCE population, there is evidence of a relationship between the degree of LUTS and the degree of chronic inflammation. Study entry criteria that selected older men and decreased enrolment of men with a greater degree of inflammation and LUTS

  2. Can Images Obtained With High Field Strength Magnetic Resonance Imaging Reduce Contouring Variability of the Prostate?

    SciTech Connect

    Usmani, Nawaid; Sloboda, Ron; Kamal, Wafa; Ghosh, Sunita; Pervez, Nadeem; Pedersen, John; Yee, Don; Danielson, Brita; Murtha, Albert; Amanie, John; Monajemi, Tara

    2011-07-01

    Purpose: The objective of this study is to determine whether there is less contouring variability of the prostate using higher-strength magnetic resonance images (MRI) compared with standard MRI and computed tomography (CT). Methods and Materials: Forty patients treated with prostate brachytherapy were accrued to a prospective study that included the acquisition of 1.5-T MR and CT images at specified time points. A subset of 10 patients had additional 3.0-T MR images acquired at the same time as their 1.5-T MR scans. Images from each of these patients were contoured by 5 radiation oncologists, with a random subset of patients repeated to quantify intraobserver contouring variability. To minimize bias in contouring the prostate, the image sets were placed in folders in a random order with all identifiers removed from the images. Results: Although there was less interobserver contouring variability in the overall prostate volumes in 1.5-T MRI compared with 3.0-T MRI (p < 0.01), there was no significant differences in contouring variability in the different regions of the prostate between 1.5-T MRI and 3.0-T MRI. MRI demonstrated significantly less interobserver contouring variability in both 1.5-T and 3.0-T compared with CT in overall prostate volumes (p < 0.01, p = 0.01), with the greatest benefits being appreciated in the base of the prostate. Overall, there was less intraobserver contouring variability than interobserver contouring variability for all of the measurements analyzed. Conclusions: Use of 3.0-T MRI does not demonstrate a significant improvement in contouring variability compared with 1.5-T MRI, although both magnetic strengths demonstrated less contouring variability compared with CT.

  3. From bench to bedside: the realities of reducing global prostate cancer disparity in black men

    PubMed Central

    Roberts, Robin

    2014-01-01

    Prostate cancer in black men of African descent has a different tumour biology compared to those of other races. Its clinical manifestations depict a more aggressive disease with higher morbidity and mortality. This study proposes, through a literature search, identifying applied laboratory and clinical research in prostate cancer directed to improve outcomes and decrease global disparities of prostate cancer in black men of African descent. This review identified five categories pertinent for research: prostate-specific antigen (PSA) testing for early detection and screening, the potential of epigenetics, cultural determinants and health-seeking behaviours, other biomarkers for prostate cancers, and the economics of treating advanced prostate cancer. The analysis revealed that in developed countries, men of African descent are underrepresented in the sampling pools in both laboratory and clinical research, and thus the applicability and relevance of these results to men of African descent are circumspect. However, developing countries with high populations of black males have limited laboratory and clinical research publications. This is due to limited funding to support research programmes and basic clinical services for early detection and treatment. The study concludes that for the involvement of developing countries in bench research, they should do it in collaboration, like fostering partnerships with credible academic-based institutions and organisations. This requires a realm of transparency, respect, protection of the rights and dignity of the patients, and an equity in participation and sharing of the benefits to be accrued. The current transatlantic and Caribbean collaborations in research, education, and health service delivery in prostate cancer care for men of African descent exemplify the successes of such partnerships. PMID:25228914

  4. Reduced Expression of GDF-15 Is Associated With Atrophic Inflammatory Lesions of the Prostate

    PubMed Central

    Lambert, James R.; Whitson, Ramon J.; Iczkowski, Kenneth A.; La Rosa, Francisco G.; Smith, Maxwell L.; Wilson, R. Storey; Smith, Elizabeth E.; Torkko, Kathleen C.; Gari, Hamid H.; Lucia, M. Scott

    2015-01-01

    BACKGROUND Accumulating evidence suggests that chronic prostatic inflammation may lead to prostate cancer development. Growth differentiation factor-15 (GDF-15) is highly expressed in the prostate and has been associated with inflammation and tumorigenesis. METHODS To examine the relationship between GDF-15 and prostatic inflammation, GDF-15 expression was measured by immunohistochemical (IHC) staining in human prostatectomy specimens containing inflammation. The relationship between GDF-15 and specific inflammatory cells was determined using non-biased computer image analysis. To provide insight into a potential suppressive role for GDF-15 in inflammation, activation of inflammatory mediator nuclear factor of kappa B (NFκB) was measured in PC3 cells. RESULTS GDF-15 expression in luminal epithelial cells was decreased with increasing inflammation severity, suggesting an inverse association between GDF-15 and inflammation. Quantification of IHC staining by image analysis for GDF-15 and inflammatory cell markers revealed an inverse correlation between GDF-15 and CD3+, CD4+, CD8+, CD68+, and inos+ leukocytes. GDF-15 suppressed NFκB activity in luciferase reporter assays. Expression of the NFκB target, interleukin 8 (IL-8), was downregulated by GDF-15. CONCLUSIONS The inverse relationship between GDF-15 and inflammation demonstrates a novel expression pattern for GDF-15 in the human prostate and suppression of NFκB activity may shed light on a potential mechanism for this inverse correlation. PMID:25327758

  5. Reducing the Cost of Proton Radiation Therapy: The Feasibility of a Streamlined Treatment Technique for Prostate Cancer

    PubMed Central

    Newhauser, Wayne D.; Zhang, Rui; Jones, Timothy G.; Giebeler, Annelise; Taddei, Phillip J.; Stewart, Robert D.; Lee, Andrew; Vassiliev, Oleg

    2015-01-01

    Proton radiation therapy is an effective modality for cancer treatments, but the cost of proton therapy is much higher compared to conventional radiotherapy and this presents a formidable barrier to most clinical practices that wish to offer proton therapy. Little attention in literature has been paid to the costs associated with collimators, range compensators and hypofractionation. The objective of this study was to evaluate the feasibility of cost-saving modifications to the present standard of care for proton treatments for prostate cancer. In particular, we quantified the dosimetric impact of a treatment technique in which custom fabricated collimators were replaced with a multileaf collimator (MLC) and the custom range compensators (RC) were eliminated. The dosimetric impacts of these modifications were assessed for 10 patients with a commercial treatment planning system (TPS) and confirmed with corresponding Monte Carlo simulations. We assessed the impact on lifetime risks of radiogenic second cancers using detailed dose reconstructions and predictive dose-risk models based on epidemiologic data. We also performed illustrative calculations, using an isoeffect model, to examine the potential for hypofractionation. Specifically, we bracketed plausible intervals of proton fraction size and total treatment dose that were equivalent to a conventional photon treatment of 79.2 Gy in 44 fractions. Our results revealed that eliminating the RC and using an MLC had negligible effect on predicted dose distributions and second cancer risks. Even modest hypofractionation strategies can yield substantial cost savings. Together, our results suggest that it is feasible to modify the standard of care to increase treatment efficiency, reduce treatment costs to patients and insurers, while preserving high treatment quality. PMID:25920039

  6. Inhibiting Vimentin or beta 1-integrin Reverts Prostate Tumor Cells in IrECM and Reduces Tumor Growth

    SciTech Connect

    Zhang, Xueping; Fournier, Marcia V.; Ware, Joy L.; Bissell, Mina J.; Zehner, Zendra E.

    2009-07-27

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphological changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional (3D) lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the parental prostate epithelial P69 cell line by selection in nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin or {alpha}6-, {beta}4- and {beta}1-integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via siRNA interference or {beta}1-integrin expression by the addition of the blocking antibody, AIIB2, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by subcutaneous injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in 3D lrECM gels. These studies suggest that the levels of vimentin and {beta}1-integrin play a key role in the homeostasis of the normal acini in prostate and that their dysregulation may lead to tumorigenesis.

  7. Reducing Router Forwarding Table Size Using Aggregation and Caching

    ERIC Educational Resources Information Center

    Liu, Yaoqing

    2013-01-01

    The fast growth of global routing table size has been causing concerns that the Forwarding Information Base (FIB) will not be able to fit in existing routers' expensive line-card memory, and upgrades will lead to a higher cost for network operators and customers. FIB Aggregation, a technique that merges multiple FIB entries into one, is probably…

  8. Unripe Rubus coreanus Miquel suppresses migration and invasion of human prostate cancer cells by reducing matrix metalloproteinase expression.

    PubMed

    Kim, Yesl; Lee, Seung Min; Kim, Jung-Hyun

    2014-01-01

    Rubus coreanus Miquel (RCM) is used to promote prostate health and has been shown to have anti-oxidant and anti-carcinogenic activities. However, the effects and mechanisms of RCM on prostate cancer metastasis remain unclear. PC-3 and DU 145 cells were treated with ethanol or water extract of unripe or ripe RCM and examined for cell invasion, migration, and matrix metalloproteinases (MMPs) activity and expression. Phosphoinositide 3-kinase (PI3K) and Akt activities were examined. Unripe RCM extracts exerted significant inhibitory effects on cell migration, invasion, and MMPs activities. A significant reduction in MMPs activities by unripe RCM ethanol extract treatment (UE) was associated with reduction of MMPs expression and induction of tissue inhibitors of metalloproteinases (TIMPs) expression. Furthermore, PI3K/Akt activity was diminished by UE treatment. In this study, we demonstrated that UE decreased metastatic potential of prostate cancer cells by reducing MMPs expression through the suppression of PI3K/Akt phosphorylation, thereby decreasing MMP activity and enhancing TIMPs expression.

  9. Reduced risk of prostate cancer in childless men as compared to fathers: a systematic review and meta-analysis

    PubMed Central

    Mao, Yeqing; Xu, Xin; Zheng, Xiangyi; Xie, Liping

    2016-01-01

    The previously reported association between fatherhood status and prostate cancer risk was controversial. We carried out the present meta-analysis of all relevant studies to summarize evidence on this association. A comprehensive literature search of studies was performed in PubMed, Web of Science, and the Chinese National Knowledge Infrastructure (CNKI) databases, covering all the papers published from their inception to September 2015. The combined risk estimates with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity and publication bias were also evaluated. A total of 11 studies were finally included in this meta-analysis. We found a significantly reduced risk of prostate cancer associated with being childless (OR 0.91, 95% CI 0.87–0.96). There was statistically significant heterogeneity across the studies (P < 0.001, I2 = 88.2%). In summary, this meta-analysis supports that being fatherless is associated with a lower risk of prostate cancer. Because of the substantial heterogeneity and residual confounding, using other study designs to further explore this association and the underling mechanism is warranted. PMID:26752096

  10. Reduced-size kernel models for nonlinear hybrid system identification.

    PubMed

    Le, Van Luong; Bloch, Grard; Lauer, Fabien

    2011-12-01

    This brief paper focuses on the identification of nonlinear hybrid dynamical systems, i.e., systems switching between multiple nonlinear dynamical behaviors. Thus the aim is to learn an ensemble of submodels from a single set of input-output data in a regression setting with no prior knowledge on the grouping of the data points into similar behaviors. To be able to approximate arbitrary nonlinearities, kernel submodels are considered. However, in order to maintain efficiency when applying the method to large data sets, a preprocessing step is required in order to fix the submodel sizes and limit the number of optimization variables. This brief paper proposes four approaches, respectively inspired by the fixed-size least-squares support vector machines, the feature vector selection method, the kernel principal component regression and a modification of the latter, in order to deal with this issue and build sparse kernel submodels. These are compared in numerical experiments, which show that the proposed approach achieves the simultaneous classification of data points and approximation of the nonlinear behaviors in an efficient and accurate manner.

  11. High Speed Gear Sized and Configured to Reduce Windage Loss

    NASA Technical Reports Server (NTRS)

    Kunz, Robert F. (Inventor); Medvitz, Richard B. (Inventor); Hill, Matthew John (Inventor)

    2013-01-01

    A gear and drive system utilizing the gear include teeth. Each of the teeth has a first side and a second side opposite the first side that extends from a body of the gear. For each tooth of the gear, a first extended portion is attached to the first side of the tooth to divert flow of fluid adjacent to the body of the gear to reduce windage losses that occur when the gear rotates. The gear may be utilized in drive systems that may have high rotational speeds, such as speeds where the tip velocities are greater than or equal to about 68 m/s. Some embodiments of the gear may also utilize teeth that also have second extended portions attached to the second sides of the teeth to divert flow of fluid adjacent to the body of the gear to reduce windage losses that occur when the gear rotates.

  12. CT, MR, and ultrasound image artifacts from prostate brachytherapy seed implants: The impact of seed size

    SciTech Connect

    Robertson, Andrew K. H.; Basran, Parminder S.; Thomas, Steven D.; Wells, Derek

    2012-04-15

    Purpose: To investigate the effects of brachytherapy seed size on the quality of x-ray computed tomography (CT), ultrasound (US), and magnetic resonance (MR) images and seed localization through comparison of the 6711 and 9011 {sup 125}I sources. Methods: For CT images, an acrylic phantom mimicking a clinical implantation plan and embedded with low contrast regions of interest (ROIs) was designed for both the 0.774 mm diameter 6711 (standard) and the 0.508 mm diameter 9011 (thin) seed models (Oncura, Inc., and GE Healthcare, Arlington Heights, IL). Image quality metrics were assessed using the standard deviation of ROIs between the seeds and the contrast to noise ratio (CNR) within the low contrast ROIs. For US images, water phantoms with both single and multiseed arrangements were constructed for both seed sizes. For MR images, both seeds were implanted into a porcine gel and imaged with pelvic imaging protocols. The standard deviation of ROIs and CNR values were used as metrics of artifact quantification. Seed localization within the CT images was assessed using the automated seed finder in a commercial brachytherapy treatment planning system. The number of erroneous seed placements and the average and maximum error in seed placements were recorded as metrics of the localization accuracy. Results: With the thin seeds, CT image noise was reduced from 48.5 {+-} 0.2 to 32.0 {+-} 0.2 HU and CNR improved by a median value of 74% when compared with the standard seeds. Ultrasound image noise was measured at 50.3 {+-} 17.1 dB for the thin seed images and 50.0 {+-} 19.8 dB for the standard seed images, and artifacts directly behind the seeds were smaller and less prominent with the thin seed model. For MR images, CNR of the standard seeds reduced on average 17% when using the thin seeds for all different imaging sequences and seed orientations, but these differences are not appreciable. Automated seed localization required an average ({+-}SD) of 7.0 {+-} 3.5 manual

  13. Prostatic Relaxation Induced by Loperamide Is Reduced in Spontaneously Hypertensive Rats

    PubMed Central

    Lee, Liang-Ming; Lu, Chih-Cheng; Chung, Hsien-Hui; Cheng, Juei-Tang

    2012-01-01

    This paper shows a new finding about the decrease of relaxative response to loperamide in prostate of spontaneously hypertensive rats (SHR) as compare to normal rats (WKY). Authors demonstrated the reduction of ATP-sensitive potassium channels is resposible for this change using immunoblotting analysis and the decrease of action induced by diazoxide. This view is not mentioned before and is the first one reporting this result. PMID:22645476

  14. Reduced 64Cu Uptake and Tumor Growth Inhibition by Knockdown of Human Copper Transporter 1 in Xenograft Mouse Model of Prostate Cancer

    PubMed Central

    Cai, Huawei; Wu, Jiu-sheng; Muzik, Otto; Hsieh, Jer-Tsong; Lee, Robert J.; Peng, Fangyu

    2015-01-01

    Copper is an element required for cell proliferation and angiogenesis. Human prostate cancer xenografts with increased 64Cu radioactivity were visualized previously by PET using 64CuCl2 as a radiotracer (64CuCl2 PET). This study aimed to determine whether the increased tumor 64Cu radioactivity was due to increased cellular uptake of 64Cu mediated by human copper transporter 1 (hCtr1) or simply due to nonspecific binding of ionic 64CuCl2 to tumor tissue. In addition, the functional role of hCtr1 in proliferation of prostate cancer cells and tumor growth was also assessed. Methods A lentiviral vector encoding short-hairpin RNA specific for hCtr1 (Lenti-hCtr1-shRNA) was constructed for RNA interference–mediated knockdown of hCtr1 expression in prostate cancer cells. The degree of hCtr1 knockdown was determined by Western blot, and the effect of hCtr1 knockdown on copper uptake and proliferation were examined in vitro by cellular 64Cu uptake and cell proliferation assays. The effects of hCtr1 knockdown on tumor uptake of 64Cu were determined by PET quantification and tissue radioactivity assay. The effects of hCtr1 knockdown on tumor growth were assessed by PET/CT and tumor size measurement with a caliper. Results RNA interference–mediated knockdown of hCtr1 was associated with the reduced cellular uptake of 64Cu and the suppression of prostate cancer cell proliferation in vitro. At 24 h after intravenous injection of the tracer 64CuCl2, the 64Cu uptake by the tumors with knockdown of hCtr1 (4.02 ± 0.31 percentage injected dose per gram [%ID/g] in Lenti-hCtr1-shRNA-PC-3 and 2.30 ± 0.59 %ID/g in Lenti-hCtr1-shRNA-DU-145) was significantly lower than the 64Cu uptake by the control tumors without knockdown of hCtr1 (7.21 ± 1.48 %ID/g in Lenti-SCR-shRNA-PC-3 and 5.57 ± 1.20 % ID/g in Lenti-SCR-shRNA-DU-145, P < 0.001) by PET quantification. Moreover, the volumes of prostate cancer xenograft tumors with knockdown of hCtr1 (179 ± 111 mm3 for Lenti-hCtr1-shRNA-PC-3

  15. Testing new submersible pumps for proper sizing and reduced costs

    SciTech Connect

    O'Toole, W.P.; O'Brien, J.B.

    1986-01-01

    This paper describes an ongoing program to improve overall submersible pump performance by Thums Long Beach Company, acting as Contractor of the City of Long Beach, Operator of the Long Beach Unit. Thums Long Beach Company currently operates 700 submersible pump installations located on four man-made islands and one land fill pier location. The program began with spot testing of submersible pumps for Thums' use. It has evolved to 100 percent pump testing and the stipulation that only pumps with newly manufactured parts are acceptable. The primary goals of this program are to increase well production and lower lifting costs. Critical to these goals is increasing the average length of run by using accurate pump performance data to design equipment and by rejecting defective pumps before they are run. Increased production is realized from better designs. Lower lifting costs result from utilizing higher efficiency pumps and a reduced frequency of pulling submersible equipment.

  16. Testing new submersible pumps for proper sizing and reduced costs

    SciTech Connect

    O'Toole, W.P.; O'Brien, J.B.

    1989-02-01

    This paper describes an ongoing program to improve overall submersible pump performance by Thums Long Beach Co., acting as contractor for the City of Long Beach, operator of the Long Beach Unit. Thums Long Beach Co. currently operates 700 submersible pump installations located on four manmade islands and one landfill pier location. The program began with spot testing of submersible pumps for Thums' use. It has evolved to 100% pump testing and the stipulation that only pumps with newly manufactured parts are acceptable. The primary goals of this program are to increase well production and to lower lifting costs. Critical to these goals is increasing the average length of run by using accurate pump-performance data to design equipment and by rejecting defective pumps before they are run. Increased production is realized from better designs. Lower lifting costs result from using more efficient pumps and a reduced frequency of pulling submersible equipment.

  17. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the... number of reindeer you are grazing; or (b) When disposal, withdrawal, natural causes, such as drought...

  18. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the... number of reindeer you are grazing; or (b) When disposal, withdrawal, natural causes, such as drought...

  19. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the... number of reindeer you are grazing; or (b) When disposal, withdrawal, natural causes, such as drought...

  20. 43 CFR 4300.53 - Can BLM reduce the size of the land in my permit?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...; ALASKA; REINDEER; GENERAL Changes in the Size of the Permit Area § 4300.53 Can BLM reduce the size of the... number of reindeer you are grazing; or (b) When disposal, withdrawal, natural causes, such as drought...

  1. Reducing Infectious Complications Following Transrectal Ultrasound-guided Prostate Biopsy: A Systematic Review

    PubMed Central

    Walker, Jordon T.; Singla, Nirmish; Roehrborn, Claus G.

    2016-01-01

    A rise in antimicrobial resistant uropathogens has generated a global increase in infections following transrectal ultrasound-guided prostate biopsy (TRUS-Bx). We performed a systematic search of Ovid MEDLINE® and PubMed to comprehensively review strategies to mitigate infections. Of 1664 articles retrieved, 62 were included. The data suggest that augmented prophylaxis and povidone-iodine bowel preparation warrant consideration in regions with high rates of antimicrobial resistance. Transperineal biopsy may be a safer, equally effective alternative to TRUS-Bx in select cases. Recent international travel appears to increase patients’ risk for experiencing infections. These findings can aid clinicians in minimizing post-TRUS-Bx infectious complications. PMID:27601966

  2. Reducing Infectious Complications Following Transrectal Ultrasound-guided Prostate Biopsy: A Systematic Review

    PubMed Central

    Walker, Jordon T.; Singla, Nirmish; Roehrborn, Claus G.

    2016-01-01

    A rise in antimicrobial resistant uropathogens has generated a global increase in infections following transrectal ultrasound-guided prostate biopsy (TRUS-Bx). We performed a systematic search of Ovid MEDLINE® and PubMed to comprehensively review strategies to mitigate infections. Of 1664 articles retrieved, 62 were included. The data suggest that augmented prophylaxis and povidone-iodine bowel preparation warrant consideration in regions with high rates of antimicrobial resistance. Transperineal biopsy may be a safer, equally effective alternative to TRUS-Bx in select cases. Recent international travel appears to increase patients’ risk for experiencing infections. These findings can aid clinicians in minimizing post-TRUS-Bx infectious complications.

  3. Reducing Infectious Complications Following Transrectal Ultrasound-guided Prostate Biopsy: A Systematic Review.

    PubMed

    Walker, Jordon T; Singla, Nirmish; Roehrborn, Claus G

    2016-01-01

    A rise in antimicrobial resistant uropathogens has generated a global increase in infections following transrectal ultrasound-guided prostate biopsy (TRUS-Bx). We performed a systematic search of Ovid MEDLINE® and PubMed to comprehensively review strategies to mitigate infections. Of 1664 articles retrieved, 62 were included. The data suggest that augmented prophylaxis and povidone-iodine bowel preparation warrant consideration in regions with high rates of antimicrobial resistance. Transperineal biopsy may be a safer, equally effective alternative to TRUS-Bx in select cases. Recent international travel appears to increase patients' risk for experiencing infections. These findings can aid clinicians in minimizing post-TRUS-Bx infectious complications. PMID:27601966

  4. Enteric-coated, highly standardized cranberry extract reduces risk of UTIs and urinary symptoms during radiotherapy for prostate carcinoma

    PubMed Central

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

    Background Cranberry (Vaccinium macrocarpon) proanthocyanidins can interfere with adhesion of bacteria to uroepithelial cells, potentially preventing lower urinary tract infections (LUTIs). Because LUTIs are a common side effect of external beam radiotherapy (EBRT) for prostate cancer, we evaluated the clinical efficacy of enteric-coated tablets containing highly standardized V. msacrocarpon (ecVM) in this condition. Methods A total of 370 consecutive patients were entered into this study. All patients received intensity-modulated radiotherapy for prostate cancer; 184 patients were also treated with ecVM while 186 served as controls. Cranberry extract therapy started on the simulation day, at which time a bladder catheterization was performed. During EBRT (over 6–7 weeks), all patients underwent weekly examination for urinary tract symptoms, including regular urine cultures during the treatment period. Results Compliance was excellent, with no adverse effects or allergic reactions being observed, apart from gastric pain in two patients. In the cranberry cohort (n = 184), 16 LUTIs (8.7%) were observed, while in the control group (n = 186) 45 LUTIs (24.2%) were recorded. This difference was statistically significant. Furthermore, lower rates of nocturia, urgency, micturition frequency, and dysuria were observed in the group that received cranberry extract. Conclusion Cranberry extracts have been reported to reduce the incidence of LUTIs significantly in women and children. Our data extend these results to patients with prostate cancer undergoing irradiation to the pelvis, who had a significant reduction in LUTIs compared with controls. These results were accompanied by a statistically significant reduction in urinary tract symptoms (dysuria, nocturia, urinary frequency, urgency), suggesting a generally protective effect of cranberry extract on the bladder mucosa. PMID:22977312

  5. Uncovering myths and transforming realities among low-SES African-American men: implications for reducing prostate cancer disparities.

    PubMed Central

    Richardson, Joann T.; Webster, J. DeWitt; Fields, Norma J.

    2004-01-01

    PURPOSE: Prostate cancer provides the most dramatic evidence of cancer disparities based on race and ethnicity among U.S. men. African-American men still hold a commanding lead in both prostate cancer incidence and mortality, particularly among those of low socioeconomic status (SES) and the medically underserved. Therefore, the need for early intervention persists. The purpose of this exploratory pilot study was to: a) assess the knowledge of a cohort of low-SES African-American men regarding prostate health/prostate cancer, and b) uncover myths/misinformation as barriers to prostate health decisions and behaviors. PROCEDURES: Asymptomatic African-American men participated in focus groups to candidly discuss: a) health concerns, b) prostate health, c) prostate cancer screening, diagnosis and treatment, and d) factors influencing prostate health decisions/behaviors. FINDINGS: Participants revealed sociocultural and psychological barriers: myths and lack of accurate/adequate knowledge about prostate health and cancer, fear, denial and apathy. CONCLUSIONS: These findings suggest factors that may explain the reluctance and limited participation in prostate health and prostate cancer services among medically underserved, socioeconomically disadvantaged, African-American men. Lack of knowledge, which affects all barriers to care, is amenable to change. Therefore, improvements in prostate cancer outcomes are achievable through culturally and linguistically appropriate health education tailored to their specific needs. PMID:15540880

  6. Cancer–Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer

    PubMed Central

    Sebastian, Aimy; Hum, Nicholas R.; Hudson, Bryan D.; Loots, Gabriela G.

    2015-01-01

    Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study, we utilized an in vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer–bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with SostKO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer. PMID:27600237

  7. Cancer–Osteoblast Interaction Reduces Sost Expression in Osteoblasts and Up-Regulates lncRNA MALAT1 in Prostate Cancer

    PubMed Central

    Sebastian, Aimy; Hum, Nicholas R.; Hudson, Bryan D.; Loots, Gabriela G.

    2015-01-01

    Dynamic interaction between prostate cancer and the bone microenvironment is a major contributor to metastasis of prostate cancer to bone. In this study, we utilized an in vitro co-culture model of PC3 prostate cancer cells and osteoblasts followed by microarray based gene expression profiling to identify previously unrecognized prostate cancer–bone microenvironment interactions. Factors secreted by PC3 cells resulted in the up-regulation of many genes in osteoblasts associated with bone metabolism and cancer metastasis, including Mmp13, Il-6 and Tgfb2, and down-regulation of Wnt inhibitor Sost. To determine whether altered Sost expression in the bone microenvironment has an effect on prostate cancer metastasis, we co-cultured PC3 cells with Sost knockout (SostKO) osteoblasts and wildtype (WT) osteoblasts and identified several genes differentially regulated between PC3-SostKO osteoblast co-cultures and PC3-WT osteoblast co-cultures. Co-culturing PC3 cells with WT osteoblasts up-regulated cancer-associated long noncoding RNA (lncRNA) MALAT1 in PC3 cells. MALAT1 expression was further enhanced when PC3 cells were co-cultured with SostKO osteoblasts and treatment with recombinant Sost down-regulated MALAT1 expression in these cells. Our results suggest that reduced Sost expression in the tumor microenvironment may promote bone metastasis by up-regulating MALAT1 in prostate cancer.

  8. Simultaneous transurethral resection of bladder cancer and prostate may reduce recurrence rates: A systematic review and meta-analysis

    PubMed Central

    LI, SHENG; ZENG, XIAN-TAO; RUAN, XIAO-LAN; WANG, XING-HUAN; GUO, YI; YANG, ZHONG-HUA

    2012-01-01

    The aim of this study was to evaluate the recurrence rate of simultaneous transurethral resection of bladder cancer and prostate (TURBT+TURP) in the treatment of non-muscle invasive bladder cancer (NMIBC) with benign prostatic hyperplasia (BPH). We searched PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE and the ISI Web of Knowledge databases from their establishment until March 2012, to collect all the original studies on TURBT+TURP vs. TURBT alone in the treatment of NMIBC with BPH. After screening the literature, methodological quality assessment and data extraction was conducted independently by two reviewers and meta-analysis was performed using the RevMan 5.1 software. The quality of data was assessed using the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Eight studies, including seven non-randomized concurrent controlled trials (NRCCTs) and one randomized controlled trial (RCT), involving a total of 1,372 patients met the criteria. Meta-analyses of NRCCTs showed that in the TURBT+TURP group, overall recurrence rates were lower [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.60–0.96; P=0.02] and the difference was statistically significant. The postoperative recurrence rate in the prostatic fossa/bladder neck (OR, 0.96; 95% CI, 0.64–1.45; P=0.86) and bladder tumor progression rates (OR, 0.96; 95% CI, 0.49–1.87; P=0.91) were similar between the TURBT+TURP and TURBT groups, but the difference was not significant. According to the GRADE approach, the level of evidence was moderate or low. Only one RCT demonstrated that overall postoperative tumor recurrence rates, recurrence rates at prostate fossa/bladder neck and bladder tumor progression rates between simultaneous groups and control groups were almost equal. There was no significant difference (P>0.05), and the level of evidence was moderate. For patients with NMIBC and BPH, simultaneous resection did not increase the overall

  9. QUANTITATIVE STUDIES OF PROSTATIC SECRETION

    PubMed Central

    Huggins, Charles; Clark, Philip Johnson

    1940-01-01

    Cystic hyperplasia of the prostate occurs spontaneously in senile dogs only when they possess physiologically effective amounts of androgenic hormone. The cysts are closely grouped and radially arranged in a conical manner with the base of the cone at the periphery of the gland. Flattened and columnar epithelium, varying from about 5 to 25µ are seen in each cyst. The cysts communicate with the urethra by way of ducts. Both normal and cystic prostates undergo marked atrophy when the testes are removed, the chief difference 3 months after orchiectomy being the persistence of slightly dilated clefts and spaces at the site of the former cysts in the senile state. In the castrate dog whose prostate gland is being reconstructed as result of the influence of daily injections of androgen, certain doses of estrogen prevent increase of secretion and still larger doses greatly depress the output of the gland. In dogs so treated by daily injections of testosterone propionate, 10 mg., the amount of secretion is maintained from day to day at a level by daily injections of stilbestrol, 0.4 to 0.6 mg. and greatly depressed by doses of 1 to 1.5 mg. When the larger amounts of estrogen are used, together with androgen, squamous metaplasia occurs in the posterior lobe of the prostate while the epithelium of the acini decreases in height to cuboidal or low columnar form; these histological signs of activity of both androgen and estrogen on the prostate show that inhibition of the male hormone by stilbestrol is incomplete at these ratios. In dogs with either normal or cystic prostate glands, the prostate decreases in size when estrogen is injected in amounts to depress prostatic secretion profoundly. The gland is maintained in an atrophic state and overdosage avoided by controlled periodic injections of stilbestrol until secretion is reduced to the minimum, followed by free intervals, the estrogen being again administered when secretion measurably increases. The shrinkage is related to

  10. Survival in prostate cancer prevention trial detailed

    Cancer.gov

    In the NCI-sponsored Prostate Cancer Prevention Trial, initial findings from a decade ago showed that the drug finasteride significantly reduced the risk of prostate cancer, but among those who did develop prostate cancer, paradoxically, the drug was asso

  11. Consumption of soy isoflavone enriched bread in men with prostate cancer is associated with reduced proinflammatory cytokines and immunosuppressive cells.

    PubMed

    Lesinski, Gregory B; Reville, Patrick K; Mace, Thomas A; Young, Gregory S; Ahn-Jarvis, Jennifer; Thomas-Ahner, Jennifer; Vodovotz, Yael; Ameen, Zeenath; Grainger, Elizabeth; Riedl, Kenneth; Schwartz, Steven; Clinton, Steven K

    2015-11-01

    We hypothesized that soy phytochemicals may have immunomodulatory properties that may affect prostate carcinogenesis and progression. A randomized, phase II trial was conducted in 32 patients with prostate cancer with asymptomatic biochemical recurrence but no measurable disease on standard staging studies. Patients were randomized to two slices of soy bread (34 mg isoflavones/slice) or soy bread containing almond powder daily as a source of β-glucosidase. Flow cytometry and bioplex assays were used to measure cytokines or immune cell phenotype in blood at baseline (day 0) and following intervention (day 56). Adequate blood samples were available at enrollment and day 56 and evaluated. Multiple plasma cytokines and chemokines were significantly decreased on day 56 versus baseline. Subgroup analysis indicated reduced TH1 (P = 0.028) and myeloid-derived suppressor cell (MDSC)-associated cytokines (P = 0.035). TH2 and TH17 cytokines were not significantly altered. Phenotypic analysis revealed no change in CD8(+) or CD4(+) T cells but showed increased CD56(+) natural killer (NK) cells (P = 0.038). The percentage of cells with a T regulatory cell phenotype (CD4(+)CD25(+)FoxP3(+)) was significantly decreased after 56 days of soy bread (P = 0.0136). Significantly decreased monocytic (CD33(+)HLADR(neg)CD14(+)) MDSC were observed in patients consuming soy bread (P = 0.0056). These data suggest that soy bread modulates systemic soluble and cellular biomarkers consistent with limiting inflammation and suppression of MDSCs. Additional studies to elucidate impact on the carcinogenic process or as a complement to immune-based therapy are required.

  12. Pyrrolopyrimidine c-Src inhibitors reduce growth, adhesion, motility and invasion of prostate cancer cells in vitro.

    PubMed

    Recchia, I; Rucci, N; Festuccia, C; Bologna, M; MacKay, A R; Migliaccio, S; Longo, M; Susa, M; Fabbro, D; Teti, A

    2003-09-01

    Two bona fide c-Src inhibitors, denominated CGP77675 and CGP76030, reduced in a time- and concentration-dependent manner (i) the proliferation of the PC3 prostate carcinoma cell line, as assessed by the [3H]-thymidine incorporation test, (ii) the capacity of PC3 cells to adhere and spread on Matrigel substrate, as determined by crystal violet staining, (iii) the ability of PC3 cells to migrate through a gelatine boundary and invade a Matrigel substrate. The latter effect was not due to a decrease of urokinase-type plasminogen activator (uPA), nor of metalloproteinase-2 (MMP-2) activities. The MMP-9 activity, along with the expression of the Tissue Inhibitor of Metalloproteinases (TIMP)-1 and TIMP-2, were reduced by the two inhibitors, consistent with the ability of c-Src to enhance MMP-9 and TIMP expression levels. Collectively, these data demonstrate that the pyrrolopyrimidine-derived c-Src inhibitors significantly reduced PC3 cell activities associated with their malignant phenotype.

  13. Ultrasonic processor reduces drill-cuttings size and eliminates subsea mounds

    SciTech Connect

    Gaddy, D.E.

    1997-10-06

    Drill cuttings size reduction using ultrasonics eliminated a subsea clean-up and significantly reduced the environmental impact in a North Sea drilling project. Reduction in cuttings size allows for a wider areal dispersion when released into the ocean because they are held in suspension longer than larger sizes. Thus, ocean currents carry the smaller cuttings farther away from the well template, leaving a much wider footprint than larger cuttings sizes. This eliminates the pile-up of cuttings that otherwise would contaminate and harm the marine habitat.

  14. Prostate Cancer

    MedlinePlus

    ... version of this page please turn Javascript on. Prostate Cancer What is Prostate Cancer? How Tumors Form The body is made up ... the Escape (Esc) button on your keyboard.) How Prostate Cancer Occurs Prostate cancer occurs when a tumor forms ...

  15. Reduced body size and cub recruitment in polar bears associated with sea ice decline

    USGS Publications Warehouse

    Rode, K.D.; Amstrup, Steven C.; Regehr, E.V.

    2010-01-01

    Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a longterm data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population. ?? 2010 by the Ecological Society of America.

  16. Reduced body size and cub recruitment in polar bears associated with sea ice decline.

    PubMed

    Rode, Karyn D; Amstrup, Steven C; Regehr, Eric V

    2010-04-01

    Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a long-term data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population.

  17. Reduced body size and cub recruitment in polar bears associated with sea ice decline.

    PubMed

    Rode, Karyn D; Amstrup, Steven C; Regehr, Eric V

    2010-04-01

    Rates of reproduction and survival are dependent upon adequate body size and condition of individuals. Declines in size and condition have provided early indicators of population decline in polar bears (Ursus maritimus) near the southern extreme of their range. We tested whether patterns in body size, condition, and cub recruitment of polar bears in the southern Beaufort Sea of Alaska were related to the availability of preferred sea ice habitats and whether these measures and habitat availability exhibited trends over time, between 1982 and 2006. The mean skull size and body length of all polar bears over three years of age declined over time, corresponding with long-term declines in the spatial and temporal availability of sea ice habitat. Body size of young, growing bears declined over time and was smaller after years when sea ice availability was reduced. Reduced litter mass and numbers of yearlings per female following years with lower availability of optimal sea ice habitat, suggest reduced reproductive output and juvenile survival. These results, based on analysis of a long-term data set, suggest that declining sea ice is associated with nutritional limitations that reduced body size and reproduction in this population. PMID:20437962

  18. Reducing On-Chip DRAM Energy via Data Transfer Size Optimization

    NASA Astrophysics Data System (ADS)

    Ono, Takatsugu; Inoue, Koji; Murakami, Kazuaki; Yoshida, Kenji

    This paper proposes a software-controllable variable line-size (SC-VLS) cache architecture for low power embedded systems. High bandwidth between logic and a DRAM is realized by means of advanced integrated technology. System-in-Silicon is one of the architectural frameworks to realize the high bandwidth. An ASIC and a specific SRAM are mounted onto a silicon interposer. Each chip is connected to the silicon interposer by eutectic solder bumps. In the framework, it is important to reduce the DRAM energy consumption. The specific DRAM needs a small cache memory to improve the performance. We exploit the cache to reduce the DRAM energy consumption. During application program executions, an adequate cache line size which produces the lowest cache miss ratio is varied because the amount of spatial locality of memory references changes. If we employ a large cache line size, we can expect the effect of prefetching. However, the DRAM energy consumption is larger than a small line size because of the huge number of banks are accessed. The SC-VLS cache is able to change a line size to an adequate one at runtime with a small area and power overheads. We analyze the adequate line size and insert line size change instructions at the beginning of each function of a target program before executing the program. In our evaluation, it is observed that the SC-VLS cache reduces the DRAM energy consumption up to 88%, compared to a conventional cache with fixed 256B lines.

  19. Reducing size-dispersion in one-pot aqueous synthesis of maghemite nanoparticles.

    PubMed

    Drummond, A L; Feitoza, N C; Duarte, G C; Sales, M J A; Silva, L P; Chaker, J A; Bakuzis, A F; Sousa, M H

    2012-10-01

    Nanosized maghemite-like particles with reduced size-distribution were obtained using a one-pot synthesis route in aqueous medium. Forced hydrolysis of iron ions in ammoniac solution led to the formation of magnetite nanoparticles that were oxidized to maghemite in a hydrothermal digestion step that reduced the polydispersity of nanograins. The prepared nanoparticles were characterized by chemical analysis, X-ray diffractometry, magnetization, Raman spectroscopy and transmission electron microscopy measurements. Data showed that 14 nm-sized particles with polydispersity of about 0.14 were produced and, differently from other procedures, neither additional steps nor toxic reagents were needed to reduce size-dispersion or to oxidize magnetite to maghemite. These facts per se turn such nanodevice into a good potential choice for biomedical applications.

  20. Size-dependent mechanical properties of PVA nanofibers reduced via air plasma treatment

    NASA Astrophysics Data System (ADS)

    Fu, Qiang; Jin, Yu; Song, Xuefeng; Gao, Jingyun; Han, Xiaobing; Jiang, Xingyu; Zhao, Qing; Yu, Dapeng

    2010-03-01

    Organic nanowires/fibers have great potential in applications such as organic electronics and soft electronic techniques. Therefore investigation of their mechanical performance is of importance. The Young's modulus of poly(vinyl alcohol) (PVA) nanofibers was analyzed by scanning probe microscopy (SPM) methods. Air plasma treatment was used to reduce the nanofibers to different sizes. Size-dependent mechanical properties of PVA nanofibers were studied and revealed that the Young's modulus increased dramatically when the scales became very small (<80 nm).

  1. Electromagnetic Transponders Indicate Prostate Size Increase Followed by Decrease During the Course of External Beam Radiation Therapy

    SciTech Connect

    King, Benjamin L.; Butler, Wayne M.; Merrick, Gregory S.; Kurko, Brian S.; Reed, Joshua L.; Murray, Brian C.; Wallner, Kent E.

    2011-04-01

    Purpose: Real-time image guidance enables more accurate radiation therapy by tracking target movement. This study used transponder positions to monitor changes in prostate volume that may be a source of dosimetric and target inaccuracy. Methods and Materials: Twenty-four men with biopsy-proven T1c-T3a prostate cancer each had three electromagnetic transponders implanted transperineally. Their coordinates were recorded by the Calypso system, and the perimeter of the triangle formed by the transponders was used to calculate prostate volumes at sequential time points throughout the course of radiation therapy to a dose of 81 Gy in 1.8-Gy fractions. Results: There was a significant decrease in mean prostate volume of 10.9% from the first to the final day of radiation therapy. The volume loss did not occur monotonically but increased in most patients (75%) during the first several weeks to a median maximum on Day 7. The volume increased by a mean of 6.1% before decreasing by a mean maximum difference of 18.4% to nadir (p < 0.001 for both increase and decrease). Glandular shrinkage was asymmetric, with the apex to right base dimension varying more than twice that of the lateral dimension. For all dimensions, the mean change was <0.5 cm. Conclusion: Real-time transponder positions indicated a volume increase during the initial days of radiation therapy and then significant and asymmetric shrinkage by the final day. Understanding and tracking volume fluctuations of the prostate during radiation therapy can help real-time imaging technology perform to its fullest potential.

  2. New mechanism to reduce the size of the monopivot magnetic suspension blood pump: direct drive mechanism.

    PubMed

    Yamane, T; Nishida, M; Kijima, T; Maekawa, J

    1997-07-01

    Size reduction of the monopivot magnetic suspension blood pump has been achieved by reducing the size of the magnetic suspension and employing a direct drive mechanism in place of a brushless DC motor and a magnetic coupling. The flow has also been improved using a closed hollow impeller to remove flow obstruction at the inlet and using radial straight vanes to reduce the impeller speed by 30%. Hemolysis testing was conducted for the new models. Results showed that model DD1 presented only a slightly higher level of hemolysis than a regular extracorporeal centrifugal pump. PMID:9212927

  3. Computed tomography of the prostate.

    PubMed

    Van Engelshoven, J M; Kreel, L

    1979-02-01

    The conventional anatomy of the prostate is reviewed and the computed tomography (CT) anatomy described and illustrated. The results of 55 "normal" cases were analyzed for size and relationship to the symphysis pubis, retropubic space, and bladder, as shown on CT sections correlating the features with age and possible urinary symptoms. Attention is also drawn to the differences between phleboliths and prostatic calcification. Computed tomography is an effective method of demonstrating the prostate and surrounding structures and of assessing prostatic enlargement.

  4. Intraoperative Frozen Section of the Prostate Reduces the Risk of Positive Margin Whilst Ensuring Nerve Sparing in Patients with Intermediate and High-Risk Prostate Cancer Undergoing Robotic Radical Prostatectomy: First Reported UK Series

    PubMed Central

    Vasdev, Nikhil; Agarwal, Samita; Rai, Bhavan P.; Soosainathan, Arany; Shaw, Gregory; Chang, Sebastian; Prasad, Venkat; Mohan-S, Gowrie; Adshead, James M.

    2016-01-01

    Introduction Nerve sparing during robotic radical prostatectomy (RRP) considerably improves post-operative potency and urinary continence as long as it does not compromise oncological outcome. Excision of the neurovascular bundle (NVB) is often performed in patients with intermediate and high risk prostate cancer to reduce the risk of positive surgical margin raising the risk of urinary incontinence and impotence. We present the first UK series outcomes of such patients who underwent an intra-operative frozen section (IOFS) analysis of the prostate during RRP allowing nerve sparing. Patients and Methods We prospectively analysed the data of 40 patients who underwent an IOFS during RRP at our centre from November 2012 until November 2014. Our IOFS technique involved whole lateral circumferential analysis of the prostate during RRP with the corresponding neurovascular tissue. An intrafascial nerve spare was performed and the specimen was removed intra-operatively via an extension of the 12 mm Autosuture™ camera port without undocking robotic arms. It was then painted by the surgeon and sprayed with “Ink Aid” prior to frozen section analysis. The corresponding NVB was excised if the histopathologist found a positive surgical margin on frozen section. Results Median time to extract the specimen, wound closure and re-establishment of pneumoperitoneum increased the operative time by 8 min. Median blood loss for IOFS was 130 ± 97 ml vs. 90 ± 72 ml (p = NS). IOFS was not associated with major complications or with blood transfusion. PSM decreased significantly from non-IOFS RRP series of 28.7 to 7.8% (p < 0.05). Intra-operative PSM on the prostate specimen was seen in 8/40 margin analysis (20%) leading to an excision of the contra-lateral nerve bundle. On analysis of the nerve bundle on a paraffin embedded block, 6 nerve bundle matched tumor on the specimen whereas 2 NVB were retrospectively removed unnecessarily in our series. All 40 patients have undetectable PSA

  5. Reduced sample sizes for atrophy outcomes in Alzheimer's disease trials: baseline adjustment.

    PubMed

    Schott, J M; Bartlett, J W; Barnes, J; Leung, K K; Ourselin, S; Fox, N C

    2010-08-01

    Cerebral atrophy rate is increasingly used as an outcome measure for Alzheimer's disease (AD) trials. We used the Alzheimer's disease Neuroimaging initiative (ADNI) dataset to assess if adjusting for baseline characteristics can reduce sample sizes. Controls (n = 199), patients with mild cognitive impairment (MCI) (n = 334) and AD (n = 144) had two MRI scans, 1-year apart; approximately 55% had baseline CSF tau, p-tau, and Abeta1-42. Whole brain (KN-BSI) and hippocampal (HMAPS-HBSI) atrophy rate, and ventricular expansion (VBSI) were calculated for each group; numbers required to power a placebo-controlled trial were estimated. Sample sizes per arm (80% power, 25% absolute rate reduction) for AD were (95% CI): brain atrophy = 81 (64,109), hippocampal atrophy = 88 (68,119), ventricular expansion = 118 (92,157); and for MCI: brain atrophy = 149 (122,188), hippocampal atrophy = 201 (160,262), ventricular expansion = 234 (191,295). To detect a 25% reduction relative to normal aging required increased sample sizes approximately 3-fold (AD), and approximately 5-fold (MCI). Disease severity and Abeta1-42 contributed significantly to atrophy rate variability. Adjusting for 11 predefined covariates reduced sample sizes by up to 30%. Treatment trials in AD should consider the effects of normal aging; adjusting for baseline characteristics can significantly reduce required sample sizes.

  6. A study on reducing of the focal spot size using spatial filtering and phase apodization

    NASA Astrophysics Data System (ADS)

    Savelyev, D.

    2016-08-01

    The resizing of focal spot using an annular diaphragm with phase jump in the scalar paraxial case was investigated numerically. Due to the apodization optical system, we succeeded in reducing the size of the focal spot in 2.3 times.

  7. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  8. Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

    SciTech Connect

    Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

    2008-06-12

    Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

  9. Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

    PubMed

    Sharma, Haripaul; Kanwal, Rajnee; Bhaskaran, Natarajan; Gupta, Sanjay

    2014-01-01

    Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities. PMID:24614817

  10. Benign prostatic hyperplasia (BPH) management in the primary care setting.

    PubMed

    Kapoor, Anil

    2012-10-01

    Benign prostate hyperplasia (BPH) occurs in up to 50% of men by age 50, and the incidence increases with age. This common clinical problem is diagnosed by history, including the International Prostate Symptom Score (IPSS) questionnaire, and physical examination by digital rectal examination (DRE). Initial management for BPH includes lifestyle modification, and smooth muscle relaxant alpha blocker therapy. Alpha blockers usually take effect quickly within 3-5 days, and have minimal side effects. Current commonly used alpha blockers include the selective alpha blockers tamsulosin (Flomax), alfusosin (Xatral), and silodosin (Rapaflo). For patients with larger prostates, the 5-alpha reductase inhibitor class (finasteride (Proscar) and dutasteride (Avodart)) work effectively to shrink prostate stroma resulting in improved voiding. The 5-ARI class of drugs, in addition to reducing prostate size, also reduce the need for future BPH-related surgery, and reduce the risk of future urinary retention. Drugs from the phosphodiesterase-5 (PDE-5) inhibitor class may now be considered for treating BPH. Once daily 5 mg tadalafil has been shown to improve BPH-related symptoms and is currently approved to treat patients with BPH. Referral to a urologist can be considered for patients with a rising prostate-specific antigen (PSA), especially while on 5-ARI, failure of urinary symptom control despite maximal medical therapy, suspicion of prostate cancer, hematuria, recurrent urinary infections, urinary retention, or renal failure. Currently the primary care physician is armed with multiple treatment options to effectively treat men with symptomatic BPH. PMID:23089343

  11. Medical management of benign prostatic hyperplasia.

    PubMed

    Kane, M M; Fields, D W; Vaughan, E D

    1990-11-01

    Medical management of clinical BPH is a reality. The only effective nonsurgical treatment now recommended is aimed at relieving the dynamic component of clinical BPH. Pharmacologic treatment using alpha-adrenoceptor antagonists may be used appropriately to manage patients with prostatism who are poor surgical risks but who could benefit from reduced sympathetic tone. In addition, alpha blockers are used to relieve acute retention, and to prevent retention when increased sympathetic discharge is expected. Thus far, nonsurgical therapy aimed at reducing the mechanical obstruction associated with BPH by prostatic size reduction has failed to produce consistent objective improvement. However, several drugs are now being investigated and may be effective for reducing prostatic size in patients with BPH. Clinical trials are complicated by a number of factors, especially very variable symptoms. Moreover, reduction in prostatic size induced by drugs is not permanent and regrowth occurs with drug withdrawal, necessitating chronic treatment. Ideally, future research should be aimed at the prevention of BPH at an early age. However, this presupposes a better understanding of the pathogenesis of BPH. BPH may not be a single, variable disease but a family of diseases with a number of predictable clinical courses. In the future, we should pay particular attention to histologic variability, to see if in fact different pathologic forms of BPH follow different clinical patterns. If urologists are to keep their predominant position in managing the patient with BPH, they will have to keep informed of medical treatment trials and of potential alternative treatment strategies to prostatectomy.

  12. Do antioxidant vitamins reduce infarct size following acute myocardial ischemia/reperfusion?

    PubMed

    Bellows, S D; Hale, S L; Simkhovich, B Z; Kay, G L; Kloner, R A

    1995-02-01

    There is controversy concerning the ability of antioxidant vitamins to reduce myocardial infarct size. We sought to determine whether a brief prophylactic treatment of vitamin C or vitamin C plus Trolox (a water-soluble form of vitamin E) could reduce myocardial infarct size in an experimental model. We used an anesthetized open-chest rabbit model in which a branch of the circumflex coronary artery was ligated for 30 minutes followed by 4 hours of reperfusion. Experiments were performed in a randomized and blinded fashion. An IV injection of normal saline pH balanced to 7.4 (control group n = 15), vitamin C (150 mg/kg, n = 14), or vitamin C plus Trolox (150 mg/kg plus 100 mg/kg, respectively, n = 15) was administered prior to coronary occlusion. Collateral blood flow during coronary occlusion was measured by radioactive microspheres, myocardial risk zone (AR) was assessed by blue dye injection, and myocardial infarct size (AN) was assessed by triphenyltetrazolium chloride staining. All rabbits received comparable ischemic insult: Collateral blood flow and AR were similar among all three groups. Infarct size, measured as a percent of AR, did not differ significantly among the controls (21%), vitamin C (29%), or the vitamin C plus Trolox (18%) groups. Therefore, in this ischemia/reperfusion model, antioxidant vitamins did not alter myocardial infarct size. PMID:7540423

  13. Shock Reactivity Study on Standard and Reduced Sensitivity RDX of Different Particle Size Distributions

    NASA Astrophysics Data System (ADS)

    McGregor, Nicholas; Lindfors, Allen

    2007-06-01

    Embedded gauge experiments have been performed using a three inch high velocity powder gun to assess the effects of RDX particle size and crystal quality on shock induced reactivity in support of the Combat Safe Insensitive Munitions (CSIM) program. Four monomodal experimental compositions containing 73% solids loading by weight and 27% HTPB binder were tested. The compositions were made using either standard or reduced sensitivity grades of RDX in Class 5 or Class 1 150-300 micron sieve cut particle size classes. Results have shown marked changes in the mode of reaction between the two particle size classes. Both RDX grades at the Class 1 sieve cut particle size distribution showed significant reaction at the shock front as well as behind the front. The Class 5 RDX compositions however showed little reaction at the shock front with rapid growth behind the front. Similar input pressures resulted in a full detonation in a similar distance for like RDX grades. Reaction modes were similar but occurring at greater input pressures for the reduced sensitivity grade of RDX compared to the corresponding particle size distribution standard grade RDX counterpart.

  14. Shock Reactivity Study on Standard and Reduced Sensitivity Rdx of Different Particle Size Distributions

    NASA Astrophysics Data System (ADS)

    McGregor, N. M.; Lindfors, A. J.

    2007-12-01

    Embedded gauge experiments have been performed using a three inch high velocity powder gun to assess the effects of RDX particle size and crystal quality on shock induced reactivity in support of the Combat Safe Insensitive Munitions (CSIM) program. Four monomodal experimental compositions containing 73% solids loading by weight and 27% HTPB binder were tested. The compositions were made using either standard or reduced sensitivity grades of RDX in Class 5 or Class 1 150-300 micron sieve cut particle size classes. Results have shown marked changes in the mode of reaction between the two particle size classes. Both RDX grades at the Class 1 sieve cut particle size distribution showed significant reaction at the shock front as well as behind the front. The Class 5 RDX compositions however showed little reaction at the shock front with rapid growth behind the front. Reaction modes were similar but occurring at greater input pressures for the reduced sensitivity grade of RDX compared to the corresponding particle size distribution standard grade RDX counterpart.

  15. Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells

    PubMed Central

    Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, Gulperi

    2015-01-01

    Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependent manner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in

  16. Enhanced G2/M Arrest, Caspase Related Apoptosis and Reduced E-Cadherin Dependent Intercellular Adhesion by Trabectedin in Prostate Cancer Stem Cells.

    PubMed

    Acikgoz, Eda; Guven, Ummu; Duzagac, Fahriye; Uslu, Ruchan; Kara, Mikail; Soner, Burak Cem; Oktem, Gulperi

    2015-01-01

    Trabectedin (Yondelis, ET-743) is a marine-derived tetrahydroisoquinoline alkaloid. It is originally derived from the Caribbean marine tunicate Ecteinascidia turbinata and currently produced synthetically. Trabectedin is active against a variety of tumor cell lines growing in culture. The present study focused on the effect of trabectedin in cell proliferation, cell cycle progression, apoptosis and spheroid formation in prostate cancer stem cells (CSCs). Cluster of differentiation (CD) 133+high/CD44+high prostate CSCs were isolated from the DU145 and PC-3 human prostate cancer cell line through flow cytometry. We studied the growth-inhibitory effects of trabectedin and its molecular mechanisms on human prostate CSCs and non-CSCs. DU-145 and PC-3 CSCs were treated with 0.1, 1, 10 and 100 nM trabectedin for 24, 48 and 72 h and the growth inhibition rates were examined using the sphere-forming assay. Annexin-V assay and immunofluorescence analyses were performed for the detection of the cell death. Concentration-dependent effects of trabectedin on the cell cycle were also evaluated. The cells were exposed to the different doses of trabectedin for 24, 48 and 72 h to evaluate the effect of trabectedin on the number and diameter of spheroids. According to the results, trabectedin induced cytotoxicity and apoptosis at the IC50 dose, resulting in a significant increase expression of caspase-3, caspase-8, caspase-9, p53 and decrease expression of bcl-2 in dose-dependent manner. Cell cycle analyses revealed that trabectedin induces dose-dependent G2/M-phase cell cycle arrest, particularly at high-dose treatments. Three-dimensional culture studies showed that trabectedin reduced the number and diameter of spheroids of DU145 and PC3 CSCs. Furthermore, we have found that trabectedin disrupted cell-cell interactions via E-cadherin in prostasphere of DU-145 and PC-3 CSCs. Our results showed that trabectedin inhibits cellular proliferation and accelerates apoptotic events in

  17. Enlarged prostate gland

    MedlinePlus

    ... enlarges in size in a process called benign hypertrophy, which means that the gland got larger without ... in several of the symptoms of benign prostatic hypertrophy, or BPH. Symptoms may include a slowed or ...

  18. Prostate brachytherapy

    MedlinePlus

    Implant therapy - prostate cancer; Radioactive seed placement; Internal radiation therapy - prostate; High dose radiation (HDR) ... plan and then place the seeds that deliver radiation into your prostate. The seeds are placed with ...

  19. Small portion sizes in worksite cafeterias: do they help consumers to reduce their food intake?

    PubMed Central

    Vermeer, W M; Steenhuis, I H M; Leeuwis, F H; Heymans, M W; Seidell, J C

    2011-01-01

    Background: Environmental interventions directed at portion size might help consumers to reduce their food intake. Objective: To assess whether offering a smaller hot meal, in addition to the existing size, stimulates people to replace their large meal with a smaller meal. Design: Longitudinal randomized controlled trial assessing the impact of introducing small portion sizes and pricing strategies on consumer choices. Setting/participants: In all, 25 worksite cafeterias and a panel consisting of 308 consumers (mean age=39.18 years, 50% women). Intervention: A small portion size of hot meals was offered in addition to the existing size. The meals were either proportionally priced (that is, the price per gram was comparable regardless of the size) or value size pricing was employed. Main outcome measures: Daily sales of small and the total number of meals, consumers' self-reported compensation behavior and frequency of purchasing small meals. Results: The ratio of small meals sales in relation to large meals sales was 10.2%. No effect of proportional pricing was found B=−0.11 (0.33), P=0.74, confidence interval (CI): −0.76 to 0.54). The consumer data indicated that 19.5% of the participants who had selected a small meal often-to-always purchased more products than usual in the worksite cafeteria. Small meal purchases were negatively related to being male (B=−0.85 (0.20), P=0.00, CI: −1.24 to −0.46, n=178). Conclusion: When offering a small meal in addition to the existing size, a percentage of consumers that is considered reasonable were inclined to replace the large meal with the small meal. Proportional prices did not have an additional effect. The possible occurrence of compensation behavior is an issue that merits further attention. PMID:21224829

  20. Concentration Effect of Reducing Agents on Green Synthesis of Gold Nanoparticles: Size, Morphology, and Growth Mechanism

    NASA Astrophysics Data System (ADS)

    Kim, Hyun-seok; Seo, Yu Seon; Kim, Kyeounghak; Han, Jeong Woo; Park, Youmie; Cho, Seonho

    2016-04-01

    Under various concentration conditions of reducing agents during the green synthesis of gold nanoparticles (AuNPs), we obtain the various geometry (morphology and size) of AuNPs that play a crucial role in their catalytic properties. Through both theoretical and experimental approaches, we studied the relationship between the concentration of reducing agent (caffeic acid) and the geometry of AuNPs. As the concentration of caffeic acid increases, the sizes of AuNPs were decreased due to the adsorption and stabilizing effect of oxidized caffeic acids (OXCAs). Thus, it turns out that optimal concentration exists for the desired geometry of AuNPs. Furthermore, we investigated the growth mechanism for the green synthesis of AuNPs. As the caffeic acid is added and adsorbed on the surface of AuNPs, the aggregation mechanism and surface free energy are changed and consequently resulted in the AuNPs of various geometry.

  1. Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis.

    PubMed

    O'Brien, Andrew J; Villani, Linda A; Broadfield, Lindsay A; Houde, Vanessa P; Galic, Sandra; Blandino, Giovanni; Kemp, Bruce E; Tsakiridis, Theodoros; Muti, Paola; Steinberg, Gregory R

    2015-07-15

    Aspirin, the pro-drug of salicylate, is associated with reduced incidence of death from cancers of the colon, lung and prostate and is commonly prescribed in combination with metformin in individuals with type 2 diabetes. Salicylate activates the AMP-activated protein kinase (AMPK) by binding at the A-769662 drug binding site on the AMPK β1-subunit, a mechanism that is distinct from metformin which disrupts the adenylate charge of the cell. A hallmark of many cancers is high rates of fatty acid synthesis and AMPK inhibits this pathway through phosphorylation of acetyl-CoA carboxylase (ACC). It is currently unknown whether targeting the AMPK-ACC-lipogenic pathway using salicylate and/or metformin may be effective for inhibiting cancer cell survival. Salicylate suppresses clonogenic survival of prostate and lung cancer cells at therapeutic concentrations achievable following the ingestion of aspirin (<1.0 mM); effects not observed in prostate (PNT1A) and lung (MRC-5) epithelial cell lines. Salicylate concentrations of 1 mM increased the phosphorylation of ACC and suppressed de novo lipogenesis and these effects were enhanced with the addition of clinical concentrations of metformin (100 μM) and eliminated in mouse embryonic fibroblasts (MEFs) deficient in AMPK β1. Supplementation of media with fatty acids and/or cholesterol reverses the suppressive effects of salicylate and metformin on cell survival indicating the inhibition of de novo lipogenesis is probably important. Pre-clinical studies evaluating the use of salicylate based drugs alone and in combination with metformin to inhibit de novo lipogenesis and the survival of prostate and lung cancers are warranted. PMID:25940306

  2. A DRAMATICALLY REDUCED SIZE IN THE GANTRY DESIGN FOR THE PROTON-CARBON THERAPY.

    SciTech Connect

    TRBOJEVIC, D.; GUPTA, R.; PARKER, B.; KEIL, E.; SESSLER, A.M.

    2006-06-23

    Gantries in the proton/carbon cancer therapy machines represent the major cost and are of the largest size. This report explains a new way to the gantry design. The size and cost of the gantries are reduced and their use is simplified by using the fixed magnetic field. The ''new'' gantry is made of a very large momentum acceptance non-scaling Fixed Field Alternating Gradient (FFAG) quarter and half arc beam lines. The gantry is made of combined function magnets with a very strong focusing and small dispersion function. Additional magnets with a fast response are required to allow adjustments of the beam position for different energies at the beginning of the gantry. Additional strong focusing magnets following the gantry have also to be adjustable to provide required spot size and radial scanning above the patients. The fixed field combined function magnets could be made of small permanent magnets for the proton machine, or of the high temperature superconductors or superconductors for the carbon machine, reducing dramatically the size.

  3. Do calorie-controlled portion sizes of snacks reduce energy intake?

    PubMed

    Stroebele, Nanette; Ogden, Lorraine G; Hill, James O

    2009-06-01

    In a cross-over study, participants (n=59) were randomly assigned to receive either 100 kcal packs or standard size packages of snacks for 1 week. After a minimum of a 1-week washout period, participants received the other form of the snack for 1 week. Snack consumption was recorded by participants in a diary. Participants consumed an average of 186.9 fewer grams of snacks per week when receiving 100 kcal snack packs compared to standard size packages of snacks. Post hoc comparisons revealed the effect of package size depended on both randomization order and study week. Total grams of snacks consumed in week 1 differed significantly between the two randomized groups. In week 2, however, grams of snacks did not differ significantly between the two groups. This interaction was primarily due to a significantly lower consumption of snacks from standard size packages in the week following the portion-controlled packages. The results suggest that portion-controlled packaging reduce total intake from the provided snacks. Further, initial exposure to portion-controlled packages might have increased awareness of portion size such that less was consumed when larger packages were available. PMID:19501784

  4. Configuring the Mesh Size, Side Taper and Wing Depth of Penaeid Trawls to Reduce Environmental Impacts

    PubMed Central

    Broadhurst, Matt K.; Sterling, David J.; Millar, Russell B.

    2014-01-01

    The effects of reducing mesh size while concomitantly varying the side taper and wing depth of a generic penaeid-trawl body were investigated to improve engineering performance and minimize bycatch. Five trawl bodies (with the same codends) were tested across various environmental (e.g. depth and current) and biological (e.g. species and sizes) conditions. The first trawl body comprised 41-mm mesh and represented conventional designs (termed the ‘41 long deep-wing'), while the remaining trawl bodies were made from 32-mm mesh and differed only in their side tapers, and therefore length (i.e. 1N3B or ‘long’ and ∼28o to the tow direction vs 1N5B or ‘short’ and ∼35o) and wing depths (‘deep’–97 T vs ‘shallow’–60 T). There were incremental drag reductions (and therefore fuel savings – by up to 18 and 12% per h and ha trawled) associated with reducing twine area via either modification, and subsequently minimizing otter-board area in attempts to standardize spread. Side taper and wing depth had interactive and varied effects on species selectivity, but compared to the conventional 41 long deep-wing trawl, the 32 short shallow-wing trawl (i.e. the least twine area) reduced the total bycatch by 57% (attributed to more fish swimming forward and escaping). In most cases, all small-meshed trawls also caught more smaller school prawns Metapenaeus macleayi but to decrease this effect it should be possible to increase mesh size slightly, while still maintaining the above engineering benefits and species selectivity. The results support precisely optimizing mesh size as a precursor to any other anterior penaeid-trawl modifications designed to improve environmental performance. PMID:24911786

  5. Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity

    PubMed Central

    Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Dhar, Deepanshi; Panigrahi, Gati K.; Hussain, Anowar; Agarwal, Chapla; El-Elimat, Tamam; Sica, Vincent P.; Oberlies, Nicholas H.; Agarwal, Rajesh

    2016-01-01

    Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1–5 μg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47phox). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity. PMID:26979487

  6. Use of selenium-silymarin mix reduces lower urinary tract symptoms and prostate specific antigen in men.

    PubMed

    Vostalova, Jitka; Vidlar, Ales; Ulrichova, Jitka; Vrbkova, Jana; Simanek, Vilim; Student, Vladimir

    2013-12-15

    The aim of this double-blind, placebo controlled clinical trial was to assess the effects of a combination of selenium and silymarin in men with lower urinary tract symptoms, benign prostatic hyperplasia and a prostate specific antigen (PSA) ≤2.5ng/ml. The volunteers were randomized to two groups: the first one (n=26) received 240μg selenium (in the form of yeast l-selenomethionine) plus 570mg silymarin daily for 6 months and the second (n=29) received placebo. Outcome measures were changes in the International Prostate Symptom Score (IPSS), bladder volume (V), urinary flow rate, ultrasound estimated postvoid residual urine volume (RV), serum PSA, testosterone and selenium levels, safety clinical biochemistry, hematology and oxidative stress parameters at baseline and on day 180. The results showed statistically significant differences (p<0.05) between treatment and control groups for the following parameters: IPSS score, urodynamic parameters: maximal rate of urine flow (Qmax), average flow (Qave), V and RV, total PSA value and serum selenium levels. There was a significant reduction in PSA in the selenium-silymarin group but no effect on blood testosterone level. Overall the treatment was well-tolerated with no adverse effects.

  7. Cerebral complexity preceded enlarged brain size and reduced olfactory bulbs in Old World monkeys

    PubMed Central

    Gonzales, Lauren A.; Benefit, Brenda R.; McCrossin, Monte L.; Spoor, Fred

    2015-01-01

    Analysis of the only complete early cercopithecoid (Old World monkey) endocast currently known, that of 15-million-year (Myr)-old Victoriapithecus, reveals an unexpectedly small endocranial volume (ECV) relative to body size and a large olfactory bulb volume relative to ECV, similar to extant lemurs and Oligocene anthropoids. However, the Victoriapithecus brain has principal and arcuate sulci of the frontal lobe not seen in the stem catarrhine Aegyptopithecus, as well as a distinctive cercopithecoid pattern of gyrification, indicating that cerebral complexity preceded encephalization in cercopithecoids. Since larger ECVs, expanded frontal lobes, and reduced olfactory bulbs are already present in the 17- to 18-Myr-old ape Proconsul these features evolved independently in hominoids (apes) and cercopithecoids and much earlier in the former. Moreover, the order of encephalization and brain reorganization was apparently different in hominoids and cercopithecoids, showing that brain size and cerebral organization evolve independently. PMID:26138795

  8. Anisotropic remastering for reducing feature sizes on UV nanoimprint lithography replica molds.

    PubMed

    Lausecker, E; Grydlik, M; Brehm, M; Bergmair, I; Mühlberger, M; Fromherz, T; Bauer, G

    2012-04-27

    We present an approach that uses existing nanoimprint molds and reduces the size of the resulting features significantly via a remastering process utilizing the anisotropic etchant tetramethylammonium hydroxide and a mold casting step. Inverted pyramidal structures and V-grooves were imprinted using these 2.5-dimensional (2.5D) replica molds. Pattern transfer into silicon (Si) substrates was established with an intermediate silicon nitride (SiN(x)) layer that can be etched with a much larger selectivity against the imprint resist than the Si substrate. The 2.5D resist profiles are thus transferred back into binary structures in the SiN(x) layer and subsequently into the Si substrate. A substantial size reduction of the diameter of pits from 91 to 33 nm and the width of lines from 600 to 142 nm was achieved.

  9. 10Be measurements at MALT using reduced-size samples of bulk sediments

    NASA Astrophysics Data System (ADS)

    Horiuchi, Kazuho; Oniyanagi, Itsumi; Wasada, Hiroshi; Matsuzaki, Hiroyuki

    2013-01-01

    In order to establish 10Be measurements on reduced-size (1-10 mg) samples of bulk sediments, we investigated four different pretreatment designs using lacustrine and marginal-sea sediments and the AMS system of the Micro Analysis Laboratory, Tandem accelerator (MALT) at The University of Tokyo. The 10Be concentrations obtained from the samples of 1-10 mg agreed within a precision of 3-5% with the values previously determined using corresponding ordinary-size (∼200 mg) samples and the same AMS system. This fact demonstrates reliable determinations of 10Be with milligram levels of recent bulk sediments at MALT. On the other hand, a clear decline of the BeO- beam with tens of micrograms of 9Be carrier suggests that the combination of ten milligrams of sediments and a few hundred micrograms of the 9Be carrier is more convenient at this stage.

  10. Anisotropic remastering for reducing feature sizes on UV nanoimprint lithography replica molds

    NASA Astrophysics Data System (ADS)

    Lausecker, E.; Grydlik, M.; Brehm, M.; Bergmair, I.; Mühlberger, M.; Fromherz, T.; Bauer, G.

    2012-04-01

    We present an approach that uses existing nanoimprint molds and reduces the size of the resulting features significantly via a remastering process utilizing the anisotropic etchant tetramethylammonium hydroxide and a mold casting step. Inverted pyramidal structures and V-grooves were imprinted using these 2.5-dimensional (2.5D) replica molds. Pattern transfer into silicon (Si) substrates was established with an intermediate silicon nitride (SiNx) layer that can be etched with a much larger selectivity against the imprint resist than the Si substrate. The 2.5D resist profiles are thus transferred back into binary structures in the SiNx layer and subsequently into the Si substrate. A substantial size reduction of the diameter of pits from 91 to 33 nm and the width of lines from 600 to 142 nm was achieved.

  11. ABA-deficiency results in reduced plant and fruit size in tomato.

    PubMed

    Nitsch, L; Kohlen, W; Oplaat, C; Charnikhova, T; Cristescu, S; Michieli, P; Wolters-Arts, M; Bouwmeester, H; Mariani, C; Vriezen, W H; Rieu, I

    2012-06-15

    Abscisic acid (ABA) deficient mutants, such as notabilis and flacca, have helped elucidating the role of ABA during plant development and stress responses in tomato (Solanum lycopersicum L.). However, these mutants have only moderately decreased ABA levels. Here we report on plant and fruit development in the more strongly ABA-deficient notabilis/flacca (not/flc) double mutant. We observed that plant growth, leaf-surface area, drought-induced wilting and ABA-related gene expression in the different genotypes were strongly correlated with the ABA levels and thus most strongly affected in the not/flc double mutants. These mutants also had reduced fruit size that was caused by an overall smaller cell size. Lower ABA levels in fruits did not correlate with changes in auxin levels, but were accompanied by higher ethylene evolution rates. This suggests that in a wild-type background ABA stimulates cell enlargement during tomato fruit growth via a negative effect on ethylene synthesis.

  12. Free radical scavenger, edaravone, reduces the lesion size of lacunar infarction in human brain ischemic stroke

    PubMed Central

    2011-01-01

    Background Although free radicals have been reported to play a role in the expansion of ischemic brain lesions, the effect of free radical scavengers is still under debate. In this study, the temporal profile of ischemic stroke lesion sizes was assessed for more than one year to evaluate the effect of edaravone which might reduce ischemic damage. Methods We sequentially enrolled acute ischemic stroke patients, who admitted between April 2003 and March 2004, into the edaravone(-) group (n = 83) and, who admitted between April 2004 and March 2005, into the edaravone(+) group (n = 93). Because, edaravone has been used as the standard treatment after April 2004 in our hospital. To assess the temporal profile of the stroke lesion size, the ratio of the area [T2-weighted magnetic resonance images (T2WI)/iffusion-weighted magnetic resonance images (DWI)] were calculated. Observations on T2WI were continued beyond one year, and observational times were classified into subacute (1-2 months after the onset), early chronic (3-6 month), late chronic (7-12 months) and old (≥13 months) stages. Neurological deficits were assessed by the National Institutes of Health Stroke Scale upon admission and at discharge and by the modified Rankin Scale at 1 year following stroke onset. Results Stroke lesion size was significantly attenuated in the edaravone(+) group compared with the edaravone(-) group in the period of early and late chronic observational stages. However, this reduction in lesion size was significant within a year and only for the small-vessel occlusion stroke patients treated with edaravone. Moreover, patients with small-vessel occlusion strokes that were treated with edaravone showed significant neurological improvement during their hospital stay, although there were no significant differences in outcome one year after the stroke. Conclusion Edaravone treatment reduced the volume of the infarct and improved neurological deficits during the subacute period, especially

  13. The Role of Social Norms in the Portion Size Effect: Reducing Normative Relevance Reduces the Effect of Portion Size on Consumption Decisions

    PubMed Central

    Versluis, Iris; Papies, Esther K.

    2016-01-01

    People typically eat more from large portions of food than from small portions. An explanation that has often been given for this so-called portion size effect is that the portion size acts as a social norm and as such communicates how much is appropriate to eat. In this paper, we tested this explanation by examining whether manipulating the relevance of the portion size as a social norm changes the portion size effect, as assessed by prospective consumption decisions. We conducted one pilot experiment and one full experiment in which participants respectively indicated how much they would eat or serve themselves from a given amount of different foods. In the pilot (N = 63), we manipulated normative relevance by allegedly basing the portion size on the behavior of either students of the own university (in-group) or of another university (out-group). In the main experiment (N = 321), we told participants that either a minority or majority of people similar to them approved of the portion size. Results show that in both experiments, participants expected to serve themselves and to eat more from larger than from smaller portions. As expected, however, the portion size effect was less pronounced when the reference portions were allegedly based on the behavior of an out-group (pilot) or approved only by a minority (main experiment). These findings suggest that the portion size indeed provides normative information, because participants were less influenced by it if it communicated the behaviors or values of a less relevant social group. In addition, in the main experiment, the relation between portion size and the expected amount served was partially mediated by the amount that was considered appropriate, suggesting that concerns about eating an appropriate amount indeed play a role in the portion size effect. However, since the portion size effect was weakened but not eliminated by the normative relevance manipulations and since mediation was only partial, other

  14. Radiation damage in protein crystals is reduced with a micron-sized X-ray beam

    PubMed Central

    Sanishvili, Ruslan; Yoder, Derek W.; Pothineni, Sudhir Babu; Rosenbaum, Gerd; Xu, Shenglan; Vogt, Stefan; Stepanov, Sergey; Makarov, Oleg A.; Corcoran, Stephen; Benn, Richard; Nagarajan, Venugopalan; Smith, Janet L.; Fischetti, Robert F.

    2011-01-01

    Radiation damage is a major limitation in crystallography of biological macromolecules, even for cryocooled samples, and is particularly acute in microdiffraction. For the X-ray energies most commonly used for protein crystallography at synchrotron sources, photoelectrons are the predominant source of radiation damage. If the beam size is small relative to the photoelectron path length, then the photoelectron may escape the beam footprint, resulting in less damage in the illuminated volume. Thus, it may be possible to exploit this phenomenon to reduce radiation-induced damage during data measurement for techniques such as diffraction, spectroscopy, and imaging that use X-rays to probe both crystalline and noncrystalline biological samples. In a systematic and direct experimental demonstration of reduced radiation damage in protein crystals with small beams, damage was measured as a function of micron-sized X-ray beams of decreasing dimensions. The damage rate normalized for dose was reduced by a factor of three from the largest (15.6 μm) to the smallest (0.84 μm) X-ray beam used. Radiation-induced damage to protein crystals was also mapped parallel and perpendicular to the polarization direction of an incident 1-μm X-ray beam. Damage was greatest at the beam center and decreased monotonically to zero at a distance of about 4 μm, establishing the range of photoelectrons. The observed damage is less anisotropic than photoelectron emission probability, consistent with photoelectron trajectory simulations. These experimental results provide the basis for data collection protocols to mitigate with micron-sized X-ray beams the effects of radiation damage. PMID:21444772

  15. Irradiation testing of full-sized, reduced-enrichment fuel elements

    SciTech Connect

    Snelgrove, J.L.; Copeland, G.L.

    1983-01-01

    The current status of the irradiation testing of full-sized, reduced-enrichment fuel elements and fuel rods under the US Reduced Enrichment Research and Test Reactor Program is reported. Being tested are UAl/sub x/-Al, U/sub 3/O/sub 8/-Al, U/sub 3/Si/sub 2/-Al, and U/sub 3/Si-Al dispersion fuels and UZrH/sub x/ (TRIGA) fuel at uranium densities in the fuel meat ranging from 1.7 to 6.0 Mg/m/sup 3/. Generally good performance has been experienced to date. Some preliminary results of postirradiation examinations are also included. A whole-core demonstration in the Oak Ridge Research Reactor is planned. Some details of this demonstration are provided.

  16. Is there a single spot size and grid for intensity modulated proton therapy? Simulation of head and neck, prostate and mesothelioma cases

    SciTech Connect

    Widesott, Lamberto; Lomax, Antony J.; Schwarz, Marco

    2012-03-15

    Purpose: To assess the quality of dose distributions in real clinical cases for different dimensions of scanned proton pencil beams. The distance between spots (i.e., the grid of delivery) is optimized for each dimension of the pencil beam. Methods: The authors vary the {sigma} of the initial Gaussian size of the spot, from {sigma}{sub x} = {sigma}{sub y} = 3 mm to {sigma}{sub x} = {sigma}{sub y} = 8 mm, to evaluate the impact of the proton beam size on the quality of intensity modulated proton therapy (IMPT) plans. The distance between spots, {Delta}x and {Delta}y, is optimized on the spot plane, ranging from 4 to 12 mm (i.e., each spot size is coupled with the best spot grid resolution). In our Hyperion treatment planning system (TPS), constrained optimization is applied with respect to the organs at risk (OARs), i.e., the optimization tries to satisfy the dose objectives in the planning target volume (PTV) as long as all planning objectives for the OARs are met. Three-field plans for a nasopharynx case, two-field plans for a prostate case, and two-field plans for a malignant pleural mesothelioma case are considered in our analysis. Results: For the head and neck tumor, the best grids (i.e., distance between spots) are 5, 4, 6, 6, and 8 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. {sigma} {<=} 5 mm is required for tumor volumes with low dose and {sigma}{<=} 4 mm for tumor volumes with high dose. For the prostate patient, the best grid is 4, 4, 5, 5, and 5 mm for {sigma} = 3, 4, 5, 6, and 8 mm, respectively. Beams with {sigma} > 3 mm did not satisfy our first clinical requirement that 95% of the prescribed dose is delivered to more than 95% of prostate and proximal seminal vesicles PTV. Our second clinical requirement, to cover the distal seminal vesicles PTV, is satisfied for beams as wide as {sigma} = 6 mm. For the mesothelioma case, the low dose PTV prescription is well respected for all values of {sigma}, while there is loss of high dose PTV coverage

  17. Charge reduced electrospray size spectrometry of mega- and gigadalton complexes: whole viruses and virus fragments.

    PubMed

    Hogan, Christopher J; Kettleson, Eric M; Ramaswami, Bala; Chen, Da-Ren; Biswas, Pratim

    2006-02-01

    The ability to analyze and identify large macromolecular complexes whose molecular weight is beyond the analyzable range of mass spectrometry is of great interest. The size of such complexes makes them suitable for analysis via mobility size spectrometry. In this work, charge reduced electrospray size spectrometry was used for the analysis of bacteriophage viruses with total molecular masses ranging from 3.6 MDa up to the gigadalton range. The electrospray source used was operated in "cone jet" mode with a mean droplet diameter of 170.56 nm. Bacteriophage MS2 was found to have a mobility diameter of 24.13 +/- 0.06 nm and remain highly viable after the electrospray process. Larger bacteriophages T2 and T4 have lengths greater than the diameter of the electrospray jet and droplets; thus, they could not be completely enclosed and were found to fragment at the virus capsid head-tail noncovalent interface during either the jet formation or jet breakup process. No viable T2 or T4 virions were detectable after being electrosprayed. While the exact mechanism of fragmentation could not be determined, it is proposed here that macromolecular fragmentation at noncovalent interfaces occurs due to mechanically and electrically induced stresses during jet formation and jet breakup. Bacteriophage T4 capsid heads were found to be statistically significantly larger than bacteriophage T2 capsid heads, with a mean peak diameter of 88.32 +/- 1.02 nm for T4 and 87.03 +/- 0.18 nm for T2. While capsid head fragments were detectable, tail and tail-fiber fragments could not be detected by size spectrometric analysis. This is attributed to the fact that the contractile tails of bacteriophage T2 and T4 virions mechanically deform to a varying degree while confined within the smaller jet and droplets. Further evidence of contractile tail deformation during the electrospray process was found by measuring the size spectrum of bacteriophage lambda, which has a noncontractile tail. Bacteriophage

  18. Walnuts lower TRAMP prostate tumor growth by altering IGF-1, energy and cholesterol metabolism and is not due to their fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary changes could potentially reduce prostate cancer morbidity and mortality. Prostate tumor size, gene expression, metabolite and plasma responses to a 100 g of fat/kg diet (whole walnuts, walnut oil and other oils; balanced for macronutrients, tocopherols (a-and ' ) for 18 weeks were assessed ...

  19. Public School Education: The Case for Reduced Class Size. Why the Present Class Size is Not Working and What Can We Do about It?

    ERIC Educational Resources Information Center

    Graham, Evol

    2009-01-01

    By reducing class size we will close the achievement gap in public school education, caused by prior neglect especially since the civil rights era of the sixties. Additional, highly qualified and specialized teachers will more effectively manage a smaller class size and serve more individual student needs in the crucial early grades, where a solid…

  20. Eplerenone reduced lesion size in early but not advanced atherosclerosis in apolipoprotein E-deficient mice.

    PubMed

    Raz-Pasteur, Ayelet; Gamliel-Lazarovich, Aviva; Coleman, Raymond; Keidar, Shlomo

    2012-12-01

    The beneficial effects of eplerenone, a specific mineralocorticoid receptor blocker, were previously demonstrated in early atherosclerosis (ATS). The aim of the present study was to evaluate the effect of eplerenone in advanced versus early ATS. Apolipoprotein E knockout mice aged 16 or 32 weeks were randomly divided into eplerenone (100 mg·kg·d) or vehicle treatment for 14 weeks. Eplerenone reduced atherosclerotic lesion size by 51% only in early ATS. In peritoneal macrophages obtained from these mice, eplerenone reduced messenger RNA expression of pro-inflammatory markers, interleukin 6, tumor necrosis factor α, monocyte chemotactic protein 1, and increased anti-inflammatory marker arginase 1 to a greater extent in early compared with advanced ATS. These changes correspond to macrophage polarization toward alternative inflammatory phenotype. Messenger RNA expression of the mineralocorticoid receptor and aldosterone synthase were also reduced by eplerenone to a greater extent in early ATS, and these might increase the sensitivity of macrophages to mineralocorticoid blockade in early ATS. The results of the present study point to the benefits of early initiation of treatment with eplerenone in reducing experimental ATS.

  1. A Randomized Controlled Trial for the Effectiveness of Progressive Muscle Relaxation and Guided Imagery as Anxiety Reducing Interventions in Breast and Prostate Cancer Patients Undergoing Chemotherapy

    PubMed Central

    Charalambous, Andreas; Giannakopoulou, Margarita; Bozas, Evangelos; Paikousis, Lefkios

    2015-01-01

    Objective. To test the effectiveness of guided imagery (GI) and progressive muscle relaxation (PMR) as stress reducing interventions in patients with prostate and breast cancer who undergo chemotherapy. Methods. Patients were randomly assigned to either the control group or the intervention group (PMR and GI). Patients were observed for a total duration of 3 weeks and assessed with the SAS and BECK-II questionnaires for anxiety and depression, respectively, in addiotion to two biological markers (saliva cortisol and saliva amylase) (trial registration number: NCT01275872). Results. 256 patients were registered and 236 were randomly assigned. In total 104 were randomised to the control group and 104 to the intervention group. Intervention's mean anxiety score and depression score changes were significantly different compared to the control's (b = −29.4, p < 0.001; b = −29.4, p < 0.001, resp.). Intervention group's cortisol levels before the intervention (0.30 ± 0.25) gradually decreased up to week 3 (0.16 ± 0.18), whilst the control group's cortisol levels before the intervention (0.21 ± 0.22) gradually increased up to week 3 (0.44 ± 0.35). The same interaction appears for the Amylase levels (p < 0.001). Conclusions. The findings showed that patients with prostate and breast cancer undergoing chemotherapy treatment can benefit from PMR and GI sessions to reduce their anxiety and depression. PMID:26347018

  2. Polyamine contents in current foods: a basis for polyamine reduced diet and a study of its long term observance and tolerance in prostate carcinoma patients.

    PubMed

    Cipolla, B G; Havouis, R; Moulinoux, J P

    2007-08-01

    Polyamine contents were assessed by mass spectrometry in 233 current foods and beverages. In order to reduce gut polyamine uptake, a polyamine reduced diet (PRD) and partial intermittent intestinal tract decontamination (PIITD) with neomycin or nifuroxazide was proposed as nutritional therapy to 33 prostate carcinoma patients, 30 of whom with hormone refractory prostate cancer (HRPC). Mean PRD observance was 22 +/- 19 (median: 16; range: 3-72) months. 10, 8 and 3 patients were respectively on PRD for more than 30, 36 and 64 months. No diet toxicity was observed. 8 patients had moderate intestinal intolerance due to PIITD which was interrupted. No significant differences in body weight, blood counts or serum protein levels were observed during the follow-up of patients under PRD. Performance status and pain scores were relatively stable during the trial with improved pain scores at 6 months. A PRD associated with intermittent PIITD is a safe and well observed nutritional regimen and long term observance is possible. PMID:17578651

  3. Luteinizing hormone (LH)-releasing hormone agonist reduces serum adrenal androgen levels in prostate cancer patients: implications for the effect of LH on the adrenal glands.

    PubMed

    Nishii, Masahiro; Nomura, Masashi; Sekine, Yoshitaka; Koike, Hidekazu; Matsui, Hiroshi; Shibata, Yasuhiro; Ito, Kazuto; Oyama, Tetsunari; Suzuki, Kazuhiro

    2012-01-01

    Recently, adrenal androgens have been targeted as key hormones for the development of castration-resistant prostate cancer therapeutics. Although circulating adrenal androgens originate mainly from the adrenal glands, the testes also supply about 10%. Although widely used in androgen deprivation medical castration therapy, the effect of luteinizing hormone-releasing hormone (LH-RH) agonist on adrenal androgens has not been fully studied. In this study, changes in testicular and adrenal androgen levels were measured and compared to adrenocorticotropic hormone levels. To assess the possible role of LH in the adrenal glands, immunohistochemical studies of the LH receptor in normal adrenal glands were performed. Forty-seven patients with localized or locally progressive prostate cancer were treated with LH-RH agonist with radiotherapy. Six months after initiation of treatment, testosterone, dihydrotestosterone, and estradiol levels were decreased by 90%-95%, and dehydroepiandrosterone-sulfate, dehydroepiandrosterone, and androstenedione levels were significantly decreased by 26%-40%. The suppressive effect of LH-RH agonist at 12 months was maintained. Adrenocorticotropic hormone levels showed an increasing trend at 6 months and a significant increase at 12 months. LH receptors were positively stained in the cortex cells of the reticular layer of the adrenal glands. The long-term LH-RH agonist treatment reduced adrenal-originated adrenal androgens. LH receptors in the adrenal cortex cells of the reticular layer might account for the underlying mechanism of reduced adrenal androgens.

  4. Insulin Resistance in Human iPS Cells Reduces Mitochondrial Size and Function

    PubMed Central

    Burkart, Alison M.; Tan, Kelly; Warren, Laura; Iovino, Salvatore; Hughes, Katelyn J.; Kahn, C. Ronald; Patti, Mary-Elizabeth

    2016-01-01

    Insulin resistance, a critical component of type 2 diabetes (T2D), precedes and predicts T2D onset. T2D is also associated with mitochondrial dysfunction. To define the cause-effect relationship between insulin resistance and mitochondrial dysfunction, we compared mitochondrial metabolism in induced pluripotent stem cells (iPSC) from 5 healthy individuals and 4 patients with genetic insulin resistance due to insulin receptor mutations. Insulin-resistant iPSC had increased mitochondrial number and decreased mitochondrial size. Mitochondrial oxidative function was impaired, with decreased citrate synthase activity and spare respiratory capacity. Simultaneously, expression of multiple glycolytic enzymes was decreased, while lactate production increased 80%. These perturbations were accompanied by an increase in ADP/ATP ratio and 3-fold increase in AMPK activity, indicating energetic stress. Insulin-resistant iPSC also showed reduced catalase activity and increased susceptibility to oxidative stress. Thus, insulin resistance can lead to mitochondrial dysfunction with reduced mitochondrial size, oxidative activity, and energy production. PMID:26948272

  5. The development of reduced size STR amplicons as tools for analysis of degraded DNA.

    PubMed

    Butler, John M; Shen, Yin; McCord, Bruce R

    2003-09-01

    New multiplex PCR sets of commonly used short tandem repeat (STR) markers have been developed to produce PCR products that are reduced in size when compared to standard commercial STR kits. The reduction in size of these amplicons can facilitate the examination and analysis of degraded DNA evidence by improving amplification efficiency. This "miniSTR" approach will permit current forensic practitioners to use STR markers and instrumentation already present in their laboratories and to generate genotyping data that is directly comparable to reference samples and searchable through the FBI's Combined DNA Index System (CODIS) databases. This paper discusses the development of these new primer sets and presents some initial results in the analysis of degraded and aged DNA samples. A method for removal of problematic fluorescent dye artifacts is also described. Comparison studies in over 100 samples have verified that these miniSTR primers can provide fully concordant results to commercial STR kits and can provide improved signal from degraded DNA specimens. These miniplex sets should prove valuable in the analysis of samples where allele dropout and reduced sensitivity of larger STR alleles occurs.

  6. REDUCED CHLOROPLAST COVERAGE genes from Arabidopsis thaliana help to establish the size of the chloroplast compartment

    PubMed Central

    Larkin, Robert M.; Stefano, Giovanni; Ruckle, Michael E.; Stavoe, Andrea K.; Sinkler, Christopher A.; Brandizzi, Federica; Malmstrom, Carolyn M.; Osteryoung, Katherine W.

    2016-01-01

    Eukaryotic cells require mechanisms to establish the proportion of cellular volume devoted to particular organelles. These mechanisms are poorly understood. From a screen for plastid-to-nucleus signaling mutants in Arabidopsis thaliana, we cloned a mutant allele of a gene that encodes a protein of unknown function that is homologous to two other Arabidopsis genes of unknown function and to FRIENDLY, which was previously shown to promote the normal distribution of mitochondria in Arabidopsis. In contrast to FRIENDLY, these three homologs of FRIENDLY are found only in photosynthetic organisms. Based on these data, we proposed that FRIENDLY expanded into a small gene family to help regulate the energy metabolism of cells that contain both mitochondria and chloroplasts. Indeed, we found that knocking out these genes caused a number of chloroplast phenotypes, including a reduction in the proportion of cellular volume devoted to chloroplasts to 50% of wild type. Thus, we refer to these genes as REDUCED CHLOROPLAST COVERAGE (REC). The size of the chloroplast compartment was reduced most in rec1 mutants. The REC1 protein accumulated in the cytosol and the nucleus. REC1 was excluded from the nucleus when plants were treated with amitrole, which inhibits cell expansion and chloroplast function. We conclude that REC1 is an extraplastidic protein that helps to establish the size of the chloroplast compartment, and that signals derived from cell expansion or chloroplasts may regulate REC1. PMID:26862170

  7. High-Dose Conformal Radiotherapy Reduces Prostate Cancer-Specific Mortality: Results of a Meta-analysis

    SciTech Connect

    Viani, Gustavo Arruda; Godoi Bernardes da Silva, Lucas; Stefano, Eduardo Jose

    2012-08-01

    Purpose: To determine in a meta-analysis whether prostate cancer-specific mortality (PCSM), biochemical or clinical failure (BCF), and overall mortality (OM) in men with localized prostate cancer treated with conformal high-dose radiotherapy (HDRT) are better than those in men treated with conventional-dose radiotherapy (CDRT). Methods and Materials: The MEDLINE, Embase, CANCERLIT, and Cochrane Library databases, as well as the proceedings of annual meetings, were systematically searched to identify randomized, controlled studies comparing conformal HDRT with CDRT for localized prostate cancer. Results: Five randomized, controlled trials (2508 patients) that met the study criteria were identified. Pooled results from these randomized, controlled trials showed a significant reduction in the incidence of PCSM and BCF rates at 5 years in patients treated with HDRT (p = 0.04 and p < 0.0001, respectively), with an absolute risk reduction (ARR) of PCSM and BCF at 5 years of 1.7% and 12.6%, respectively. Two trials evaluated PCSM with 10 years of follow up. The pooled results from these trials showed a statistical benefit for HDRT in terms of PCSM (p = 0.03). In the subgroup analysis, trials that used androgen deprivation therapy (ADT) showed an ARR for BCF of 12.9% (number needed to treat = 7.7, p < 0.00001), whereas trials without ADT had an ARR of 13.6% (number needed to treat = 7, p < 0.00001). There was no difference in the OM rate at 5 and 10 years (p = 0.99 and p = 0.11, respectively) between the groups receiving HDRT and CDRT. Conclusions: This meta-analysis is the first study to show that HDRT is superior to CDRT in preventing disease progression and prostate cancer-specific death in trials that used conformational technique to increase the total dose. Despite the limitations of our study in evaluating the role of ADT and HDRT, our data show no benefit for HDRT arms in terms of BCF in trials with or without ADT.

  8. Eco-evolutionary dynamics: fluctuations in population growth rate reduce effective population size in chinook salmon.

    PubMed

    Waples, Robin S; Jensen, David W; McClure, Michelle

    2010-03-01

    We empirically assess the relationship between population growth rate (lambda, a parameter central to ecology) and effective population size (N(e), a key parameter in evolutionary biology). Recent theoretical and numerical studies indicate that in semelparous species with variable age at maturity (such as Pacific salmon, many monocarpic plants, and various other species), differences in mean reproductive success among individuals reproducing in different years leads to variation in lambda, and this in turn can reduce N(e). However, this phenomenon has received little empirical evaluation. We examined time series of abundance data for 56 populations of chinook salmon (Onchorhynchus tshawytscha) from the northwestern United States and compared N(e) (calculated from demographic data) with the total number of spawners each generation (NT). Important results include: (1) The mean multigenerational ratio N(e)/N(T) was 0.64 (median = 0.67), indicating that annual variation in lambda reduces effective population size in chinook salmon by an average of approximately 35%. These reductions are independent of, and in addition to, factors that reduce N(e) within individual cohorts (uneven sex ratio and greater-than-random variance in reproductive success). (2) The coefficient of variation of lambda was the most important factor associated with reductions in N(e), explaining up to two-thirds of the variance in N(e)/N(T). (3) Within individual generations, N(e) was lower when there was a negative correlation between annual N(i) and lambda, i.e., when relatively few breeders produced relatively high numbers of offspring. Our results thus highlight an important and little-studied eco-evolutionary trade-off: density-dependent compensation has generally favorable ecological consequences (promoting stability and long-term viability) but incurs an evolutionary cost (reducing N(e) because a few individuals make a disproportionate genetic contribution). (4) For chinook salmon, N(eH) (an

  9. CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice.

    PubMed

    Wolf, Risa M; Lei, Xia; Yang, Zhi-Chun; Nyandjo, Maeva; Tan, Stefanie Y; Wong, G William

    2016-03-01

    C1q/TNF-related protein 3 (CTRP3) is a secreted metabolic regulator whose circulating levels are reduced in human and rodent models of obesity and diabetes. Previously, we showed that CTRP3 infusion lowers blood glucose by suppressing gluconeogenesis and that transgenic overexpression of CTRP3 protects mice against diet-induced hepatic steatosis. Here, we used a genetic loss-of-function mouse model to further address whether CTRP3 is indeed required for metabolic homeostasis under normal and obese states. Both male and female mice lacking CTRP3 had similar weight gain when fed a control low-fat (LFD) or high-fat diet (HFD). Regardless of diet, no differences were observed in adiposity, food intake, metabolic rate, energy expenditure, or physical activity levels between wild-type (WT) and Ctrp3-knockout (KO) animals of either sex. Contrary to expectations, loss of CTRP3 in LFD- or HFD-fed male and female mice also had minimal or no impact on whole body glucose metabolism, insulin sensitivity, and fasting-induced hepatic gluconeogenesis. Unexpectedly, the liver sizes of HFD-fed Ctrp3-KO male mice were markedly reduced despite a modest increase in triglyceride content. Furthermore, liver expression of fat oxidation genes was upregulated in the Ctrp3-KO mice. Whereas the liver and adipose expression of profibrotic TGFβ1, as well as its serum levels, was suppressed in HFD-fed KO mice, circulating proinflammatory IL-6 levels were markedly increased; these changes, however, were insufficient to affect systemic metabolic outcome. We conclude that, although it is dispensable for physiological control of energy balance, CTRP3 plays a previously unsuspected role in modulating liver size and circulating cytokine levels in response to obesity. PMID:26670485

  10. Is more better? Higher sterilization of infected hosts need not result in reduced pest population size.

    PubMed

    Maxin, Daniel; Berec, Luděk; Bingham, Adrienna; Molitor, Denali; Pattyson, Julie

    2015-05-01

    We analyze the effect of sterilization in the infected hosts in several epidemiological models involving infectious diseases that can be transmitted both vertically and horizontally. Sterilizing pathogens can be used as pest control agents by intentionally inoculating the target population, with the goal of reducing or eliminating it completely. Contrary to previous models that did not include vertical transmission we found that the population size at the endemic equilibrium may actually increase with higher levels of sterility. This effect is proved to exist for low to high efficiencies of vertical transmission. On the other hand, if the disease is sexually transmitted and the host reproduction and disease transmission are both consistently mediated by mating, we do not observe such a counter-intuitive effect and the population size in the stable endemic equilibrium is decreasing with higher levels of sterility. We suggest that models of the pest control techniques involving the release of sterilizing pathogens have to carefully consider the routes such pathogens use for transmission.

  11. Incorporating gold into nanocrystalline silver dressings reduces grain boundary size and maintains suitable antimicrobial properties.

    PubMed

    Unrau, Kevin R; Cavanagh, Marion H; Cheng, On Kwan; Wang, Shiman; Burrell, Robert E

    2013-12-01

    Nanocrystalline silver dressings are widely known to be potent antimicrobial and anti-inflammatory agents and have long been used to treat topical wounds. Gold is known to be a strong anti-inflammatory agent and has been used in the treatment of rheumatoid arthritis for >70 years. The purpose of this work was to study the effect of incorporating gold into nanocrystalline silver dressings from antimicrobial and anti-inflammatory perspectives. Gold and silver dressing alloys were created by direct current magnetron sputtering and compared with pure silver nanocrystalline dressings using conventional biological (log reduction and corrected zone of inhibition) and physical (X-ray diffraction, X-ray photoelectron spectroscopy, energy-dispersive X-ray spectroscopy, atomic absorption spectroscopy, atomic force microscopy and scanning electron microscopy) characterisation techniques. While the gold/silver dressings were slightly weaker antimicrobials than the pure silver nanocrystalline structures, the addition of gold to the nanostructure reduces the minimum crystallite size from 17 to 4 nm. This difference increases the number of grain boundary atoms from 12% to 40% which could augment the anti-inflammatory properties of the dressings. The formation of gold oxide (Au2O3) was thought to be responsible for the observed decrease in crystallite size.

  12. Xenoendocrine pollutants may reduce size of sexual organs in East Greenland polar bears (Ursus maritimus).

    PubMed

    Sonne, Christian; Leifsson, Pall S; Dietz, Rune; Born, Erik W; Letcher, Robert J; Hyldstrup, Lars; Riget, Frank F; Kirkegaard, Maja; Muir, Derek C G

    2006-09-15

    Reproductive organs from 55 male and 44 female East Greenland polar bears were examined to investigate the potential negative impact from organohalogen pollutants (OHCs). Multiple regressions normalizing for age showed a significant inverse relationship between OHCs and testis length and baculum length and weight, respectively, and was found in both subadults (dichlorodiphenyl trichloroethanes, dieldrin, chlordanes, hexacyclohexanes, polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs)) and adults (hexachlorobenzene [HCB]) (all p < 0.05). Baculum bone mineral densities decreased with increasing chlordanes, DDTs, and HCB in subadults and adults, respectively (all p < 0.05). In females, a significant inverse relationship was found between ovary length and sigma PCB (p = 0.03) and sigma CHL (p < 0.01), respectively, and between ovary weight and sigma PBDE (p < 0.01) and uterine horn length and HCB (p = 0.02). The study suggests thatthere is an impact from xenoendocrine pollutants on the size of East Greenland polar bear genitalia. This may pose a riskto this polar bear subpopulation in the future because of reduced sperm and egg quality/quantity and uterus and penis size/robustness.

  13. Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

    PubMed

    Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C

    2008-06-01

    The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level. PMID:18477205

  14. Antagonistic effect of Lepidium meyenii (red maca) on prostatic hyperplasia in adult mice.

    PubMed

    Gonzales, G F; Gasco, M; Malheiros-Pereira, A; Gonzales-Castañeda, C

    2008-06-01

    The plants from the Lepidium gender have demonstrated to have effect on the size of the prostate. Lepidium meyenii (Maca) is a Peruvian plant that grows exclusively over 4000 m above sea level. The present study was designed to determine the effect of red maca (RM) in the prostate hyperplasia induced with testosterone enanthate (TE) in adult mice. Prostate hyperplasia was induced by administering TE, and then these animals (n = 6, each group) were treated with RM or Finasteride (positive control) for 21 days. There was an additional group without prostate hyperplasia (vehicle). Mice were killed on days 7, 14 and 21 after treatment with RM. Testosterone and oestradiol levels were measured on the last day of treatment. Prostatic stroma, epithelium and acini were measured histologically. RM reduced prostate weight at 21 days of treatment. Weights of seminal vesicles, testis and epididymis were not affected by RM treatment. The reduction in prostate size by RM was 1.59 times. Histological analysis showed that TE increased 2-fold the acinar area, effect prevented in the groups receiving TE + RM for 14 (P < 0.05) and 21 (P < 0.05) days and the group receiving TE + Finasteride for 21 days (P < 0.05). TE increased prostatic stroma area and this effect was prevented by treatment with RM since 7 days of treatment or Finasteride. The reduction in prostatic stroma area by RM was 1.42 times. RM has an anti-hyperplastic effect on the prostate of adult mice when hyperplasia was induced with TE acting first at prostatic stromal level.

  15. Chemoprevention of prostate cancer.

    PubMed

    Vemana, Goutham; Hamilton, Robert J; Andriole, Gerald L; Freedland, Stephen J

    2014-01-01

    Large prospective randomized trials, such as the Prostate Cancer Prevention Trial (PCPT), Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, and Selenium and Vitamin E Cancer Prevention Trial (SELECT), have provided practitioners with considerable data regarding methods of treatment and prevention of prostate cancer. The best-studied medications for prevention are 5 alpha-reductase inhibitors. Their efficacy and side effects are well characterized. Other medications, dietary nutrients, and supplements have not been as well studied and generally do not demonstrate efficacy for disease prevention with an acceptable level of evidence. PMID:24188663

  16. Somatostatin analogue, octreotide, reduces increased glomerular filtration rate and kidney size in insulin-dependent diabetes

    SciTech Connect

    Serri, O.; Beauregard, H.; Brazeau, P.; Abribat, T.; Lambert, J.; Harris, A.; Vachon, L. Sandoz Canada Inc., Dorval, Quebec )

    1991-02-20

    To determine whether treatment with a somatostatin analogue can reduce kidney hyperfiltration and hypertrophy in insulin-dependent diabetes mellitus, the authors studied 11 patients with insulin-dependent diabetes mellitus and glomerular hyperfiltration. The patients were assigned randomly to receive continuous subcutaneous infusion of either octreotide, 300 {mu}g/24 h (five patients) or placebo (six patients) for 12 weeks. At baseline, mean glomerular filtration rate and mean total kidney volume were not significantly different in the two groups. However, after 12 weeks of treatment, the mean glomerular filtration rate was significantly lower in the octreotide group than in the placebo group. Furthermore, the mean total kidney volume was significantly lower after treatment in the octreotide group than in the placebo group. Glycemic control did not change significantly in either group. They conclude that subcutaneous infusion of octreotide for 12 weeks reduces increased glomerular filtration rate and kidney size in patients with insulin-dependent diabetes mellitus despite the fact that glycemic control remains unchanged.

  17. Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.

    PubMed

    García-Gallastegui, P; Luzuriaga, J; Aurrekoetxea, M; Baladrón, V; Ruiz-Hidalgo, M J; García-Ramírez, J J; Laborda, J; Unda, F; Ibarretxe, G

    2016-06-01

    DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance.

  18. Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms

    PubMed Central

    Fowke, Jay H.; Koyama, Tatsuki; Fadare, Oluwole; Clark, Peter E.

    2016-01-01

    The WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes. PMID:27336586

  19. Chemoprevention of prostate cancer.

    PubMed

    Rittmaster, Roger S

    2011-06-01

    Over the past two decades, many more men are diagnosed with prostate cancer then die of the disease. This increase in diagnosis has led to aggressive treatment of indolent disease in many individuals and has been the impetus for finding a means of reducing the risk of prostate cancer. In the past decade, there have been eight large trials of prostate cancer risk reduction using dietary supplements, 5α-reductase inhibitors, or anti-estrogens. The only two trials which have demonstrated efficacy are those involving 5α-reductase inhibitors: the PCPT (finasteride) and REDUCE (dutasteride). This review examines prostate cancer risk reduction, with emphasis on conclusions that can be drawn from these two landmark studies. PMID:21604953

  20. An Evaluation of a Community-Academic-Clinical Partnership to Reduce Prostate Cancer Disparities in the South

    PubMed Central

    Friedman, Daniela B.; Owens, Otis L.; Jackson, Dawnyea D.; Johnson, Kim M.; Gansauer, Lucy; Dickey, Joe; Miller, Ron; Payne, Johnny; Bearden, James D.; Hebert, James R.

    2013-01-01

    Background Engaging partners in the planning, implementation, and evaluation of cancer education programs is critical for improving the health of our communities. A two-year pilot education intervention on prostate cancer decision making and participation in medical research was funded by the National Cancer Institute. The partnership involving community members and clinical staff at a cancer center was used to develop recruitment strategies and plan for the implementation of the intervention with African-American (AA) middle-age and older men and female family members. We assessed partners’ perceptions of this community-academic-clinical research collaboration. Methods In year 2, eight project advisory council members were selected among existing partners and year 1 participants to serve as a formal committee. Council members were required to participate in telephone and in-person meetings and actively support recruitment/implementation efforts. At the conclusion of the project, 20 individuals (all clinical and community partners, including the eight advisory council members) were invited to complete a survey to assess their perceived impact of the collaboration on the community and provide suggestions for future collaborations. Results Most partners agreed that their organization benefitted from the collaboration and that various aspects of the advisory council process (e.g., both formal and informal communication) worked well. The most noted accomplishment of the partnership related to leveraging the collaboration to make men more knowledgeable about prostate cancer decision making. Suggested improvements for future collaborations included distributing more frequent updates regarding project successes. Conclusions Evaluating partners’ perceptions of this collaboration provided important recommendations for future planning, implementation, and evaluation of community-based cancer education programs. PMID:24078315

  1. Reduced Activity of Double-Strand Break Repair Genes in Prostate Cancer Patients With Late Normal Tissue Radiation Toxicity

    SciTech Connect

    Oorschot, Bregje van; Hovingh, Suzanne E.; Moerland, Perry D.; Medema, Jan Paul; Stalpers, Lukas J.A.; Vrieling, Harry; Franken, Nicolaas A.P.

    2014-03-01

    Purpose: To investigate clinical parameters and DNA damage response as possible risk factors for radiation toxicity in the setting of prostate cancer. Methods and Materials: Clinical parameters of 61 prostate cancer patients, 34 with (overresponding, OR) and 27 without (non-responding, NR) severe late radiation toxicity were assembled. In addition, for a matched subset the DNA damage repair kinetics (γ-H2AX assay) and expression profiles of DNA repair genes were determined in ex vivo irradiated lymphocytes. Results: Examination of clinical data indicated none of the considered clinical parameters to be correlated with the susceptibility of patients to develop late radiation toxicity. Although frequencies of γ-H2AX foci induced immediately after irradiation were similar (P=.32), significantly higher numbers of γ-H2AX foci were found 24 hours after irradiation in OR compared with NR patients (P=.03). Patient-specific γ-H2AX foci decay ratios were significantly higher in NR patients than in OR patients (P<.0001). Consequently, NR patients seem to repair DNA double-strand breaks (DSBs) more efficiently than OR patients. Moreover, gene expression analysis indicated several genes of the homologous recombination pathway to be stronger induced in NR compared with OR patients (P<.05). A similar trend was observed in genes of the nonhomologous end-joining repair pathway (P=.09). This is congruent with more proficient repair of DNA DSBs in patients without late radiation toxicity. Conclusions: Both gene expression profiling and DNA DSB repair kinetics data imply that less-efficient repair of radiation-induced DSBs may contribute to the development of late normal tissue damage. Induction levels of DSB repair genes (eg, RAD51) may potentially be used to assess the risk for late radiation toxicity.

  2. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance.

  3. [Prostate cancer].

    PubMed

    Morote, Joan; Maldonado, Xavier; Morales-Bárrera, Rafael

    2016-02-01

    The Vall d'Hebron multidisciplinary prostate cancer (PC) team reviews recent advances in the management of this neoplasm. Screening studies with long follow-up show a reduction in mortality, whereas active surveillance is emerging as a therapeutic approach of non-aggressive cancers. New markers increase the specificity of PSA and also allow targeting suspected aggressive cancers. Multiparametric magnetic resonance (mMRI) has emerged as the most effective method in the selection of patients for biopsy and also for local tumor staging. The paradigm of random prostatic biopsy is changing through the fusion techniques that allow guiding ultrasonography-driven biopsy of suspicious areas detected in mMRI. Radical prostatectomy (RP) and radiotherapy (RT) are curative treatments of localized PC and both have experienced significant technological improvements. RP is highly effective and the incorporation of robotic surgery is reducing morbidity. Modern RT allows the possibility of high tumor dose with minimal adjacent dose reducing its toxicity. Androgen deprivation therapy with LHRH analogues remains the treatment of choice for advanced PC, but should be limited to this indication. The loss of bone mass and adverse metabolic effects increases the frequency of fractures and cardiovascular morbimortality. After castration resistance in metastatic disease, new hormone-based drugs have demonstrated efficacy even after chemotherapy resistance. PMID:25727526

  4. Prostate Cancer

    MedlinePlus

    ... man's bladder that produces fluid for semen. Prostate cancer is common among older men. It is rare ... younger than 40. Risk factors for developing prostate cancer include being over 65 years of age, family ...

  5. Restaurant Owners’ Perspectives on a Voluntary Program to Recognize Restaurants for Offering Reduced-Size Portions, Los Angeles County, 2012

    PubMed Central

    Dunning, Lauren; Kuo, Tony; Simon, Paul; Fielding, Jonathan E.

    2014-01-01

    Introduction Reducing the portion size of food and beverages served at restaurants has emerged as a strategy for addressing the obesity epidemic; however, barriers and facilitators to achieving this goal are not well characterized. Methods In fall 2012, the Los Angeles County Department of Public Health conducted semistructured interviews with restaurant owners to better understand contextual factors that may impede or facilitate participation in a voluntary program to recognize restaurants for offering reduced-size portions. Results Interviews were completed with 18 restaurant owners (representing nearly 350 restaurants). Analyses of qualitative data revealed 6 themes related to portion size: 1) perceived customer demand is central to menu planning; 2) multiple portion sizes are already being offered for at least some food items; 3) numerous logistical barriers exist for offering reduced-size portions; 4) restaurant owners have concerns about potential revenue losses from offering reduced-size portions; 5) healthful eating is the responsibility of the customer; and 6) a few owners want to be socially responsible industry leaders. Conclusion A program to recognize restaurants for offering reduced-size portions may be a feasible approach in Los Angeles County. These findings may have applications for jurisdictions interested in engaging restaurants as partners in reducing the obesity epidemic. PMID:24650622

  6. Prostate cancer.

    PubMed

    Castillejos-Molina, Ricardo Alonso; Gabilondo-Navarro, Fernando Bernardo

    2016-04-01

    Prostate cancer is the most frequent tumor found in men worldwide and in Mexico in particular. Age and family history are the main risk factors. The diagnosis is made by prostate biopsy in patients with abnormalities detected in their prostate-specific antigen (PSA) levels or digital rectal exam (DRE). This article reviews screening and diagnostic methods as well as treatment options for patients diagnosed with prostate cancer. PMID:27557386

  7. Handling large datasets of hyperspectral images: reducing data size without loss of useful information.

    PubMed

    Ferrari, Carlotta; Foca, Giorgia; Ulrici, Alessandro

    2013-11-13

    Hyperspectral Imaging (HSI) is gaining increasing interest in the field of analytical chemistry, since this fast and non-destructive technique allows one to easily acquire a large amount of spectral and spatial information on a wide number of samples in very short times. However, the large size of hyperspectral image data often limits the possible uses of this technique, due to the difficulty of evaluating many samples altogether, for example when one needs to consider a representative number of samples for the implementation of on-line applications. In order to solve this problem, we propose a novel chemometric strategy aimed to significantly reduce the dataset size, which allows to analyze in a completely automated way from tens up to hundreds of hyperspectral images altogether, without losing neither spectral nor spatial information. The approach essentially consists in compressing each hyperspectral image into a signal, named hyperspectrogram, which is created by combining several quantities obtained by applying PCA to each single hyperspectral image. Hyperspectrograms can then be used as a compact set of descriptors and subjected to blind analysis techniques. Moreover, a further improvement of both data compression and calibration/classification performances can be achieved by applying proper variable selection methods to the hyperspectrograms. A visual evaluation of the correctness of the choices made by the algorithm can be obtained by representing the selected features back into the original image domain. Likewise, the interpretation of the chemical information underlying the selected regions of the hyperspectrograms related to the loadings is enabled by projecting them in the original spectral domain. Examples of applications of the hyperspectrogram-based approach to hyperspectral images of food samples in the NIR range (1000-1700 nm) and in the vis-NIR range (400-1000 nm), facing a calibration and a defect detection issue respectively, demonstrate the

  8. Using Ancillary Information to Reduce Sample Size in Discovery Sampling and the Effects of Measurement Error

    SciTech Connect

    Axelrod, M

    2005-08-18

    big sample size might bust the budget, or the number seems intuitively excessive. To reduce the sample size, you can increase the tolerable number of defectives, the ''10'' in the preceding example, or back off on the confidence level, say from 95% to 90%. Auditors also frequently bump up the sample size as a safety factor. They know that something can go wrong. For example, they might find out that the measurements or inspections were subject to errors. Unless the auditors know exactly how measurement error affects sample size, they might be forced to give up the safety factor. Clients often choose to ''live dangerously'' (without a compelling argument to the contrary) to save money. Thus, sometimes the auditor finds that ''you just can't get there from here'', because the goals of the audit and the resources available are inherently in conflict. For discovery audits, there is a way out of this apparent conundrum. It turns out that the classical method of confidence intervals uses an implicit and very conservative assumption. We will see that this assumption is too pessimistic and too conservative in the context of a discovery audit. If we abandon this assumption and use ancillary information about the inventory, then we can significantly reduce the sample size required to achieve the desired confidence level. We will see exactly how the classical method ignores this ancillary information and misses the opportunity for an efficient audit. In the following sections, we first review the standard approach using confidence intervals. Then we present a method that incorporates the ancillary information about the inventory to design a very efficient discovery audit. We also provide results on how measurement errors affect the audit, and how exactly how much the sample size must be modified to compensate for these errors. Finally, we state asymptotic formulas that provide useful approximations for large inventories. It is suggested that the reader review the glossary of

  9. Reduced salivary gland size and increased presence of epithelial progenitor cells in DLK1-deficient mice.

    PubMed

    García-Gallastegui, P; Luzuriaga, J; Aurrekoetxea, M; Baladrón, V; Ruiz-Hidalgo, M J; García-Ramírez, J J; Laborda, J; Unda, F; Ibarretxe, G

    2016-06-01

    DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis. Here, we have extended our studies of the salivary gland phenotype of Dlk1 knock-out mice. We have observed that salivary glands are smaller and weigh significantly less in both Dlk1 knock-out males and females compared with gender and age-matched wild-type mice and regardless of the natural sexual dimorphism in rodent salivary glands. This reduced size correlates with a reduced capacity of Dlk1-deficient mice to secrete saliva after stimulation with pilocarpine. However, histological and ultrastructural analyses of both adult and developing salivary gland tissues have revealed no defects in Dlk1 ((-/-)) mice, indicating that genetic compensation accounts for the relatively mild salivary phenotype in these animals. Finally, despite their lack of severe anomalies, we have found that salivary glands from Dlk1-deficient mice present a higher amount of CK14-positive epithelial progenitors at various developmental stages, suggesting a role for DLK1 in the regulation of salivary epithelial stem cell balance. PMID:26711912

  10. Epigenetic Upregulation of Endogenous VEGF-A Reduces Myocardial Infarct Size in Mice

    PubMed Central

    Musthafa, Haja; Laidinen, Svetlana; Dragneva, Galina; Laham-Karam, Nihay; Honkanen, Sanna; Paakinaho, Anne; Laakkonen, Johanna P.; Gao, Erhe; Vihinen-Ranta, Maija; Liimatainen, Timo; Ylä-Herttuala, Seppo

    2014-01-01

    “Epigenetherapy” alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model. shRNA complementary to the promoter of vascular endothelial growth factor (VEGF-A) was able to upregulate endogenous VEGF-A expression. Histological and multiphoton microscope analysis confirmed the therapeutic effect in the transduced hearts. Magnetic resonance imaging (MRI) showed in vivo that the infarct size was significantly reduced in the treatment group 14 days after the epigenetherapy. Importantly, we show that promoter-targeted shRNA upregulates all isoforms of endogenous VEGF-A and that an intact hairpin structure is required for the shRNA activity. In conclusion, regulation of gene expression at the promoter level is a promising new treatment strategy for myocardial infarction and also potentially useful for the upregulation of other endogenous genes. PMID:24587164

  11. From micro- to nanomagnetic dots: evolution of the eigenmode spectrum on reducing the lateral size

    NASA Astrophysics Data System (ADS)

    Carlotti, G.; Gubbiotti, G.; Madami, M.; Tacchi, S.; Hartmann, F.; Emmerling, M.; Kamp, M.; Worschech, L.

    2014-07-01

    Brillouin light scattering experiments and micromagnetic simulations have been exploited to investigate the spectrum of thermally excited magnetic eigenmodes in 10 nm-thick elliptical Permalloy dots, when the longer axis D is scaled down from about 1000 to 100 nm. It is shown that for D larger than about 200 nm the characteristics of the spin-wave eigenmodes are dominated by dipolar energy, while for D in the range of about 100 to 200 nm exchange energy effects cause qualitative and quantitative differences in the spin-wave spectrum. In this ‘mesoscopic’ regime, the usual classification scheme, involving one fundamental mode with large average magnetization and many other modes collected in families with specific symmetries, no longer holds. Rather, one finds the simultaneous presence of two modes with ‘fundamental’ character, i.e. with a significant and comparable value of the average dynamical magnetization: the former is at larger frequency and has its maximum amplitude at the dot's centre, while the latter occurs at lower frequency and is localized at the dot's edges. Interestingly, the maximum intensity swaps from the higher frequency mode to the lower frequency one, just when the dot size is reduced from about 200 to 100 nm. This is relevant in view of the exploitation of nanodots for the design of nanomagnetic devices with lateral dimensions in the above interval, such as memory cells, logic gates, reading heads and spin-torque oscillators.

  12. Pentoxifylline does not reduce infarct size in a canine model of acute myocardial infarction.

    PubMed Central

    Campbell, C. A.; Clavenna, C. F.; Wynne, J.; Kloner, R. A.

    1988-01-01

    1. The effect of the haemorrheological agent pentoxifylline was investigated in a canine model of acute myocardial infarction, induced by occlusion of the left anterior descending coronary for 6 h. Thirty minutes post-occlusion the dogs were randomized to receive either distilled water or pentoxifylline (0.3 mg kg-1 min-1 for 1 h followed by 0.15 mg kg-1 min-1 for 4.5 h) intravenously. 2. At 6 h post-occlusion the in vivo area at risk was determined with monastral blue dye and the area of necrosis was determined with triphenyltetrazolium chloride. The area at risk was 16.5 +/- 1.3% in the control group (n = 10) and 17.2 +/- 1.8% in the pentoxifylline treated group (n = 10; NS). The area of necrosis was 12.3 +/- 1.9% in the control group and 11.9 +/- 2.2% in the pentoxifylline treated group (NS). The area of necrosis expressed as a percentage of the area at risk was 69.3 +/- 7.7% in the control group and 63.6 +/- 7.4% in the pentoxifylline treated group (NS). 3. Pentoxifylline had no significant effects on heart rate, systolic or diastolic blood pressure. Regional myocardial blood flow, measured by the radioactive microsphere technique, was not significantly different between the groups. 4. Thus, pentoxifylline does not reduce infarct size in this model of acute myocardial infarction and does not enhance coronary collateral blood flow. PMID:3370389

  13. Design considerations for efficient prostate cancer chemoprevention trials.

    PubMed

    Lee, J J; Lieberman, R; Sloan, J A; Piantadosi, S; Lippman, S M

    2001-04-01

    Prostate cancer, even with its substantial public health impact of 180,400 new cases and 31,900 deaths estimated for 2000, still has a very low annual incidence (0.27% for men 34.4 years and older), which makes designing and conducting efficient prostate cancer prevention trials a challenge. Definitive prevention trials with cancer endpoints, such as the Breast Cancer Prevention Trial (BCPT), Prostate Cancer Prevention Trial (PCPT), and Selenium and Vitamin E Cancer Prevention Trial (SELECT), require long trial duration (up to 12 years) and large sample size (up to 32,400 subjects) to accomplish their objectives. This article discusses design concepts for potential prostate cancer prevention trials that require fewer years, subjects, and resources to complete. Design elements, such as high-risk populations, randomization, surrogate endpoints, including quality-of-life endpoints, masking/blinding, and various clinical/statistical designs (including 1-way layout, all-versus-none, factorial, and adaptive designs), are discussed, along with the ultimate goal of gaining US Food and Drug Administration approval for prostate-cancer preventive agents that can improve public health by reducing prostate cancer incidence and mortality. PMID:11295629

  14. Chemoprevention of prostate cancer.

    PubMed

    Stephenson, Andrew J; Abouassaly, Robert; Klein, Eric A

    2010-02-01

    Prostate cancer is an appropriate target for primary chemoprevention because of its ubiquity, disease-related mortality, treatment-related morbidity, and long latency period. The PCPT and REDUCE trials demonstrate that this cancer can be prevented by a relatively nontoxic oral pharmacologic agent (5alpha-reductase inhibitors). Evidence from the SELECT trial argues against the recommendation of the use of vitamins and micronutrients as chemoprevention of prostate cancer. Dietary modification may substantially alter a man's risk of prostate cancer, but the specific dietary manipulations that are necessary are poorly defined and these may need to be instituted in early adulthood to be successful. 5alpha-reductase inhibitors represent an effective primary prevention strategy, and these agents should be used more liberally for the prevention of prostate cancer, particularly in high-risk patients. PMID:20152515

  15. A probability tracking approach to segmentation of ultrasound prostate images using weak shape priors

    NASA Astrophysics Data System (ADS)

    Xu, Robert S.; Michailovich, Oleg V.; Solovey, Igor; Salama, Magdy M. A.

    2010-03-01

    Prostate specific antigen density is an established parameter for indicating the likelihood of prostate cancer. To this end, the size and volume of the gland have become pivotal quantities used by clinicians during the standard cancer screening process. As an alternative to manual palpation, an increasing number of volume estimation methods are based on the imagery data of the prostate. The necessity to process large volumes of such data requires automatic segmentation algorithms, which can accurately and reliably identify the true prostate region. In particular, transrectal ultrasound (TRUS) imaging has become a standard means of assessing the prostate due to its safe nature and high benefit-to-cost ratio. Unfortunately, modern TRUS images are still plagued by many ultrasound imaging artifacts such as speckle noise and shadowing, which results in relatively low contrast and reduced SNR of the acquired images. Consequently, many modern segmentation methods incorporate prior knowledge about the prostate geometry to enhance traditional segmentation techniques. In this paper, a novel approach to the problem of TRUS segmentation, particularly the definition of the prostate shape prior, is presented. The proposed approach is based on the concept of distribution tracking, which provides a unified framework for tracking both photometric and morphological features of the prostate. In particular, the tracking of morphological features defines a novel type of "weak" shape priors. The latter acts as a regularization force, which minimally bias the segmentation procedure, while rendering the final estimate stable and robust. The value of the proposed methodology is demonstrated in a series of experiments.

  16. 30 CFR 203.76 - When might MMS withdraw or reduce the approved size of my relief?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 2 2011-07-01 2011-07-01 false When might MMS withdraw or reduce the approved... Development and Expansion Projects § 203.76 When might MMS withdraw or reduce the approved size of my relief... system within18 months of the date we approved your application, unless the MMS Director grants you...

  17. MnTE-2-PyP reduces prostate cancer growth and metastasis by suppressing p300 activity and p300/HIF-1/CREB binding to the promoter region of the PAI-1 gene.

    PubMed

    Tong, Qiang; Weaver, Michael R; Kosmacek, Elizabeth A; O'Connor, Brian P; Harmacek, Laura; Venkataraman, Sujatha; Oberley-Deegan, Rebecca E

    2016-05-01

    To improve radiation therapy-induced quality of life impairments for prostate cancer patients, the development of radio-protectors is needed. Our previous work has demonstrated that MnTE-2-PyP significantly protects urogenital tissues from radiation-induced damage. So, in order for MnTE-2-PyP to be used clinically as a radio-protector, it is fully necessary to explore the effect of MnTE-2-PyP on human prostate cancer progression. MnTE-2-PyP inhibited prostate cancer growth in the presence and absence of radiation and also inhibited prostate cancer migration and invasion. MnTE-2-PyP altered p300 DNA binding, which resulted in the inhibition of HIF-1β and CREB signaling pathways. Accordingly, we also found that MnTE-2-PyP reduced the expression of three genes regulated by HIF-1β and/or CREB: TGF-β2, FGF-1 and PAI-1. Specifically, MnTE-2-PyP decreased p300 complex binding to a specific HRE motif within the PAI-1 gene promoter region, suppressed H3K9 acetylation, and consequently, repressed PAI-1 expression. Mechanistically, less p300 transcriptional complex binding is not due to the reduction of binding between p300 and HIF-1/CREB transcription factors, but through inhibiting the binding of HIF-1/CREB transcription factors to DNA. Our data provide an in depth mechanism by which MnTE-2-PyP reduces prostate cancer growth and metastasis, which validates the clinical use of MnTE-2-PyP as a radio-protector to enhance treatment outcomes in prostate cancer radiotherapy. PMID:26944191

  18. Kava components down-regulate expression of AR and AR splice variants and reduce growth in patient-derived prostate cancer xenografts in mice.

    PubMed

    Li, Xuesen; Liu, Zhongbo; Xu, Xia; Blair, Christopher A; Sun, Zheng; Xie, Jun; Lilly, Michael B; Zi, Xiaolin

    2012-01-01

    Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5'6'-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR. PMID:22347450

  19. What is Prostate Cancer?

    MedlinePlus

    ... Topic Key statistics for prostate cancer What is prostate cancer? Cancer starts when cells in the body begin ... through the center of the prostate. Types of prostate cancer Almost all prostate cancers are adenocarcinomas . These cancers ...

  20. Association of genetic and non-genetic risk factors with the development of prostate cancer in Malaysian men.

    PubMed

    Munretnam, Khamsigan; Alex, Livy; Ramzi, Nurul Hanis; Chahil, Jagdish Kaur; Kavitha, I S; Hashim, Nikman Adli Nor; Lye, Say Hean; Velapasamy, Sharmila; Ler, Lian Wee

    2014-01-01

    There is growing global interest to stratify men into different levels of risk to developing prostate cancer, thus it is important to identify common genetic variants that confer the risk. Although many studies have identified more than a dozen common genetic variants which are highly associated with prostate cancer, none have been done in Malaysian population. To determine the association of such variants in Malaysian men with prostate cancer, we evaluated a panel of 768 SNPs found previously associated with various cancers which also included the prostate specific SNPs in a population based case control study (51 case subjects with prostate cancer and 51 control subjects) in Malaysian men of Malay, Chinese and Indian ethnicity. We identified 21 SNPs significantly associated with prostate cancer. Among these, 12 SNPs were strongly associated with increased risk of prostate cancer while remaining nine SNPs were associated with reduced risk. However, data analysis based on ethnic stratification led to only five SNPs in Malays and 3 SNPs in Chinese which remained significant. This could be due to small sample size in each ethnic group. Significant non-genetic risk factors were also identified for their association with prostate cancer. Our study is the first to investigate the involvement of multiple variants towards susceptibility for PC in Malaysian men using genotyping approach. Identified SNPs and non-genetic risk factors have a significant association with prostate cancer.

  1. Intra- and Trans-Generational Costs of Reduced Female Body Size Caused by Food Limitation Early in Life in Mites

    PubMed Central

    Walzer, Andreas; Schausberger, Peter

    2013-01-01

    Background Food limitation early in life may be compensated for by developmental plasticity resulting in accelerated development enhancing survival at the expense of small adult body size. However and especially for females in non-matching maternal and offspring environments, being smaller than the standard may incur considerable intra- and trans-generational costs. Methodology/Principal Findings Here, we evaluated the costs of small female body size induced by food limitation early in life in the sexually size-dimorphic predatory mite Phytoseiulus persimilis. Females are larger than males. These predators are adapted to exploit ephemeral spider mite prey patches. The intra- and trans-generational effects of small maternal body size manifested in lower maternal survival probabilities, decreased attractiveness for males, and a reduced number and size of eggs compared to standard-sized females. The trans-generational effects of small maternal body size were sex-specific with small mothers producing small daughters but standard-sized sons. Conclusions/Significance Small female body size apparently intensified the well-known costs of sexual activity because mortality of small but not standard-sized females mainly occurred shortly after mating. The disadvantages of small females in mating and egg production may be generally explained by size-associated morphological and physiological constraints. Additionally, size-assortative mate preferences of standard-sized mates may have rendered small females disproportionally unattractive mating partners. We argue that the sex-specific trans-generational effects were due to sexual size dimorphism – females are the larger sex and thus more strongly affected by maternal stress than the smaller males – and to sexually selected lower plasticity of male body size. PMID:24265745

  2. Use of Implanted Markers and Interportal Adjustment With Real-Time Tracking Radiotherapy System to Reduce Intrafraction Prostate Motion

    SciTech Connect

    Shimizu, Shinichi; Osaka, Yasuhiro; Shinohara, Nobuo; Sazawa, Ataru; Nishioka, Kentaro; Suzuki, Ryusuke; Onimaru, Rikiya; Shirato, Hiroki

    2011-11-15

    Purpose: Interportal adjustment was applied to patients with prostate cancer using three fiducial markers and two sets of fluoroscopy in a real-time tumor-tracking radiotherapy (RTRT) system. The incidence of table position adjustment required to keep intrafractional uncertainty within 2.0 mm was investigated in this study. Methods and Materials: The coordinates of the center of gravity of the three fiducial markers were measured at the start of every portal irradiation in intensity-modulated radiotherapy (IMRT) with seven ports. The table position was adjusted to the planned position if the discrepancy was larger than 2.0 mm in the anterior-posterior (AP), cranial-caudal (CC), or left-right (LR) directions. In total, we analyzed 4,541 observations in 20 patients who received 70 Gy in 30 fractions (7.6 times a day on average). Results: The incidence of table position adjustment at 10 minutes from the initial setup of each treatment was 14.2%, 12.3%, and 5.0% of the observations in the AP, CC, and LR directions, respectively. The accumulated incidence of the table position adjustment was significantly higher at 10 minutes than at 2 minutes for AP (p = 0.0033) and CC (p = 0.0110) but not LR (p = 0.4296). An adjustment greater than 5 mm was required at least once in the treatment period in 11 (55%) patients. Conclusions: Interportal adjustment of table position was required in more than 10% of portal irradiations during the 10-minute period after initial setup to maintain treatment accuracy within 2.0 mm.

  3. Treatment with the gap junction modifier rotigaptide (ZP123) reduces infarct size in rats with chronic myocardial infarction.

    PubMed

    Haugan, Ketil; Marcussen, Niels; Kjølbye, Anne Louise; Nielsen, Morten Schak; Hennan, James K; Petersen, Jørgen Søberg

    2006-02-01

    Treatment with non-selective drugs (eg, long-chain alcohols, halothane) that reduce gap junction intercellular communication (GJIC) is associated with reduced infarct size after myocardial infarction (MI). Therefore, it has been suggested that gap junction intercellular communication stimulating compounds may increase infarct size. The antiarrhythmic peptide analogue rotigaptide (ZP123) increases cardiac gap junction intercellular communication and the purpose of the present study was to examine the effects of rotigaptide treatment on infarct size. Myocardial infarction was induced in male rats by ligation of the left anterior descending artery (LAD). Rats (n = 156) were treated with rotigaptide at three dose levels or vehicle from the onset of ischemia and for 3 weeks following LAD occlusion. Infarct size was determined using histomorphometry after 3 weeks treatment. Rotigaptide treatment producing steady state plasma levels of 0.8 +/- 0.1, 5.5 +/- 0.5, and 86 +/- 8 nmol/L had no effect on mortality, but reduced infarct size to 90 +/- 10% (P = 0.41), 67 +/- 7% (P = 0.005), and 82 +/- 7% (P = 0.13), respectively relative to vehicle-treated myocardial infarction rats (100 +/- 12%). In contrast to what was predicted, our data demonstrates that rotigaptide treatment was associated with a significant infarct size reduction. We conclude that whereas treatment with non-selective inhibitors of gap junction intercellular communication cause a reduction in infarct size, this information cannot be extrapolated to the effects of compounds that selectively increase gap junction intercellular communication.

  4. Ecological constraints on sensory systems: compound eye size in Daphnia is reduced by resource limitation.

    PubMed

    Brandon, Christopher S; Dudycha, Jeffry L

    2014-08-01

    Eye size is an indicator of visual capability, and macroevolutionary patterns reveal that taxa inhabiting dim environments have larger eyes than taxa from bright environments. This suggests that the light environment is a key driver of variation in eye size. Yet other factors not directly linked with visual tasks (i.e., non-sensory factors) may influence eye size. We sought to jointly investigate the roles of sensory (light) and non-sensory factors (food) in determining eye size and ask whether non-sensory factors could constrain visual capabilities. We tested environmental influences on eye size in four species of the freshwater crustacean Daphnia, crossing bright and dim light levels with high and low resource levels. We measured absolute eye size and eye size relative to body size in early and late adulthood. In general, Daphnia reared on low resources had smaller eyes, both absolutely and relatively. In contrast to the dominant macroevolutionary pattern, phenotypic plasticity in response to light was rarely significant. These patterns of phenotypic plasticity were true for overall diameter of the eye and the diameter of individual facets. We conclude that non-sensory environmental factors can influence sensory systems, and in particular, that resource availability may be an important constraint on visual capability.

  5. Reducing Class Size: A Smart Way To Improve America's Urban Schools. Second Edition.

    ERIC Educational Resources Information Center

    Naik, Manish; Casserly, Michael; Uro, Gabriela

    The Council of the Great City Schools, a coalition of the largest urban public schools in the United States, surveyed its membership to determine how they were using federal class size reduction funds in the 2000-2001 school year. Thirty-six major urban school systems responded. Results indicate that the federal class size reduction program is…

  6. Intraventricular brain-derived neurotrophic factor reduces infarct size after focal cerebral ischemia in rats.

    PubMed

    Schäbitz, W R; Schwab, S; Spranger, M; Hacke, W

    1997-05-01

    Brain-derived neurotrophic factor (BDNF), acting through the high-affinity receptor tyrosine kinase (TrkB), is widely distributed throughout the central nervous system and displays in vitro trophic effects on a wide range of neuronal cells, including hippocampal, cerebellar, and cortical neurons. In vivo, BDNF rescues motorneurons, hippocampal, and substantia nigral dopaminergic cells from traumatic and toxic brain injury. After transient middle cerebral artery occlusion (MCAO), upregulation of BDNF-mRNA in cortical neurons suggests that BDNF potentially plays a neuroprotective role in focal cerebral ischemia. In the current study, BDNF (2.1 micrograms/d) in vehicle or vehicle alone (controls) was delivered intraventricularly for 8 days, beginning 24 hours before permanent middle cerebral artery occlusion by intraluminal suture in Wistar rats (n = 13 per group). There were no differences in physiological variables recorded during surgery for the two groups. Neurological deficit (0 to 4 scale), which was assessed on a daily basis, improved in BDNF-treated animals compared with controls (P < 0.05; analysis of variance and Scheffe's test). There were no significant differences in weight in BDNF-treated animals and controls during the experiment. After elective killing on day 7 after MCAO, brains underwent 2,3,5-triphenyltetrazolium chloride staining for calculation of the infarct volume and for histology (hematoxylin and eosin and glial fibrillary acid protein). The mean total infarct volume was 83.1 +/- 27.1 mm3 in BDNF-treated animals and 139.2 +/- 56.4 mm3 in controls (mean +/- SD; P < 0.01, unpaired, two-tailed t-test). The cortical infarct volume was 10.8 +/- 7.1 mm3 in BDNF-treated animals and 37.9 +/- 19.8 mm3 in controls (mean +/- SD; P < 0.05; unpaired, two-tailed t-test), whereas ischemic lesion volume in caudoputaminal infarction was not significantly different. These results show that pretreatment with intraventricular BDNF reduces infarct size after focal

  7. Human phosphodiesterase 4D7 (PDE4D7) expression is increased in TMPRSS2-ERG-positive primary prostate cancer and independently adds to a reduced risk of post-surgical disease progression

    PubMed Central

    Böttcher, R; Henderson, D J P; Dulla, K; van Strijp, D; Waanders, L F; Tevz, G; Lehman, M L; Merkle, D; van Leenders, G J L H; Baillie, G S; Jenster, G; Houslay, M D; Hoffmann, R

    2015-01-01

    Background: There is an acute need to uncover biomarkers that reflect the molecular pathologies, underpinning prostate cancer progression and poor patient outcome. We have previously demonstrated that in prostate cancer cell lines PDE4D7 is downregulated in advanced cases of the disease. To investigate further the prognostic power of PDE4D7 expression during prostate cancer progression and assess how downregulation of this PDE isoform may affect disease outcome, we have examined PDE4D7 expression in physiologically relevant primary human samples. Methods: About 1405 patient samples across 8 publically available qPCR, Affymetrix Exon 1.0 ST arrays and RNA sequencing data sets were screened for PDE4D7 expression. The TMPRSS2-ERG gene rearrangement status of patient samples was determined by transformation of the exon array and RNA seq expression data to robust z-scores followed by the application of a threshold >3 to define a positive TMPRSS2-ERG gene fusion event in a tumour sample. Results: We demonstrate that PDE4D7 expression positively correlates with primary tumour development. We also show a positive association with the highly prostate cancer-specific gene rearrangement between TMPRSS2 and the ETS transcription factor family member ERG. In addition, we find that in primary TMPRSS2-ERG-positive tumours PDE4D7 expression is significantly positively correlated with low-grade disease and a reduced likelihood of progression after primary treatment. Conversely, PDE4D7 transcript levels become significantly decreased in castration resistant prostate cancer (CRPC). Conclusions: We further characterise and add physiological relevance to PDE4D7 as a novel marker that is associated with the development and progression of prostate tumours. We propose that the assessment of PDE4D7 levels may provide a novel, independent predictor of post-surgical disease progression. PMID:26575822

  8. Inhibitor of p52 NF-κB subunit and androgen receptor (AR) interaction reduces growth of human prostate cancer cells by abrogating nuclear translocation of p52 and phosphorylated AR(ser81).

    PubMed

    Mehraein-Ghomi, Farideh; Church, Dawn R; Schreiber, Cynthia L; Weichmann, Ashley M; Basu, Hirak S; Wilding, George

    2015-09-01

    Accumulating evidence shows that androgen receptor (AR) activation and signaling plays a key role in growth and progression in all stages of prostate cancer, even under low androgen levels or in the absence of androgen in the castration-resistant prostate cancer. Sustained activation of AR under androgen-deprived conditions may be due to its interaction with co-activators, such as p52 NF-κB subunit, and/or an increase in its stability by phosphorylation that delays its degradation. Here we identified a specific inhibitor of AR/p52 interaction, AR/p52-02, via a high throughput screen based on the reconstitution of Gaussia Luciferase. We found that AR/p52-02 markedly inhibited growth of both castration-resistant C4-2 (IC50 ∼6 μM) and parental androgen-dependent LNCaP (IC50 ∼4 μM) human prostate cancer cells under low androgen conditions. Growth inhibition was associated with significantly reduced nuclear p52 levels and DNA binding activity, as well as decreased phosphorylation of AR at serine 81, increased AR ubiquitination, and decreased AR transcriptional activity as indicated by decreased prostate-specific antigen (PSA) mRNA levels in both cell lines. AR/p52-02 also caused a reduction in levels of p21(WAF/CIP1), which is a direct AR targeted gene in that its expression correlates with androgen stimulation and mitogenic proliferation in prostate cancer under physiologic levels of androgen, likely by disrupting the AR signaling axis. The reduced level of cyclinD1 reported previously for this compound may be due to the reduction in nuclear presence and activity of p52, which directly regulates cyclinD1 expression, as well as the reduction in p21(WAF/CIP1), since p21(WAF/CIP1) is reported to stabilize nuclear cyclinD1 in prostate cancer. Overall, the data suggest that specifically inhibiting the interaction of AR with p52 and blocking activity of p52 and pARser81 may be an effective means of reducing castration-resistant prostate cancer cell growth.

  9. Tree Size Inequality Reduces Forest Productivity: An Analysis Combining Inventory Data for Ten European Species and a Light Competition Model

    PubMed Central

    Bourdier, Thomas; Cordonnier, Thomas; Kunstler, Georges; Piedallu, Christian; Lagarrigues, Guillaume; Courbaud, Benoit

    2016-01-01

    Plant structural diversity is usually considered as beneficial for ecosystem functioning. For instance, numerous studies have reported positive species diversity-productivity relationships in plant communities. However, other aspects of structural diversity such as individual size inequality have been far less investigated. In forests, tree size inequality impacts directly tree growth and asymmetric competition, but consequences on forest productivity are still indeterminate. In addition, the effect of tree size inequality on productivity is likely to vary with species shade-tolerance, a key ecological characteristic controlling asymmetric competition and light resource acquisition. Using plot data from the French National Geographic Agency, we studied the response of stand productivity to size inequality for ten forest species differing in shade tolerance. We fitted a basal area stand production model that included abiotic factors, stand density, stand development stage and a tree size inequality index. Then, using a forest dynamics model we explored whether mechanisms of light interception and light use efficiency could explain the tree size inequality effect observed for three of the ten species studied. Size inequality negatively affected basal area increment for seven out of the ten species investigated. However, this effect was not related to the shade tolerance of these species. According to the model simulations, the negative tree size inequality effect could result both from reduced total stand light interception and reduced light use efficiency. Our results demonstrate that negative relationships between size inequality and productivity may be the rule in tree populations. The lack of effect of shade tolerance indicates compensatory mechanisms between effect on light availability and response to light availability. Such a pattern deserves further investigations for mixed forests where complementarity effects between species are involved. When studying the

  10. Reducing bias in rainfall estimates from microwave links by considering variable drop size distribution

    NASA Astrophysics Data System (ADS)

    Fencl, Martin; Jörg, Rieckermann; Vojtěch, Bareš

    2015-04-01

    Commercial microwave links (MWL) are point-to-point radio systems which are used in backhaul networks of cellular operators. For several years, they have been suggested as rainfall sensors complementary to rain gauges and weather radars, because, first, they operate at frequencies where rain drops represent significant source of attenuation and, second, cellular networks almost completely cover urban and rural areas. Usually, path-average rain rates along a MWL are retrieved from the rain-induced attenuation of received MWL signals with a simple model based on a power law relationship. The model is often parameterized based on the characteristics of a particular MWL, such as frequency, polarization and the drop size distribution (DSD) along the MWL. As information on the DSD is usually not available in operational conditions, the model parameters are usually considered constant. Unfortunately, this introduces bias into rainfall estimates from MWL. In this investigation, we propose a generic method to eliminate this bias in MWL rainfall estimates. Specifically, we search for attenuation statistics which makes it possible to classify rain events into distinct groups for which same power-law parameters can be used. The theoretical attenuation used in the analysis is calculated from DSD data using T-Matrix method. We test the validity of our approach on observations from a dedicated field experiment in Dübendorf (CH) with a 1.85-km long commercial dual-polarized microwave link transmitting at a frequency of 38 GHz, an autonomous network of 5 optical distrometers and 3 rain gauges distributed along the path of the MWL. The data is recorded at a high temporal resolution of up to 30s. It is further tested on data from an experimental catchment in Prague (CZ), where 14 MWLs, operating at 26, 32 and 38 GHz frequencies, and reference rainfall from three RGs is recorded every minute. Our results suggest that, for our purpose, rain events can be nicely characterized based on

  11. Reducing particle size of corn in lactation diets from 1,200 to 400 micrometers improves sow and litter performance.

    PubMed

    Wondra, K J; Hancock, J D; Kennedy, G A; Hines, R H; Behnke, K C

    1995-02-01

    One hundred primiparous sows were used to determine the effects of particle size of corn in lactation diets on sow and litter performance. The sows were fed a corn-soybean meal-based diet with the corn ground to 1,200, 900, 600, or 400 microns. Particle size of corn had no influence on sow BW or backfat loss (P > .30), subsequent weaning-to-estrus interval (P > .40), or percentage of sows returning to estrus (P > .09). However, ADFI was increased (linear effect, P < .04) as particle size was reduced from 1,200 to 400 microns. Pig survivability was not affected (P > .30) but litter BW gain was increased by 11% when sows were fed diets with 400 vs 1,200 microns corn (linear effect, P < .05). Apparent digestibilities of DM, N, and GE were increased by 5, 7, and 7%, respectively, as particle size was reduced from 1,200 to 400 microns (linear effects, P < .001). Intake of DE was increased 14% (13.7 to 15.6 Mcal/d) as corn particle size was reduced from 1,200 to 400 microns. Intakes of digestible DM and N also were increased (11 and 14%, respectively), whereas fecal excretions of DM and N were decreased by 21 and 31%, respectively (linear effects, P < .001). Reducing particle size increased severity of ulceration and keratinization (nonzero correlations of P < .04 and P < .004, respectively) in the esophageal region of the stomach, although the changes were not associated with reduced sow performance.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. An Informatics Based Approach to Reduce the Grain Size of Cast Hadfield Steel

    NASA Astrophysics Data System (ADS)

    Dey, Swati; Pathak, Shankha; Sheoran, Sumit; Kela, Damodar H.; Datta, Shubhabrata

    2016-04-01

    Materials Informatics concept using computational intelligence based approaches are employed to bring out the significant alloying additions to achieve grain refinement in cast Hadfield steel. Castings of Hadfield steels used for railway crossings, requires fine grained austenitic structure. Maintaining proper grain size of this component is very crucial in order to achieve the desired properties and service life. This work studies the important variables affecting the grain size of such steels which includes the compositional and processing variables. The computational findings and prior knowledge is used to design the alloy, which is subjected to a few trials to validate the findings.

  13. Eosinophilic prostatitis and prostatic specific antigen.

    PubMed

    Liu, S; Miller, P D; Holmes, S A; Christmas, T J; Kirby, R S

    1992-01-01

    Eosinophilic prostatitis is a rare form of abacterial prostatitis with uncertain aetiology. Its clinical presentation, like other types of abacterial prostatitis, commonly mimics carcinoma of the prostate. Transrectal ultrasound may be helpful in the diagnosis of prostatitis but histological confirmation is necessary. Prostatic specific antigen has been widely used in the diagnosis and follow-up of patients with prostatic carcinoma. High levels of this antigen (greater than 30 micrograms/l) have been claimed to be highly specific for prostate cancer, although lesser elevations may also occur in patients with large benign prostate glands and in bacterial prostatitis. We report 3 patients with histologically proven eosinophilic prostatitis and high levels of prostatic specific antigen. This diagnosis may closely mimic carcinoma of the prostate and must be excluded by histological examination of biopsy material before treatment for presumed prostate carcinoma is initiated.

  14. Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

    PubMed Central

    Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

    2008-01-01

    Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

  15. Reduced-size microchips for identification of horses: response to implantation and readability during a six-month period.

    PubMed

    Wulf, M; Aurich, C; von Lewinski, M; Möstl, E; Aurich, J E

    2013-11-01

    In this study, readability of reduced-size microchips in horses and the response to implantation were analysed. It was hypothesised that small microchips can be implanted stress-free but are less readable than larger microchips. Adult mares (n=40) were implanted with a reduced-size microchip (10.9×1.6 mm) at the left side of the neck (size of conventional microchips 11.4×2.2 mm). Microchips were identified with three different scanners (A, B, C) immediately, and at 6, 12 and 28 weeks after implantation. Twelve out of the 40 mares were submitted to microchip implantation and control treatments and cortisol, heart rate and heart rate variability (HRV) were determined. From the chip-bearing side of the neck, microchips were identified with all scanners in all horses at all times. From the contralateral side, correct readings were always 100 per cent with scanner C and with scanners A and B ranged between 60 and 100 per cent. Heart rate and HRV variable sd of beat-to-beat interval increased slightly (P<0.01) at microchip implantation and control treatment, but cortisol concentration did not increase. In conclusion, reduced-size microchips are highly reliable for identification of horses. Compared with conventional microchips, the reduction in size did not impair readability. Microchip implantation is no pronounced stressor for horses.

  16. Motor-Reducer Sizing through a MATLAB-Based Graphical Technique

    ERIC Educational Resources Information Center

    Giberti, H.; Cinquemani, S.

    2012-01-01

    The design of the drive system for an automatic machine and its correct sizing is a very important competence for an electrical or mechatronic engineer. This requires knowledge that crosses the fields of electrical engineering, electronics and mechanics, as well as the skill to choose commercial components based upon their technical documentation.…

  17. Size sorting of citrate reduced gold nanoparticles by sedimentation field-flow fractionation.

    PubMed

    Contado, Catia; Argazzi, Roberto

    2009-12-25

    Gold nanoparticles (GNPs) have been synthesized through the citrate reduction method; the citrate/gold(III) ratio was changed from 1:1 up to 10:1 and the size of the resulting nanoparticles was measured by sedimentation field-flow fractionation (SdFFF). Experimental data showed that the GNPs size decreases in the ratio range 1:1-3:1 and then increases from 5:1 to 10:1 passing through a plateau region in between, and is almost independent of the precursor solution concentrations. In the zone of minimum diameters the synthetic process does not produce monodispersed GNPs but often multiple distributions, very close in size, are observed as evidenced by the particle size distributions (PSDs) derived from the SdFFF fractograms. UV-vis spectrophotometry, being the most common technique employed in the optical characterization of nanoparticles suspensions, was used throughout this work. A confirmation of the nucleation-aggregation-fragmentation mechanism was inferred from the cross-correlation between UV-vis and SdFFF results.

  18. Winter grazing can reduce wildfire size, intensity, and behavior in a shrub-grassland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    1. An increase in mega-fires and wildfires in general is a global issue that is expected to become worse with climate change. Fuel treatments are often recommended to decrease the risk, size, intensity, and severity of wildfires; however, the extensive nature of rangelands limits the use of many po...

  19. Community size and metabolic rates of psychrophilic sulfate-reducing bacteria in Arctic marine sediments

    SciTech Connect

    Knoblauch, C.; Joergensen, B.B.; Harder, J.

    1999-09-01

    The numbers of sulfate reducers in two Arctic sediments with in situ temperatures of 2.6 and {minus}1.7C were determined. Most-probable-number counts were higher at 10 C than at 20 C, indicating the predominance of a psychrophilic community. Mean specific sulfate reduction rates of 19 isolated psychrophiles were compared to corresponding rates of 9 marine, mesophilic sulfate-reducing bacteria. The results indicate that, as a physiological adaptation to the permanently cold Arctic environment, psychrophilic sulfate reducers have considerably higher specific metabolic rates than their mesophilic counterparts at similarly low temperatures.

  20. A M-MLV reverse transcriptase with reduced RNaseH activity allows greater sensitivity of gene expression detection in formalin fixed and paraffin embedded prostate cancer samples.

    PubMed

    Hagen, Rachel M; Rhodes, Anthony; Oxley, Jon; Ladomery, Michael R

    2013-08-01

    Formalin fixed and paraffin embedded (FFPE) human tissue collections are an invaluable resource for retrospective gene expression studies. However formalin fixation results in chemical modification of RNA and increased RNA degradation. This can affect RNA yield and quality. A critical step when analysing gene expression is the conversion of RNA to complementary DNA (cDNA) using a reverse transcriptase (RT) enzyme. FFPE derived RNA may affect the performance and efficiency of the RT enzyme and cDNA synthesis. We directly compared three commonly used FFPE RNA isolation methods and measured RNA yield, purity and integrity. We also assessed the effectiveness of three commercially available Moloney Murine Leukemia Virus (M-MLV) RTs on cDNA synthesis and gene expression sensitivity when using FFPE RNA as a template. Our results show that gene detection sensitivity is dependent on the isolation method, RT and length of the PCR amplicon (<200bp) when using FFPE RNA. The use of an M-MLV RT enzyme with reduced RNaseH activity gave significantly increased qRT-PCR sensitivity when using FFPE RNA derived from prostate tissue. The choice of RT can also affect perceived changes in target gene expression and thus the same RT should be used when attempting to reproduce results from different studies. This study highlights the need to optimise and evaluate RNA isolation methods and RTs when using FFPE RNA as a template in order to maximise a successful outcome in PCR applications.

  1. Estrogen alone or combined with medroxyprogesterone but not raloxifene reduce myocardial infarct size.

    PubMed

    Sbarouni, Eftihia; Iliodromitis, Efstathios K; Bofilis, Elias; Kyriakides, Zenon S; Kremastinos, Dimitrios Th

    2003-04-25

    We investigated whether estrogen protects the ischemic myocardium in oophorectomized female rabbits fed with a cholesterol-enriched diet, whether the addition of a progestin compound attenuates the beneficial effect of estrogen and whether raloxifene also limits myocardial necrosis. We treated 32 female oophorectomized hypercholesterolemic rabbits with (a) placebo (N=8, group I), (b) conjugated estrogens alone (N=8, group II), (c) conjugated estrogens combined continuously with medroxyprogesterone acetate (N=8, group III) and (d) raloxifene (N=8, group IV) all for 4 weeks. All rabbits underwent 30 min of ischemia and 120 min of reperfusion. Both infarct size (0.38+/-0.08 and 0.45+/-0.05 in groups II and III, respectively, vs. 0.78+/-0.07 in group I, P<0.005) and infarct size/risk zone% (26.34+/-4.18 and 35.01+/-4.39 in groups II and III, respectively, vs. 52.18+/-7.84 in group I, P<0.05) were significantly smaller in the estrogen treatment groups compared to placebo. No significant difference was observed between groups II and III. There was no significant difference between groups I and IV for infarct size (0.78+/-0.07 vs. 0.69+/-0.08, respectively) or for infarct size/risk zone% (52.18+/-7.84 vs. 47.17+/-4.3). Short-term estrogen protects ischemic myocardium in hypercholesterolemic oophorectomized female rabbits; this effect is not attenuated by the addition of a progestin compound. Raloxifene, however, does not decrease infarct size compared to placebo.

  2. Testing Probation Outcomes in an Evidence-Based Practice Setting: Reduced Caseload Size and Intensive Supervision Effectiveness

    ERIC Educational Resources Information Center

    Jalbert, Sarah Kuck; Rhodes, William; Flygare, Christopher; Kane, Michael

    2010-01-01

    Probation and parole professionals argue that supervision outcomes would improve if caseloads were reduced below commonly achieved standards. Criminal justice researchers are skeptical because random assignment and strong observation studies have failed to show that criminal recidivism falls with reductions in caseload sizes. One explanation is…

  3. BIOREACTOR ECONOMICS, SIZE AND TIME OF OPERATION (BEST) COMPUTER SIMULATOR FOR DESIGNING SULFATE-REDUCING BACTERIA FIELD BIOREACTORS

    EPA Science Inventory

    BEST (bioreactor economics, size and time of operation) is an Excel™ spreadsheet-based model that is used in conjunction with the public domain geochemical modeling software, PHREEQCI. The BEST model is used in the design process of sulfate-reducing bacteria (SRB) field bioreacto...

  4. The Cumulative Effects of Indiana PRIME TIME: A State Sponsored Reduced Class Size Program, on Basic Skills Achievement.

    ERIC Educational Resources Information Center

    Malloy, Leanne; Gilman, David

    The purpose of this paper was to analyze the initial results of statewide implementation of the PRIME TIME program in Indiana. PRIME TIME is a state-wide program to reduce class size in the primary grades. Mean scores from 65,911 third graders who had completed the Indiana Competency Test in the spring of 1987 after completing 3 years of the…

  5. Derivatives of a statically reduced stiffness matrix with respect to sizing variables. [for aircraft weight minimization with flutter constraints

    NASA Technical Reports Server (NTRS)

    Oconnell, R. F.; Hassig, H. J.; Radovcich, N. A.

    1976-01-01

    An expression is obtained for the first derivatives with respect to the sizing variables of a statically reduced stiffness matrix that is a nonlinear function of the sizing variables, where the unreduced stiffness matrix is a linear function of the sizing variables. An accepted procedure to reduce the number of degrees of freedom is to eliminate a number of nodal displacements from the degrees of freedom such that the accuracy of the flutter analysis is not significantly affected. In a typical optimization procedure with flutter constraints, the derivative of the stiffness matrix may be used in a form that contains the characteristic vector of the flutter matrix equation and the transpose of the characteristic vector of the adjoint flutter matrix equation corresponding to a particular solution of the flutter equation.

  6. The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy.

    PubMed

    Bell, Linda J; Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-01-01

    Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more

  7. The importance of prostate bed tilt during postprostatectomy intensity-modulated radiotherapy

    SciTech Connect

    Bell, Linda J.; Cox, Jennifer; Eade, Thomas; Rinks, Marianne; Kneebone, Andrew

    2014-10-01

    Variations in rectal and bladder filling can create a tilt of the prostate bed, which generates the potential for a geographic miss during postprostatectomy radiotherapy. The aim of this study is to assess the effect that bladder and rectum filling has on planning target volume angle, to determine a method to assess prostate bed tilt leading to potential geographic miss, and to discuss possible implementation issues. The cone-beam computed tomography images (n = 377) of 40 patients who received postprostatectomy radiotherapy with intensity-modulated radiotherapy were reviewed. The amount of tilt in the prostate bed was defined as the angle change between 2 surgical clips, one in the upper prostate bed and another in the lower. A potential geographic miss was defined as movement of any clip of more than 1 cm in any direction or 0.5 cm posteriorly when aligned to bone anatomy. Variations in bladder and rectum size were correlated with the degree of prostate bed tilt, and the rate of potential geographic miss was determined. A possible clinical use of prostate bed tilt was then assessed for different imaging techniques. A tilt of more than 10° was seen in 20.2% of images, which resulted in a 57.9% geographic miss rate of the superior clip. When tilt remained within 10°, there was only a 9% rate of geographic miss. Potential geographic miss of the inferior surgical clip was rare, occurring in only 1.9% of all images reviewed. The most common occurrence when the prostate bed tilt increased by more than 10° was a smaller bladder and larger rectum (6.4% of all images). The most common occurrence when the prostate bed tilt decreased by more than 10° was a larger bladder and smaller rectum (1.3% of all images). Significant prostate bed tilt (>± 10°) occurred in more than 20% of images, creating a 58% rate of geographic miss. Greatest prostate bed tilt occurred when the bladder size increased or reduced by more than 2 cm or the superior rectum size increased by more

  8. Faltering lemming cycles reduce productivity and population size of a migratory Arctic goose species.

    PubMed

    Nolet, Bart A; Bauer, Silke; Feige, Nicole; Kokorev, Yakov I; Popov, Igor Yu; Ebbinge, Barwolt S

    2013-07-01

    The huge changes in population sizes of Arctic-nesting geese offer a great opportunity to study population limitation in migratory animals. In geese, population limitation seems to have shifted from wintering to summering grounds. There, in the Arctic, climate is rapidly changing, and this may impact reproductive performance, and perhaps population size of geese, both directly (e.g. by changes in snow melt) or indirectly (e.g. by changes in trophic interactions). Dark-bellied brent geese (Branta bernicla bernicla L.) increased 20-fold since the 1950s. Its reproduction fluctuates strongly in concert with the 3-year lemming cycle. An earlier analysis, covering the growth period until 1988, did not find evidence for density dependence, but thereafter the population levelled off and even decreased. The question is whether this is caused by changes in lemming cycles, population density or other factors like carry-over effects. Breeding success was derived from proportions of juveniles. We used an information-theoretical approach to investigate which environmental factors best explained the variation in breeding success over nearly 50 years (1960-2008). We subsequently combined GLM predictions of breeding success with published survival estimates to project the population trajectory since 1991 (year of maximum population size). In this way, we separated the effects of lemming abundance and population density on population development. Breeding success was mainly dependent on lemming abundance, the onset of spring at the breeding grounds, and the population size of brent goose. No evidence was found for carry-over effects (i.e. effects of conditions at main spring staging site). Negative density dependence was operating at a population size above c. 200 000 individuals, but the levelling off of the population could be explained by faltering lemming cycles alone. Lemmings have long been known to affect population productivity of Arctic-nesting migratory birds and, more

  9. Faltering lemming cycles reduce productivity and population size of a migratory Arctic goose species

    PubMed Central

    Nolet, Bart A; Bauer, Silke; Feige, Nicole; Kokorev, Yakov I; Popov, Igor Yu; Ebbinge, Barwolt S

    2013-01-01

    1. The huge changes in population sizes of Arctic-nesting geese offer a great opportunity to study population limitation in migratory animals. In geese, population limitation seems to have shifted from wintering to summering grounds. There, in the Arctic, climate is rapidly changing, and this may impact reproductive performance, and perhaps population size of geese, both directly (e.g. by changes in snow melt) or indirectly (e.g. by changes in trophic interactions). 2. Dark-bellied brent geese (Branta bernicla bernicla L.) increased 20-fold since the 1950s. Its reproduction fluctuates strongly in concert with the 3-year lemming cycle. An earlier analysis, covering the growth period until 1988, did not find evidence for density dependence, but thereafter the population levelled off and even decreased. The question is whether this is caused by changes in lemming cycles, population density or other factors like carry-over effects. 3. Breeding success was derived from proportions of juveniles. We used an information-theoretical approach to investigate which environmental factors best explained the variation in breeding success over nearly 50 years (1960–2008). We subsequently combined GLM predictions of breeding success with published survival estimates to project the population trajectory since 1991 (year of maximum population size). In this way, we separated the effects of lemming abundance and population density on population development. 4. Breeding success was mainly dependent on lemming abundance, the onset of spring at the breeding grounds, and the population size of brent goose. No evidence was found for carry-over effects (i.e. effects of conditions at main spring staging site). Negative density dependence was operating at a population size above c. 200 000 individuals, but the levelling off of the population could be explained by faltering lemming cycles alone. 5. Lemmings have long been known to affect population productivity of Arctic-nesting migratory

  10. Faltering lemming cycles reduce productivity and population size of a migratory Arctic goose species.

    PubMed

    Nolet, Bart A; Bauer, Silke; Feige, Nicole; Kokorev, Yakov I; Popov, Igor Yu; Ebbinge, Barwolt S

    2013-07-01

    The huge changes in population sizes of Arctic-nesting geese offer a great opportunity to study population limitation in migratory animals. In geese, population limitation seems to have shifted from wintering to summering grounds. There, in the Arctic, climate is rapidly changing, and this may impact reproductive performance, and perhaps population size of geese, both directly (e.g. by changes in snow melt) or indirectly (e.g. by changes in trophic interactions). Dark-bellied brent geese (Branta bernicla bernicla L.) increased 20-fold since the 1950s. Its reproduction fluctuates strongly in concert with the 3-year lemming cycle. An earlier analysis, covering the growth period until 1988, did not find evidence for density dependence, but thereafter the population levelled off and even decreased. The question is whether this is caused by changes in lemming cycles, population density or other factors like carry-over effects. Breeding success was derived from proportions of juveniles. We used an information-theoretical approach to investigate which environmental factors best explained the variation in breeding success over nearly 50 years (1960-2008). We subsequently combined GLM predictions of breeding success with published survival estimates to project the population trajectory since 1991 (year of maximum population size). In this way, we separated the effects of lemming abundance and population density on population development. Breeding success was mainly dependent on lemming abundance, the onset of spring at the breeding grounds, and the population size of brent goose. No evidence was found for carry-over effects (i.e. effects of conditions at main spring staging site). Negative density dependence was operating at a population size above c. 200 000 individuals, but the levelling off of the population could be explained by faltering lemming cycles alone. Lemmings have long been known to affect population productivity of Arctic-nesting migratory birds and, more

  11. Povidone Iodine Rectal Preparation at Time of Prostate Needle Biopsy is a Simple and Reproducible Means to Reduce Risk of Procedural Infection.

    PubMed

    Raman, Jay D; Lehman, Kathleen K; Dewan, Kalyan; Kirimanjeswara, Girish

    2015-09-21

    Single institution and population-based studies highlight that infectious complications following transrectal ultrasound guided prostate needle biopsy (TRUS PNB) are increasing. Such infections are largely attributable to quinolone resistant microorganisms which colonize the rectal vault and are translocated into the bloodstream during the biopsy procedure. A povidone iodine rectal preparation (PIRP) at time of biopsy is a simple, reproducible method to reduce rectal microorganism colony counts and therefore resultant infections following TRUS PNB. All patients are administered three days of oral antibiotic therapy prior to biopsy. The PIRP technique involves initially positioning the patient in the standard manner for a TRUS PNB. Following digital rectal examination, 15 ml of a 10% solution of commercially available povidone iodine is mixed with 5 ml of 1% lidocaine jelly to create slurry. A 4 cmx4 cm sterile gauze is soaked in this slurry and then inserted into the rectal vault for 2 min after which it is removed. Thereafter, a disposable cotton gynecologic swab is used to paint both the perianal area and the rectal vault to a distance of 3 cm from the anus. The povidone iodine solution is then allowed to dry for 2-3 min prior to proceeding with standard transrectal ultrasonography and subsequent biopsy. This PIRP technique has been in practice at our institution since March of 2012 with an associated reduction of post-biopsy infections from 4.3% to 0.6% (p=0.02). The principal advantage of this prophylaxis regimen is its simplicity and reproducibility with use of an easily available, inexpensive agent to reduce infections. Furthermore, the technique avoids exposing patients to additional systemic antibiotics with potential further propagation of multi-drug resistant organisms. Usage of PIRP at TRUS PNB, however, is not applicable for patients with iodine or shellfish allergies.

  12. Povidone Iodine Rectal Preparation at Time of Prostate Needle Biopsy is a Simple and Reproducible Means to Reduce Risk of Procedural Infection.

    PubMed

    Raman, Jay D; Lehman, Kathleen K; Dewan, Kalyan; Kirimanjeswara, Girish

    2015-01-01

    Single institution and population-based studies highlight that infectious complications following transrectal ultrasound guided prostate needle biopsy (TRUS PNB) are increasing. Such infections are largely attributable to quinolone resistant microorganisms which colonize the rectal vault and are translocated into the bloodstream during the biopsy procedure. A povidone iodine rectal preparation (PIRP) at time of biopsy is a simple, reproducible method to reduce rectal microorganism colony counts and therefore resultant infections following TRUS PNB. All patients are administered three days of oral antibiotic therapy prior to biopsy. The PIRP technique involves initially positioning the patient in the standard manner for a TRUS PNB. Following digital rectal examination, 15 ml of a 10% solution of commercially available povidone iodine is mixed with 5 ml of 1% lidocaine jelly to create slurry. A 4 cmx4 cm sterile gauze is soaked in this slurry and then inserted into the rectal vault for 2 min after which it is removed. Thereafter, a disposable cotton gynecologic swab is used to paint both the perianal area and the rectal vault to a distance of 3 cm from the anus. The povidone iodine solution is then allowed to dry for 2-3 min prior to proceeding with standard transrectal ultrasonography and subsequent biopsy. This PIRP technique has been in practice at our institution since March of 2012 with an associated reduction of post-biopsy infections from 4.3% to 0.6% (p=0.02). The principal advantage of this prophylaxis regimen is its simplicity and reproducibility with use of an easily available, inexpensive agent to reduce infections. Furthermore, the technique avoids exposing patients to additional systemic antibiotics with potential further propagation of multi-drug resistant organisms. Usage of PIRP at TRUS PNB, however, is not applicable for patients with iodine or shellfish allergies. PMID:26436913

  13. Reducing the size of a data base by using pattern-recognition techniques

    SciTech Connect

    Clapp, N.E. Jr.

    1982-01-01

    An on-line surveillance system at a nuclear power plant samples data and calculates the power spectral density. A method of reducing the amount of stored data by screening the data using a pattern recognition technique was developed. The system stores only the spectra that differ from normal, plus the corresponding plant operating conditions. 7 figures.

  14. High-intensity training reduces intermittent hypoxia-induced ER stress and myocardial infarct size.

    PubMed

    Bourdier, Guillaume; Flore, Patrice; Sanchez, Hervé; Pepin, Jean-Louis; Belaidi, Elise; Arnaud, Claire

    2016-01-15

    Chronic intermittent hypoxia (IH) is described as the major detrimental factor leading to cardiovascular morbimortality in obstructive sleep apnea (OSA) patients. OSA patients exhibit increased infarct size after a myocardial event, and previous animal studies have shown that chronic IH could be the main mechanism. Endoplasmic reticulum (ER) stress plays a major role in the pathophysiology of cardiovascular disease. High-intensity training (HIT) exerts beneficial effects on the cardiovascular system. Thus, we hypothesized that HIT could prevent IH-induced ER stress and the increase in infarct size. Male Wistar rats were exposed to 21 days of IH (21-5% fraction of inspired O2, 60-s cycle, 8 h/day) or normoxia. After 1 wk of IH alone, rats were submitted daily to both IH and HIT (2 × 24 min, 15-30m/min). Rat hearts were either rapidly frozen to evaluate ER stress by Western blot analysis or submitted to an ischemia-reperfusion protocol ex vivo (30 min of global ischemia/120 min of reperfusion). IH induced cardiac proapoptotic ER stress, characterized by increased expression of glucose-regulated protein kinase 78, phosphorylated protein kinase-like ER kinase, activating transcription factor 4, and C/EBP homologous protein. IH-induced myocardial apoptosis was confirmed by increased expression of cleaved caspase-3. These IH-associated proapoptotic alterations were associated with a significant increase in infarct size (35.4 ± 3.2% vs. 22.7 ± 1.7% of ventricles in IH + sedenary and normoxia + sedentary groups, respectively, P < 0.05). HIT prevented both the IH-induced proapoptotic ER stress and increased myocardial infarct size (28.8 ± 3.9% and 21.0 ± 5.1% in IH + HIT and normoxia + HIT groups, respectively, P = 0.28). In conclusion, these findings suggest that HIT could represent a preventive strategy to limit IH-induced myocardial ischemia-reperfusion damages in OSA patients. PMID:26566725

  15. Analysis of reduced monoclonal antibodies using size exclusion chromatography coupled with mass spectrometry

    NASA Astrophysics Data System (ADS)

    Liu, Hongcheng; Gaza-Bulseco, Georgeen; Chumsae, Chris

    2009-12-01

    Size-exclusion chromatography (SEC) has been widely used to detect antibody aggregates, monomer, and fragments. SEC coupled to mass spectrometry has been reported to measure the molecular weights of antibody; antibody conjugates, and antibody light chain and heavy chain. In this study, separation of antibody light chain and heavy chain by SEC and direct coupling to a mass spectrometer was further studied. It was determined that employing mobile phases containing acetonitrile, trifluoroacetic acid, and formic acid allowed the separation of antibody light chain and heavy chain after reduction by SEC. In addition, this mobile phase allowed the coupling of SEC to a mass spectrometer to obtain a direct molecular weight measurement. The application of the SEC-MS method was demonstrated by the separation of the light chain and the heavy chain of multiple recombinant monoclonal antibodies. In addition, separation of a thioether linked light chain and heavy chain from the free light chain and the free heavy chain of a recombinant monoclonal antibody after reduction was also achieved. This optimized method provided a separation of antibody light chain and heavy chain based on size and allowed a direct measurement of molecular weights by mass spectrometry. In addition, this method may help to identify peaks eluting from SEC column directly.

  16. Significant enhancement of the thermoelectric figure of merit of polycrystalline Si films by reducing grain size

    NASA Astrophysics Data System (ADS)

    Valalaki, K.; Vouroutzis, N.; Nassiopoulou, A. G.

    2016-08-01

    The thermoelectric properties of p-type polycrystalline silicon thin films deposited by low pressure chemical vapour deposition (LPCVD) were accurately determined at room temperature and the thermoelectric figure of merit was deduced as a function of film thickness, ranging from 100 to 500 nm. The effect of film thickness on their thermoelectric performance is discussed. More than threefold increase in the thermoelectric figure of merit of the 100 nm thick polysilicon film was observed compared to the 500 nm thick film, reaching a value as high as 0.033. This enhancement is mainly the result of the smaller grain size in the thinner films. With the decrease in grain size the resistivity of the films is increased twofold and electrical conductivity decreased, however the Seebeck coefficient is increased by 30% and the thermal conductivity is decreased eightfold, being mainly at the origin of the increased figure of merit of the 100 nm film. Our experimental results were compared to known theoretical models and the possible mechanisms involved are presented and discussed.

  17. Salt stress reduces root meristem size by nitric oxide-mediated modulation of auxin accumulation and signaling in Arabidopsis.

    PubMed

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei; Lu, Ying-Tang

    2015-05-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor N(ω)-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels.

  18. Prostatic and dietary omega-3 fatty acids and prostate cancer progression during active surveillance.

    PubMed

    Moreel, Xavier; Allaire, Janie; Léger, Caroline; Caron, André; Labonté, Marie-Ève; Lamarche, Benoît; Julien, Pierre; Desmeules, Patrice; Têtu, Bernard; Fradet, Vincent

    2014-07-01

    The association between omega-3 (ω-3) fatty acids and prostate cancer has been widely studied. However, little is known about the impact of prostate tissue fatty acid content on prostate cancer progression. We hypothesized that compared with the estimated dietary ω-3 fatty acids intake and the ω-3 fatty acids levels measured in red blood cells (RBC), the prostate tissue ω-3 fatty acid content is more strongly related to prostate cancer progression. We present the initial observations from baseline data of a phase II clinical trial conducted in a cohort of 48 untreated men affected with low-risk prostate cancer, managed under active surveillance. These men underwent a first repeat biopsy session within 6 months after the initial diagnosis of low-risk prostate cancer, at which time 29% of the men had progressed from a Gleason score of 6 to a Gleason score of 7. At the first repeat biopsy session, fatty acid levels were assessed with a food-frequency questionnaire, and determined in the RBC and in the prostate tissue biopsy. We found that eicosapentaenoic acid (EPA) was associated with a reduced risk of prostate cancer progression when measured directly in the prostate tissue. Thus, this initial interim study analysis suggests that prostate tissue ω-3 fatty acids, especially EPA, may be protective against prostate cancer progression in men with low-risk prostate cancer.

  19. Transient response in longitudinal grain size to reduced sediment supply in a large river

    NASA Astrophysics Data System (ADS)

    Singer, Michael

    2010-05-01

    Bed material grain size is an important degree of freedom in fluvial systems as they adjust to system-wide perturbations such as sediment supply changes. However, little is known about processes and patterns of such adjustment in longitudinal grain size sorting in large rivers. This research uses unprecedented datasets collected in a large fluvial system to investigate transient response to recent supply changes associated with anthropogenic activities. Separate fining trends for gravel and fines, a protracted gravel-sand (G-S) transition, and bed patchiness identified in Singer (2008) were interrogated using output from a hydraulic model with grain size distributions (GSDs) extracted from ~125 cross sections spanning ~400 river kilometers of the Sacramento River, California. The analysis suggests that interactions between hydraulics, bed material sorting, and sediment flux explain these previously identified anomalies. Highest values of sorting occur in the G-S transition and represent the overlap of separate fining trends for gravel and fines, where the long profile is jagged with evidence of progressive incision. Much of the sediment in this poorly sorted zone is organized into patches, where transport apparently occurs as bedload sheets. Patchiness occurs over short length scales leading to strong differences in entrainment and flux, regardless of hydraulic conditions. A modified Shields stress is proposed that is scaled by GSD sorting to improve characterization of entrainment/disentrainment. Sediment flux calculations based on an equation sensitive bed material conditions (Singer and Dunne, 2004) reveal a strong relationship between fine sediment flux and d90, suggesting that the efficiency of fine patch flux controls bed material bed surface roughness. Results are in part consistent with Paola and Seal (1995) suggesting that patches are a result of overlapping pdfs of shear stress and sorting and with Ferguson (2003) in that the final end of the protracted G

  20. What keeps insects small? Time limitation during oviposition reduces the fecundity benefit of female size in a butterfly.

    PubMed

    Gotthard, Karl; Berger, David; Walters, Richard

    2007-06-01

    Laboratory studies of insects suggest that female fecundity may increase very rapidly with adult size and that mass may often increase close to exponentially with time during larval growth. These relationships make it difficult to see how realistic levels of larval mortality can outweigh the fecundity benefit of prolonged growth. Hence, it is unclear why many insects do not become bigger. In this study, we experimentally explore the relationship between female size and fecundity in the butterfly Pararge aegeria and show that thermally induced time limitation during oviposition may substantially reduce the fecundity benefit of larger females. We model time-limited oviposition under natural temperature conditions and show that fecundity is also likely to increase asymptotically with female size in the field. With realistic estimates of juvenile mortality, the model predicts optimal body sizes within the observed range even when larvae grow exponentially. We conclude that one important reason for why insects with a high capacity of larval growth do not evolve toward larger sizes may be that the fecundity benefit is in fact relatively limited under natural conditions. If so, these results may help resolve some of the inconsistencies between theory and empirical patterns in explaining optimal size in insects.

  1. Reducing Size, Weight, and Power (SWaP) of Perception Systems in Small Autonomous Aerial Systems

    NASA Technical Reports Server (NTRS)

    Jones, Kennie H.; Gross, Jason

    2014-01-01

    The objectives are to examine recent trends in the reduction of size, weight, and power (SWaP) requirements of sensor systems for environmental perception and to explore new technology that may overcome limitations in current systems. Improving perception systems to facilitate situation awareness is critical in the move to introduce increasing autonomy in aerial systems. Whether the autonomy is in the current state-of-the-art of increasing automation or is enabling cognitive decisions that facilitate adaptive behavior, collection of environmental information and fusion of that information into knowledge that can direct actuation is imperative to decisions resulting in appropriate behavior. Artificial sensory systems such as cameras, radar, LIDAR, and acoustic sensors have been in use on aircraft for many years but, due to the large size and weight of the airplane and electrical power made available through powerful engines, the SWaP requirements of these sensors was inconsequential. With the proliferation of Remote Piloted Vehicles (RPV), the trend is in significant reduction in SWaP of the vehicles. This requires at least an equivalent reduction in SWaP for the sensory systems. A survey of some currently available sensor systems and changing technology will reveal the trend toward reduction of SWaP of these systems and will predict future reductions. A new technology will be introduced that provides an example of a desirable new trend. A new device replaces multiple conventional sensory devices facilitating synchronization, localization, altimetry, collision avoidance, terrain mapping, and data communication in a single integrated, small form-factor, extremely lightweight, and low power device that it is practical for integration into small autonomous vehicles and can facilitate cooperative behavior. The technology is based on Ultra WideBand (UWB) radio using short pulses of energy rather than continuous sine waves. The characteristics of UWB yield several

  2. Laser system refinements to reduce variability in infarct size in the rat photothrombotic stroke model

    PubMed Central

    Alaverdashvili, Mariam; Paterson, Phyllis G.; Bradley, Michael P.

    2015-01-01

    Background The rat photothrombotic stroke model can induce brain infarcts with reasonable biological variability. Nevertheless, we observed unexplained high inter-individual variability despite using a rigorous protocol. Of the three major determinants of infarct volume, photosensitive dye concentration and illumination period were strictly controlled, whereas undetected fluctuation in laser power output was suspected to account for the variability. New method The frequently utilized Diode Pumped Solid State (DPSS) lasers emitting 532 nm (green) light can exhibit fluctuations in output power due to temperature and input power alterations. The polarization properties of the Nd:YAG and Nd:YVO4 crystals commonly used in these lasers are another potential source of fluctuation, since one means of controlling output power uses a polarizer with a variable transmission axis. Thus, the properties of DPSS lasers and the relationship between power output and infarct size were explored. Results DPSS laser beam intensity showed considerable variation. Either a polarizer or a variable neutral density filter allowed adjustment of a polarized laser beam to the desired intensity. When the beam was unpolarized, the experimenter was restricted to using a variable neutral density filter. Comparison with existing method(s) Our refined approach includes continuous monitoring of DPSS laser intensity via beam sampling using a pellicle beamsplitter and photodiode sensor. This guarantees the desired beam intensity at the targeted brain area during stroke induction, with the intensity controlled either through a polarizer or variable neutral density filter. Conclusions Continuous monitoring and control of laser beam intensity is critical for ensuring consistent infarct size. PMID:25840363

  3. Optical coherence tomography of the prostate nerves

    NASA Astrophysics Data System (ADS)

    Chitchian, Shahab

    Preservation of the cavernous nerves during prostate cancer surgery is critical in preserving a man's ability to have spontaneous erections following surgery. These microscopic nerves course along the surface of the prostate within a few millimeters of the prostate capsule, and they vary in size and location from one patient to another, making preservation of the nerves difficult during dissection and removal of a cancerous prostate gland. These observations may explain in part the wide variability in reported sexual potency rates (9--86%) following prostate cancer surgery. Any technology capable of providing improved identification, imaging, and visualization of the cavernous nerves during prostate cancer surgery would be of great assistance in improving sexual function after surgery, and result in direct patient benefit. Optical coherence tomography (OCT) is a noninvasive optical imaging technique capable of performing high-resolution cross-sectional in vivo and in situ imaging of microstructures in biological tissues. OCT imaging of the cavernous nerves in the rat and human prostate has recently been demonstrated. However, improvements in the OCT system and the quality of the images for identification of the cavernous nerves is necessary before clinical use. The following chapters describe complementary approaches to improving identification and imaging of the cavernous nerves during OCT of the prostate gland. After the introduction to OCT imaging of the prostate gland, the optimal wavelength for deep imaging of the prostate is studied in Chapter 2. An oblique-incidence single point measurement technique using a normal-detector scanning system was implemented to determine the absorption and reduced scattering coefficients, mua and m's , of fresh canine prostate tissue, ex vivo, from the diffuse reflectance profile of near-IR light as a function of source-detector distance. The effective attenuation coefficient, mueff, and the Optical Penetration Depth (OPD) were

  4. Comparing fuel reduction treatments for reducing wildfire size and intensity in a boreal forest landscape of northeastern China.

    PubMed

    Wu, Zhiwei; He, Hong S; Liu, Zhihua; Liang, Yu

    2013-06-01

    Fuel load is often used to prioritize stands for fuel reduction treatments. However, wildfire size and intensity are not only related to fuel loads but also to a wide range of other spatially related factors such as topography, weather and human activity. In prioritizing fuel reduction treatments, we propose using burn probability to account for the effects of spatially related factors that can affect wildfire size and intensity. Our burn probability incorporated fuel load, ignition probability, and spread probability (spatial controls to wildfire) at a particular location across a landscape. Our goal was to assess differences in reducing wildfire size and intensity using fuel-load and burn-probability based treatment prioritization approaches. Our study was conducted in a boreal forest in northeastern China. We derived a fuel load map from a stand map and a burn probability map based on historical fire records and potential wildfire spread pattern. The burn probability map was validated using historical records of burned patches. We then simulated 100 ignitions and six fuel reduction treatments to compare fire size and intensity under two approaches of fuel treatment prioritization. We calibrated and validated simulated wildfires against historical wildfire data. Our results showed that fuel reduction treatments based on burn probability were more effective at reducing simulated wildfire size, mean and maximum rate of spread, and mean fire intensity, but less effective at reducing maximum fire intensity across the burned landscape than treatments based on fuel load. Thus, contributions from both fuels and spatially related factors should be considered for each fuel reduction treatment.

  5. Awns reduce grain number to increase grain size and harvestable yield in irrigated and rainfed spring wheat

    PubMed Central

    Rebetzke, G. J.; Bonnett, D. G.; Reynolds, M. P.

    2016-01-01

    Genotypic variation in ear morphology is linked to differences in photosynthetic potential to influence grain yield in winter cereals. Awns contribute to photosynthesis, particularly under water-limited conditions when canopy assimilation is restricted. We assessed performance of up to 45 backcross-derived, awned–awnletted NILs representing four diverse genetic backgrounds in 25 irrigated or rainfed, and droughted environments in Australia and Mexico. Mean environment grain yields were wide-ranging (1.38–7.93 t ha−1) with vegetative and maturity biomass, plant height, anthesis date, spike number, and harvest index all similar (P >0.05) for awned and awnletted NILs. Overall, grain yields of awned–awnletted sister-NILs were equivalent, irrespective of yield potential and genetic background. Awnletted wheats produced significantly more grains per unit area (+4%) and per spike (+5%) reflecting more fertile spikelets and grains in tertiary florets. Increases in grain number were compensated for by significant reductions in grain size (–5%) and increased frequency (+0.8%) of small, shrivelled grains (‘screenings’) to reduce seed-lot quality of awnletted NILs. Post-anthesis canopies of awnletted NILs were marginally warmer over all environments (+0.27 °C) but were not different and were sometimes cooler than awned NILs at cooler air temperatures. Awns develop early and represented up to 40% of total spikelet biomass prior to ear emergence. We hypothesize that the allocation of assimilate to large and rapidly developing awns decreases spikelet number and floret fertility to reduce grain number, particularly in distal florets. Individual grain size is increased to reduce screenings and to increase test weight and milling quality, particularly in droughted environments. Despite the average reduction in grain size, awnless lines could be identified that combined higher grain yield with larger grain size, increased grain protein concentration, and reduced

  6. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischemia-reperfusion in a rat model

    PubMed Central

    Grönros, Julia; Kiss, Attila; Palmér, Malin; Jung, Christian; Berkowitz, Dan; Pernow, John

    2013-01-01

    Aim Ischemia-reperfusion injury is associated with reduced bioavailability of nitric oxide and microvascular dysfunction. One emerging mechanism behind reduced nitric oxide bioavailability is upregulation of arginase which metabolizes the nitric oxide synthase substrate L-arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion. Methods Anaesthetized rats, subjected to 30 min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor Nω-hydroxy-nor-L-arginine (nor-NOHA; 100 mg/kg) intravenously 15 min before ischemia. Coronary flow velocity was determined repeatedly during reperfusion. Results Arginase activity in the ischemic-reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 ± 3% of the area at risk vs. 51 ± 2% in the vehicle group, P<0.01) and at 8 days of reperfusion (13 ± 2% of the left ventricle vs. 22 ± 2%, P<0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor-NOHA and it correlated inversely to infarct size (P<0.01, r=−0.60). Hyperemic coronary flow velocity was also increased in the nor-NOHA treated group compared to vehicle at 24 h and at day 8 (P<0.05). Conclusion It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischemia-reperfusion. PMID:23497275

  7. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes.

  8. Staging of prostate cancer.

    PubMed

    Cheng, Liang; Montironi, Rodolfo; Bostwick, David G; Lopez-Beltran, Antonio; Berney, Daniel M

    2012-01-01

    Prostatic carcinoma (PCa) is a significant cause of cancer morbidity and mortality worldwide. Accurate staging is critical for prognosis assessment and treatment planning for PCa. Despite the large volume of clinical activity and research, the challenge to define the most appropriate and clinically relevant staging system remains. The pathologically complex and uncertain clinical course of prostate cancer further complicates the design of staging classification and a substaging system suitable for individualized care. This review will focus on recent progress and controversial issues related to prostate cancer staging. The 2010 revision of the American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumour, node and metastasis (TNM) system is the most widely used staging system at this time. Despite general acceptance of the system as a whole, there is controversy and uncertainty about its application, particularly for T2 subclassification. The three-tiered T2 classification system for organ-confined prostate cancer is superfluous, considering the biology and anatomy of PCa. A tumour size-based substaging system may be considered in the future TNM subclassification of pT2 cancer. Lymph node status is one of the most important prognostic factors for prostate cancer. Nevertheless, clinical outcomes in patients with positive lymph nodes are variable. Identification of patients at the greatest risk of systemic progression helps in the selection of appropriate therapy. The data suggest that the inherent aggressiveness of metastatic prostate cancer is closely linked to the tumour volume of lymph node metastasis. We recommend that a future TNM staging system should consider subclassification of node-positive cancer on the basis of nodal cancer volume, using the diameter of the largest nodal metastasis and/or the number of positive nodes. PMID:22212080

  9. Effect of homogenization techniques on reducing the size of microcapsules and the survival of probiotic bacteria therein.

    PubMed

    Ding, W K; Shah, N P

    2009-08-01

    This study investigated 2 different homogenization techniques for reducing the size of calcium alginate beads during the microencapsulation process of 8 probiotic bacteria strains, namely, Lactobacillus rhamnosus, L. salivarius, L. plantarum, L. acidophilus, L. paracasei, Bifidobacterium longum, B. lactis type Bi-04, and B. lactis type Bi-07. Two different homogenization techniques were used, namely, ultra-turrax benchtop homogenizer and Microfluidics microfluidizer. Various settings on the homogenization equipment were studied such as the number of passes, speed (rpm), duration (min), and pressure (psi). The traditional mixing method using a magnetic stirrer was used as a control. The size of microcapsules resulting from the homogenization technique, and the various settings were measured using a light microscope and a stage micrometer. The smallest capsules measuring (31.2 microm) were created with the microfluidizer using 26 passes at 1200 psi for 40 min. The greatest loss in viability of 3.21 log CFU/mL was observed when using the ultra-turrax benchtop homogenizer with a speed of 1300 rpm for 5 min. Overall, both homogenization techniques reduced capsule sizes; however, homogenization settings at high rpm also greatly reduced the viability of probiotic organisms.

  10. A reduced estimate of the number of kilometre-sized near-Earth asteroids.

    PubMed

    Rabinowitz, D; Helin, E; Lawrence, K; Pravdo, S

    2000-01-13

    Near-Earth asteroids are small (diameters < 10 km), rocky bodies with orbits that approach that of the Earth (they come within 1.3 AU of the Sun). Most have a chance of approximately 0.5% of colliding with the Earth in the next million years. The total number of such bodies with diameters > 1 km has been estimated to be in the range 1,000-2,000, which translates to an approximately 1% chance of a catastrophic collision with the Earth in the next millennium. These numbers are, however, poorly constrained because of the limitations of previous searches using photographic plates. (One kilometre is below the size of a body whose impact on the Earth would produce global effects.) Here we report an analysis of our survey for near-Earth asteroids that uses improved detection technologies. We find that the total number of asteroids with diameters > 1 km is about half the earlier estimates. At the current rate of discovery of near-Earth asteroids, 90% will probably have been detected within the next 20 years.

  11. CV205-502, a new non-ergot dopamine agonist, reduces prolactinoma size in man.

    PubMed

    Barnett, P S; Dawson, J M; Butler, J; Coskeran, P B; Maccabe, J J; McGregor, A M

    1990-08-01

    Seven patients with large prolactin-secreting pituitary adenomas were treated for 8 weeks with once-daily doses of the new, potent, non-ergot, long-acting dopamine agonist CV205-502. In five patients previous treatment with bromocriptine had failed to control their disease or been poorly tolerated and had therefore ceased. In all seven patients serum prolactin levels fell over the 8-week period of CV205-502 treatment with the decrease ranging from 33 to 99%. Associated with this decline in prolactin all patients showed symptomatic improvement with two of the five women beginning to menstruate and the two patients with visual field impairment showing marked improvement. Tolerance of the drug, with doses at 8 weeks ranging from 0.075 to 0.3 mg, was excellent with only minimal and transient side-effects being noted in three patients in none of whom was discontinuation of therapy necessary. In one patient noncompliance after 6 weeks of therapy was associated with a rapid return of her serum prolactin towards pretreatment levels. In all seven patients the clinical and biochemical improvement was accompanied by a marked reduction in tumour size.

  12. Reducing the size of the human physiological blind spot through training.

    PubMed

    Miller, Paul A; Wallis, Guy; Bex, Peter J; Arnold, Derek H

    2015-08-31

    The physiological blind spot refers to a zone of functional blindness all normally sighted people have in each eye, due to an absence of photoreceptors where the optic nerve passes through the surface of the retina. Here we report that the functional size of the physiological blind spot can be shrunk through training to distinguish direction signals at the blind spot periphery. Training on twenty successive weekdays improved sensitivity to both direction and colour, suggesting a generalizable benefit. Training on one blind spot, however, did not transfer to the blind spot in the untrained eye, ruling out mediation via a generic practice effect; nor could training benefits be attributed to eye movements, which were monitored to ensure stable fixation. These data suggest that training enhances the response gains of neurons with receptive fields that partially overlap, or abut, the physiological blind spot, thereby enhancing sensitivity to weak signals originating primarily from within the functionally-defined region of blindness [1-3]. Our results have important implications for situations where localised blindness has been acquired through damage to components of the visual system [4,5], and support proposals that these situations might be improved through perceptual training [5-7]. PMID:26325131

  13. Reduced molecular size and altered disaccharide composition of cerebral chondroitin sulfate upon Alzheimer's pathogenesis in mice.

    PubMed

    Zhang, Zui; Ohtake-Niimi, Shiori; Kadomatsu, Kenji; Uchimura, Kenji

    2016-08-01

    Alzheimer's disease (AD) is a progressive disorder leading to cognitive impairment and neuronal loss. Cerebral extracellular accumulation and deposition of amyloid ß plaques is a pathological hallmark of AD. Chondroitin sulfate (CS) is an extracellular component abundant in the brain. CS is a sulfated glycosaminoglycan covalently attached to a core protein, forming chondroitin sulfate proteoglycan. The structure of CS is heterogeneous with sulfation modification and elongation of the chain. The structural diversity of CS allows it to play various roles in the brain. Increasing evidence has shown that CS promotes aggregation of amyloid ß peptides into higher-order species such as insoluble amyloid ß fibrils. Difficulties in the structural analysis of brain CS, as well as its heterogeneity, limit the study of potential roles of CS in AD pathology. Here we established a microanalysis method with reversed-phase ion-pair high performance liquid chromatography and found that CS in the brains of Tg2576 AD model mice show a lower molecular size and an increased ratio of CS-B motif di-sulfated disaccharide. Our findings provide insight into the structural changes of cerebral CS upon Alzheimer's pathogenesis. PMID:27578913

  14. Reducing the size of the human physiological blind spot through training.

    PubMed

    Miller, Paul A; Wallis, Guy; Bex, Peter J; Arnold, Derek H

    2015-08-31

    The physiological blind spot refers to a zone of functional blindness all normally sighted people have in each eye, due to an absence of photoreceptors where the optic nerve passes through the surface of the retina. Here we report that the functional size of the physiological blind spot can be shrunk through training to distinguish direction signals at the blind spot periphery. Training on twenty successive weekdays improved sensitivity to both direction and colour, suggesting a generalizable benefit. Training on one blind spot, however, did not transfer to the blind spot in the untrained eye, ruling out mediation via a generic practice effect; nor could training benefits be attributed to eye movements, which were monitored to ensure stable fixation. These data suggest that training enhances the response gains of neurons with receptive fields that partially overlap, or abut, the physiological blind spot, thereby enhancing sensitivity to weak signals originating primarily from within the functionally-defined region of blindness [1-3]. Our results have important implications for situations where localised blindness has been acquired through damage to components of the visual system [4,5], and support proposals that these situations might be improved through perceptual training [5-7].

  15. Intensity-Modulated Radiotherapy Reduces Gastrointestinal Toxicity in Patients Treated With Androgen Deprivation Therapy for Prostate Cancer

    SciTech Connect

    Sharma, Navesh K.; Li Tianyu; Chen, David Y.; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

    2011-06-01

    Purpose: Androgen deprivation therapy (AD) has been shown to increase late Grade 2 or greater rectal toxicity when used concurrently with three-dimensional conformal radiotherapy (3D-CRT). Intensity-modulated radiotherapy (IMRT) has the potential to reduce toxicity by limiting the radiation dose received by the bowel and bladder. The present study compared the genitourinary and gastrointestinal (GI) toxicity in men treated with 3D-CRT+AD vs. IMRT+AD. Methods and Materials: Between July 1992 and July 2004, 293 men underwent 3D-CRT (n = 170) or IMRT (n = 123) with concurrent AD (<6 months, n = 123; {>=}6 months, n = 170). The median radiation dose was 76 Gy for 3D-CRT (International Commission on Radiation Units and Measurements) and 76 Gy for IMRT (95% to the planning target volume). Toxicity was assessed by a patient symptom questionnaire that was completed at each visit and recorded using a Fox Chase Modified Late Effects Normal Tissue Task radiation morbidity scale. Results: The mean follow-up was 86 months (standard deviation, 29.3) for the 3D-CRT group and 40 months (standard deviation, 9.7) for the IMRT group. Acute GI toxicity (odds ratio, 4; 95% confidence interval, 1.6-11.7; p = .005) was significantly greater with 3D-CRT than with IMRT and was independent of the AD duration (i.e., <6 vs. {>=}6 months). The interval to the development of late GI toxicity was significantly longer in the IMRT group. The 5-year Kaplan-Meier estimate for Grade 2 or greater GI toxicity was 20% for 3D-CRT and 8% for IMRT (p = .01). On multivariate analysis, Grade 2 or greater late GI toxicity (hazard ratio, 2.1; 95% confidence interval, 1.1-4.3; p = .04) was more prevalent in the 3D-CRT patients. Conclusion: Compared with 3D-CRT, IMRT significantly decreased the acute and late GI toxicity in patients treated with AD.

  16. Benign prostate hyperplasia (BPH) - resources

    MedlinePlus

    Resources - benign prostatic hyperplasia (BPH); Prostate enlargement resources; BPH resources ... organizations provide information on benign prostatic hyperplasia ( prostate enlargement ): National Kidney and Urologic Diseases Information Clearinghouse -- www. ...

  17. Prostate Cancer

    PubMed Central

    Vickers, Andrew J.; Lilja, Hans

    2010-01-01

    Two groundbreaking trials have this year reported conflicting results as to the benefit of screening for prostate cancer. Careful interpretation in the light of contemporary data might, however, reveal the true value of this intervention. PMID:19498406

  18. Enlarged prostate

    MedlinePlus

    ... Possible side effects include decreased sex drive and impotence . Antibiotics may be prescribed to treat chronic prostatitis ( ... less-invasive procedures carry a lower risk for impotence and incontinence than TURP, although the risk with ...

  19. Prostatitis - bacterial

    MedlinePlus

    ... emptying the bladder Foul-smelling urine Weak urine stream Other symptoms that may occur with this condition: ... the risk of spreading bacteria into the blood stream. The exam may reveal that the prostate is: ...

  20. Effective size of a wild salmonid population is greatly reduced by hatchery supplementation.

    PubMed

    Christie, M R; Marine, M L; French, R A; Waples, R S; Blouin, M S

    2012-10-01

    Many declining and commercially important populations are supplemented with captive-born individuals that are intentionally released into the wild. These supplementation programs often create large numbers of offspring from relatively few breeding adults, which can have substantial population-level effects. We examined the genetic effects of supplementation on a wild population of steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, by matching 12 run-years of hatchery steelhead back to their broodstock parents. We show that the effective number of breeders producing the hatchery fish (broodstock parents; N(b)) was quite small (harmonic mean N(b)=25 fish per brood-year vs 373 for wild fish), and was exacerbated by a high variance in broodstock reproductive success among individuals within years. The low N(b) caused hatchery fish to have decreased allelic richness, increased average relatedness, more loci in linkage disequilibrium and substantial levels of genetic drift in comparison with their wild-born counterparts. We also documented a substantial Ryman-Laikre effect whereby the additional hatchery fish doubled the total number of adult fish on the spawning grounds each year, but cut the effective population size of the total population (wild and hatchery fish combined) by nearly two-thirds. We further demonstrate that the Ryman-Laikre effect is most severe in this population when (1) >10% of fish allowed onto spawning grounds are from hatcheries and (2) the hatchery fish have high reproductive success in the wild. These results emphasize the trade-offs that arise when supplementation programs attempt to balance disparate goals (increasing production while maintaining genetic diversity and fitness).

  1. Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

    PubMed Central

    Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

    2015-01-01

    Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

  2. Effect of endorectal balloon positioning errors on target deformation and dosimetric quality during prostate SBRT

    NASA Astrophysics Data System (ADS)

    Jones, Bernard L.; Gan, Gregory; Kavanagh, Brian; Miften, Moyed

    2013-11-01

    An inflatable endorectal balloon (ERB) is often used during stereotactic body radiation therapy (SBRT) for treatment of prostate cancer in order to reduce both intrafraction motion of the target and risk of rectal toxicity. However, the ERB can exert significant force on the prostate, and this work assessed the impact of ERB position errors on deformation of the prostate and treatment dose metrics. Seventy-one cone-beam computed tomography (CBCT) image datasets of nine patients with clinical stage T1cN0M0 prostate cancer were studied. An ERB (Flexi-Cuff, EZ-EM, Westbury, NY) inflated with 60 cm3 of air was used during simulation and treatment, and daily kilovoltage (kV) CBCT imaging was performed to localize the prostate. The shape of the ERB in each CBCT was analyzed to determine errors in position, size, and shape. A deformable registration algorithm was used to track the dose received by (and deformation of) the prostate, and dosimetric values such as D95, PTV coverage, and Dice coefficient for the prostate were calculated. The average balloon position error was 0.5 cm in the inferior direction, with errors ranging from 2 cm inferiorly to 1 cm superiorly. The prostate was deformed primarily in the AP direction, and tilted primarily in the anterior-posterior/superior-inferior plane. A significant correlation was seen between errors in depth of ERB insertion (DOI) and mean voxel-wise deformation, prostate tilt, Dice coefficient, and planning-to-treatment prostate inter-surface distance (p < 0.001). Dosimetrically, DOI is negatively correlated with prostate D95 and PTV coverage (p < 0.001). For the model of ERB studied, error in ERB position can cause deformations in the prostate that negatively affect treatment, and this additional aspect of setup error should be considered when ERBs are used for prostate SBRT. Before treatment, the ERB position should be verified, and the ERB should be adjusted if the error is observed to exceed tolerable values.

  3. Total Mechanical Unloading Minimizes Metabolic Demand of Left Ventricle and Dramatically Reduces Infarct Size in Myocardial Infarction

    PubMed Central

    Kakino, Takamori; Arimura, Takahiro; Sakamoto, Takafumi; Nishikawa, Takuya; Sakamoto, Kazuo; Ikeda, Masataka; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2016-01-01

    Background Left ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion. Methods In 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support. Results t-LVAD markedly reduced MVO2 (% reduction against Control: -56 ± 9%, p<0.01) whereas p-LVAD did less (-21 ± 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: Control; 41.8 ± 6.4, p-LVAD; 29.1 ± 5.6 and t-LVAD; 5.0 ± 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size. Conclusions Total LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction. PMID:27124411

  4. Selective endothelin A receptor antagonism with sitaxentan reduces neointimal lesion size in a mouse model of intraluminal injury

    PubMed Central

    Duthie, Karolina M; Hadoke, Patrick W F; Kirkby, Nicholas S; Miller, Eileen; Ivy, Jessica R; McShane, John F; Lim, Win Gel; Webb, David J

    2015-01-01

    Background and Purpose Endothelin (ET) receptor antagonism reduces neointimal lesion formation in animal models. This investigation addressed the hypothesis that the selective ETA receptor antagonist sitaxentan would be more effective than mixed ETA/B receptor antagonism at inhibiting neointimal proliferation in a mouse model of intraluminal injury. Experimental Approach Antagonism of ETA receptors by sitaxentan (1–100 nM) was assessed in femoral arteries isolated from adult, male C57Bl6 mice using isometric wire myography. Neointimal lesion development was induced by intraluminal injury in mice receiving sitaxentan (ETA antagonist; 15 mg·kg−1·day−1), A192621 (ETB antagonist; 30 mg·kg−1·day−1), the combination of both antagonists or vehicle. Treatment began 1 week before, and continued for 28 days after, surgery. Femoral arteries were then harvested for analysis of lesion size and composition. Key Results Sitaxentan produced a selective, concentration-dependent parallel rightward shift of ET-1-mediated contraction in isolated femoral arteries. Sitaxentan reduced neointimal lesion size, whereas ETB and combined ETA/B receptor antagonism did not. Macrophage and α-smooth muscle actin content were unaltered by ET receptor antagonism but sitaxentan reduced the amount of collagen in lesions. Conclusions and Implications These results suggest that ETA receptor antagonism would be more effective than combined ETA/ETB receptor antagonism at reducing neointimal lesion formation. PMID:25598351

  5. Reduced size of the amygdala in individuals with 47,XXY and 47,XXX karyotypes.

    PubMed

    Patwardhan, Anil J; Brown, Wendy E; Bender, Bruce G; Linden, Mary G; Eliez, Stephan; Reiss, Allan L

    2002-01-01

    The excess of 47,XXX and 47,XXY karyotypes found in cytogenetic screening studies of individuals with schizophrenia has given support for an increased risk of psychiatric illness among men and women with sex chromosomal aneuploidy (SCA). Mesial temporal lobe structures, including the amygdala and hippocampus, are thought to be associated with abnormalities of mood and behavior in humans and in the neurobiology of schizophrenia. This study focuses on variations in volumes of mesial temporal lobe structures in men and women with SCA. Utilizing an unselected birth cohort of subjects with SCA and high-resolution magnetic resonance imaging (MRI), we investigated the neuroanatomical consequences of a supernumerary X chromosome on the morphology of the amygdala and hippocampus. Regional and total brain volumes were measured in 10 subjects with 47,XXY, 10 subjects with 47,XXX, and 20 euploid controls. Amygdala volumes were significantly reduced in men with 47,XXY, compared to control men, while the decrease in women with 47,XXX was not as pronounced. Hippocampus volumes were preserved in both groups, compared to same-gender controls. Longitudinal studies of SCA individuals have shown an increased incidence of mild psychopathology and behavioral dysfunction in men with 47,XXY and more overt psychiatric illness in women with 47,XXX, compared to control populations. The alteration in amygdala volumes in individuals with a supernumerary X chromosome may provide a neuroanatomic basis for these findings.

  6. Anabolic steroids activate calcineurin-NFAT signaling and thereby increase myotube size and reduce denervation atrophy.

    PubMed

    Qin, Weiping; Pan, Jiangping; Wu, Yong; Bauman, William A; Cardozo, Christopher

    2015-01-01

    Anabolic androgens have been shown to reduce muscle loss due to immobilization, paralysis and many other medical conditions, but the molecular basis for these actions is poorly understood. We have recently demonstrated that nandrolone, a synthetic androgen, slows muscle atrophy after nerve transection associated with down-regulation of regulator of calcineurin 2 (RCAN2), a calcineurin inhibitor, suggesting a possible role of calcineurin-NFAT signaling. To test this possibility, rat gastrocnemius muscle was analyzed at 56 days after denervation. In denervated muscle, calcineurin activity declined and NFATc4 was excluded from the nucleus and these effects were reversed by nandrolone. Similarly, nandrolone increased calcineurin activity and nuclear NFATc4 levels in cultured L6 myotubes. Nandrolone also induced cell hypertrophy that was blocked by cyclosporin A or overexpression of RCAN2. Finally protection against denervation atrophy by nandrolone in rats was blocked by cyclosporin A. These results demonstrate for the first time that nandrolone activates calcineurin-NFAT signaling, and that such signaling is important in nandrolone-induced cell hypertrophy and protection against paralysis-induced muscle atrophy.

  7. Soluble epoxide hydrolase gene deletion improves blood flow and reduces infarct size after cerebral ischemia in reproductively senescent female mice

    PubMed Central

    Zuloaga, Kristen L.; Zhang, Wenri; Roese, Natalie E.; Alkayed, Nabil J.

    2015-01-01

    Soluble epoxide hydrolase (sEH), a key enzyme in the metabolism of vasodilatory epoxyeicosatrienoic acids (EETs), is sexually dimorphic, suppressed by estrogen, and contributes to underlying sex differences in cerebral blood flow and injury after cerebral ischemia. We tested the hypothesis that sEH inhibition or gene deletion in reproductively senescent (RS) female mice would increase cerebral perfusion and decrease infarct size following stroke. RS (15–18 month old) and young (3–4 month old) female sEH knockout (sEHKO) mice and wild type (WT) mice were subjected to 45 min middle cerebral artery occlusion (MCAO) with laser Doppler perfusion monitoring. WT mice were treated with vehicle or a sEH inhibitor t-AUCB at the time of reperfusion and every 24 h thereafter for 3 days. Differences in regional cerebral blood flow were measured in vivo using optical microangiography (OMAG). Infarct size was measured 3 days after reperfusion. Infarct size and cerebral perfusion 24 h after MCAO were not altered by age. Both sEH gene deletion and sEH inhibition increased cortical perfusion 24 h after MCAO. Neither sEH gene deletion nor sEH inhibition reduced infarct size in young mice. However, sEH gene deletion, but not sEH inhibition of the hydrolase domain of the enzyme, decreased infarct size in RS mice. Results of these studies show that sEH gene deletion and sEH inhibition enhance cortical perfusion following MCAO and sEH gene deletion reduces damage after ischemia in RS female mice; however this neuroprotection in absent is young mice. PMID:25642188

  8. Photoacoustic imaging of prostate brachytherapy seeds in ex vivo prostate

    NASA Astrophysics Data System (ADS)

    Kuo, Nathanael; Kang, Hyun Jae; DeJournett, Travis; Spicer, James; Boctor, Emad

    2011-03-01

    The localization of brachytherapy seeds in relation to the prostate is a key step in intraoperative treatment planning (ITP) for improving outcomes in prostate cancer patients treated with low dose rate prostate brachytherapy. Transrectal ultrasound (TRUS) has traditionally been the modality of choice to guide the prostate brachytherapy procedure due to its relatively low cost and apparent ease of use. However, TRUS is unable to visualize seeds well, precluding ITP and producing suboptimal results. While other modalities such as X-ray and magnetic resonance imaging have been investigated to localize seeds in relation to the prostate, photoacoustic imaging has become an emerging and promising modality to solve this challenge. Moreover, photoacoustic imaging may be more practical in the clinical setting compared to other methods since it adds little additional equipment to the ultrasound system already adopted in procedure today, reducing cost and simplifying engineering steps. In this paper, we demonstrate the latest efforts of localizing prostate brachytherapy seeds using photoacoustic imaging, including visualization of multiple seeds in actual prostate tissue. Although there are still several challenges to be met before photoacoustic imaging can be used in the operating room, we are pleased to present the current progress in this effort.

  9. Expansion of prostate epithelial progenitor cells after inflammation of the mouse prostate

    PubMed Central

    Wang, Liang; Zoetemelk, Marloes; Chitteti, Brahmananda R.; Ratliff, Timothy L.; Myers, Jason D.; Srour, Edward F.; Broxmeyer, Hal

    2015-01-01

    Prostatic inflammation is a nearly ubiquitous pathological feature observed in specimens from benign prostate hyperplasia and prostate cancer patients. The microenvironment of the inflamed prostate is highly reactive, and epithelial hyperplasia is a hallmark feature of inflamed prostates. How inflammation orchestrates epithelial proliferation as part of its repair and recovery action is not well understood. Here, we report that a novel epithelial progenitor cell population is induced to expand during inflammation. We used sphere culture assays, immunofluorescence, and flow cytometry to show that this population is increased in bacterially induced inflamed mouse prostates relative to naïve control prostates. We confirmed from previous reports that this population exclusively possesses the ability to regrow entire prostatic structures from single cell culture using renal grafts. In addition, putative progenitor cells harvested from inflamed animals have greater aggregation capacity than those isolated from naïve control prostates. Expansion of this critical cell population requires IL-1 signaling, as IL-1 receptor 1-null mice exhibit inflammation similar to wild-type inflamed animals but exhibit significantly reduced progenitor cell proliferation and hyperplasia. These data demonstrate that inflammation promotes hyperplasia in the mouse prostatic epithelium by inducing the expansion of a selected epithelial progenitor cell population in an IL-1 receptor-dependent manner. These findings may have significant impact on our understanding of how inflammation promotes proliferative diseases such as benign prostatic hyperplasia and prostate cancer, both of which depend on expansion of cells that exhibit a progenitor-like nature. PMID:25925259

  10. Enhanced hydrogenation and reduced lattice distortion in size selected Pd-Ag and Pd-Cu alloy nanoparticles

    SciTech Connect

    Sengar, Saurabh K.; Mehta, B. R.; Kulriya, P. K.; Khan, S. A.

    2013-10-21

    Important correlation between valence band spectra and hydrogenation properties in Pd alloy nanoparticles is established by studying the properties of size selected and monocrystalline Pd, Ag, Cu, Pd-Ag, and Pd-Cu nanoparticles. The X-ray photoelectron spectroscopy and elastic recoil detection analysis show that size induced Pd4d centroid shift is related to enhanced hydrogenation with H/Pd ratio of 0.57 and 0.49 in Pd-Ag and Pd-Cu nanoparticles in comparison to reported bulk values of 0.2 and 0.1, respectively. Pd-alloy nanoparticles show lower hydrogen induced lattice distortion. The reduced distortion and higher hydrogen reactivity of Pd-alloy nanoparticles is important for numerous hydrogen related applications.

  11. Remediation of chromium-contaminated water using biogenic nano-sized materials and metal-reducing bacteria.

    PubMed

    Seo, Hyunhee; Sun, Eunyoung; Roh, Yul

    2013-06-01

    As an environmental nanotechnology, nano-sized materials have the potential to create novel and effective in-situ and ex-situ treatments for contaminated groundwater due to its high catalytic reactivity, large surface area, and dispersibility. In this study the efficiency of Cr(VI) reduction and immobilization using biotic and abiotic nano-sized materials (NSMs) and metal-reducing bacteria (MRB) was evaluated to remediate Cr(VI)-contaminated groundwater in batch and column tests. The results of this study revealed that the combination of the mixed MRB and bio-FeS/siderite performed the highest efficiency of Cr(VI) reduction and immobilization. Cr(VI) reduction by MRB and NSMs could impact on solubility of Cr(VI) and geochemical changes favorable for precipitation and adsorption.

  12. [The use of prostatilen in treating patients with prostatic diseases].

    PubMed

    Vozianov, A F; Gorpinchenko, I I; Boĭko, N I; Drannik, G N; Khavinson, V Kh

    1991-01-01

    A clinical trial of polypeptide prostatic preparation prostatilen has been performed in 37 and 15 patients with chronic prostatitis and prostatic adenoma, respectively. The treatment resulted in attenuation of algetic and dysuria symptoms. Copulative function and spermatogenesis improved. The uroflowmetric index rose, while residual urine and leukocyte count in prostatic secretion reduced. The drug demonstrated antibacterial and immunomodulation effects in the absence of adverse reactions. Prostatilen is indicated in: chronic prostatitis, prostatic adenoma stage I, normospermatogenic and toxic sterility, interoceptive copulative dysfunction, dysuria. The drug in recommended for clinical application.

  13. The Effect of Size and Taper of Apical Preparation in Reducing Intra-Canal Bacteria: A Quantitative SEM Study

    PubMed Central

    Mohammadzadeh Akhlaghi, Nahid; Rahimifard, Nahid; Moshari, Amirabbas; Vatanpour, Mehdi; Darmiani, Soheila

    2014-01-01

    Introduction: Bacteria and their byproducts are major etiologic factors in endodontic diseases. Prevention or reduction of root canal bacterial contamination is the main aim of endodontic treatment. The purpose of this in vitro study was to evaluate the effect of size and taper of master apical file (MAF) in reducing bacteria from the apical third of the curved canals using a quantitative scanning electron microscope (SEM) study. Methods and Materials: Eighty-nine human mandibular first molars with curved MB canals (20º-35º) were divided into one control group (n=5) (without rotary instrumentation) and 6 experimental groups (n=14). The canals were prepared using RaCe rotary files to the MAF sizes 25/0.04, 25/0.06, 30/0.04, 30/0.06, 35/0.04 and 35/0.06, in groups 1 to 6, respectively. All the experimental groups were finally rinsed with 2 mL of 17% EDTA followed by 3 mL of 5.25% NaOCl. The mesial roots were split longitudinally. Remaining bacteria in the apical third of MB canals were evaluated using SEM (2000×). Data analysis was performed using one way ANOVA with Tukey’s post hoc test. The level of significance was set at 0.05. Results: All the experimental groups showed significant bacterial reduction (P<0.001). Although the greater size and/or taper resulted in decrease in bacteria, differences between the groups were not significant. Conclusion: Based on this in vitro study the MAF #25/0.04 had no significant difference compared to other groups with greater apical size/taper; all groups could effectively reduce intra-canal bacteria. PMID:24396378

  14. Use of High-Frequency In-Home Monitoring Data May Reduce Sample Sizes Needed in Clinical Trials

    PubMed Central

    Dodge, Hiroko H.; Zhu, Jian; Mattek, Nora C.; Austin, Daniel; Kornfeld, Judith; Kaye, Jeffrey A.

    2015-01-01

    individual-specific distributions of walking speed collected at baseline, 262 subjects are required. Similarly for computer use, 26 subjects are required. Conclusions Individual-specific thresholds of low functional performance based on high-frequency in-home monitoring data distinguish trajectories of MCI from NC and could substantially reduce sample sizes needed in dementia prevention RCTs. PMID:26379170

  15. Impact of Prostate Inflammation on Lesion Development in the POET3+Pten+/− Mouse Model of Prostate Carcinogenesis

    PubMed Central

    Burcham, Grant N.; Cresswell, Gregory M.; Snyder, Paul W.; Chen, Long; Liu, Xiaoqi; Crist, Scott A.; Henry, Michael D.; Ratliff, Timothy L.

    2015-01-01

    Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten+/−) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten+/− mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b+Gr1+ cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten+/− model of cancer. PMID:25455686

  16. Impact of prostate inflammation on lesion development in the POET3(+)Pten(+/-) mouse model of prostate carcinogenesis.

    PubMed

    Burcham, Grant N; Cresswell, Gregory M; Snyder, Paul W; Chen, Long; Liu, Xiaoqi; Crist, Scott A; Henry, Michael D; Ratliff, Timothy L

    2014-12-01

    Evidence linking prostatitis and prostate cancer development is contradictory. To study this link, the POET3 mouse, an inducible model of prostatitis, was crossed with a Pten-loss model of prostate cancer (Pten(+/-)) containing the ROSA26 luciferase allele to monitor prostate size. Prostatitis was induced, and prostate bioluminescence was tracked over 12 months, with lesion development, inflammation, and cytokine expression analyzed at 4, 8, and 12 months and compared with mice without induction of prostatitis. Acute prostatitis led to more proliferative epithelium and enhanced bioluminescence. However, 4 months after initiation of prostatitis, mice with induced inflammation had lower grade pre-neoplastic lesions. A trend existed toward greater development of carcinoma 12 months after induction of inflammation, including one of two mice with carcinoma developing perineural invasion. Two of 18 mice at the later time points developed lesions with similarities to proliferative inflammatory atrophy, including one mouse with associated carcinoma. Pten(+/-) mice developed spontaneous inflammation, and prostatitis was similar among groups of mice at 8 and 12 months. Analyzed as one cohort, lesion number and grade were positively correlated with prostatitis. Specifically, amounts of CD11b(+)Gr1(+) cells were correlated with lesion development. These results support the hypothesis that myeloid-based inflammation is associated with lesion development in the murine prostate, and previous bouts of CD8-driven prostatitis may promote invasion in the Pten(+/-) model of cancer.

  17. Sildenafil increases chemotherapeutic efficacy of doxorubicin in prostate cancer and ameliorates cardiac dysfunction.

    PubMed

    Das, Anindita; Durrant, David; Mitchell, Clint; Mayton, Eric; Hoke, Nicholas N; Salloum, Fadi N; Park, Margaret A; Qureshi, Ian; Lee, Ray; Dent, Paul; Kukreja, Rakesh C

    2010-10-19

    We have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor sildenafil (Viagra) induces a powerful effect on reduction of infarct size following ischemia/reperfusion injury and improvement of left ventricular dysfunction in the failing heart after myocardial infarction or doxorubicin (DOX) treatment. In the present study, we further investigated the potential effects of sildenafil on improving antitumor efficacy of DOX in prostate cancer. Cotreatment with sildenafil enhanced DOX-induced apoptosis in PC-3 and DU145 prostate cancer cells, which was mediated by enhanced generation of reactive oxygen species, up-regulation of caspase-3 and caspase-9 activities, reduced expression of Bcl-xL, and phosphorylation of Bad. Overexpression of Bcl-xL or dominant negative caspase 9 attenuated the synergistic effect of sildenafil and DOX on prostate cancer cell killing. Furthermore, treatment with sildenafil and DOX in mice bearing prostate tumor xenografts resulted in significant inhibition of tumor growth. The reduced tumor size was associated with amplified apoptotic cell death and increased expression of activated caspase 3. Doppler echocardiography showed that sildenafil treatment ameliorated DOX-induced left ventricular dysfunction. In conclusion, these results provide provocative evidence that sildenafil is both a powerful sensitizer of DOX-induced killing of prostate cancer while providing concurrent cardioprotective benefit. PMID:20884855

  18. Decoration of BiOI quantum size nanoparticles with reduced graphene oxide in enhanced visible-light-driven photocatalytic studies

    NASA Astrophysics Data System (ADS)

    Liu, Zhang; Xu, Weicheng; Fang, Jianzhang; Xu, Xiaoxin; Wu, Shuxing; Zhu, Ximiao; Chen, Zehua

    2012-10-01

    Herein, a reverse microemulsion route was developed to synthesize bismuth oxyiodide (BiOI) nanocrystals and reduced graphene oxide (RGO) nanocomposites as a highly efficient photocatalyst, and both the formation of BiOI and the reduction of RGO were achieved in situ in microemulsions simultaneously at low temperature (60 °C). The uniform nanocrystal size and structure were indicated by XRD, TEM, and the reduction of GO by ascorbic acid was evidenced by FTIR, XPS, and Raman spectra techniques. The enhanced photoactivity of RGO/BiOI nanocomposites under visible light was attributed to improved light absorption and efficient charge separation and transportation.

  19. Deletion of the presynaptic scaffold CAST reduces active zone size in rod photoreceptors and impairs visual processing.

    PubMed

    tom Dieck, Susanne; Specht, Dana; Strenzke, Nicola; Hida, Yamato; Krishnamoorthy, Vidhyasankar; Schmidt, Karl-Friedrich; Inoue, Eiji; Ishizaki, Hiroyoshi; Tanaka-Okamoto, Miki; Miyoshi, Jun; Hagiwara, Akari; Brandstätter, Johann H; Löwel, Siegrid; Gollisch, Tim; Ohtsuka, Toshihisa; Moser, Tobias

    2012-08-29

    How size and shape of presynaptic active zones are regulated at the molecular level has remained elusive. Here we provide insight from studying rod photoreceptor ribbon-type active zones after disruption of CAST/ERC2, one of the cytomatrix of the active zone (CAZ) proteins. Rod photoreceptors were present in normal numbers, and the a-wave of the electroretinogram (ERG)--reflecting their physiological population response--was unchanged in CAST knock-out (CAST(-/-)) mice. Using immunofluorescence and electron microscopy, we found that the size of the rod presynaptic active zones, their Ca(2+) channel complement, and the extension of the outer plexiform layer were diminished. Moreover, we observed sprouting of horizontal and bipolar cells toward the outer nuclear layer indicating impaired rod transmitter release. However, rod synapses of CAST(-/-) mice, unlike in mouse mutants for the CAZ protein Bassoon, displayed anchored ribbons, normal vesicle densities, clustered Ca(2+) channels, and essentially normal molecular organization. The reduction of the rod active zone size went along with diminished amplitudes of the b-wave in scotopic ERGs. Assuming, based on the otherwise intact synaptic structure, an unaltered function of the remaining release apparatus, we take our finding to suggest a scaling of release rate with the size of the active zone. Multielectrode-array recordings of retinal ganglion cells showed decreased contrast sensitivity. This was also observed by optometry, which, moreover, revealed reduced visual acuity. We conclude that CAST supports large active zone size and high rates of transmission at rod ribbon synapses, which are required for normal vision.

  20. Using a Reduced Spot Size for Intensity-Modulated Proton Therapy Potentially Improves Salivary Gland-Sparing in Oropharyngeal Cancer

    SciTech Connect

    Water, Tara A. van de; Lomax, Antony J.; Bijl, Hendrik P.; Schilstra, Cornelis; Hug, Eugen B.; Langendijk, Johannes A.

    2012-02-01

    Purpose: To investigate whether intensity-modulated proton therapy with a reduced spot size (rsIMPT) could further reduce the parotid and submandibular gland dose compared with previously calculated IMPT plans with a larger spot size. In addition, it was investigated whether the obtained dose reductions would theoretically translate into a reduction of normal tissue complication probabilities (NTCPs). Methods: Ten patients with N0 oropharyngeal cancer were included in a comparative treatment planning study. Both IMPT plans delivered simultaneously 70 Gy to the boost planning target volume (PTV) and 54 Gy to the elective nodal PTV. IMPT and rsIMPT used identical three-field beam arrangements. In the IMPT plans, the parotid and submandibular salivary glands were spared as much as possible. rsIMPT plans used identical dose-volume objectives for the parotid glands as those used by the IMPT plans, whereas the objectives for the submandibular glands were tightened further. NTCPs were calculated for salivary dysfunction and xerostomia. Results: Target coverage was similar for both IMPT techniques, whereas rsIMPT clearly improved target conformity. The mean doses in the parotid glands and submandibular glands were significantly lower for three-field rsIMPT (14.7 Gy and 46.9 Gy, respectively) than for three-field IMPT (16.8 Gy and 54.6 Gy, respectively). Hence, rsIMPT significantly reduced the NTCP of patient-rated xerostomia and parotid and contralateral submandibular salivary flow dysfunction (27%, 17%, and 43% respectively) compared with IMPT (39%, 20%, and 79%, respectively). In addition, mean dose values in the sublingual glands, the soft palate and oral cavity were also decreased. Obtained dose and NTCP reductions varied per patient. Conclusions: rsIMPT improved sparing of the salivary glands and reduced NTCP for xerostomia and parotid and submandibular salivary dysfunction, while maintaining similar target coverage results. It is expected that rsIMPT improves quality

  1. Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways

    SciTech Connect

    Aguado, Andrea; Galán, María; Zhenyukh, Olha; Wiggers, Giulia A.; Roque, Fernanda R.; Redondo, Santiago; Peçanha, Franck; Martín, Angela; Fortuño, Ana; Cachofeiro, Victoria; Tejerina, Teresa; Salaices, Mercedes; and others

    2013-04-15

    MAPK activation, oxidative stress and COX-2 expression. ► Inhibition of MAPK reduces HgCl{sub 2}-induced oxidative stress and COX-2 expression. ► Inhibition of MAPK, oxidative stress and COX-2 restores the altered cell proliferation and size.

  2. Reduced neuronal size and mTOR pathway activity in the Mecp2 A140V Rett syndrome mouse model

    PubMed Central

    Rangasamy, Sampathkumar; Olfers, Shannon; Gerald, Brittany; Hilbert, Alex; Svejda, Sean; Narayanan, Vinodh

    2016-01-01

    Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model ( Mecp2 A140V “knock-in” mutant) expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant ( Mecp2 A140V/y) and wild type ( Mecp2 +/y) male mice. Cultured hippocampus and cerebellar granule neurons from mutant animals were significantly smaller than neurons from wild type animals. We also examined soma size in hippocampus neurons from individual female transgenic mice that express both a mutant  (maternal allele) and a wild type Mecp2 gene linked to an eGFP transgene (paternal allele). In cultures from such doubly heterozygous female mice, the size of neurons expressing the mutant (A140V) allele also showed a significant reduction compared to neurons expressing wild type MeCP2, supporting a cell-autonomous role for MeCP2 in neuronal development. IGF-1 (insulin growth factor-1) treatment of neuronal cells from Mecp2 mutant mice rescued the soma size phenotype. We also found that Mecp2   mutation leads to down-regulation of the mTOR signaling pathway, known to be involved in neuronal size regulation. Our results suggest that i) reduced neuronal size is an important in vitro cellular phenotype of Mecp2 mutation in mice, and ii) MeCP2 might play a critical role in the maintenance of neuronal structure by modulation of the mTOR pathway. The definition of a quantifiable cellular phenotype supports using neuronal size as a biomarker in the development of a high-throughput, in vitro assay to screen for compounds that rescue small neuronal phenotype (“phenotypic assay”). PMID:27781091

  3. Acute Bacterial Prostatitis: Diagnosis and Management.

    PubMed

    Coker, Timothy J; Dierfeldt, Daniel M

    2016-01-15

    Acute bacterial prostatitis is an acute infection of the prostate gland that causes pelvic pain and urinary tract symptoms, such as dysuria, urinary frequency, and urinary retention, and may lead to systemic symptoms, such as fevers, chills, nausea, emesis, and malaise. Although the true incidence is unknown, acute bacterial prostatitis is estimated to comprise approximately 10% of all cases of prostatitis. Most acute bacterial prostatitis infections are community acquired, but some occur after transurethral manipulation procedures, such as urethral catheterization and cystoscopy, or after transrectal prostate biopsy. The physical examination should include abdominal, genital, and digital rectal examination to assess for a tender, enlarged, or boggy prostate. Diagnosis is predominantly made based on history and physical examination, but may be aided by urinalysis. Urine cultures should be obtained in all patients who are suspected of having acute bacterial prostatitis to determine the responsible bacteria and its antibiotic sensitivity pattern. Additional laboratory studies can be obtained based on risk factors and severity of illness. Radiography is typically unnecessary. Most patients can be treated as outpatients with oral antibiotics and supportive measures. Hospitalization and broad-spectrum intravenous antibiotics should be considered in patients who are systemically ill, unable to voluntarily urinate, unable to tolerate oral intake, or have risk factors for antibiotic resistance. Typical antibiotic regimens include ceftriaxone and doxycycline, ciprofloxacin, and piperacillin/tazobactam. The risk of nosocomial bacterial prostatitis can be reduced by using antibiotics, such as ciprofloxacin, before transrectal prostate biopsy. PMID:26926407

  4. YAP is closely correlated with castration-resistant prostate cancer, and downregulation of YAP reduces proliferation and induces apoptosis of PC-3 cells.

    PubMed

    Sheng, Xia; Li, Wen-Bin; Wang, De-Lin; Chen, Ke-Hong; Cao, Jian-Jia; Luo, Zhao; He, Jiang; Li, Mei-Cai; Liu, Wu-Jiang; Yu, Chao

    2015-10-01

    Yes-associated protein 65 (YAP65) has been implicated as an oncogene, and its expression is increased in human cancer. Previous studies have demonstrated that alterations in YAP activity may result in tumourigenesis of the prostate. With androgen deprivation therapies becoming progressively ineffective, often leading to life‑threatening androgen‑resistant prostate cancer (CRPC). The present study aimed to analyse the role of YAP in prostate cancer (PCa), particularly in CRPC. YAP protein was detected using immunohistochemistry and western blot analysis in different prostatic tissues. In addition, three specific RNA interference vectors targeting the human YAP gene were synthesised, and PC‑3 cells with a stable inhibition of YAP were obtained by transfection. MTT, flow cytometry, reverse transcription‑quantitative polymerase chain reaction and western blot assays were used to analyse the effects of YAP inhibition on the proliferation and apoptosis of PC‑3 cells. The frequency of cells that were positive for YAP protein in PCa (78.13%) was significantly higher, compared with para‑PCa (26.67%; P=0.007) and benign prostatic hyperplasia (0%; P=0.002). The frequency of cells, which were positive for the expression of YAP exhibited a positive correlation (P=0.008) with the Gleason score, the tumour‑node‑metastasis staging (P=0.033) and the level of prostate specific antigens (P=0.0032) in PCa. The proliferative capacity of the transfected group was significantly lower, compared with the negative control group (P=0.022). The cell‑cycle of the transfected group was arrested in the G1 stage, which was detected using flow cytometry, and there was a significant increase in the apoptosis of cells in the transfected group (P=0.002). The mRNA and protein levels of TEA domain family member 1 were inhibited in the transfected group (P=0.001 and P=0.00, respectively). Therefore, it was concluded that gene transcription and protein expression of YAP may be involved

  5. Blood lipids and prostate cancer: a Mendelian randomization analysis.

    PubMed

    Bull, Caroline J; Bonilla, Carolina; Holly, Jeff M P; Perks, Claire M; Davies, Neil; Haycock, Philip; Yu, Oriana Hoi Yun; Richards, J Brent; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Amin Al Olama, Ali; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; MacInnis, Robert J; Wiklund, Fredrik; Gronberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Neal, David; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Micheal, Agnieszka; Pandha, Hardev; Smith, George Davey; Lewis, Sarah J; Martin, Richard M

    2016-06-01

    Genetic risk scores were used as unconfounded instruments for specific lipid traits (Mendelian randomization) to assess whether circulating lipids causally influence prostate cancer risk. Data from 22,249 prostate cancer cases and 22,133 controls from 22 studies within the international PRACTICAL consortium were analyzed. Allele scores based on single nucleotide polymorphisms (SNPs) previously reported to be uniquely associated with each of low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels, were first validated in an independent dataset, and then entered into logistic regression models to estimate the presence (and direction) of any causal effect of each lipid trait on prostate cancer risk. There was weak evidence for an association between the LDL genetic score and cancer grade: the odds ratio (OR) per genetically instrumented standard deviation (SD) in LDL, comparing high- (≥7 Gleason score) versus low-grade (<7 Gleason score) cancers was 1.50 (95% CI: 0.92, 2.46; P = 0.11). A genetically instrumented SD increase in TGs was weakly associated with stage: the OR for advanced versus localized cancer per unit increase in genetic risk score was 1.68 (95% CI: 0.95, 3.00; P = 0.08). The rs12916-T variant in 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) was inversely associated with prostate cancer (OR: 0.97; 95% CI: 0.94, 1.00; P = 0.03). In conclusion, circulating lipids, instrumented by our genetic risk scores, did not appear to alter prostate cancer risk. We found weak evidence that higher LDL and TG levels increase aggressive prostate cancer risk, and that a variant in HMGCR (that mimics the LDL lowering effect of statin drugs) reduces risk. However, inferences are limited by sample size and evidence of pleiotropy. PMID:26992435

  6. Reduced survival and body size in the terrestrial isopod Porcellio scaber from a metal-polluted environment.

    PubMed

    Jones, D T; Hopkin, S P

    1998-01-01

    Terrestrial isopods (woodlice) may show trade-offs in life history parameters when exposed to toxins. We have shown previously [Jones and Hopkin (1996) Functional Ecology 10, 741-750] that woodlice which survive to reproduce in sites heavily polluted with metals from an industrial smelting works do not alter their reproductive allocation. This study investigates whether there are differences in the survival and body size of Porcellio scaber from these same populations. Specimens were collected from eight sites at different distances from the Avonmouth smelter, UK. The sites represented a gradient of concentrations of Zn, Cd, Pb and Cu in the woodlice, from background levels to a grossly contaminated sites close to the smelter. In laboratory trials, the number of days survived by starved males showed a significant decline with increased concentrations of Zn in those animals. The maximum size of both sexes declined significantly from the least to the most polluted sites. The most polluted sites had significantly fewer large animals. The cost of detoxifying assimilated metals appears to be reduced energy reserves and smaller body size.

  7. Comparative efficacies of oral ketoconazole and terbinafine for reducing Malassezia population sizes on the skin of Basset Hounds.

    PubMed

    Guillot, Jacques; Bensignor, Emmanuel; Jankowski, François; Seewald, Wolfgang; Chermette, René; Steffan, Jean

    2003-06-01

    The objective of this study was to compare the efficacy of oral ketoconazole and terbinafine for reducing population sizes of Malassezia yeasts on canine skin. Twenty-one Basset Hounds were randomised in three groups of seven according to Malassezia populations. Dogs in the first group were treated by oral administration of ketoconazole (Ketofungol) 200 mg, Janssen-Cilag) at 10 mg x kg-1, every 24 h with food, for 3 weeks. Dogs in the second group were treated by oral administration of terbinafine (Lamisil) 250 mg, Novartis) at 30 mg x kg-1, every 24 h with food, for 3 weeks. The seven remaining dogs were used as controls. Malassezia population sizes were assessed by use of contact plates on four cutaneous sites at days 7, 14 and 21. Both ketoconazole and terbinafine were effective in reducing the baseline levels of Malassezia organisms with no significant difference between the two drugs. In further studies, oral terbinafine should be evaluated for the management of canine cases of Malassezia dermatitis. PMID:12791049

  8. Detection of prostate cancer with a blood-based assay for early prostate cancer antigen.

    PubMed

    Paul, Barbara; Dhir, Rajiv; Landsittel, Douglas; Hitchens, Moira R; Getzenberg, Robert H

    2005-05-15

    Prostate-specific antigen lacks specificity for prostate cancer, so the identification and characterization of a unique blood-based marker for the disease would provide for a more accurate diagnosis, reducing both unnecessary biopsies and patient uncertainty. We previously identified a novel biomarker for prostate cancer, early prostate cancer antigen (EPCA). EPCA antibodies positively stained the negative biopsies of men who, as much as 5 years later, were diagnosed with prostate cancer. The goal of this study was to determine whether EPCA antibodies could be used in a clinically applicable plasma-based immunoassay to specifically detect prostate cancer. Using an EPCA-based ELISA, the protein was measured in the plasma of 46 individuals, including prostate cancer patients, healthy individuals, other cancer patients, spinal cord injury victims, and patients with prostatitis. With a predetermined cutoff value of 1.7 absorbance at 450 nm, only the prostate cancer population, as a whole, expressed plasma-EPCA levels above the cutoff. Statistical analysis showed a significant difference in EPCA levels between the prostate cancer population and each of the other groups, specifically the healthy donors (P < 0.0001), bladder cancer patients (P = 0.03), and spinal cord injury patients (P = 0.001). Sensitivity of the EPCA assay for prostate cancer patients was 92% whereas the overall specificity was 94%. Specificity for the healthy donors was 100%. Although larger trials are required, this initial study shows the potential of EPCA to serve as a highly specific blood-based marker for prostate cancer. EPCA, when coupled with prostate-specific antigen, may help reduce the number of both unnecessary biopsies and undetected prostate tumors.

  9. Prostatic Artery Embolization for Enlarged Prostates Due to Benign Prostatic Hyperplasia. How I Do It

    SciTech Connect

    Carnevale, Francisco C.; Antunes, Alberto A.

    2013-12-15

    Prostatic artery embolization (PAE) has emerged as an alternative to surgical treatments for benign prostatic hyperplasia (BPH). Patient selection and refined technique are essential for good results. Urodynamic evaluation and magnetic resonance imaging are very important and technical limitations are related to elderly patients with tortuous and atherosclerotic vessels, anatomical variations, difficulty visualizing and catheterizing small diameter arteries feeding the prostate, and the potential risk of bladder and rectum ischemia. The use of small-diameter hydrophilic microcatheters is mandatory. Patients can be treated safely by PAE with low rates of side effects, reducing prostate volume with clinical symptoms and quality of life improvement without urinary incontinence, ejaculatory disorders, or erectile dysfunction. A multidisciplinary approach with urologists and interventional radiologists is essential to achieve better results.

  10. 3′,4′-Dihydroxyflavonol reduces infarct size and injury associated with myocardial ischaemia and reperfusion in sheep

    PubMed Central

    Wang, Sheng; Dusting, Gregory J; May, Clive N; Woodman, Owen L

    2004-01-01

    The antioxidant properties of flavonols in vivo and their potential benefits in myocardial ischaemia/reperfusion (I/R) injury have been little investigated. We evaluated the ability of a synthetic flavonol, 3′,4′-dihydroxyflavonol (DiOHF) to scavenge superoxide in post-I/R myocardium and to prevent myocardial I/R injury. Anaesthetized sheep were studied in four groups (n=5–6): control, ischaemic preconditioning (IPC), vehicle and DiOHF (before reperfusion, 5 mg kg−1, i.v.). The left anterior descending coronary artery was occluded distal to the second diagonal branch for 1 h followed by 2 h of reperfusion. Infarct size, myocardial function, NADPH-activated superoxide generation and biochemical markers of injury were measured. DiOHF (10−8–10−4 M) incubated in vitro with post-I/R myocardium from the vehicle group suppressed superoxide production dose-dependently. DiOHF administered in vivo also significantly reduced superoxide generation in vitro. DiOHF and IPC markedly reduced infarct size, which was 73±2% of the area at risk in vehicle, 50±4% in DiOHF, 75±5% in control and 44±4% in IPC. Post-I/R segment shortening within the ischaemic zone was greater in DiOHF (2.3±0.7%; P<0.01) and IPC (1.7±0.5%; P<0.01) than those in corresponding controls (−1.7±0.4; −2.1±0.4%). DiOHF and IPC improved coronary blood flow to the ischaemic area and preserved higher levels of nitric oxide metabolites in the venous outflow from the ischaemic zone. DiOHF attenuated superoxide production in post-I/R myocardium, and significantly reduced infarct size and injury following I/R in anaesthetized sheep. The extent of protection by DiOHF is comparable to that afforded by IPC. Thus, DiOHF has clinical potential for improving recovery from acute myocardial infarction and other ischaemic syndromes. PMID:15148246

  11. Effects of seed migration on post-implant dosimetry of prostate brachytherapy

    SciTech Connect

    Gao, M.; Wang, J. Z.; Nag, S.; Gupta, N.

    2007-02-15

    Brachytherapy using permanent seed implants has been an effective treatment for prostate cancer. However, seeds will migrate after implant, thus making the evaluation of post-implant dosimetry difficult. In this study, we developed a computer program to simulate seed migration and analyzed dosimetric changes due to seed migration at various migration amounts. The study was based on 14 patients treated with Pd-103 at the James Cancer Hospital. Modeling of seed migration, including direction, distance as well as day of migration, was based on clinical observations. Changes of commonly used dosimetric parameters as a function of migration amount (2, 4, 6 mm respectively), prostate size (from 20 to 90 cc), and prostate region (central vs peripheral) were studied. Change of biological outcome (tumor control probability) due to migration was also estimated. Migration reduced prostate D90 to 99{+-}2% of original value in 2 mm migration, and the reduction increased to 94{+-}6% in 6 mm migration. The reduction of prostate dose led to a 14% (40%) drop in the tumor control probability for 2 mm (6 mm) migration, assuming radiosensitive tumors. However, migration has less effect on a prostate implanted with a larger number of seeds. Prostate V100 was less sensitive to migration than D90 since its mean value was still 99% of original value even in 6 mm migration. Migration also showed a different effect in the peripheral region vs the central region of the prostate, where the peripheral mean dose tended to drop more significantly. Therefore, extra activity implanted in the peripheral region during pre-plan can be considered. The detrimental effects of migration were more severe in terms of increasing the dose to normal structures, as rectum V50 may be 70% higher and urethra V100 may be 50% higher in the case of 6 mm migration. Quantitative knowledge of these effects is helpful in treatment planning and post-implant evaluation.

  12. Localized Prostate Cancer

    MedlinePlus

    ... a decision aid for men with clinically localized prostate cancer (available at http://effectivehealthcare.ahrq.gov/prostate_da) ... A Decision Aid for Men With Clinically Localized Prostate Cancer Page 1 of 24 Introduction Men with clinically ...

  13. Prostate Cancer Prevention

    MedlinePlus

    ... finasteride who did have prostate cancer had more aggressive tumors . The number of deaths from prostate cancer ... men that did not. The number of less aggressive prostate cancers was lower, but the number of ...

  14. Prostate cancer

    MedlinePlus

    ... spread of the cancer. But it does not cure the cancer. If prostate cancer spreads even after hormone therapy, ... the Gleason score) when you are diagnosed. A cure is possible if the cancer has not spread. Hormone treatment can improve survival, ...

  15. Extraglandular and intraglandular vascularization of canine prostate.

    PubMed

    Stefanov, Miroslav

    2004-03-01

    The literature on the vascularization of the canine prostate is reviewed and the clinical significance of prostate morphology is described. Scanning Electron Microscopy (SEM), combined with improved corrosion casting methods, reveal new morphological details that promise better diagnostics and treatment but also require expansion of clinical nomenclature. A proposal is made for including two previously unnamed veins in Nomina Anatomica Veterinaria (NAV). The canine prostate has two lobes with independent vascularization. Each lobe is supplied through the left and right a. prostatica, respectively. The a. prostatica sprouts three small vessels (cranial, middle, and caudal) towards the prostate gland. A. prostatica is a small-size artery whose wall structure is similar to the arteries of the muscular type. V. prostatica is a small-size valved vein. The canine prostate has capsular, parenchymal, and urethral vascular zones. The surface vessels of the capsule are predominantly veins and the diameter of arterial vessels is larger than that of the veins. The trabecular vessels are of two types: direct and branched. The prostate parenchyma is supplied by branches of the trabecular vessels. The periacinary capillaries are fenestrated and form a net in a circular pattern. The processes of the myoepithelial cells embrace both the acins and the periacinar capillaries. In the prostate ductal system. there are spermatozoa. The prostatic part of the urethra is supplied by an independent branch of a. prostatica. The prostatic urethral part is drained by v. prostatica, the vein of the urethral bulb and the ventral prostate veins. M. urethralis begins as early as the urethral prostatic part. The greater part of the white muscle fibers in m. urethralis suggest an enhanced anaerobic metabolism.

  16. Prostatic cellular changes after injection of cadmium and lead into rat prostate.

    PubMed

    Khare, N; Der, R; Ross, G; Fahim, M

    1978-05-01

    Forty male rats were divided into four groups. Group I served as control. Group II received 1 mg. lead injected into the prostate; Group III received 1 mg. cadmium chloride; and Group IV received 0.5 mg. lead acetate and 0.5 mg. cadmium chloride. Results indicated that lead caused stone formation in the bladder and calcification of both bladder and prostate; cadmium caused reduction in size and weight of prostate, and histological observation showed marked atrophy of the gland, cuboidal epithelium, and squamous metaplasia in the acini of the prostate; there was no synergistic effect of lead acetate and cadmium chloride when combined at the level administered to Group IV.

  17. Size-Controlled Synthesis of Copper Oxide Particles on Reduced Graphene Oxide for Lithium-Ion Battery Anode Applications.

    PubMed

    Jang, Haneul; Kim, Kyungbae; Chang, Hyejung; Kim, Jae-Hun; Choi, Hyunjoo

    2015-11-01

    Copper oxide/reduced graphene oxide (rGO) hybrids have been successfully synthesized by attaching copper ions onto the functional groups of GO by means of a solution process, which causes precipitation and agglomeration of copper oxides during subsequent thermal reduction of the GO. The resulting copper oxide/rGO hybrid exhibited improved electrochemical performance compared to monolithic CuO, which is presumed to be due to rGO acting as a mechanical support that buffers the volume change in copper oxides that occurs as a result of the conversion reaction during charge/discharge cycling. Furthermore, it was found that the size of the copper oxide particles can be optimized by adjusting the annealing time, with a hybrid annealed for 30 min achieving a reversible capacity of 544 mA h g(-1) and an initial coulombic efficiency of 62.7%.

  18. Prostatitis and male infertility.

    PubMed

    Alshahrani, Saad; McGill, John; Agarwal, Ashok

    2013-11-01

    The prostate gland plays an important role in male reproduction. Inflammation of the prostate gland (prostatitis) is a common health problem affecting many young and middle aged men. Prostatitis is considered a correctable cause of male infertility, but the pathophysiology and appropriate treatment options of prostatitis in male infertility remain unclear. This literature review will focus on current data regarding prostatitis and its impact on male infertility.

  19. Clinorotation reduces number, but not size, of cartilaginous nodules formed in micromass cultures of mouse limbbud cells

    NASA Astrophysics Data System (ADS)

    Duke, P. J.; Montufar-Solis, D.; Hamazaki, T.; Sato, A.

    In previous studies we used a ground based model to investigate the cellular responses to microgravity by exposing micromass cultures of embryonic limb cells to simulated weightlessness on a clinostat. Cultures set up in T-flasks and rotated at 30 rpm showed that clinostatted cultures had less chondrocyte differentiation than stationary or rotation controls, as assessed by number of nodules/culture stained with cartilage specific Alcian blue. In the current study, nodule size and shape of these nodules was assessed by interactive measurement of area, perimeter, circularity, and equivalent diameters, using the Optimas imaging software. Results show no significant difference in any of the measurements, indicating that clinorotation has no effect on expansion of the nodules either by differentiation of cells within the nodule, or by recruitment of cells into the nodule. The reduction in number of nodules without an alteration in size and shape indicates that the effect of simulated microgravity is to reduce the cell interactions required for the initial condensation of cells into a nodule, probably by interference with cell adhesion molecules.

  20. Challenging the Inevitability of Prostate Enlargement: Low Levels of Benign Prostatic Hyperplasia Among Tsimane Forager-Horticulturalists

    PubMed Central

    Stieglitz, Jonathan; Rodriguez, Daniel Eid; Linares, Edhitt Cortez; Kaplan, Hillard S.; Gurven, Michael D.

    2015-01-01

    Background. Often considered an inevitable part of male aging, benign prostatic hyperplasia (BPH) is the most common non-life threatening disease to affect men in Western populations. We examine age-related change in prostate size and BPH risk and related serum biomarkers among the Tsimane Amerindians of the Bolivian Amazon who live a traditional lifestyle of hunting and small-scale horticulture. The Tsimane are a critical case study for understanding the etiology of BPH as they have low levels of obesity and metabolic syndrome, as well as lower levels of testosterone than age matched U.S. males, factors associated with BPH in previous research. Methods. Ultrasounds were conducted on 348 men aged 28–89 years (median age 56 years). Testosterone, prostate specific antigen, sex hormone binding globulin, and glycosylated hemoglobin were examined in relationship to prostate size and BPH. Results. Tsimane have less than half of the BPH prevalence experienced by U.S. men, and prostate volumes 62.6% smaller. While Tsimane have low levels of testosterone and subclinical levels of metabolic syndrome compared to U.S. men, Tsimane with high testosterone were more likely to experience BPH, as were those with higher glycosylated hemoglobin, suggesting targets for clinical interventions to reduce BPH. Conclusions. These results have clinical significance for the growing number of men taking testosterone supplementation; even at low levels the additional testosterone exposure could be placing these men at higher risk of BPH. Overall, these data suggest that BPH may not have been an inevitable part of male aging throughout human evolutionary history. PMID:25922348

  1. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    SciTech Connect

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  2. Extended lifespan, reduced body size and leg skeletal muscle mass, and decreased mitochondrial function in clk-1 transgenic mice.

    PubMed

    Takahashi, Kazuhide; Noda, Yoshihiro; Ohsawa, Ikuroh; Shirasawa, Takuji; Takahashi, Mayumi

    2014-10-01

    Mutational inactivation of clk-1, which encodes an enzyme necessary for the biosynthesis of coenzyme Q (CoQ), extends the lifespan of Caenorhabditis elegans. However, whether mammalian clk-1 regulates the lifespan of mice is not known because clk-1-deficiencies are embryonic lethal. Here, we investigated the lifespan of clk-1 transgenic mice (Tg96/I), which were rescued from embryonic lethality via the transgenic expression of mouse clk-1. Tg96/I mice lived longer and had smaller bodies than wild-type mice, but Tg96/I mice had CoQ levels equivalent to wild-type mice. The small-sized Tg96/I mice exhibited reduced whole-body oxygen consumption (VO2) during the dark period, and lean leg skeletal muscles with reduced mitochondrial VO2 and ATP content compared with wild-type mice. These findings indicate a close relationship between lifespan extension and decreased mitochondrial function, which was induced by the transgenic expression of clk-1, in leg skeletal muscles that exhibit high metabolic activity. PMID:25106098

  3. Benign Prostatic Hyperplasia: from Bench to Clinic

    PubMed Central

    Cho, Hee Ju

    2012-01-01

    Benign prostatic hyperplasia (BPH) is a prevalent disease, especially in old men, and often results in lower urinary tract symptoms (LUTS). This chronic disease has important care implications and financial risks to the health care system. LUTS are caused not only by mechanical prostatic obstruction but also by the dynamic component of obstruction. The exact etiology of BPH and its consequences, benign prostatic enlargement and benign prostatic obstruction, are not identified. Various theories concerning the causes of benign prostate enlargement and LUTS, such as metabolic syndrome, inflammation, growth factors, androgen receptor, epithelial-stromal interaction, and lifestyle, are discussed. Incomplete overlap of prostatic enlargement with symptoms and obstruction encourages focus on symptoms rather than prostate enlargement and the shifting from surgery to medicine as the treatment of BPH. Several alpha antagonists, including alfuzosin, doxazosin, tamsulosin, and terazosin, have shown excellent efficacy without severe adverse effects. In addition, new alpha antagonists, silodosin and naftopidil, and phosphodiesterase 5 inhibitors are emerging as BPH treatments. In surgical treatment, laser surgery such as photoselective vaporization of the prostate and holmium laser prostatectomy have been introduced to reduce complications and are used as alternatives to transurethral resection of the prostate (TURP) and open prostatectomy. The status of TURP as the gold standard treatment of BPH is still evolving. We review several preclinical and clinical studies about the etiology of BPH and treatment options. PMID:22468207

  4. Does Hormone Therapy Reduce Disease Recurrence in Prostate Cancer Patients Receiving Dose-Escalated Radiation Therapy? An Analysis of Radiation Therapy Oncology Group 94-06

    SciTech Connect

    Valicenti, Richard K.; Bae, Kwounghwa; Michalski, Jeff; Sandler, Howard; Shipley, William; Lin, Alex; Cox, James

    2011-04-01

    Purpose: The purpose of this study was to evaluate the effect on freedom from biochemical failure (bNED) or disease-free survival (DFS) by adding hormone therapy (HT) to dose-escalated radiation therapy (HDRT). Methods and Materials: We used 883 analyzable prostate cancer patients who enrolled on Radiation Therapy Oncology Group (RTOG) 94-06, a Phase I/II dose escalation trial, and whose mean planning target volume dose exceeded 73.8 Gy (mean, 78.5 Gy; maximum, 84.3 Gy). We defined biochemical failure according to the Phoenix definition. Results: A total of 259 men started HT 2 to 3 months before HDRT, but not longer than 6 months, and 66 men with high-risk prostate cancer received HT for a longer duration. At 5 years, the biochemical failure rates after HDRT alone were 12%, 18%, and 29% for low-, intermediate-, and high-risk patients, respectively (p < 0.0001). Cox proportional hazards regression analysis adjusted for covariates revealed that pretreatment PSA level was a significant factor, whereas risk group, Gleason score, T-stage, and age were not. When the patients were stratified by risk groups, the Cox proportion hazards regression model (after adjusting for pretreatment PSA, biopsy Gleason score, and T stage) did not reveal a significant effect on bNED or DFS by adding HT to HDRT Conclusion: The addition of HT did not significantly improve bNED survival or DFS in all prostate cancer patients receiving HDRT, but did approach significance in high-risk patient subgroup. The result of this study is hypothesis generating and requires testing in a prospective randomized trial.

  5. [Screening for prostate cancer].

    PubMed

    Koch, Klaus; Büchter, Roland; Lange, Stefan

    2013-04-01

    Prostate cancer screening has been a controversial for decades. The recently published findings of large trials have further intensified the debate. The prospect of reducing mortality from prostate cancer is measured against the risk of over-diagnosing the disease. In individual cases, the trade-off between possible benefits and harms is possible to ascertain, so general recommendations in favor of or against PSA tests for individuals cannot be made. The majority of men, however, are not well-informed on the possible advantages and drawbacks of screening. This situation urgently needs to be corrected. The PSA test is promoted to healthy men, who need to be provided with especially detailed information. If not provided with clear and unbiased information on the risks associated with the test (above all over-diagnosis and over-treatment), these men cannot be considered to be fully informed. PMID:23535548

  6. A natural antipredation experiment: predator control and reduced sea ice increases colony size in a long-lived duck.

    PubMed

    Hanssen, Sveinn A; Moe, Børge; Bårdsen, Bård-Jørgen; Hanssen, Frank; Gabrielsen, Geir W

    2013-09-01

    Anthropogenic impact on the environment and wildlife are multifaceted and far-reaching. On a smaller scale, controlling for predators has been increasing the yield from local natural prey resources. Globally, human-induced global warming is expected to impose severe negative effects on ecosystems, an effect that is expected to be even more pronounced in the scarcely populated northern latitudes. The clearest indication of a changing Arctic climate is an increase in both air and ocean temperatures leading to reduced sea ice distribution. Population viability is for long-lived species dependent on adult survival and recruitment. Predation is the main mortality cause in many bird populations, and egg predation is considered the main cause of reproductive failure in many birds. To assess the effect of predation and climate, we compared population time series from a natural experiment where a trapper/down collector has been licensed to actively protect breeding common eiders Somateria mollissima (a large seaduck) by shooting/chasing egg predators, with time series from another eider colony located within a nature reserve with no manipulation of egg predators. We found that actively limiting predator activity led to an increase in the population growth rate and carrying capacity with a factor of 3-4 compared to that found in the control population. We also found that population numbers were higher in years with reduced concentration of spring sea ice. We conclude that there was a large positive impact of human limitation of egg predators, and that this lead to higher population growth rate and a large increase in size of the breeding colony. We also report a positive effect of warming climate in the high arctic as reduced sea-ice concentrations was associated with higher numbers of breeding birds.

  7. Inhibition of protein kinase CK2 reduces CYP24A1 expression and enhances 1,25-dihydroxyvitamin D3 anti-tumor activity in human prostate cancer cells

    PubMed Central

    Luo, Wei; Yu, Wei-Dong; Ma, Yingyu; Chernov, Mikhail; Trump, Donald L.; Johnson, Candace S.

    2013-01-01

    Vitamin D has broad range of physiological functions and anti-tumor effects. 24-hydroxylase, encoded by the CYP24A1 gene, is the key enzyme for degrading many forms of vitamin D including the most active form, 1,25D3. Inhibition of CYP24A1 enhances 1,25D3 anti-tumor activity. In order to isolate regulators of CYP24A1 expression in prostate cancer cells, we established a stable prostate cancer cell line PC3 with CYP24A1 promoter driving luciferase expression to screen a small molecular library for compounds that inhibit CYP24A1 promoter activity. From this screening, we identified, 4,5,6,7-tetrabromobenzimidazole (TBBz), a protein kinase CK2 selective inhibitor as a disruptor of CYP24A1 promoter activity. We show that TBBz inhibits CYP24A1 promoter activity induced by 1,25D3 in prostate cancer cells. In addition, TBBz downregulates endogenous CYP24A1 mRNA level in TBBz treated PC3 cells. Furthermore, siRNA-mediated CK2 knockdown reduces 1,25D3 induced CYP24A1 mRNA expression in PC3 cells. These results suggest that CK2 contributes to 1,25D3 mediated target gene expression. Lastly, inhibition of CK2 by TBBz or CK2 siRNA significantly enhanced 1,25D3 mediated anti-proliferative effect in vitro and in vivo in a xenograft model. In summary, our findings reveal that protein kinase CK2 is involved in the regulation of CYP24A1 expression by 1,25D3 and CK2 inhibitor enhances 1,25D3 mediated anti-tumor effect. PMID:23358686

  8. Metabolomic Imaging for Human Prostate Cancer Detection

    PubMed Central

    Wu, Chin-Lee; Jordan, Kate W.; Ratai, Eva M.; Sheng, Jinhua; Adkins, Christen B.; DeFeo, Elita M; Jenkins, Bruce G.; Ying, Leslie; McDougal, W. Scott; Cheng, Leo L.

    2010-01-01

    As current radiological approaches cannot accurately localize prostate cancer in vivo, biopsies are conducted at random within prostates for at-risk patients, leading to high false-negative rates. Metabolomic imaging can map cancer-specific biomolecular profile values onto anatomical structures to direct biopsy. In this preliminary study, we evaluated five prostatectomy-removed whole prostates from biopsy-proven cancer patients on a 7 Tesla human, whole-body magnetic resonance scanner. Localized, multi-cross-sectional, multi-voxel magnetic resonance spectra were used to construct a malignancy index based on prostate cancer metabolomic profiles obtained from previous, intact tissue analyses by a 14 Tesla spectrometer. This calculated Malignancy Index shows linear correlation with lesion size (p<0.013) and demonstrates a 93–97% overall accuracy for detecting the presence of prostate cancer lesions. PMID:20371475

  9. Laser-induced interstitial thermotherapy of benign prostatic hyperplasia and prostate cancer

    NASA Astrophysics Data System (ADS)

    Muschter, Rolf

    1994-12-01

    Urinary outflow obstruction by prostatic enlargement is usually treated by resection or, recently, less invasively by thermal `ablation' of tissue through the urethra. With the latter technique, the amount of tissue that can be removed is limited by the limited penetration depth of suitable radiation sources, e.g. lasers, or conduction of heat. Interstitial thermotherapy was expected to overcome this problem. Our initial in vitro and animal studies with different light guides for interstitial application of Nd:YAG laser radiation showed small carbonized lesions with bare fibers, but large homogeneous coagulation zones with special `ITT' (interstitial thermotherapy) fibers. Further studies using these applicators resulted in a technique to be apt for clinical routine in the treatment of symptomatic prostatic enlargement. The tip of the light guide was repeatedly inserted into the prostate either transurethrally through a cystoscope under direct vision or percutaneously from the perineum under transrectal ultrasound guidance. The number of fiber placements depended on the size and configuration of the gland. Irradiation was performed either for 10 min with 5 or 7 W or in the advanced `turbo'- mode for 5 or 3 min per fiber placement using automatically stepwise reduced power (20 W for 30 s, 15 W for 30 s, 10 W for 30 s, and 7 W for 210 or 90 s). By optical feedback control the laser was switched off automatically in the case of carbonization to avoid fiber damage. From July 15, 1991 to October 1, 1993 239 patients with BPH and 14 patients with advanced prostate cancer, suffering from severe urinary outflow obstruction, were treated by laser induced interstitial thermotherapy. The results and complications of treatment are reported.

  10. Reduced Fetal Cerebral Oxygen Consumption is Associated With Smaller Brain Size in Fetuses With Congenital Heart Disease

    PubMed Central

    Sun, Liqun; Macgowan, Christopher K; Sled, John G; Yoo, Shi-Joon; Manlhiot, Cedric; Porayette, Prashob; Grosse-Wortmann, Lars; Jaeggi, Edgar; McCrindle, Brian W; Kingdom, John; Hickey, Edward; Miller, Steven; Seed, Mike

    2015-01-01

    Background Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging (MRI) technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation. Methods and Results We measured fetal brain size, oxygen saturation and blood flow in the major vessels of the fetal circulation in 30 late gestation fetuses with CHD and 30 normal controls using phase contrast MRI and T2 mapping. Fetal hemodynamic parameters were calculated using a combination of MRI flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (p<0.001), and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (p < 0.001), while cerebral blood flow and cerebral oxygen extraction were no different from controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (p = 0.08) and 32% reduction cerebral VO2 in CHD fetuses (p < 0.001), which were associated with a 13% reduction in fetal brain volume (p < 0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral VO2 (r = 0.37 p = 0.004). Conclusions This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy. PMID:25762062

  11. Dietary gamma-linolenate attenuates tumor growth in a rodent model of prostatic adenocarcinoma via suppression of elevated generation of PGE(2) and 5S-HETE.

    PubMed

    Pham, Hung; Vang, Kao; Ziboh, Vincent A

    2006-04-01

    Prostate cancer poses considerable threat to the aging male population as it has become a leading cause of cancer death to this group. Due to the complexity of this age-related disease, the mechanism(s) and factors resulting in prostate cancer remain unclear. Reports showing an increase risk in prostatic cancer with increasing dietary fat are contrasted by other studies suggesting the beneficial effects of certain polyunsaturated fatty acid (PUFA) in the modulation of tumor development. The n-6 PUFA, gamma-linolenic acid (GLA), has been shown to suppress tumor growth in vitro. Therefore, using the Lobund-Wistar (L-W) rat model of prostate cancer, we tested the hypothesis whether dietary supplementation of GLA could suppress tumor growth and development in vivo. Prostatic adenocarcinomas were induced in two groups of L-W rats, the experimental group (N-nitroso-N-methylurea, NMU/testosterone propionate, TP) and the GLA group (NMU/TP/GLA fed) undergoing similar treatment but fed a purified diet supplemented with GLA. Our findings revealed a decrease in prostate growth in the NMU/TP/GLA-fed group as determined by weight, tissue size, DNA content and prostate-specific antigen (tumor marker of prostate cancer). Comparison between the two groups showed a significant increase in 5S-hydroxyeicosatetraenoic acid and prostaglandin E(2) in the NMU/TP group. These increases paralleled the increased protein expression and activity of cyclooxygenase-2 as well as increased activity of 5-lipoxygenase. Taken together, the findings showed that intake of GLA-enriched diet does reduce prostatic cancer development in L-W rats and could serve as a non-toxic adjunct in management of human prostatic cancer. PMID:16567086

  12. Temporary prostatic stenting and androgen suppression: a new minimally invasive approach to malignant prostatic retention.

    PubMed Central

    Anson, K M; Barnes, D G; Briggs, T P; Watson, G M; Miller, R A

    1993-01-01

    Urinary retention secondary to carcinoma of the prostate is usually treated by 'channel' transurethral resection of the prostate either performed alone or in combination with hormone manipulation. The combination of temporary prostatic stenting and androgen suppression may reduce the morbidity and mortality associated with this treatment. We report on our initial experience using the combination of a temporary prostatic stent with the oral anti-androgen Flutamide in 10 patients with urinary retention or severe bladder outflow obstruction secondary to prostatic carcinoma. Eight of the ten patients successfully voided and maintained normal voiding after stent removal. There were two treatment failures requiring prostatic resection. We believe the cost of stenting and medication is entirely justified by patient preference and clearance of hospital beds. PMID:8258796

  13. Dietary Lycopene, Angiogenesis, and Prostate Cancer: A Prospective Study in the Prostate-Specific Antigen Era

    PubMed Central

    2014-01-01

    Background The role of lycopene in prostate cancer prevention remains controversial. We examined the associations between dietary lycopene intake and prostate cancer, paying particular attention to the influence of prostate-specific antigen screening, and evaluated tissue biomarkers in prostate cancers in relation to lycopene intake. Methods Among 49898 male health professionals, we obtained dietary information through questionnaires and ascertained total and lethal prostate cancer cases from 1986 through January 31, 2010. Cox regression was used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs). Tissue microarrays and immunohistochemistry were used to assess tumor biomarker expression in a subset of men. Two-sided χ2 tests were used to calculate the P values. Results Higher lycopene intake was inversely associated with total prostate cancer and more strongly with lethal prostate cancer (top vs bottom quintile: HR = 0.72; 95% CI = 0.56 to 0.94; P trend = .04). In a restricted population of screened participants, the inverse associations became markedly stronger (for lethal prostate cancer: HR = 0.47; 95% CI = 0.29 to 0.75; P trend = .009). Comparing different measures of dietary lycopene, early intake, but not recent intake, was inversely associated with prostate cancer. Higher lycopene intake was associated with biomarkers in the cancer indicative of less angiogenic potential. Conclusions Dietary intake of lycopene was associated with reduced risk of lethal prostate cancer and with a lesser degree of angiogenesis in the tumor. Because angiogenesis is a strong progression factor, an endpoint of lethal prostate cancer may be more relevant than an endpoint of indolent prostate cancer for lycopene in the era of highly prevalent prostate-specific antigen screening. PMID:24463248

  14. Effectiveness of a Comprehensive Stress Management Program to Reduce Work-Related Stress in a Medium-Sized Enterprise

    PubMed Central

    2014-01-01

    Objectives To assess the effectiveness of a comprehensive workplace stress management program consisting of participatory action-oriented training (PAOT) and individual management. Methods A comprehensive workplace stress management program was conducted in a medium-sized enterprise. The baseline survey was conducted in September 2011, using the Korean Occupational Stress Scale (KOSS) and Worker’s Stress Response Inventory (WSRI). After implementing both organizational and individual level interventions, the follow up evaluation was conducted in November 2011. Results Most of the workers participated in the organizational level PAOT and made Team-based improvement plans. Based on the stress survey, 24 workers were interviewed by a researcher. After the organizational and individual level interventions, there was a reduction of several adverse psychosocial factors and stress responses. In the case of blue-collar workers, psychosocial factors such as the physical environment, job demands, organizational system, lack of rewards, and occupational climate were significantly improved; in the case of white-collar workers, the occupational climate was improved. Conclusions In light of these results, we concluded that the comprehensive stress management program was effective in reducing work-related stress in a short-term period. A persistent long-term follow up is necessary to determine whether the observed effects are maintained over time. Both team-based improvement activities and individual interviews have to be sustainable and complementary to each other under the long-term plan. PMID:24524591

  15. A Self-Organizing Map-Based Approach to Generating Reduced-Size, Statistically Similar Climate Datasets

    NASA Astrophysics Data System (ADS)

    Cabell, R.; Delle Monache, L.; Alessandrini, S.; Rodriguez, L.

    2015-12-01

    Climate-based studies require large amounts of data in order to produce accurate and reliable results. Many of these studies have used 30-plus year data sets in order to produce stable and high-quality results, and as a result, many such data sets are available, generally in the form of global reanalyses. While the analysis of these data lead to high-fidelity results, its processing can be very computationally expensive. This computational burden prevents the utilization of these data sets for certain applications, e.g., when rapid response is needed in crisis management and disaster planning scenarios resulting from release of toxic material in the atmosphere. We have developed a methodology to reduce large climate datasets to more manageable sizes while retaining statistically similar results when used to produce ensembles of possible outcomes. We do this by employing a Self-Organizing Map (SOM) algorithm to analyze general patterns of meteorological fields over a regional domain of interest to produce a small set of "typical days" with which to generate the model ensemble. The SOM algorithm takes as input a set of vectors and generates a 2D map of representative vectors deemed most similar to the input set and to each other. Input predictors are selected that are correlated with the model output, which in our case is an Atmospheric Transport and Dispersion (T&D) model that is highly dependent on surface winds and boundary layer depth. To choose a subset of "typical days," each input day is assigned to its closest SOM map node vector and then ranked by distance. Each node vector is treated as a distribution and days are sampled from them by percentile. Using a 30-node SOM, with sampling every 20th percentile, we have been able to reduce 30 years of the Climate Forecast System Reanalysis (CFSR) data for the month of October to 150 "typical days." To estimate the skill of this approach, the "Measure of Effectiveness" (MOE) metric is used to compare area and overlap

  16. Uric acid: a modulator of prostate cells and activin sensitivity.

    PubMed

    Sangkop, Febbie; Singh, Geeta; Rodrigues, Ely; Gold, Elspeth; Bahn, Andrew

    2016-03-01

    Elevated serum uric acid (SUA) or urate is associated with inflammation and gout. Recent evidence has linked urate to cancers, but little is known about urate effects in prostate cancer. Activins are inflammatory cytokines and negative growth regulators in the prostate. A hallmark of prostate cancer progression is activin insensitivity; however, mechanisms underlying this are unclear. We propose that elevated SUA is associated with prostate cancer counteracting the growth inhibitory effects of activins. The expression of activins A and B, urate transporter GLUT9 and tissue urate levels were examined in human prostate disease. Intracellular and secreted urate and GLUT9 expression were assessed in human prostate cancer cell lines. Furthermore, the effects of urate and probenecid, a known urate transport inhibitor, were determined in combination with activin A. Activin A expression was increased in low-grade prostate cancer, whereas activin B expression was reduced in high-grade prostate cancer. Intracellular urate levels decreased in all prostate pathologies, while GLUT9 expression decreased in benign prostatic hyperplasia, prostatitis and high-grade prostate cancer. Activin responsive LNCaP cells had higher intracellular and lower secreted urate levels than activin-insensitive PC3 cells. GLUT9 expression in prostate cancer cells was progressively lower than in prostate epithelial cells. Elevated extracellular urate was growth promoting in vitro, which was abolished by the gout medication probenecid, and it antagonized the growth inhibitory effects of activins. This study shows for the first time that a change in plasma or intracellular urate levels, possibly involving GLUT9 and a urate efflux transporter, has an impact on prostate cancer cell growth, and that lowering SUA levels in prostate cancer is likely to be therapeutically beneficial. PMID:26910779

  17. The role of targeted prophylactic antimicrobial therapy before transrectal ultrasonography-guided prostate biopsy in reducing infection rates: a systematic review.

    PubMed

    Cussans, Amelia; Somani, Bhaskar K; Basarab, Adriana; Dudderidge, Timothy J

    2016-05-01

    To compare the incidence of infective complications after transrectal ultrasonography (TRUS)-guided biopsy with either empirical fluoroquinolone or culture-based targeted antimicrobial prophylaxis, and the prevalence of fluoroquinolone resistance (FQ-R) in men undergoing prostate biopsy. A systematic review of the literature was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included studies of patients undergoing TRUS-guided biopsy that compared infective outcomes of those who received targeted antimicrobial therapy based on the results of pre-procedural rectal swab cultures, with those receiving empiric fluoroquinolone antimicrobial prophylaxis. The prevalence of FQ-R was recorded as a secondary outcome measure. Studies with no control group were excluded. From 125 studies screened, nine studies (4 571 patients) met the inclusion criteria. All studies were of cohort design, and included a combination of retrospective and prospective data. Six studies included were undertaken in North America. The remaining studies were undertaken in Spain, Turkey and Columbia. Within these studies, 2 484 (54.3%) patients received empirical fluoroquinolone prophylaxis, whilst 2 087 (45.7%) patients had pre-biopsy rectal swabs and targeted antibiotics. The mean FQ-R was 22.8%. Post-biopsy infection and sepsis rates were significantly higher in groups given empirical prophylaxis (4.55% and 2.21%) compared with groups receiving targeted antibiotics (0.72% and 0.48%). Based on these results 27 men would need to receive targeted antibiotics to prevent one infective complication. Our systematic review suggests that targeted prophylactic antimicrobial therapy before TRUS-guided prostate biopsy is associated with lower rates of sepsis. We therefore recommend changing current pathways to adopt this measure. PMID:26709240

  18. Lymph node staging in prostate cancer.

    PubMed

    Sankineni, Sandeep; Brown, Anna M; Fascelli, Michele; Law, Yan Mee; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-05-01

    Nodal staging is important in prostate cancer treatment. While surgical lymph node dissection is the classic method of determining whether lymph nodes harbor malignancy, this is a very invasive technique. Current noninvasive approaches to identifying malignant lymph nodes are limited. Conventional imaging methods rely on size and morphology of lymph nodes and have notoriously low sensitivity for detecting malignant nodes. New imaging techniques such as targeted positron emission tomography (PET) imaging and magnetic resonance lymphography (MRL) with iron oxide particles are promising for nodal staging of prostate cancer. In this review, the strengths and limitations of imaging techniques for lymph node staging of prostate cancer are discussed.

  19. Nevada's Class-Size Reduction Program. Nevada Revised Statutes 388.700-388.730: "Program To Reduce the Pupil-Teacher Ratio." Background Paper 97-7.

    ERIC Educational Resources Information Center

    Sturm, H. Pepper

    In 1989, the Nevada Legislature enacted the Class-Size Reduction (CSR) Act. The measure was designed to reduce the pupil-teacher ratio in the public schools, particularly in the earliest grades. The program was scheduled to proceed in several phases. The first step reduced the student-teacher ratio in selected kindergartens and first grade classes…

  20. Finasteride Concentrations and Prostate Cancer Risk: Results from the Prostate Cancer Prevention Trial

    PubMed Central

    Till, Cathee; Goodman, Phyllis J.; Chen, Xiaohong; Leach, Robin J.; Johnson-Pais, Teresa L.; Hsing, Ann W.; Hoque, Ashraful; Tangen, Catherine M.; Chu, Lisa; Parnes, Howard L.; Schenk, Jeannette M.; Reichardt, Juergen K. V.; Thompson, Ian M.; Figg, William D.

    2015-01-01

    Objective In the Prostate Cancer Prevention Trial (PCPT), finasteride reduced the risk of prostate cancer by 25%, even though high-grade prostate cancer was more common in the finasteride group. However, it remains to be determined whether finasteride concentrations may affect prostate cancer risk. In this study, we examined the association between serum finasteride concentrations and the risk of prostate cancer in the treatment arm of the PCPT and determined factors involved in modifying drug concentrations. Methods Data for this nested case-control study are from the PCPT. Cases were drawn from men with biopsy-proven prostate cancer and matched controls. Finasteride concentrations were measured using a liquid chromatography-mass spectrometry validated assay. The association of serum finasteride concentrations with prostate cancer risk was determined by logistic regression. We also examine whether polymorphisms in the enzyme target and metabolism genes of finasteride are related to drug concentrations using linear regression. Results and Conclusions Among men with detectable finasteride concentrations, there was no association between finasteride concentrations and prostate cancer risk, low-grade or high-grade, when finasteride concentration was analyzed as a continuous variable or categorized by cutoff points. Since there was no concentration-dependent effect on prostate cancer, any exposure to finasteride intake may reduce prostate cancer risk. Of the twenty-seven SNPs assessed in the enzyme target and metabolism pathway, five SNPs in two genes, CYP3A4 (rs2242480; rs4646437; rs4986910), and CYP3A5 (rs15524; rs776746) were significantly associated with modifying finasteride concentrations. These results suggest that finasteride exposure may reduce prostate cancer risk and finasteride concentrations are affected by genetic variations in genes responsible for altering its metabolism pathway. Trial Registration ClinicalTrials.gov NCT00288106 PMID:25955319

  1. [Prostatilen treatment of prostatic adenoma].

    PubMed

    Al'-Shukri, S Kh; Gorbachev, A G; Borovets, S Iu; Belousov, V Ia; Kuz'min, I V; Chushkin, K A

    2006-01-01

    We studied efficacy of repeated courses of prostatilen in suppositories with dimexide in prostatic adenoma patients with normal micturition. Rectal suppositories contain 30 mg prostatilen and 90 mg dimexide. The course consisted of 15 suppositories. The treatment reduced clinical symptoms of infravesical obstruction, residual urine volume in administration of prostatilen in 15-day courses each 3 months. This suggests possibility of suppository prostatilen use not only as an alternative for expensive drugs but also in combination with them in treatment of initial prostatic adenoma.

  2. Widespread telomere instability in prostatic lesions.

    PubMed

    Tu, LiRen; Huda, Nazmul; Grimes, Brenda R; Slee, Roger B; Bates, Alison M; Cheng, Liang; Gilley, David

    2016-05-01

    A critical function of the telomere is to disguise chromosome ends from cellular recognition as double strand breaks, thereby preventing aberrant chromosome fusion events. Such chromosome end-to-end fusions are known to initiate genomic instability via breakage-fusion-bridge cycles. Telomere dysfunction and other forms of genomic assault likely result in misregulation of genes involved in growth control, cell death, and senescence pathways, lowering the threshold to malignancy and likely drive disease progression. Shortened telomeres and anaphase bridges have been reported in a wide variety of early precursor and malignant cancer lesions including those of the prostate. These findings are being extended using methods for the analysis of telomere fusions (decisive genetic markers for telomere dysfunction) specifically within human tissue DNA. Here we report that benign prostatic hyperplasia (BPH), high-grade prostatic intraepithelial neoplasia (PIN), and prostate cancer (PCa) prostate lesions all contain similarly high frequencies of telomere fusions and anaphase bridges. Tumor-adjacent, histologically normal prostate tissue generally did not contain telomere fusions or anaphase bridges as compared to matched PCa tissues. However, we found relatively high levels of telomerase activity in this histologically normal tumor-adjacent tissue that was reduced but closely correlated with telomerase levels in corresponding PCa samples. Thus, we present evidence of high levels of telomere dysfunction in BPH, an established early precursor (PIN) and prostate cancer lesions but not generally in tumor adjacent normal tissue. Our results suggest that telomere dysfunction may be a common gateway event leading to genomic instability in prostate tumorigenesis. .

  3. Transurethral resection of the prostate

    MedlinePlus

    TURP; Prostate resection - transurethral ... used to remove the inside part of your prostate gland using electricity. ... if you have benign prostatic hyperplasia ( BPH ). The prostate gland often grows larger as men get older. ...

  4. Intrameal Hepatic Portal and Intraperitoneal Infusions of Glucagon-Like Peptide-1 Reduce Spontaneous Meal Size in the Rat via Different Mechanisms

    PubMed Central

    Rüttimann, Elisabeth B.; Arnold, Myrtha; Hillebrand, Jacquelien J.; Geary, Nori; Langhans, Wolfgang

    2009-01-01

    Peripheral administration of glucagon-like peptide (GLP)-1 reduces food intake in animals and humans, but the sites and mechanism of this effect and its physiological significance are not yet clear. To investigate these issues, we prepared rats with chronic catheters and infused GLP-1 (0.2 ml/min; 2.5 or 5.0 min) during the first spontaneous dark-phase meals. Infusions were remotely triggered 2–3 min after meal onset. Hepatic portal vein (HPV) infusion of 1.0 or 3.0 (but not 0.33) nmol/kg GLP-1 reduced the size of the ongoing meal compared with vehicle without affecting the subsequent intermeal interval, the size of subsequent meals, or cumulative food intake. In double-cannulated rats, HPV and vena cava infusions of 1.0 nmol/kg GLP-1 reduced meal size similarly. HPV GLP-1 infusions of 1.0 nmol/kg GLP-1 also reduced meal size similarly in rats with subdiaphragmatic vagal deafferentations and in sham-operated rats. Finally, HPV and ip infusions of 10 nmol/kg GLP-1 reduced meal size similarly in sham-operated rats, but only HPV GLP-1 reduced meal size in subdiaphragmatic vagal deafferentation rats. These data indicate that peripherally infused GLP-1 acutely and specifically reduces the size of ongoing meals in rats and that the satiating effect of ip, but not iv, GLP-1 requires vagal afferent signaling. The findings suggest that iv GLP-1 infusions do not inhibit eating via hepatic portal or hepatic GLP-1 receptors but may act directly on the brain. PMID:18948395

  5. Prevention strategies for prostate cancer.

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2012-12-01

    Through the last decade consideration of the role of vitamins and minerals in primary prevention of genitourinary tumors has dramatically changed. Despite all efforts efficacy of a specific compound has not been proven, so far. In consequence, recommendations for a use of vitamins or other supplements with the intention of prostate cancer prevention should be avoided today. In contrast, there is some evidence that life style modification might be helpful: recent investigations suggest that smoking may be involved in prostate cancer carcinogenesis. In addition, there is evidence that moderate food consumption, reduction of dairy products and an Asian or Mediterranean diet might not only prevent prostate cancer but also harbors additional beneficial effects on general health. This move from single compounds to more complex diets can be considered as a change of paradigm in prostate cancer prevention and could be the starting point of future epidemiological research. Disappointing findings with regards to nutritional cancer prevention contrast with a solid evidence concerning the efficacy of chemoprevention using 5a-reductase inhibitors: Long-term use of Finasteride and Dutasteride significantly reduces prostate cancer detection. Further candidate drugs are under investigation. However, translation of these findings into urological practice remains a matter of controversial discussion. PMID:23288209

  6. Active surveillance for prostate cancer.

    PubMed

    Romero-Otero, Javier; García-Gómez, Borja; Duarte-Ojeda, José M; Rodríguez-Antolín, Alfredo; Vilaseca, Antoni; Carlsson, Sigrid V; Touijer, Karim A

    2016-03-01

    It is worth distinguishing between the two strategies of expectant management for prostate cancer. Watchful waiting entails administering non-curative androgen deprivation therapy to patients on development of symptomatic progression, whereas active surveillance entails delivering curative treatment on signs of disease progression. The objectives of the two management strategies and the patients enrolled in either are different: (i) to review the role of active surveillance as a management strategy for patients with low-risk prostate cancer; and (ii) review the benefits and pitfalls of active surveillance. We carried out a systematic review of active surveillance for prostate cancer in the literature using the National Center for Biotechnology Information's electronic database, PubMed. We carried out a search in English using the terms: active surveillance, prostate cancer, watchful waiting and conservative management. Selected studies were required to have a comprehensive description of the demographic and disease characteristics of the patients at the time of diagnosis, inclusion criteria for surveillance, and a protocol for the patients' follow up. Review articles were included, but not multiple papers from the same datasets. Active surveillance appears to reduce overtreatment in patients with low-risk prostate cancer without compromising cancer-specific survival at 10 years. Therefore, active surveillance is an option for select patients who want to avoid the side-effects inherent to the different types of immediate treatment. However, inclusion criteria for active surveillance and the most appropriate method of monitoring patients on active surveillance have not yet been standardized.

  7. Lycopene: Redress for Prostate Cancer

    PubMed Central

    Pisipati, Sai Venkata Vedavyas; Pathapati, Harshavardhan; Bhukya, Ganesh; Nuthakki, Suresh; Chandu, Baburao; Nama, SreeKanth; Adeps, RajDev

    2012-01-01

    Lycopene, a carotenoid is what that gives red colour to some fruits like pomegranate, tomato, papaya etc... People with a sound diet of lycopene may have a less risk of cancers especially prostate cancer which is most impedent for the males of age 40-50 years. So, in countries of north America and Europe food contains much of the lycopene supplements. In accordance with the American journal of epidemiology 2002 studies implies that men with crushed serum lycopene levels are more divulged to prostate cancer and those with sound diet of lycopene have a less risk of prostate cancer. In a care study conveyed by The British journal of urology, men with prostate cancer are subjected to surgery and the tumour is detonated. Amongst the men half a set were supplemented with lycopene supplements and half were not. Those subjected with lycopene supplements have less bone pains and live longer than those not supplemented. This paints a picture about importance of lycopene in treatment of prostate cancer. This article evokes the importance of lycopene and its way of destroying the cancer. Lycopene reduces the risk of cancer by diverging its effect on the plasma Insulin like growth factor, on Connexins , and the most acceptable one, by quench of free radicals. PMID:24826034

  8. Impact of margin size on the predicted risk of radiogenic second cancers following proton arc therapy and volumetric modulated arc therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Rechner, Laura A.; Howell, Rebecca M.; Zhang, Rui; Newhauser, Wayne D.

    2012-12-01

    We previously determined that the predicted risk of radiogenic second cancer in the bladder and rectum after proton arc therapy (PAT) was less than or equal to that after volumetric modulated arc therapy (VMAT) with photons, but we did not consider the impact of margin size on that risk. The current study was thus conducted to evaluate margin size's effect on the predicted risks of second cancer for the two modalities and the relative risk between them. Seven treatment plans with margins ranging from 0 mm in all directions to 6 mm posteriorly and 8 mm in all other directions were considered for both modalities. We performed risk analyses using three risk models with varying amounts of cell sterilization and calculated ratios of risk for the corresponding PAT and VMAT plans. We found that the change in risk with margin size depended on the risk model but that the relative risk remained nearly constant with margin size, regardless of the amount of cell sterilization modeled. We conclude that while margin size influences the predicted risk of a second cancer for a given modality, it appears to affect both modalities in roughly equal proportions so that the relative risk between PAT and VMAT is approximately equivalent.

  9. Flaxseed suppressed prostatic epithelial proliferation in a rat model of benign prostatic hyperplasia.

    PubMed

    Said, Mahmoud M; Hassan, Nahla S; Schlicht, Michael J; Bosland, Maarten C

    2015-01-01

    Benign prostatic hyperplasia (BPH), a disease occurring frequently among elderly males, is a slow progressive enlargement of the fibromuscular and epithelial structures of the prostate gland. Dietary factors may influence the prostate and exert an influence on prostatic growth and disease. The current study was undertaken to investigate the protective effect of dietary flaxseed supplementation against testosterone-induced prostatic hyperplasia in male rats. Forty male Wistar rats were divided into 5 groups: (1) untreated control; (2) treatment with testosterone propionate (TP) to induce prostate enlargement; (3) TP-treated group fed a diet containing 5% milled flaxseed; (4) TP-treated group fed a diet containing 10% milled flaxseed; and (5) TP-treated group fed a diet containing 20 ppm finasteride. Treatment with TP significantly increased the absolute and relative weights of different prostatic lobes, serum testosterone (T), and testosterone/estradiol ratio, as well as prostatic vascular endothelial growth factor (VEGF) expression, RNA synthesis per cell, and epithelial cell proliferation, detected as Ki67 labeling. Histopathological examination did not reveal marked differences in acinar morphology in ventral prostate, whereas morphometric analysis showed significantly increased epithelial cell height. Co-administration of flaxseed or finasteride with TP significantly reduced prostatic VEFG, epithelial cell proliferation, and RNA/DNA ratio, along with a significant increase in serum T and testosterone/estradiol ratio compared with TP-only-treated rats. Our results indicate that flaxseed, similar to the 5α-reductase inhibitor finasteride, blocked TP-induced prostate enlargement in a rat model of BPH, likely through suppression of prostatic VEFG and cellular proliferation.

  10. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice.

    PubMed

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W; Kumar, Nagi; Park, Jong Y

    2014-04-01

    Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. A total of 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of 3 doses of Polyphenon E (200, 500, and 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed before treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22, and 32 weeks old. The number and size of tumors in treated TRAMP mice were significantly decreased compared with untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared with 13% of mice (2/16) treated with high-dose Polyphenon E during the same period. Furthermore, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P = 0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of prostate cancer.

  11. Allocating Sample Sizes to Reduce Budget for Fixed-Effect 2×2 Heterogeneous Analysis of Variance

    ERIC Educational Resources Information Center

    Luh, Wei-Ming; Guo, Jiin-Huarng

    2016-01-01

    This article discusses the sample size requirements for the interaction, row, and column effects, respectively, by forming a linear contrast for a 2×2 factorial design for fixed-effects heterogeneous analysis of variance. The proposed method uses the Welch t test and its corresponding degrees of freedom to calculate the final sample size in a…

  12. PDEF in prostate cancer.

    PubMed

    Sood, Ashwani K; Kim, Hyung; Geradts, Joseph

    2012-05-01

    Prostate-derived Ets factor (PDEF) is a relatively recently described member of the Ets family of transcription factors. It differs from other family members in its restricted and epithelial-specific expression in normal tissues and its unique DNA-binding motif that together may impart interesting specificity to its function. This communication reviews our current understanding of the expression characteristics of PDEF in normal prostate and in prostate cancer. Also, the biochemical and genetic evidence relating to the role of this transcription factor in prostate cancer is reviewed. Most evidence is consistent with an oncogenic role for PDEF in prostate cancer. Specific observations about the loss of PDEF expression in prostate tumors and its apparent role as a prostate tumor suppressor are also discussed. PDEF is one of the few transcription factors with potential to have a significant impact on the management of prostate cancer. A better understanding of its biology and its role in prostate cancer is urgently needed.

  13. Placental restriction of fetal growth reduces size at birth and alters postnatal growth, feeding activity, and adiposity in the young lamb.

    PubMed

    De Blasio, Miles J; Gatford, Kathryn L; Robinson, Jeffrey S; Owens, Julie A

    2007-02-01

    Intrauterine growth restriction (IUGR) is associated with accelerated growth after birth. Together, IUGR and accelerated growth after birth predict reduced lean tissue mass and increased obesity in later life. Although placental insufficiency is a major cause of IUGR, whether it alters growth and adiposity in early postnatal life is not known. We hypothesized that placental restriction (PR) in the sheep would reduce size at birth and increase postnatal growth rate, fat mass, and feeding activity in the young lamb. PR reduced survival rate and size at birth, with soft tissues reduced to a greater extent than skeletal tissues and relative sparing of head width (P < 0.05 for all). PR did not alter absolute growth rates (i.e., the slope of the line of best fit for age vs. parameter size from birth to 45 days of age) but increased neonatal fractional growth rates (absolute growth rate relative to size at birth) for body weight (+24%), tibia (+15%) and metatarsal (+18%) lengths, hindlimb (+23%) and abdominal (+19%) circumferences, and fractional growth rates for current weight (P < 0.05) weekly throughout the first 45 days of life. PR and small size at birth reduced individual skeletal muscle weights and increased visceral adiposity in absolute and relative terms. PR also altered feeding activity, which increased with decreasing size at birth and was predictive of increased postnatal growth and adiposity. In conclusion, PR reduced size at birth and induced catch-up growth postnatally, normalizing weight and length but increasing adiposity in early postnatal life. Increased feeding activity may contribute to these alterations in growth and body composition following prenatal restraint and, if they persist, may lead to adverse metabolic and cardiovascular outcomes in later life. PMID:17023666

  14. Applicability of colloid filtration theory in size-distributed, reduced porosity, granular media in the absence of energy barriers.

    PubMed

    Pazmino, Eddy F; Ma, Huilian; Johnson, William P

    2011-12-15

    The vast majority of colloid transport experiments use granular porous media with narrow size distribution to facilitate comparison with colloid filtration theory, which represents porous media with a single collector size. In this work we examine retention of colloids ranging in size from 0.21 to 9.1 μm in diameter, in columns packed with uniform and size-distributed borosilicate glass bead porous media with porosity ranging from 0.38 to 0.28. Conditions were favorable to attachment (absent a significant energy barrier). The goal was to determine the applicability of colloid filtration theory to colloid retention in these media. We also directly observed deposition at the pore scale in packed flow cells. The pore domain was characterized via high resolution computerized X-ray micro tomography (HRXMT). The flow field was examined using Lattice-Boltzmann flow simulation methods (LBM). The influence of preferential flow paths on colloid retention in the lowest porosity media was accounted for by correcting the fluid velocity. Straining in pore throats too small to pass was not a significant contributor to colloid retention despite colloid-to-collector size ratios up to 0.05. Mechanistic simulations via the Ma-Pedel-Fife-Johnson correlation equation (MPFJ) for colloid filtration predicted the experimentally observed trends in deposition with porosity when a number-based mean grain size was used.

  15. The insulin-like growth factor 1 receptor (IGF1R) contributes to reduced size in dogs

    PubMed Central

    Hoopes, Barbara C.; Rimbault, Maud; Liebers, David; Ostrander, Elaine A.

    2012-01-01

    Domestic dog breeds have undergone intense selection for a variety of morphologic features, including size. Among small-dog breeds, defined as those averaging less than ~15 in. at the withers, there remains still considerable variation in body size. Yet essentially all such dogs are fixed for the same allele at the insulin-like growth factor 1 gene, which we and others previously found to be a size locus of large effect. In this study we sought to identify additional genes that contribute to tiny size in dogs using an association scan with the single nucleotide polymorphism (SNP) dataset CanMap, in which 915 purebred dogs were genotyped at 60,968 SNP markers. Our strongest association for tiny size (defined as breed-average height not more than 10 in. at the withers) was on canine chromosome 3 (p = 1.9 × 10−70). Fine mapping revealed a nonsynonymous SNP at chr3:44,706,389 that changes a highly conserved arginine at amino acid 204 to histidine in the insulin-like growth factor 1 receptor (IGF1R). This mutation is predicted to prevent formation of several hydrogen bonds within the cysteine-rich domain of the receptor’s ligand-binding extracellular subunit. Nine of 13 tiny dog breeds carry the mutation and many dogs are homozygous for it. This work underscores the central importance of the IGF1 pathway in controlling the tremendous size diversity of dogs. PMID:22903739

  16. Prevention strategies in prostate cancer.

    PubMed

    Trottier, Greg; Lawrentschuk, N; Fleshner, N E

    2010-09-01

    Prostate cancer (PCa) prevention has been an exciting and controversial topic since the results of the Prostate Cancer Prevention Trial (PCPT) were published. With the recently published results of the reduce (Reduction by Dutasteride of Prostate Cancer Events) trial, interest in this topic is at a peak. Primary pca prevention will be unlikely to affect mortality significantly, but the reduction in overtreatment and the effect on quality of life from the avoidance of a cancer diagnosis are important factors to consider.This review provides a comparative update on the REDUCE and PCPT trials and some clinical recommendations. Other potential primary preventive strategies with statins, selective estrogen response modulators, and nutraceutical compounds-including current evidence for these agents and their roles in clinical practice-are discussed. Many substances that have been examined in the primary prevention of pca and for which clinical data are either negative or particularly weak are not covered.The future of PCa prevention continues to expand, with several ongoing clinical trials and much interest in tertiary prostate cancer prevention. PMID:20882132

  17. Prostate resection - minimally invasive

    MedlinePlus

    Laser prostatectomy; Transurethral needle ablation; TUNA; Transurethral incision; TUIP; Holmium laser enucleation of the prostate; HoLep; Interstitial laser coagulation; ILC; Photoselective vaporization of the prostate; PVP; Transurethral ...

  18. Screening for Prostate Cancer

    MedlinePlus

    ... of Internal Medicine Summaries for Patients Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ... Physicians The full report is titled “Screening for Prostate Cancer: A Guidance Statement From the Clinical Guidelines Committee ...

  19. Prostate cancer screenings

    MedlinePlus

    ... not do an accurate job of screening for prostate cancer. ... and anxiety, even if you do not have prostate cancer. Side effects from further testing. If your PSA test is higher than normal, you may need to ...

  20. Enlarged prostate - after care

    MedlinePlus

    BPH - self-care; Benign prostatic hypertrophy - self-care; Benign prostatic hyperplasia - self-care ... Your health care provider may have you take a medicine called alpha-1- blocker. Most people find that these drugs help ...

  1. Prostate Cancer Screening

    MedlinePlus

    ... treat. There is no standard screening test for prostate cancer. Researchers are studying different tests to find those ... PSA level may be high if you have prostate cancer. It can also be high if you have ...

  2. Cryotherapy for prostate cancer

    MedlinePlus

    ... the needles to the prostate gland. Then, very cold gas passes through the needles, creating ice balls that destroy the prostate gland. Warm salt water will flow through the catheter to keep your urethra (the tube from the bladder to ...

  3. Prostate cancer - resources

    MedlinePlus

    Resources - prostate cancer ... The following organizations are good resources for information on prostate cancer : American Cancer Society -- www.cancer.org/cancer/prostatecancer/index National Cancer Institute -- www.cancer.gov/cancertopics/ ...

  4. N-Myc Drives Neuroendocrine Prostate Cancer Initiated from Human Prostate Epithelial Cells.

    PubMed

    Lee, John K; Phillips, John W; Smith, Bryan A; Park, Jung Wook; Stoyanova, Tanya; McCaffrey, Erin F; Baertsch, Robert; Sokolov, Artem; Meyerowitz, Justin G; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M; Shokat, Kevan M; Gustafson, W Clay; Huang, Jiaoti; Witte, Owen N

    2016-04-11

    MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance, and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. PMID:27050099

  5. Characterization of a PET Camera Optimized for ProstateImaging

    SciTech Connect

    Huber, Jennifer S.; Choong, Woon-Seng; Moses, William W.; Qi,Jinyi; Hu, Jicun; Wang, G.C.; Wilson, David; Oh, Sang; Huesman, RonaldH.; Derenzo, Stephen E.

    2005-11-11

    We present the characterization of a positron emission tomograph for prostate imaging that centers a patient between a pair of external curved detector banks (ellipse: 45 cm minor, 70 cm major axis). The distance between detector banks adjusts to allow patient access and to position the detectors as closely as possible for maximum sensitivity with patients of various sizes. Each bank is composed of two axial rows of 20 HR+ block detectors for a total of 80 detectors in the camera. The individual detectors are angled in the transaxial plane to point towards the prostate to reduce resolution degradation in that region. The detectors are read out by modified HRRT data acquisition electronics. Compared to a standard whole-body PET camera, our dedicated-prostate camera has the same sensitivity and resolution, less background (less randoms and lower scatter fraction) and a lower cost. We have completed construction of the camera. Characterization data and reconstructed images of several phantoms are shown. Sensitivity of a point source in the center is 946 cps/mu Ci. Spatial resolution is 4 mm FWHM in the central region.

  6. Conformal external radiotherapy of prostatic carcinoma: requirements and experimental results.

    PubMed

    Troccaz, J; Menguy, Y; Bolla, M; Cinquin, P; Vassal, P; Laieb, N; Desbat, L; Dusserre, A; Dal Soglio, S

    1993-11-01

    The aim of conformal radiotherapy is to deliver, with high precision, a specific dose (which may be a high dose) to a planning target volume, concurrently with irradiating as little as possible healthy tissue and organs at risk. Radiation therapy may suffer from a number of problems that result in both over- or under-sizing the irradiation fields, making over-rough simplifications of the irradiation ballistics and delivering an insufficient tumoral dose (to spare critical organs and reduce toxicity). One of these problems lies in the accurate positioning of the planning target volume with respect to the irradiation system, thence in the correct execution of the ballistics. In this paper, we describe a system aiming at achieving a higher overall accuracy in the delivery of prostatic boost for carcinoma of the prostate. The system is based on the use of ultrasonic images for measuring the actual position of the prostate just before irradiation. Since these images are registered with pre-operative (CT or MR) images, the position and orientation of the planning target volume is computed with respect to the irradiation system, and can be corrected accordingly. First experiments have been performed on dummies, and the results are discussed.

  7. A Perspective on Prostate Carcinogenesis and Chemoprevention

    PubMed Central

    Bosland, Maarten C.; Ozten, Nur; Eskra, Jillian N.; Mahmoud, Abeer M.

    2015-01-01

    In this perspective, modifiable carcinogenic factors for the prostate are summarized. This is followed by a discussion of how current knowledge about causation of prostate cancer and chemoprevention of prostate cancer can be used to develop preventive strategies. Prostate cancer is a slowly developing cancer which offers opportunities for preventive interventions. Only a few randomized clinical trials of prostate cancer prevention have been completed. The SELECT study with selenium and vitamin E did not find protective effects, but in two trials with 5α-reductase inhibitors risk was reduced about 25%, showing that chemoprevention is possible and indicating that the androgen receptor is a suitable target. Besides smoking cessation and reduction of obesity, there are no known dietary or life style interventions that will have a major impact on prostate cancer risk. Inflammation of the prostate is an attractive target and aspirin may be a promising candidate agent, but has not been addressed yet in preclinical and clinical studies. Antioxidants other than selenium and vitamin E are unlikely to be very effective and data on several dietary supplements are not encouraging. More candidate agents need to be identified and tested in relevant and adequate preclinical models and Phase II trials that have predictive value for outcome of Phase III randomized studies. Doing this will require a systematic approach comparing preclinical and clinical study outcomes to determine their predictive value of preventive efficacy. PMID:26442200

  8. Enlarged Prostate (BPH)

    MedlinePlus

    The prostate is a gland in men. It helps make semen, the fluid that contains sperm. The prostate surrounds the tube that carries urine out of the body. As men age, their prostate grows bigger. If it gets too large, it ...

  9. The ability of winter grazing to reduce wildfire size, intensity, and fire-induced plant mortality was not demonstrated: A comment on Davies et al. (2015)

    EPA Science Inventory

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience more fire-induced mortality of native peren...

  10. The ability of winter grazing to reduce wildfire size, intensity, and fire-induced plant mortality was not demonstrated: a comment on Davies et al. (2015)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent study by Davies et al. sought to test whether winter grazing could reduce wildfire size, fire behavior and intensity metrics, and fire-induced plant mortality in shrub-grasslands. The authors concluded that ungrazed rangelands may experience fire-induced mortality of native perennial bunchg...

  11. Computed Tomography of the Prostate Gland in Healthy Intact Dogs and Dogs with Benign Prostatic Hyperplasia.

    PubMed

    Pasikowska, J; Hebel, M; Niżański, W; Nowak, M

    2015-10-01

    To date, there is only scarce data on the evaluation of the prostate gland in dogs using computed tomography (CT). The aims of our study were to describe CT features of BPH in dogs and to determine the size of the prostate gland in healthy male dogs and dogs with benign prostatic hyperplasia (BPH) through CT. Additionally, we aimed to compare and establish the most useful parameters for CT measurements of the prostate in patients with BPH. The study population consisted of 20 healthy intact male dogs and 20 male intact dogs with confirmed BPH. Pre- and post-contrast CT studies were evaluated. The most common CT features in dogs with recognized BPH were symmetrical prostatomegaly and heterogeneity of the prostatic parenchyma. The mean prostatic density (D) was 56HU (±4.39) in pre-contrast CT images and 84HU (±8) in post-contrast images in dogs with BPH. The mean prostatic length (L) was 43.87 mm (±11), the mean width (W) amounted to 48.95 mm (±8.76) and the mean height (H) reached 44.9 mm (±9.48) in clinically affected patients. The mean ratios were: rL - 2,12 (±0.5); rW - 2.39 (±0.53) and rH - 2.16 (±0.39) in the BPH group. The prostate should be considered to be enlarged when rL exceeds 3.05; rW exceeds 3.38 and rH exceeds 2.94. Our findings indicated that CT is a useful tool in diagnosing prostate disorders, including BPH. The heterogeneity, density and ratios of prostatic length, width and height can be useful parameters in the diagnosis of BPH.

  12. Computed Tomography of the Prostate Gland in Healthy Intact Dogs and Dogs with Benign Prostatic Hyperplasia.

    PubMed

    Pasikowska, J; Hebel, M; Niżański, W; Nowak, M

    2015-10-01

    To date, there is only scarce data on the evaluation of the prostate gland in dogs using computed tomography (CT). The aims of our study were to describe CT features of BPH in dogs and to determine the size of the prostate gland in healthy male dogs and dogs with benign prostatic hyperplasia (BPH) through CT. Additionally, we aimed to compare and establish the most useful parameters for CT measurements of the prostate in patients with BPH. The study population consisted of 20 healthy intact male dogs and 20 male intact dogs with confirmed BPH. Pre- and post-contrast CT studies were evaluated. The most common CT features in dogs with recognized BPH were symmetrical prostatomegaly and heterogeneity of the prostatic parenchyma. The mean prostatic density (D) was 56HU (±4.39) in pre-contrast CT images and 84HU (±8) in post-contrast images in dogs with BPH. The mean prostatic length (L) was 43.87 mm (±11), the mean width (W) amounted to 48.95 mm (±8.76) and the mean height (H) reached 44.9 mm (±9.48) in clinically affected patients. The mean ratios were: rL - 2,12 (±0.5); rW - 2.39 (±0.53) and rH - 2.16 (±0.39) in the BPH group. The prostate should be considered to be enlarged when rL exceeds 3.05; rW exceeds 3.38 and rH exceeds 2.94. Our findings indicated that CT is a useful tool in diagnosing prostate disorders, including BPH. The heterogeneity, density and ratios of prostatic length, width and height can be useful parameters in the diagnosis of BPH. PMID:26303126

  13. Using measured equipment load profiles to 'right-size' HVACsystems and reduce energy use in laboratory buildings (Pt. 2)

    SciTech Connect

    Mathew, Paul; Greenberg, Steve; Frenze, David; Morehead, Michael; Sartor, Dale; Starr, William

    2005-06-29

    There is a general paucity of measured equipment load datafor laboratories and other complex buildings and designers often useestimates based on nameplate rated data or design assumptions from priorprojects. Consequently, peak equipment loads are frequentlyoverestimated, and load variation across laboratory spaces within abuilding is typically underestimated. This results in two design flaws.Firstly, the overestimation of peak equipment loads results in over-sizedHVAC systems, increasing initial construction costs as well as energy usedue to inefficiencies at low part-load operation. Secondly, HVAC systemsthat are designed without accurately accounting for equipment loadvariation across zones can significantly increase simultaneous heatingand cooling, particularly for systems that use zone reheat fortemperature control. Thus, when designing a laboratory HVAC system, theuse of measured equipment load data from a comparable laboratory willsupport right-sizing HVAC systems and optimizing their configuration tominimize simultaneous heating and cooling, saving initial constructioncosts as well as life-cycle energy costs.In this paper, we present datafrom recent studies to support the above thesis. We first presentmeasured equipment load data from two sources: time-series measurementsin several laboratory modules in a university research laboratorybuilding; and peak load data for several facilities recorded in anational energy benchmarking database. We then contrast this measureddata with estimated values that are typically used for sizing the HVACsystems in these facilities, highlighting the over-sizing problem. Next,we examine the load variation in the time series measurements and analyzethe impact of this variation on energy use, via parametric energysimulations. We then briefly discuss HVAC design solutions that minimizesimultaneous heating and cooling energy use.

  14. Dendritic Nonlinearities Reduce Network Size Requirements and Mediate ON and OFF States of Persistent Activity in a PFC Microcircuit Model

    PubMed Central

    Papoutsi, Athanasia; Sidiropoulou, Kyriaki; Poirazi, Panayiota

    2014-01-01

    Technological advances have unraveled the existence of small clusters of co-active neurons in the neocortex. The functional implications of these microcircuits are in large part unexplored. Using a heavily constrained biophysical model of a L5 PFC microcircuit, we recently showed that these structures act as tunable modules of persistent activity, the cellular correlate of working memory. Here, we investigate the mechanisms that underlie persistent activity emergence (ON) and termination (OFF) and search for the minimum network size required for expressing these states within physiological regimes. We show that (a) NMDA-mediated dendritic spikes gate the induction of persistent firing in the microcircuit. (b) The minimum network size required for persistent activity induction is inversely proportional to the synaptic drive of each excitatory neuron. (c) Relaxation of connectivity and synaptic delay constraints eliminates the gating effect of NMDA spikes, albeit at a cost of much larger networks. (d) Persistent activity termination by increased inhibition depends on the strength of the synaptic input and is negatively modulated by dADP. (e) Slow synaptic mechanisms and network activity contain predictive information regarding the ability of a given stimulus to turn ON and/or OFF persistent firing in the microcircuit model. Overall, this study zooms out from dendrites to cell assemblies and suggests a tight interaction between dendritic non-linearities and network properties (size/connectivity) that may facilitate the short-memory function of the PFC. PMID:25077940

  15. Biomarkers for prostate cancer.

    PubMed

    Makarov, Danil V; Loeb, Stacy; Getzenberg, Robert H; Partin, Alan W

    2009-01-01

    The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. We review the literature on prostate cancer biomarkers, including serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing biomarkers and the discovery of new markers to identify men with aggressive prostate cancer.

  16. Depot medroxyprogesterone in the management of benign prostatic hyperplasia.

    PubMed

    Onu, P E

    1995-01-01

    The effects of depot medroxyprogesterone (DMPA), a 5 alpha-reductase, luteinizing-hormone release and human androgen receptor adhesion inhibitor, were assessed in 80 patients with benign prostatic hyperplasia (BPH) in a double-blind, placebo-controlled study. Patients were randomized to DMPA 150 mg single-dose intramuscular injection or placebo in a similar fashion. The following changes were seen with DMPA after 3 months (duration of DMPA effect): (1) serum testosterone reached castration levels within 3 days as compared to no changes in the placebo group; (2) the prostate volume was reduced by 25% compared to a 3% decrease with placebo (p < 0.001); (3) maximum urinary-flow rates increased by 3.7 ml/s compared to placebo (p < 0.001); (4) total urinary symptom scores decreased by 4.9 points compared to a nonsignificant decrease with placebo (p < 0.005). There was a 2.5-point decrease in irritative symptoms (urinary frequency, nocturia and urgency) as compared to a nonsignificant decrease with placebo (p < 0.005). After 3 months, the urinary symptoms and urodynamic changes were reversed but significantly greater than the baseline values (p < 0.001). The prostates showed regrowth to the initial sizes within 18-36 weeks. DMPA was better tolerated, except for a higher incidence of impotence, decreased libido and ejaculatory disorders, than in the placebo group. The quality of life is improved with DMPA since it did not produce hot flashes. It was concluded that single-dose DMPA 150 mg is a safe and effective treatment for prostatic obstruction where potency is a secondary consideration.

  17. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice.

    PubMed

    Chen, Junmei; Reheman, Adili; Gushiken, Francisca C; Nolasco, Leticia; Fu, Xiaoyun; Moake, Joel L; Ni, Heyu; López, José A

    2011-02-01

    Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterized by systemic microvascular thrombosis caused by adhesion of platelets to ultra-large vWF (ULVWF) multimers. These multimers accumulate because of a deficiency of the processing enzyme ADAMTS13. vWF protein forms long multimers from homodimers that first form through C-terminal disulfide bonds and then join through their N termini by further disulfide bonding. N-acetylcysteine (NAC) is an FDA-approved drug that has long been used to treat chronic obstructive lung disease and acetaminophen toxicity and is known to function in the former disorder by reducing mucin multimers. Here, we examined whether NAC could reduce vWF multimers, which polymerize in a manner similar to mucins. In vitro, NAC reduced soluble plasma-type vWF multimers in a concentration-dependent manner and rapidly degraded ULVWF multimer strings extruded from activated ECs. The effect was preceded by reduction of the intrachain disulfide bond encompassing the platelet-binding A1 domain. NAC also inhibited vWF-dependent platelet aggregation and collagen binding. Injection of NAC into ADAMTS13-deficient mice led to the rapid resolution of thrombi produced by ionophore treatment of the mesenteric venules and reduced plasma vWF multimers. These results suggest that NAC may be a rapid and effective treatment for patients with TTP. PMID:21266777

  18. Salt Stress Reduces Root Meristem Size by Nitric Oxide-Mediated Modulation of Auxin Accumulation and Signaling in Arabidopsis1[OPEN

    PubMed Central

    Liu, Wen; Li, Rong-Jun; Han, Tong-Tong; Cai, Wei; Fu, Zheng-Wei

    2015-01-01

    The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor Nω-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels. PMID:25818700

  19. Enlarged prostate - what to ask your doctor

    MedlinePlus

    ... body? What does the prostate gland do? What causes the prostate gland to enlarge? Do many other men have prostate problems? How do I know my problem is not prostate cancer? What are the symptoms of an enlarged prostate? ...

  20. Prostate cancer: a serious disease suitable for prevention.

    PubMed

    Fitzpatrick, John M; Schulman, Claude; Zlotta, Alexandre R; Schröder, Fritz H

    2009-04-01

    Prostate cancer is among the most common causes of death from cancer in men, and accounts for 10% of all new male cancers worldwide. The diagnosis and treatment of prostate cancer place a substantial physical and emotional burden on patients and their families, and have considerable financial implications for healthcare providers and society. Given that the risk of prostate cancer continues to increase with age, the burden of the disease is likely to increase in line with population life-expectancy. Reducing the risk of prostate cancer has gained increasing coverage in recent years, with proof of principle shown in the Prostate Cancer Prevention Trial with the type 2 5alpha-reductase (5AR) inhibitor, finasteride. The long latency period, high disease prevalence, and significant associated morbidity and mortality make prostate cancer a suitable target for a risk-reduction approach. Several agents are under investigation for reducing the risk of prostate cancer, including selenium/vitamin E and selective oestrogen receptors modulators (e.g. toremifene). In addition, the Reduction by Dutasteride of Prostate Cancer Events trial, involving >8000 men, is evaluating the effect of the dual 5AR inhibitor, dutasteride, on the risk of developing prostate cancer. A successful risk-reduction strategy might decrease the incidence of the disease, as well as the anxiety, cost and morbidity associated with its diagnosis and treatment. PMID:19302133

  1. Marine reserves reduce risk of climate-driven phase shift by reinstating size- and habitat-specific trophic interactions.

    PubMed

    Ling, S D; Johnson, C R

    2012-06-01

    Spatial closures in the marine environment are widely accepted as effective conservation and fisheries management tools. Given increasing human-derived stressors acting on marine ecosystems, the need for such effective action is urgently clear. Here we explore mechanisms underlying the utility of marine reserves to reinstate trophic dynamics and to increase resilience of kelp beds against climate-driven phase shift to sea urchin barrens on the rapidly warming Tasmanian east coast. Tethering and tagging experiments were used to examine size- and shelter-specific survival of the range-extending sea urchin Centrostephanus rodgersii (Diadematidae) translocated to reefs inside and outside no-take Tasmanian marine reserves. Results show that survival rates of C. rodgersii exposed on flat reef substratum by tethering were approximately seven times (small urchins 10.1 times; large urchins 6.1 times) lower on protected reef within marine reserve boundaries (high abundance of large predatory-capable lobsters) compared to fished reef (large predatory lobsters absent). When able to seek crevice shelter, tag-resighting models estimated that mortality rates of C. rodgersii were lower overall but remained 3.3 times (small urchins 2.1 times; large urchins 6.4 times) higher in the presence of large lobsters inside marine reserves, with higher survival of small urchins owing to greater access to crevices relative to large urchins. Indeed, shelter was 6.3 times and 3.1 times more important to survival of small and large urchins, respectively, on reserved relative to fished reef. Experimental results corroborate with surveys throughout the range extension region, showing greater occurrence of overgrazing on high-relief rocky habitats where shelter for C. rodgersii is readily available. This shows that ecosystem impacts mediated by range extension of such habitat-modifying organisms will be heterogeneous in space, and that marine systems with a more natural complement of large and thus

  2. Marine reserves reduce risk of climate-driven phase shift by reinstating size- and habitat-specific trophic interactions.

    PubMed

    Ling, S D; Johnson, C R

    2012-06-01

    Spatial closures in the marine environment are widely accepted as effective conservation and fisheries management tools. Given increasing human-derived stressors acting on marine ecosystems, the need for such effective action is urgently clear. Here we explore mechanisms underlying the utility of marine reserves to reinstate trophic dynamics and to increase resilience of kelp beds against climate-driven phase shift to sea urchin barrens on the rapidly warming Tasmanian east coast. Tethering and tagging experiments were used to examine size- and shelter-specific survival of the range-extending sea urchin Centrostephanus rodgersii (Diadematidae) translocated to reefs inside and outside no-take Tasmanian marine reserves. Results show that survival rates of C. rodgersii exposed on flat reef substratum by tethering were approximately seven times (small urchins 10.1 times; large urchins 6.1 times) lower on protected reef within marine reserve boundaries (high abundance of large predatory-capable lobsters) compared to fished reef (large predatory lobsters absent). When able to seek crevice shelter, tag-resighting models estimated that mortality rates of C. rodgersii were lower overall but remained 3.3 times (small urchins 2.1 times; large urchins 6.4 times) higher in the presence of large lobsters inside marine reserves, with higher survival of small urchins owing to greater access to crevices relative to large urchins. Indeed, shelter was 6.3 times and 3.1 times more important to survival of small and large urchins, respectively, on reserved relative to fished reef. Experimental results corroborate with surveys throughout the range extension region, showing greater occurrence of overgrazing on high-relief rocky habitats where shelter for C. rodgersii is readily available. This shows that ecosystem impacts mediated by range extension of such habitat-modifying organisms will be heterogeneous in space, and that marine systems with a more natural complement of large and thus

  3. Interstitial photodynamic therapy for the prostate: a canine feasibility study

    NASA Astrophysics Data System (ADS)

    Shetty, Sugandh D.; Sirls, Larry T.; Chen, Qun; Hetzel, Fred W.; Cerny, Joseph C.

    1996-05-01

    Prior to a possible clinical application of photodynamic therapy (PDT) for prostatic diseases such as benign prostatic hyperplasia and prostate cancer, optical properties of the prostate gland need to be studied. The specific objectives of this study were (1) to determine the light penetration depth, (2) to document the photosensitizer levels in the prostate, and (3) to document the lesion size after PDT. Sixteen dogs were injected with Photofrin II (1, 3 and 5 mg/kg) 24 hrs prior to laser application. After laparotomy and exposure of prostate, monochromatic light (630 nm, via an argon pumped dye laser) was applied through an isotropic fiber at 100 mw for a total dose of 400 joules. Continuous light fluence and temperature were documented. Prostates were harvested at 1 week and examined histologically for the lesion size. Four sham dogs were treated without Photofrin II. At Photofrin doses of 1, 3 and 5 mg/kg the mean prostatic Photofrin levels were 1.78 plus or minus 0.33, 1.47 plus or minus 0.08 and 1.95 plus or minus 0.44 (mu) gm/ml. The mean light penetration depths were 2.08, 1.37 and 1.64 mm respectively. Photofrin dose escalation (1, 3 and 5 mg/kg) increased the lesion size to radius of 4.1 plus or minus 0.9 mm, 4.4 plus or minus 0.8 mm and 6.3 plus or minus 0.9 mm. There were no lesions seen in sham dogs. These results demonstrate that light penetration in prostate is consistent and therapeutic levels of photosensitizer are achieved in prostatic tissue. Moreover, increasing size of the lesions were documented with dose escalation.

  4. Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats.

    PubMed

    Erfanian, Arezoo; Mirhosseini, Hamed; Rasti, Babak; Hair-Bejo, Mohd; Bin Mustafa, Shuhaimi; Abd Manap, Mohd Yazid

    2015-06-24

    The aim of this study was to evaluate the effects of fortification and nano-size reduction on calcium absorption and bioavailability of milk powder formula in sham, ovariectomized, and ovariectomized-osteoporosis rats as a menopause and menopause-osteoporosis model. Skim milk powder and skim milk powder fortified with calcium citrate and the suitable doses of inulin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamins D3, K1, and B6 were formulated based on the North American and Western European recommended dietary allowances. Optimization on cycle and pressure of high-pressure homogenizer was done to produce nano-fortified milk powder. In vivo study demonstrated that fortification and calcium citrate nano-fortified milk powder increased absorption and bioavailability of calcium, as well as bone stiffness and bone strength in sham, ovariectomized, and ovariectomized-osteoporosis rats. This study successfully developed an effective fortified milk powder for food application.

  5. Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats.

    PubMed

    Erfanian, Arezoo; Mirhosseini, Hamed; Rasti, Babak; Hair-Bejo, Mohd; Bin Mustafa, Shuhaimi; Abd Manap, Mohd Yazid

    2015-06-24

    The aim of this study was to evaluate the effects of fortification and nano-size reduction on calcium absorption and bioavailability of milk powder formula in sham, ovariectomized, and ovariectomized-osteoporosis rats as a menopause and menopause-osteoporosis model. Skim milk powder and skim milk powder fortified with calcium citrate and the suitable doses of inulin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamins D3, K1, and B6 were formulated based on the North American and Western European recommended dietary allowances. Optimization on cycle and pressure of high-pressure homogenizer was done to produce nano-fortified milk powder. In vivo study demonstrated that fortification and calcium citrate nano-fortified milk powder increased absorption and bioavailability of calcium, as well as bone stiffness and bone strength in sham, ovariectomized, and ovariectomized-osteoporosis rats. This study successfully developed an effective fortified milk powder for food application. PMID:26022498

  6. Reduction in the risk of prostate cancer: future directions after the Prostate Cancer Prevention Trial.

    PubMed

    Crawford, E David; Andriole, Gerald L; Marberger, Michael; Rittmaster, Roger S

    2010-03-01

    The landmark Prostate Cancer Prevention Trial (PCPT) generated interest in the potential health benefits and cost of reducing prostate cancer risk--specifically, the potential role of 5alpha-reductase inhibitors. However, the PCPT raised several unanswered questions, including the cause and significance of the increased incidence of high-grade tumors associated with finasteride. In the present study, we review the PCPT findings and unanswered questions, next steps in this field, and ongoing prostate cancer prevention trials addressing these unanswered questions. Particular emphasis is placed on the design of the second large-scale trial of a 5alpha-reductase inhibitor, the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. PMID:20035983

  7. Angiogenesis Is Induced and Wound Size Is Reduced by Electrical Stimulation in an Acute Wound Healing Model in Human Skin

    PubMed Central

    Ud-Din, Sara; Sebastian, Anil; Giddings, Pamela; Colthurst, James; Whiteside, Sigrid; Morris, Julie; Nuccitelli, Richard; Pullar, Christine; Baguneid, Mo; Bayat, Ardeshir

    2015-01-01

    Angiogenesis is critical for wound healing. Insufficient angiogenesis can result in impaired wound healing and chronic wound formation. Electrical stimulation (ES) has been shown to enhance angiogenesis. We previously showed that ES enhanced angiogenesis in acute wounds at one time point (day 14). The aim of this study was to further evaluate the role of ES in affecting angiogenesis during the acute phase of cutaneous wound healing over multiple time points. We compared the angiogenic response to wounding in 40 healthy volunteers (divided into two groups and randomised), treated with ES (post-ES) and compared them to secondary intention wound healing (control). Biopsy time points monitored were days 0, 3, 7, 10, 14. Objective non-invasive measures and H&E analysis were performed in addition to immunohistochemistry (IHC) and Western blotting (WB). Wound volume was significantly reduced on D7, 10 and 14 post-ES (p = 0.003, p = 0.002, p<0.001 respectively), surface area was reduced on days 10 (p = 0.001) and 14 (p<0.001) and wound diameter reduced on days 10 (p = 0.009) and 14 (p = 0.002). Blood flow increased significantly post-ES on D10 (p = 0.002) and 14 (p = 0.001). Angiogenic markers were up-regulated following ES application; protein analysis by IHC showed an increase (p<0.05) in VEGF-A expression by ES treatment on days 7, 10 and 14 (39%, 27% and 35% respectively) and PLGF expression on days 3 and 7 (40% on both days), compared to normal healing. Similarly, WB demonstrated an increase (p<0.05) in PLGF on days 7 and 14 (51% and 35% respectively). WB studies showed a significant increase of 30% (p>0.05) on day 14 in VEGF-A expression post-ES compared to controls. Furthermore, organisation of granulation tissue was improved on day 14 post-ES. This randomised controlled trial has shown that ES enhanced wound healing by reduced wound dimensions and increased VEGF-A and PLGF expression in acute cutaneous wounds, which further substantiates the role of ES in up

  8. Caspase-dependent and serine protease-dependent DNA fragmentation of myocytes in the ischemia-reperfused rabbit heart: these inhibitors do not reduce infarct size.

    PubMed

    Minatoguchi, S; Kariya, T; Uno, Y; Arai, M; Nishida, Y; Hashimoto, K; Wang, N; Aoyama, T; Takemura, G; Fujiwara, T; Fujiwara, H

    2001-10-01

    Some infarcted myocytes undergo caspase-dependent DNA fragmentation, but serine protease-dependent DNA fragmentation may also be involved. There is controversy regarding whether caspase inhibitors can reduce infarct size, so the present study investigated whether serine protease inhibitor can reduce the DNA fragmentation of infarcted myocytes and whether serine protease or caspase inhibitors attenuates myocardial infarct size in Japanese white rabbits without collateral circulation. Rabbits were subjected to 30-min coronary occlusion followed by 48-h reperfusion. A vehicle (dimethylsulfoxide, control group, n=8) or Z-Val-Ala-Asp(Ome)-CH2F (ZVAD-fmk, a caspase inhibitor, ZVAD group, 0.8 mg/kg iv at 20 min before coronary occlusion and 0.8 mg/kg at 90 min after reperfusion, n=8) or 3,4-dichloroisocoumarin (DCI, a serine protease inhibitor, 2 mg/kg iv at 20 min before coronary occlusion, DCI group, n=8) was administered. Animals were killed at 48h after reperfusion for the detection of myocardial infarct size and at 4h after reperfusion for the detection of dUTP nick end-labeling (TUNEL)-positive myocytes, the electrophoretic pattern of DNA fragmentation and ultrastructural analysis. The left ventricle (LV) was excised and sliced. The myocardial infarct size as a percentage of the area at risk was assessed by triphenyltetrazolium chloride staining. DNA fragmentation was assessed by in situ TUNEL at the light microscopic level. ZVAD and DCI significantly reduced the mean blood pressure during reperfusion without affecting heart rate. There was no significant difference in the % area at risk (AAR) of LV among the 3 groups (control: 26.3+/-3.0%; ZVAD: 25.6+/-2.6%; DCI: 25.6+/-2.0%). The % infarct size as a percentage of the AAR in the ZVAD group (41.3+/-4.5%) and the DCI group (50.4+/-3.8%) was not significantly different from the control group (43.5+/-4.5%). However, the percent DNA fragmentation in the infarcted area in the ZVAD (3.5+/-0.8%) and DCI groups (4

  9. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  10. Outcomes following Thulium vapoenucleation of large prostates

    PubMed Central

    Pearce, Shane M.; Pariser, Joseph J.; Malik, Rena D.; Famakinwa, Olufenwa J.; Chung, Doreen E.

    2016-01-01

    ABSTRACT Introduction: Thulium laser VapoEnucleation of the prostate (ThuVEP) is an evolving surgical technique for BPH. Most studies have focused on outcomes in small to medium sized prostates and have originated from Europe and Asia. We sought to describe our experience with ThuVEP for very large prostates in a North American cohort. Materials and Methods: From December 2010 to October 2014, 25 men underwent ThuVEP using the CyberTM® (Quantastem, Italy) thulium laser, all with prostate volume >75mL. Data collected included patient demographics, comorbidities, intraoperative parameters, complications, and post-operative outcomes including maximum flow rate (Qmax), post-void residual (PVR), International Prostate Symptom Score (IPSS), and quality of life score (QoL) in one year of follow-up. Statistical analysis was done using Wilcoxon signed-rank test. Results: At baseline, mean age was 70±9 years and prostate size was 163±62g. Most patients (84%) were in retention and 10 (40%) patients were on anticoagulation. Seven (28%) patients went home the day of surgery (mean hospital stay: 1.2±1.2d). There were 2 intraoperative complications (8%), both cystotomies related to morcellation. Nine patients (36%) experienced a complication, all within 30 days. There were no Clavien ≥III complications. Significant improvements were seen in Qmax, PVR, IPSS, and QoL score at each time interval to 12-months following surgery (all p<0.05). Of 21 patients initially in retention, all were voiding at last follow-up. Conclusions: Our findings suggest that ThuVEP is an effective treatment for BPH in patients with large prostates with sustained results for one year. PMID:27564287

  11. Is angiotensin-converting enzyme inhibitors/angiotensin receptor blockers therapy protective against prostate cancer?

    PubMed Central

    Mao, Yeqing; Xu, Xin; Wang, Xiao; Zheng, Xiangyi; Xie, Liping

    2016-01-01

    Emerging evidence suggests that renin-angiotensin system (RAS) may act as a molecular and therapeutic target for treating site-specific cancers, including prostate cancer. However, previous observational studies regarding the association between RAS inhibitors and prostate cancer risk have reported inconsistent results. We examined this association by performing a systematic review and meta-analysis. A total of 20,267 patients from nine cohort studies were enrolled. Compared with non-users of RAS inhibitors, individuals using RAS inhibitors had a reduced risk of prostate cancer (RR 0.92, 95 % CI 0.87-0.98), without statistically significant heterogeneity among studies (P = 0.118 for heterogeneity, I2 = 37.6 %). In addition, when subgroup analyses by study quality and number of cases, more statistically significant associations were observed in studies of high quality (RR 0.93, 95 % CI 0.88-0.97) and large sample size (RR 0.94, 95 % CI 0.91-0.98). There was no evidence of significant publication bias with Begg's test (P = 0.602) or with Egger's test (P = 0.350). Overall, this study indicates that use of RAS inhibitors may be associated with a decreased risk of prostate cancer. Large-scale well designed studies are needed to further explore this association. PMID:26760503

  12. Analysis of Interfraction Prostate Motion Using Megavoltage Cone Beam Computed Tomography

    SciTech Connect

    Bylund, Kevin C. Bayouth, John E.; Smith, Mark C.; Hass, A. Curtis; Bhatia, Sudershan K.; Buatti, John M..

    2008-11-01

    Purpose: Determine the degree of interfraction prostate motion and its components measured by using daily megavoltage (MV) cone beam computed tomography (CBCT) imaging. Methods and Materials: A total of 984 daily MV CBCT images from 24 patients undergoing definitive intensity-modulated radiotherapy for localized prostate cancer were analyzed retrospectively. Pretreatment couch shifts, based on physician registration of MV CBCT to planning CT data sets, were used as a measure of daily interfraction motion. Off-line bony registration was performed to separate bony misalignment from internal organ motion. Interobserver and intraobserver variation studies were performed on 20 MV CBCT images. Results: Mean interfraction prostate motion was 6.7 mm, with the greatest single-axis deviation in the anterior-posterior (AP) direction. The largest positional inaccuracy was accounted for by systematic deviations in bony misalignment, whereas random deviations occurred from bony misalignment and internal prostate motion. In the aggregate, AP motion did not correlate with days elapsed since beginning therapy or on average with rectal size at treatment planning. Interobserver variation was greatest in the AP direction, decreased in experienced observers, and further decreased in intraobserver studies. Mean interfraction motion during the first 6 days of therapy, when used as a subsequent offset, reduced acceptable AP planning target volume margins by 50%. Conclusion: The MV CBCT is a practical direct method of daily localization that shows significant interfraction motion with respect to conventional three-dimensional conformal and intensity-modulated radiotherapy margins, similar to that measured in other modalities.

  13. Chromium-Modified Li4Ti5O12 with a Synergistic Effect of Bulk Doping, Surface Coating, and Size Reducing.

    PubMed

    Zou, Hailin; Liang, Xin; Feng, Xuyong; Xiang, Hongfa

    2016-08-24

    Bulk doping, surface coating, and size reducing are three strategies for improving the electrochemical properties of Li4Ti5O12 (LTO). In this work, chromium (Cr)-modified LTO with a synergistic effect of bulk doping, surface coating, and size reducing is synthesized by a facile sol-gel method. X-ray diffraction (XRD) and Raman analysis prove that Cr dopes into the LTO bulk lattice, which effectively inhibits the generation of TiO2 impurities. Transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) verifies the surface coating of Li2CrO4 on the LTO surface, which decreases impedance of the LTO electrode. More importantly, the size of LTO particles can be significantly reduced from submicroscale to nanoscale as a result of the protection of the Li2CrO4 surface layer and the suppression from Cr atoms on the long-range order in the LTO lattice. As anode material, Li4-xCr3xTi5-2xO12 (x = 0.1) delivers a reversible capacity of 141 mAh g(-1) at 10 °C, and over 155 mAh g(-1) at 1 °C after 1000 cycles. Therefore, the Cr-modified Li4Ti5O12 prepared via a sol-gel method has potential for applications in high-power, long-life lithium-ion batteries. PMID:27479172

  14. Reduced molecular size and altered disaccharide composition of cerebral chondroitin sulfate upon Alzheimer’s pathogenesis in mice

    PubMed Central

    Zhang, Zui; Ohtake-Niimi, Shiori; Kadomatsu, Kenji; Uchimura, Kenji

    2016-01-01

    ABSTRACT Alzheimer’s disease (AD) is a progressive disorder leading to cognitive impairment and neuronal loss. Cerebral extracellular accumulation and deposition of amyloid ß plaques is a pathological hallmark of AD. Chondroitin sulfate (CS) is an extracellular component abundant in the brain. CS is a sulfated glycosaminoglycan covalently attached to a core protein, forming chondroitin sulfate proteoglycan. The structure of CS is heterogeneous with sulfation modification and elongation of the chain. The structural diversity of CS allows it to play various roles in the brain. Increasing evidence has shown that CS promotes aggregation of amyloid ß peptides into higher-order species such as insoluble amyloid ß fibrils. Difficulties in the structural analysis of brain CS, as well as its heterogeneity, limit the study of potential roles of CS in AD pathology. Here we established a microanalysis method with reversed-phase ion-pair high performance liquid chromatography and found that CS in the brains of Tg2576 AD model mice show a lower molecular size and an increased ratio of CS-B motif di-sulfated disaccharide. Our findings provide insight into the structural changes of cerebral CS upon Alzheimer’s pathogenesis. PMID:27578913

  15. Modified carbon fibers to improve composite properties. [sizing fibers for reduced electrical conductivity and adhesion during combustion

    NASA Technical Reports Server (NTRS)

    Shepler, R. E.

    1979-01-01

    Thin coatings, 5 to 10 wt. percent, were applied to PAN-based carbon fibers. These coatings were intended to make the carbon fibers less electrically conductive or to cause fibers to stick together when a carbon fiber/epoxy composite burned. The effectiveness of the coatings in these regards was evaluated in burn tests with a test rig designed to simulate burning, impact and wind conditions which might release carbon fibers. The effect of the coatings on fiber and composite properties and handling was also investigated. Attempts at sizing carbon fibers with silicon dioxide, silicon carbide and boron nitride meet with varying degrees of success; however, none of these materials provided an electrically nonconductive coating. Coatings intended to stick carbon fibers together after a composite burned were sodium silicate, silica gel, ethyl silicate, boric acid and ammonium borate. Of these, only the sodium silicate and silica gel provided any sticking together of fibers. The amount of sticking was insufficient to achieve the desired objectives.

  16. The influence of isotope and prostate volume on urinary morbidity after prostate brachytherapy

    SciTech Connect

    Niehaus, Angela; Merrick, Gregory S. . E-mail: gmerrick@wheelinghospital.com; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Galbreath, Robert W.; Adamovich, Edward

    2006-01-01

    Purpose: To evaluate the influence of isotope and prostate size on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after prostate brachytherapy. Methods and Materials: Between January 1998 and June 2003, 976 consecutive patients underwent brachytherapy for clinical stage T1b-T3a (2002 American Joint Committee on Cancer) prostate cancer. Seven hundred eighty-nine (80.8%) were implanted with {sup 103}Pd and 187 (19.2%) with {sup 125}I. The median follow-up was 41.2 months. Patients were stratified into size cohorts {<=}25 cm{sup 3}, 25.1-35 cm{sup 3}, 35.1-45 cm{sup 3}, and >45 cm{sup 3}. Four hundred eighteen patients (42.8%) received androgen deprivation therapy (ADT). Four hundred eighty-six patients (49.7%) received supplemental external-beam radiation therapy (XRT). In all patients, an alpha blocker was initiated before implantation and continued at least until the IPSS returned to baseline. IPSS resolution was defined as a return to within one point of baseline. The median number of IPSS determinations per patient was 21. Clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment PSA, Gleason score, clinical T stage, percent positive biopsies, preimplant IPSS, ultrasound volume, planning volume, isotope, V{sub 100/150/20}, D{sub 9}, urethral dose (average and maximum), supplemental XRT, ADT, and the duration of ADT ({<=}6 months vs. >6 months). Catheter dependency and the need for postsurgical intervention were also evaluated. Results: For both isotopes and all prostate size cohorts, IPSS peaked 1 month after implantation and returned to baseline at a mean of 1.9 months. Stratification of prostate size cohorts by isotope demonstrated no significant differences in prolonged catheter dependency ({>=}5 days), IPSS resolution, or postimplant surgical intervention. In Cox regression analysis, IPSS normalization was best

  17. Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats.

    PubMed

    Fisher, M; Meadows, M E; Do, T; Weise, J; Trubetskoy, V; Charette, M; Finklestein, S P

    1995-11-01

    Basic fibroblast growth factor (bFGF) is a polypeptide that supports the survival of brain cells (including neurons, glia, and endothelia) and protects neurons against a number of toxins and insults in vitro. This factor is also a potent dilator of cerebral pial arterioles in vivo. In previous studies, we found that intraventricularly administered bFGF reduced infarct volume in a model of focal cerebral ischemia in rats. In the current study, bFGF (45 micrograms/kg/h) in vehicle, or vehicle alone, was infused intravenously for 3 h, beginning at 30 min after permanent middle cerebral artery occlusion by intraluminal suture in mature Sprague-Dawley rats. After 24 h, neurological deficit (as assessed by a 0- to 5-point scale, with 5 = most severe) was 2.6 +/- 1.0 in vehicle-treated and 1.5 +/- 1.3 in bFGF-treated rats (mean +/- SD; N = 12 vs. 11; p = 0.009). Infarct volume was 297 +/- 65 mm3 in vehicle- and 143 +/- 135 mm3 in bFGF-treated animals (p = 0.002). During infusion, there was a modest decrease in mean arterial blood pressure but no changes in arterial blood gases or core or brain temperature in bFGF-treated rats. Autoradiography following intravenous administration of 111In-labeled bFGF showed that labeled bFGF crossed the damaged blood-brain barrier to enter the ischemic (but not the nonischemic) hemisphere. Whether the infarct-reducing effects of bFGF depend on intraparenchymal or intravascular mechanisms requires further study.

  18. Cyclosporin variably and inconsistently reduces infarct size in experimental models of reperfused myocardial infarction: a systematic review and meta-analysis.

    PubMed

    Lim, W Y; Messow, C M; Berry, C

    2012-04-01

    Cyclosporin is an immunosuppressant that has recently been proposed as a treatment to prevent reperfusion injury in acute myocardial infarction (MI). We aimed to determine the overall efficacy of cyclosporin in experimental studies of acute reperfused MI. We conducted a systematic review and stratified meta-analysis of published studies describing the efficacy of cyclosporin in experimental models of acute reperfused MI. We included all in vivo publications of cyclosporin where infarct size was measured. A literature search identified 29 potential studies of which 20 fulfilled the eligibility criteria. In these studies (involving four species of animals), cyclosporin reduced myocardial infarct size by a standardized mean (95% confidence interval) difference of -1.60 (-2.17, -1.03) compared with controls. Cyclosporin failed to demonstrate a convincing benefit in studies involving pigs. Despite this observation, the overall efficacy of cyclosporin did not differ across species (P= 0.358). The dose of cyclosporin given did not affect final infarct size (P= 0.203). Funnel plots of these data suggested heterogeneity among the studies. Cyclosporin had variable effects on infarct size compared with placebo. Cyclosporin had no effect on myocardial infarct size in swine, raising a question over the potential cardioprotective effects of cyclosporin in man.

  19. Breast Intensity-Modulated Radiation Therapy Reduces Time Spent With Acute Dermatitis for Women of All Breast Sizes During Radiation

    SciTech Connect

    Freedman, Gary M. Li Tianyu; Nicolaou, Nicos; Chen Yan; Ma, Charlie C.-M.; Anderson, Penny R.

    2009-07-01

    Purpose: To study the time spent with radiation-induced dermatitis during a course of radiation therapy for breast cancer in women treated with conventional or intensity-modulated radiation therapy (IMRT). Methods and Materials: The study population consisted of 804 consecutive women with early-stage breast cancer treated with breast-conserving surgery and radiation from 2001 to 2006. All patients were treated with whole-breast radiation followed by a boost to the tumor bed. Whole-breast radiation consisted of conventional wedged photon tangents (n = 405) earlier in the study period and mostly of photon IMRT (n = 399) in later years. All patients had acute dermatitis graded each week of treatment. Results: The breakdown of the cases of maximum acute dermatitis by grade was as follows: 3%, Grade 0; 34%, Grade 1; 61%, Grade 2; and 2%, Grade 3. The breakdown of cases of maximum toxicity by technique was as follows: 48%, Grade 0/1, and 52%, Grade 2/3, for IMRT; and 25%, Grade 0/1, and 75%, Grade 2/3, for conventional radiation therapy (p < 0.0001). The IMRT patients spent 82% of weeks during treatment with Grade 0/1 dermatitis and 18% with Grade 2/3 dermatitis, compared with 29% and 71% of patients, respectively, treated with conventional radiation (p < 0.0001). Furthermore, the time spent with Grade 2/3 toxicity was decreased in IMRT patients with small (p = 0.0015), medium (p < 0.0001), and large (p < 0.0001) breasts. Conclusions: Breast IMRT is associated with a significant decrease both in the time spent during treatment with Grade 2/3 dermatitis and in the maximum severity of dermatitis compared with that associated with conventional radiation, regardless of breast size.

  20. Warring arthropod societies: Social spider colonies can delay annihilation by predatory ants via reduced apparency and increased group size.

    PubMed

    Keiser, Carl N; Wright, Colin M; Pruitt, Jonathan N

    2015-10-01

    Sociality provides individuals with benefits via collective foraging and anti-predator defense. One of the costs of living in large groups, however, is increased apparency to natural enemies. Here, we test how the individual-level and collective traits of spider societies can increase the risk of discovery and death by predatory ants. We transplanted colonies of the social spider Stegodyphus dumicola into a habitat dense with one of their top predators, the pugnacious ant Anoplolepis custodiens. With three different experiments, we test how colony-wide survivorship in a predator-dense habitat can be altered by colony apparency (i.e., the presence of a capture web), group size, and group composition (i.e., the proportion of bold and shy personality types present). We also test how spiders' social context (i.e., living solitarily vs. among conspecifics) modifies their behaviour toward ants in their capture web. Colonies with capture webs intact were discovered by predatory ants on average 25% faster than colonies with the capture web removed, and all discovered colonies eventually collapsed and succumbed to predation. However, the lag time from discovery by ants to colony collapse was greater for colonies containing more individuals. The composition of individual personality types in the group had no influence on survivorship. Spiders in a social group were more likely to approach ants caught in their web than were isolated spiders. Isolated spiders were more likely to attack a safe prey item (a moth) than they were to attack ants and were more likely to retreat from ants after contact than they were after contact with moths. Together, our data suggest that the physical structures produced by large animal societies can increase their apparency to natural enemies, though larger groups can facilitate a longer lag time between discovery and demise. Lastly, the interaction between spiders and predatory ants seems to depend on the social context in which spiders reside

  1. Warring arthropod societies: Social spider colonies can delay annihilation by predatory ants via reduced apparency and increased group size.

    PubMed

    Keiser, Carl N; Wright, Colin M; Pruitt, Jonathan N

    2015-10-01

    Sociality provides individuals with benefits via collective foraging and anti-predator defense. One of the costs of living in large groups, however, is increased apparency to natural enemies. Here, we test how the individual-level and collective traits of spider societies can increase the risk of discovery and death by predatory ants. We transplanted colonies of the social spider Stegodyphus dumicola into a habitat dense with one of their top predators, the pugnacious ant Anoplolepis custodiens. With three different experiments, we test how colony-wide survivorship in a predator-dense habitat can be altered by colony apparency (i.e., the presence of a capture web), group size, and group composition (i.e., the proportion of bold and shy personality types present). We also test how spiders' social context (i.e., living solitarily vs. among conspecifics) modifies their behaviour toward ants in their capture web. Colonies with capture webs intact were discovered by predatory ants on average 25% faster than colonies with the capture web removed, and all discovered colonies eventually collapsed and succumbed to predation. However, the lag time from discovery by ants to colony collapse was greater for colonies containing more individuals. The composition of individual personality types in the group had no influence on survivorship. Spiders in a social group were more likely to approach ants caught in their web than were isolated spiders. Isolated spiders were more likely to attack a safe prey item (a moth) than they were to attack ants and were more likely to retreat from ants after contact than they were after contact with moths. Together, our data suggest that the physical structures produced by large animal societies can increase their apparency to natural enemies, though larger groups can facilitate a longer lag time between discovery and demise. Lastly, the interaction between spiders and predatory ants seems to depend on the social context in which spiders reside.

  2. Comparison of 180-degree and 90-degree needle rotation to reduce wound size in PIT-injected juvenile Chinook salmon

    SciTech Connect

    Bryson, Amanda J.; Woodley, Christa M.; Karls, Rhonda K.; Hall, Kathleen D.; Weiland, Mark A.; Deng, Zhiqun; Carlson, Thomas J.; Eppard, Matthew B.

    2013-04-30

    Animal telemetry, which requires the implantation of passive transponders or active transmitters, is used to monitor and assess fish stock and conservation to gain an understanding of fish movement and behavior. As new telemetry technologies become available, studies of their effects on species of interest are imperative as is development of implantation techniques. In this study, we investigated the effects of bevel rotation (0-, 90-, 180-degree axis rotation) on wound extent, tag loss, and wound healing rates in juvenile Chinook salmon injected with an 8-gauge needle, which is required for implantation of the novel injectable Juvenile Salmon Acoustic Telemetry Systems (JSATS) acoustic transmitter or large passive integrated transponder (PIT) tags. Although the injection sites were not closed after injection (e.g., with sutures or glue), there were no mortalities, dropped tags, or indications of fungus, ulceration, and/or redness around the wound. On Day 0 and post-implantation Day 7, the 90-degree bevel rotation produced smaller wound extent than the 180-degree bevel rotation. No axis rotation (0-degrees) resulted in the PIT tag frequently misleading or falling out upon injection. The results of this study indicated the 90-degree bevel rotation was the more efficient technique, produced less wound extent. Given the wound extent compared to size of fish, we recommend researchers should consider a 90-degree rotation over the 180-degree rotation in telemetry studies. Highlights •Three degrees of needle rotation were examined for effects in Chinook salmon. •Mortality, tag loss, wound extent, healing, and infection indicators were measured. •There were no mortalities, tag loss, or indications of infection. •The 90-degree needle rotation through Day 7 produced the smallest wound extent.

  3. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols

    PubMed Central

    2011-01-01

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  4. Nigerian foodstuffs with prostate cancer chemopreventive polyphenols.

    PubMed

    Atawodi, Sunday Eneojo

    2011-09-23

    Dietary polyphenols are antioxidants that can scavenge biological free radicals, and chemoprevent diseases with biological oxidation as their main etiological factor. In this paper, we review our laboratory data vis-ὰ-vis available literature on prostate cancer chemopreventive substances in Nigerian foodstuffs. Dacryodes edulis fruit, Moringa oleifera and Syzygium aromaticum contained prostate active polyphenols like ellagic acid, gallate, methylgallate, catechol, kaempferol quercetin and their derivatives. Also Canarium schweinfurthii Engl oil contained ten phenolic compounds and lignans, namely; catechol, p-hydroxybenzaldehyde, dihydroxyphenylacetic acid, tyrosol, p-hydroxybenzoic acid, dihydroxybenzoic acid, vanillic acid, phloretic acid, pinoresinol, secoisolariciresinol. In addition, tomatoes (Lycopersicon esculentum Mill) which contains the powerful antioxidant and anti-prostate cancer agent, lycopene; cabbage (Brassica oleracea) containing indole-3-carbinol; citrus fruits containing pectin; Soursop (Annona muricata) containing annonaceous acetogenins; soya beans (Glycine max) containing isoflavones; chilli pepper (Capsicum annuum) containing capsaicin, and green tea (Camellia sinensis) containing (-) epigallocatechin gallate (EGCG), (-) epicatechin, (-) epicatechin-3-gallate and (-) epigallocatechin -3-gallate which are widely reported to posses prostate cancer chemopreventive compounds are also grown in Nigeria and other African countries. Thus, the high incidence of prostate cancer among males of African extraction can be dramatically reduced, and the age of onset drastically increased, if the population at risk consumes the right kinds of foods in the right proportion, beginning early in life, especially as prostate cancer has a latency period of about 50 years. PMID:21992488

  5. [Prostate cancer. Current and practice-relevant news from urology in 2011].

    PubMed

    Wirth, M; Zastrow, S

    2011-09-01

    The effect of 5α reductase inhibitors in prostate cancer has been extensively investigated. The studies determined that finasteride and also dutasteride reduced the risk of prostate cancer; however, particularly high-grade cancer was not reduced and may possibly even have been increased. This is appropriately reflected in the S3 guideline on prostate cancer. New data on early recognition show that after longer term observation prostate cancer-specific mortality can be more effectively reduced by screening than was initially shown by the original data from the ERSPC study. Active surveillance is becoming more important for the therapy of early prostate cancer. Other new publications have shown good results for patients who underwent surgery for high risk prostate cancer. For metastasized prostate cancer new immunotherapeutic, chemotherapeutic and hormonal options are now available or will soon be approved. PMID:21842194

  6. Hormone therapy for prostate cancer

    MedlinePlus

    Androgen deprivation therapy; ADT; Androgen suppression therapy; Combined androgen blockade ... Androgens cause prostate cancer cells to grow. Hormone therapy for prostate cancer lowers the effect level of ...

  7. Targeting of αv-Integrins in Stem/Progenitor Cells and Supportive Microenvironment Impairs Bone Metastasis in Human Prostate Cancer12

    PubMed Central

    van der Horst, Geertje; van den Hoogen, Christel; Buijs, Jeroen T; Cheung, Henry; Bloys, Henny; Pelger, Rob CM; Lorenzon, Giocondo; Heckmann, Bertrand; Feyen, Jean; Pujuguet, Philippe; Blanque, Roland; Clément-Lacroix, Philippe; van der Pluijm, Gabri

    2011-01-01

    Acquisition of an invasive phenotype by cancer cells is a requirement for bone metastasis. Transformed epithelial cells can switch to a motile, mesenchymal phenotype by epithelial-mesenchymal transition (EMT). Recently, it has been shown that EMT is functionally linked to prostate cancer stem cells, which are not only critically involved in prostate cancer maintenance but also in bone metastasis. We showed that treatment with the non-peptide αv-integrin antagonist GLPG0187 dose-dependently increased the E-cadherin/vimentin ratio, rendering the cells a more epithelial, sessile phenotype. In addition, GLPG0187 dose-dependently diminished the size of the aldehyde dehydrogenase high subpopulation of prostate cancer cells, suggesting that αv-integrin plays an important role in maintaining the prostate cancer stem/progenitor pool. Our data show that GLPG0187 is a potent inhibitor of osteoclastic bone resorption and angiogenesis in vitro and in vivo. Real-time bioluminescent imaging in preclinical models of prostate cancer demonstrated that blocking αv-integrins by GLPG0187 markedly reduced their metastatic tumor growth according to preventive and curative protocols. Bone tumor burden was significantly lower in the preventive protocol. In addition, the number of bone metastases/mouse was significantly inhibited. In the curative protocol, the progression of bone metastases and the formation of new bone metastases during the treatment period was significantly inhibited. In conclusion, we demonstrate that targeting of integrins by GLPG0187 can inhibit the de novo formation and progression of bone metastases in prostate cancer by antitumor (including inhibition of EMT and the size of the prostate cancer stem cell population), antiresorptive, and antiangiogenic mechanisms. PMID:21677875

  8. REDUCED INFARCT SIZE AND ACCUMULATION OF MICROGLIA IN RATS TREATED WITH WIN 55,212-2 AFTER NEONATAL STROKE

    PubMed Central

    Fernández-López, David; Faustino, Joel; Derugin, Nikita; Wendland, Michael; Lizasoain, Ignacio; Moro, Maria A.; Vexler, Zinaida S.

    2012-01-01

    Cannabinoids have emerged as brain protective agents under neurodegenerative conditions. Many neuroprotective actions of cannabinoids depend on the activation of specific receptors, cannabinoid receptor type 1 (CB1R) and type 2 (CB2R). The aim of the present study was to determine whether the CB2R and CB1R agonist WIN 55,212-2 (WIN) protects neonatal brain against focal cerebral ischemia-reperfusion and whether anti-inflammatory mechanisms play a role in protection. 7-day-old rats were subjected to 90 minutes middle cerebral artery occlusion (MCAO) and injured rats identified by diffusion-weighted MRI during the occlusion. After reperfusion rats were subcutaneously administered 1mg/kg of WIN or vehicle twice daily until sacrifice. MCAO led to increased mRNA expression of CB2R (but not CB1R), chemokine receptors (CCR2 and CX3CR1) and cytokines (IL-1β and TNFα), as well as increased protein expression of chemokines MCP-1 and MIP-1α and microglial activation 24 hours after MCAO. WIN administration significantly reduced microglial activation at this point and attenuated infarct volume and microglial accumulation and proliferation in the injured cortex 72 hours after MCAO. Cumulatively, our results show that the cannabinoid agonist WIN protects against neonatal focal stroke in part due to inhibitory effects on microglia. PMID:22285309

  9. Loss of the Drosophila melanogaster DEAD box protein Ddx1 leads to reduced size and aberrant gametogenesis.

    PubMed

    Germain, Devon R; Li, Lei; Hildebrandt, Matthew R; Simmonds, Andrew J; Hughes, Sarah C; Godbout, Roseline

    2015-11-15

    Mammalian DDX1 has been implicated in RNA trafficking, DNA double-strand break repair and RNA processing; however, little is known about its role during animal development. Here, we report phenotypes associated with a null Ddx1 (Ddx1(AX)) mutation generated in Drosophila melanogaster. Ddx1 null flies are viable but significantly smaller than control and Ddx1 heterozygous flies. Female Ddx1 null flies have reduced fertility with egg chambers undergoing autophagy, whereas males are sterile due to disrupted spermatogenesis. Comparative RNA sequencing of control and Ddx1 null third instars identified several transcripts affected by Ddx1 inactivation. One of these, Sirup mRNA, was previously shown to be overexpressed under starvation conditions and implicated in mitochondrial function. We demonstrate that Sirup is a direct binding target of Ddx1 and that Sirup mRNA is differentially spliced in the presence or absence of Ddx1. Combining Ddx1 null mutation with Sirup dsRNA-mediated knock-down causes epistatic lethality not observed in either single mutant. Our data suggest a role for Drosophila Ddx1 in stress-induced regulation of splicing.

  10. Discovery and validation of urinary biomarkers for prostate cancer

    PubMed Central

    Theodorescu, Dan; Schiffer, Eric; Bauer, Hartwig W.; Douwes, Friedrich; Eichhorn, Frank; Polley, Reinhard; Schmidt, Thomas; Schöfer, Wolfgang; Zürbig, Petra; Good, David M.; Coon, Joshua J.

    2009-01-01

    Only 30% of patients with elevated serum prostate specific antigen (PSA) levels who undergo prostate biopsy are diagnosed with prostate cancer (PCa). Novel methods are needed to reduce the number of unnecessary biopsies. We report on the identification and validation of a panel of 12 novel biomarkers for prostate cancer (PCaP), using CE coupled MS. The biomarkers could be defined by comparing first void urine of 51 men with PCa and 35 with negative prostate biopsy. In contrast, midstream urine samples did not allow the identification of discriminatory molecules, suggesting that prostatic fluids may be the source of the defined biomarkers. Consequently, first void urine samples were tested for sufficient amounts of prostatic fluid, using a prostatic fluid indicative panel (“informative” polypeptide panel; IPP). A combination of IPP and PCaP to predict positive prostate biopsy was evaluated in a blinded prospective study. Two hundred thirteen of 264 samples matched the IPP criterion. PCa was detected with 89% sensitivity, 51% specificity. Including age and percent free PSA to the proteomic signatures resulted in 91% sensitivity, 69% specificity. PMID:19759844

  11. Stromal microcalcification in prostate.

    PubMed

    Muezzinoglu, B; Gurbuz, Y

    2001-06-01

    Prostatic calcification is most commonly encountered as calculus or intraluminal calcifications within atypical small glandular proliferations. This study was undertaken to detect stromal microcalcifications in prostate tissue. All slides from 194 needle biopsies were retrospectively reviewed. Six cases (3.1%) had stromal microcalcifications constantly associated with mononuclear inflammatory infiltrate around the each focus. Association with prostatic glands was not seen in any of the microcalcification foci. Three cases had simultaneous adenocarcinoma and one had high-grade prostatic intraepithelial neoplasia, all of which were apart from the microcalcification foci. In conclusion, stromal microcalcification is a dystrophic, inflammation-mediated, benign process.

  12. Screening for prostate cancer

    NASA Technical Reports Server (NTRS)

    Weirich, Stephen A.

    1993-01-01

    Despite recent advances in both the survival and cure rates for many forms of cancer, unfortunately the same has not been true for prostate cancer. In fact, the age-adjusted death rate from prostate cancer has not significantly improved since 1949, and prostate cancer remains the most common cancer in American men, causing the second highest cancer mortality rate. Topics discussed include the following: serum testosterone levels; diagnosis; mortality statistics; prostate-sppecific antigen (PSA) tests; and the Occupational Medicine Services policy at LeRC.

  13. Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

    PubMed

    Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N; Mitrache, Nicoleta; Do, Kieu C; Jankowski, Michelle; Chitale, Dhananjay A; Trudeau, Sheri; Belinsky, Steven A; Tang, Deliang

    2016-06-15

    In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease. PMID:26860439

  14. Methylation in benign prostate and risk of disease progression in men subsequently diagnosed with prostate cancer.

    PubMed

    Rybicki, Benjamin A; Rundle, Andrew; Kryvenko, Oleksandr N; Mitrache, Nicoleta; Do, Kieu C; Jankowski, Michelle; Chitale, Dhananjay A; Trudeau, Sheri; Belinsky, Steven A; Tang, Deliang

    2016-06-15

    In DNA from prostate tumors, methylation patterns in gene promoter regions can be a biomarker for disease progression. It remains unclear whether methylation patterns in benign prostate tissue--prior to malignant transformation--may provide similar prognostic information. To determine whether early methylation events predict prostate cancer outcomes, we evaluated histologically benign prostate specimens from 353 men who eventually developed prostate cancer and received "definitive" treatment [radical prostatectomy (58%) or radiation therapy (42%)]. Cases were drawn from a large hospital-based cohort of men with benign prostate biopsy specimens collected between 1990 and 2002. Risk of disease progression associated with methylation was estimated using time-to-event analyses. Average follow-up was over 5 years; biochemical recurrence (BCR) occurred in 91 cases (26%). In White men, methylation of the APC gene was associated with increased risk of BCR, even after adjusting for standard clinical risk factors for prostate cancer progression (adjusted hazard ratio (aHR) = 2.26; 95%CI 1.23-4.16). APC methylation was most strongly associated with a significant increased risk of BCR in White men with low prostate specific antigen at cohort entry (HR = 3.66; 95%CI 1.51-8.85). In additional stratified analyses, we found that methylation of the RARB gene significantly increased risk of BCR in African American cases who demonstrated methylation of at least one of the other four genes under study (HR = 3.80; 95%CI 1.07-13.53). These findings may have implications in the early identification of aggressive prostate cancer as well as reducing unnecessary medical procedures and emotional distress for men who present with markers of indolent disease.

  15. Prostatitis - nonbacterial

    MedlinePlus

    ... Nerve problem involving the lower urinary tract Parasites Pelvic floor muscle problem Sexual abuse Viruses Life stresses and ... cyclobenzaprine can help to reduce spasms in the pelvic floor. Some people have found some relief from pollen ...

  16. Bitter melon extract impairs prostate cancer cell-cycle progression and delays prostatic intraepithelial neoplasia in TRAMP model.

    PubMed

    Ru, Peng; Steele, Robert; Nerurkar, Pratibha V; Phillips, Nancy; Ray, Ratna B

    2011-12-01

    Prostate cancer remains the second leading cause of cancer deaths among American men. Earlier diagnosis increases survival rate in patients. However, treatments for advanced disease are limited to hormone ablation techniques and palliative care. Thus, new methods of treatment and prevention are necessary for inhibiting disease progression to a hormone refractory state. One of the approaches to control prostate cancer is prevention through diet, which inhibits one or more neoplastic events and reduces the cancer risk. For centuries, Ayurveda has recommended the use of bitter melon (Momordica charantia) as a functional food to prevent and treat human health related issues. In this study, we have initially used human prostate cancer cells, PC3 and LNCaP, as an in vitro model to assess the efficacy of bitter melon extract (BME) as an anticancer agent. We observed that prostate cancer cells treated with BME accumulate during the S phase of the cell cycle and modulate cyclin D1, cyclin E, and p21 expression. Treatment of prostate cancer cells with BME enhanced Bax expression and induced PARP cleavage. Oral gavage of BME, as a dietary compound, delayed the progression to high-grade prostatic intraepithelial neoplasia in TRAMP (transgenic adenocarcinoma of mouse prostate) mice (31%). Prostate tissue from BME-fed mice displayed approximately 51% reduction of proliferating cell nuclear antigen expression. Together, our results suggest for the first time that oral administration of BME inhibits prostate cancer progression in TRAMP mice by interfering cell-cycle progression and proliferation. PMID:21911444

  17. Apparent quiescence of the metallothionein gene in the rat ventral prostate: association with cadmium-induced prostate tumors in rats.

    PubMed

    Coogan, T P; Shiraishi, N; Waalkes, M P

    1994-09-01

    Several chronic studies in rats indicating that cadmium exposure can induce tumors of the ventral prostate have recently been completed in our laboratory. In one such study, a single dose of cadmium, s.c., increased prostatic tumor incidence only at doses below 5.0 mumol/kg, the approximate threshold for cadmium-induced testicular damage. In a further study, prostatic tumors were elevated with higher doses of cadmium (30 mumol/kg, s.c.) if testicular damage was prevented by zinc pretreatment. Most recently, we found that dietary cadmium (25 to 200 micrograms/g) also can increase prostatic neoplastic lesions, but these were reduced by zinc-deficient diets. Thus it appears that cadmium produces prostatic tumors only if testicular function is maintained. Furthermore, we find that metallothionein (MT), a protein associated with cadmium tolerance, may be deficient in the rat prostate, and the prostatic MT gene, at least in the ventral lobe, is unresponsive to metal stimuli. In liver, MT gene expression, as assessed by MT-1 mRNA, was quite apparent in control tissue and was induced in a dose-dependent manner 24 hr following cadmium exposure (1 to 10 mumol/kg, s.c.). However, in the ventral prostate very low constitutive levels of MT-1 mRNA were detected and increases did not occur with cadmium exposure. Cadmium concentrations in the ventral prostate were in excess of those that cause significant induction in the liver. In sharp contrast to the gene in the ventral prostate, in the dorsal prostate the MT gene was quite active. The dorsal prostate is not susceptible to cadmium carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7843088

  18. Topical application of a cleanser containing extracts of Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis reduces skin oil content and pore size in human skin

    PubMed Central

    LEE, BO MI; AN, SUNGKWAN; KIM, SOO-YEON; HAN, HYUN JOO; JEONG, YU-JIN; LEE, KYOUNG-ROK; ROH, NAM KYUNG; AHN, KYU JOONG; AN, IN-SOOK; CHA, HWA JUN

    2015-01-01

    The effects of skin pores on skin topographic features can be reduced by decreasing excessive production and accumulation of sebum and elimination of comedones. Therefore, a cosmetic cleanser that regulates sebum homeostasis is required. In the present study, the effects of a cosmetic cleanser that contained Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis (DPC) was examined on the removal of sebum and on skin pore size. Healthy volunteers (n=23) aged 20–50 years were asked to apply the test materials to the face. Skin oil content, pore size, pore number and extracted sebum surface area were measured using various measurement methods. All the measurements were performed at pre- and post-application of the test materials. When the cosmetic cleanser containing DPC was applied to the skin, the oil content decreased by 77.3%, from 6.19 to 1.40. The number of skin pores decreased by 24.83%, from 125.39 to 94.23. Skin pore size decreased from 0.07 to 0.02 µm3 (71.43% decrease). The amount of extracted sebum increased by 335% when the DPC cleanser was used. Compared to the control cleanser, skin oil content was significantly decreased when the cleanser that contained DPC was used. The cleanser containing DPC also decreased pore size and number. Finally, the DPC cleanser easily removed solidified sebum from the skin. PMID:26137233

  19. Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner.

    PubMed

    Eichhorn, Tanja; Rauscher, Sabine; Hammer, Caroline; Gröger, Marion; Fischer, Michael B; Weber, Viktoria

    2016-10-01

    Endothelial activation with excessive recruitment and adhesion of immune cells plays a central role in the progression of sepsis. We established a microfluidic system to study the activation of human umbilical vein endothelial cells by conditioned medium containing plasma from lipopolysaccharide-stimulated whole blood or from septic blood and to investigate the effect of adsorption of inflammatory mediators on endothelial activation. Treatment of stimulated whole blood with polystyrene-divinylbenzene-based cytokine adsorbents (average pore sizes 15 or 30 nm) prior to passage over the endothelial layer resulted in significantly reduced endothelial cytokine and chemokine release, plasminogen activator inhibitor-1 secretion, adhesion molecule expression, and in diminished monocyte adhesion. Plasma samples from sepsis patients differed substantially in their potential to induce endothelial activation and monocyte adhesion despite their almost identical interleukin-6 and tumor necrosis factor-alpha levels. Pre-incubation of the plasma samples with a polystyrene-divinylbenzene-based adsorbent (30 nm average pore size) reduced endothelial intercellular adhesion molecule-1 expression to baseline levels, resulting in significantly diminished monocyte adhesion. Our data support the potential of porous polystyrene-divinylbenzene-based adsorbents to reduce endothelial activation under septic conditions by depletion of a broad range of inflammatory mediators. PMID:27503310

  20. Polystyrene-Divinylbenzene-Based Adsorbents Reduce Endothelial Activation and Monocyte Adhesion Under Septic Conditions in a Pore Size-Dependent Manner.

    PubMed

    Eichhorn, Tanja; Rauscher, Sabine; Hammer, Caroline; Gröger, Marion; Fischer, Michael B; Weber, Viktoria

    2016-10-01

    Endothelial activation with excessive recruitment and adhesion of immune cells plays a central role in the progression of sepsis. We established a microfluidic system to study the activation of human umbilical vein endothelial cells by conditioned medium containing plasma from lipopolysaccharide-stimulated whole blood or from septic blood and to investigate the effect of adsorption of inflammatory mediators on endothelial activation. Treatment of stimulated whole blood with polystyrene-divinylbenzene-based cytokine adsorbents (average pore sizes 15 or 30 nm) prior to passage over the endothelial layer resulted in significantly reduced endothelial cytokine and chemokine release, plasminogen activator inhibitor-1 secretion, adhesion molecule expression, and in diminished monocyte adhesion. Plasma samples from sepsis patients differed substantially in their potential to induce endothelial activation and monocyte adhesion despite their almost identical interleukin-6 and tumor necrosis factor-alpha levels. Pre-incubation of the plasma samples with a polystyrene-divinylbenzene-based adsorbent (30 nm average pore size) reduced endothelial intercellular adhesion molecule-1 expression to baseline levels, resulting in significantly diminished monocyte adhesion. Our data support the potential of porous polystyrene-divinylbenzene-based adsorbents to reduce endothelial activation under septic conditions by depletion of a broad range of inflammatory mediators.

  1. A Single-Phase Current Source Solar Inverter with Constant Instantaneous Power, Improved Reliability, and Reduced-Size DC-Link Filter

    NASA Astrophysics Data System (ADS)

    Bush, Craig R.

    This dissertation presents a novel current source converter topology that is primarily intended for single-phase photovoltaic (PV) applications. In comparison with the existing PV inverter technology, the salient features of the proposed topology are: a) the low frequency (double of line frequency) ripple that is common to single-phase inverters is greatly reduced; b) the absence of low frequency ripple enables significantly reduced size pass components to achieve necessary DC-link stiffness and c) improved maximum power point tracking (MPPT) performance is readily achieved due to the tightened current ripple even with reduced-size passive components. The proposed topology does not utilize any electrolytic capacitors. Instead an inductor is used as the DC-link filter and reliable AC film capacitors are utilized for the filter and auxiliary capacitor. The proposed topology has a life expectancy on par with PV panels. The proposed modulation technique can be used for any current source inverter where an unbalanced three-phase operation is desires such as active filters and power controllers. The proposed topology is ready for the next phase of microgrid and power system controllers in that it accepts reactive power commands. This work presents the proposed topology and its working principle supported by with numerical verifications and hardware results. Conclusions and future work are also presented.

  2. What's wrong with chemoprevention of prostate cancer?

    PubMed

    Justman, Stewart

    2011-12-01

    When prostate-specific antigen (PSA) testing was introduced, proponents expected it to cut prostate-cancer mortality and did not expect it to unleash an epidemic of unnecessary treatments. Now that evidence of a mortality benefit remains unclear while evidence of overtreatment in undeniable, there is understandable interest in reducing the human costs of the PSA system. Two related drugs, finasteride and dutasteride, both proven to reduce the incidence of prostate cancer and the "risk of diagnosis," are being promoted accordingly. However, if not for the flaws of the PSA system the use of these drugs for purposes of prevention would lose its rationale. Not only are the drugs in this sense dependent on a faulty system, but their own mortality benefits are as speculative as PSA's-in addition to which, they introduce new risks. PMID:22146025

  3. Loss of Vascular Endothelial Growth Factor A (VEGFA) Isoforms in Granulosa Cells Using pDmrt-1-Cre or Amhr2-Cre Reduces Fertility by Arresting Follicular Development and by Reducing Litter Size in Female Mice

    PubMed Central

    Sargent, Kevin M.; Lu, Ningxia; Clopton, Debra T.; Pohlmeier, William E.; Brauer, Vanessa M.; Ferrara, Napoleone; Silversides, David W.; Cupp, Andrea S.

    2015-01-01

    Because VEGFA has been implicated in follicle development, the objective of this study was to determine the effects of granulosa- and germ cell-specific VEGFA loss on ovarian morphogenesis, function, and female fertility. pDmrt1-Cre mice were mated to floxed VEGFA mice to develop granulosa-/germ cell-specific knockouts (pDmrt1-Cre;Vegfa-/-). The time from mating to first parturition was increased when pDmrt1-Cre;Vegfa-/- females were mated to control males (P = 0.0008) and tended to be longer for heterozygous females (P < 0.07). Litter size was reduced for pDmrt1-Cre;Vegfa-/- females (P < 0.007). The time between the first and second parturitions was also increased for heterozygous females (P < 0.04) and tended to be increased for pDmrt1-Cre;Vegfa-/- females (P < 0.07). pDmrt1-Cre;Vegfa-/- females had smaller ovaries (P < 0.04), reduced plasma estradiol (P < 0.007), fewer developing follicles (P < 0.008) and tended to have fewer corpora lutea (P < 0.08). Expression of Igf1r was reduced (P < 0.05); expression of Foxo3a tended to be increased (P < 0.06); and both Fshr (P < 0.1) and Sirt6 tended to be reduced (P < 0.06) in pDmrt1-Cre;Vegfa-/- ovaries. To compare VEGFA knockouts, we generated Amhr2-Cre;Vegfa-/- mice that required more time from mating to first parturition (P < 0.003) with variable ovarian size. Both lines had more apoptotic granulosa cells, and vascular staining did not appear different. Taken together these data indicate that the loss of all VEGFA isoforms in granulosa/germ cells (proangiogenic and antiangiogenic) causes subfertility by arresting follicular development, resulting in reduced ovulation rate and fewer pups per litter. PMID:25658474

  4. Androgens and prostate disease

    PubMed Central

    Cooper, Lori A; Page, Stephanie T

    2014-01-01

    A growing body of literature has established the anabolic benefits of testosterone (T) therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease. PMID:24407178

  5. TRAMP prostate tumor growth is slowed by walnut diets through altered IGF-1 levels, energy pathways, and cholesterol metabolism.

    PubMed

    Kim, Hyunsook; Yokoyama, Wallace; Davis, Paul Andrew

    2014-12-01

    Dietary changes could potentially reduce prostate cancer morbidity and mortality. Transgenic adenocarcinoma of the mouse prostate (TRAMP) prostate tumor responses to a 100 g of fat/kg diet (whole walnuts, walnut oil, and other oils; balanced for macronutrients, tocopherols [α-and γ]) for 18 weeks ad libitum were assessed. TRAMP mice (n=17 per group) were fed diets with 100 g fat from either whole walnuts (diet group WW), walnut-like fat (diet group WLF, oils blended to match walnut's fatty acid profile), or as walnut oil (diet group WO, pressed from the same walnuts as WW). Fasted plasma glucose was from tail vein blood, blood was obtained by cardiac puncture, and plasma stored frozen until analysis. Prostate (genitourinary intact [GUI]) was weighed and stored frozen at -80°C. Plasma triglyceride, lipoprotein cholesterol, plasma multianalyte levels (Myriad RBM Rat Metabolic MAP), prostate (GUI), tissue metabolites (Metabolon, Inc., Durham, NC, USA), and mRNA (by Illumina NGS) were determined. The prostate tumor size, plasma insulin-like growth factor-1 (IGF-1), high density lipoprotein, and total cholesterol all decreased significantly (P<.05) in both WW and WO compared to WLF. Both WW and WO versus WLF showed increased insulin sensitivity (Homeostasis Model Assessment [HOMA]), and tissue metabolomics found reduced glucose-6-phosphate, succinylcarnitine, and 4-hydroxybutyrate in these groups suggesting effects on cellular energy status. Tissue mRNA levels also showed changes suggestive of altered glucose metabolism with WW and WO diet groups having increased PCK1 and CIDEC mRNA expression, known for their roles in gluconeogenesis and increased insulin sensitivity, respectively. WW and WO group tissues also had increased MSMB mRNa a tumor suppressor and decreased COX-2 mRNA, both reported to inhibit prostate tumor growth. Walnuts reduced prostate tumor growth by affecting energy metabolism along with decreased plasma IGF-1 and cholesterol. These effects are

  6. Current Laser Treatments for Benign Prostatic Hyperplasia

    PubMed Central

    Son, Hwancheol; Song, Sang Hoon

    2010-01-01

    The latest technical improvements in the surgical armamentarium are remarkable. In particular, advancements in the urologic field are so exceptional that we could observe the flare-up of robot-assisted laparoscopic radical prostatectomy for prostate cancer and laser prostatectomy for benign prostatic hyperplasia (BPH). Photoselective vaporization of the prostate (PVP) and holmium laser prostatectomy are the most generalized options for laser surgery of BPH, and both modalities have shown good postoperative results. In comparison to transurethral prostatectomy (TURP), they showed similar efficacy and a much lower complication rate in randomized prospective clinical trials. Even in cases of large prostates, laser prostatectomy showed comparable efficacy and safety profiles compared to open prostatectomy. From a technical point of view, PVP is considered to be an easier technique for the urologist to master. Furthermore, patients can be safely followed up in an outpatient clinic. Holmium laser enucleation of the prostate (HoLEP) mimics open prostatectomy because the adenomatous tissue is peeled off the surgical capsule in both procedures. Therefore, HoLEP shows notable volume reduction of the prostate similar to open prostatectomy with fewer blood transfusions, shorter hospital stay, and cost reduction regardless of prostate size. Outcomes of laser prostatectomy for BPH are encouraging but sometimes are unbalanced because safety and feasibility studies were reported mainly for PVP, whereas long-term data are mostly available for HoLEP. We need longer-term randomized clinical data to identify the reoperation rate of PVP and to determine which procedure is the ideal alternative to TURP and open prostatectomy for each patient. PMID:21165192

  7. Palladium nanoparticles decorated on reduced graphene oxide rotating disk electrodes toward ultrasensitive hydrazine detection: effects of particle size and hydrodynamic diffusion.

    PubMed

    Krittayavathananon, Atiweena; Srimuk, Pattarachai; Luanwuthi, Santamon; Sawangphruk, Montree

    2014-12-16

    Although metal nanoparticle/graphene composites have been widely used as the electrode in electrochemical sensors, two effects, consisting of the particle size of the nanoparticles and the hydrodynamic diffusion of analytes to the electrodes, are not yet fully understood. In this work, palladium nanoparticles/reduced graphene oxide (PdNPs/rGO) composites were synthesized using an in situ polyol method. Palladium(II) ions and graphene oxide were reduced together with a reducing agent, ethylene glycol. By varying the concentration of palladium(II) nitrate, PdNPs with different sizes were decorated on the surface of rGO sheets. The as-fabricated PdNPs/rGO rotating disk electrodes (RDEs) were investigated toward hydrazine detection. Overall, a 3.7 ± 1.4 nm diameter PdNPs/rGO RDE exhibits high performance with a rather low limit of detection of about 7 nM at a rotation speed of 6000 rpm and provides a wide linear range of 0.1-1000 μM with R(2) = 0.995 at 2000 rpm. This electrode is highly selective to hydrazine without interference from uric acid, glucose, ammonia, caffeine, methylamine, ethylenediamine, hydroxylamine, n-butylamine, adenosine, cytosine, guanine, thymine, and l-arginine. The PdNPs/rGO RDEs with larger sizes show lower detection performance. Interestingly, the detection performance of the electrodes is sensitive to the hydrodynamic diffusion of hydrazine. The as-fabricated electrode can detect trace hydrazine in wastewater with high stability, demonstrating its practical use as an electrochemical sensor. These findings may lead to an awareness of the effect of the hydrodynamic diffusion of analyte that has been previously ignored, and the 3.7 ± 1.4 nm PdNPs/rGO RDE may be useful toward trace hydrazine detection, especially in wastewater from related chemical industries.

  8. Online Adaptive Replanning Method for Prostate Radiotherapy

    SciTech Connect

    Ahunbay, Ergun E.; Peng Cheng; Holmes, Shannon; Godley, Andrew; Lawton, Colleen; Li, X. Allen

    2010-08-01

    Purpose: To report the application of an adaptive replanning technique for prostate cancer radiotherapy (RT), consisting of two steps: (1) segment aperture morphing (SAM), and (2) segment weight optimization (SWO), to account for interfraction variations. Methods and Materials: The new 'SAM+SWO' scheme was retroactively applied to the daily CT images acquired for 10 prostate cancer patients on a linear accelerator and CT-on-Rails combination during the course of RT. Doses generated by the SAM+SWO scheme based on the daily CT images were compared with doses generated after patient repositioning using the current planning target volume (PTV) margin (5 mm, 3 mm toward rectum) and a reduced margin (2 mm), along with full reoptimization scans based on the daily CT images to evaluate dosimetry benefits. Results: For all cases studied, the online replanning method provided significantly better target coverage when compared with repositioning with reduced PTV (13% increase in minimum prostate dose) and improved organ sparing when compared with repositioning with regular PTV (13% decrease in the generalized equivalent uniform dose of rectum). The time required to complete the online replanning process was 6 {+-} 2 minutes. Conclusion: The proposed online replanning method can be used to account for interfraction variations for prostate RT with a practically acceptable time frame (5-10 min) and with significant dosimetric benefits. On the basis of this study, the developed online replanning scheme is being implemented in the clinic for prostate RT.

  9. Genistein alters growth but is not toxic to the rat prostate.

    PubMed

    Fritz, Wayne A; Eltoum, Isam-Eldin; Cotroneo, Michelle S; Lamartiniere, Coral A

    2002-10-01

    The mortality of clinical prostate cancer is lower in Asian populations than in American or European men. Asian men typically consume more soy than their Western counterparts, leading to the investigation of individual components, particularly phytoestrogens, as protective factors against prostate cancer. Genistein, the predominant isoflavone in soy, has been reported to reduce the incidence of prostate cancer in animal models, but the underlying biological action remains to be elucidated. The purpose of this investigation was to identify the effects of the phytoestrogen, genistein and the synthetic estrogen diethylstilbestrol (DES), as a control, on development and function of the rat dorsolateral prostate (DLP) when given in the diet. The effects of testosterone and dihydrotestosterone (DHT) injections were also tested. Analysis of individual lobes of the DLP revealed that 1000 mg/kg, but not 250 mg/kg, of a genistein AIN-76A diet slightly reduced lateral prostate type 1 (LP1) bud perimeter. However, expression of the secretory dorsal protein 1 (DP1) and 5alpha-reductase type II activity were not altered in the prostate. This suggested that prostate differentiation, and not toxicity, had occurred. DES in the diet reduced and testosterone injections elevated relative prostate weights and perimeters of the dorsal, LP1, lateral prostate type 2 and DP1 expression. DHT increased relative prostate weights but did not significantly increase individual lobe perimeter. Unlike DES, maximally tolerated doses of genistein in the diet were not toxic to the rat prostate. PMID:12368387

  10. Relationship of ultrasonographic findings to histology in prostate cancer.

    PubMed

    Hasegawa, Y; Sakamoto, N

    1994-01-01

    We compared ultrasonic findings and histology in 25 patients with prostate cancer. Ultrasonically guided transperineal biopsy of focal prostatic lesions was performed in 19 patients, in whom prostate cancer was suspected. Six of them had two different echogenic areas in the same focal lesion, so a total of 25 echogenic areas were assessed. Fourteen of these 25 areas were hypoechoic. The Gleason score varied, but residual prostatic glands and cancer glands with slightly enlarged lumen did not exist. Six of the areas were slightly more echogenic than the above 14 areas, and cribriform cancer with slightly enlarged glands occupied the greater part of these specimens. Four of the areas were isoechoic, and they contained residual prostatic glands showing a normal distribution, regardless of the Gleason score or grade of tumor infiltration. The only hyperechoic lesion contained numerous tiny areas of calcification. In the 6 patients without focal lesions, the peripheral and transition zones showed a normal echogenicity. Two of these patients had cancer in the transition zone, and biopsy showed tumor glands with slightly enlarged lumens. In the 4 patients, various-sized tumors were seen, but there was a normal distribution of residual prostatic glands and stroma. These results indicated that prostatic echogenicity is determined by the presence of tumor glands with enlarged lumina as well as residual prostatic glands and stroma.

  11. Effect of D-004, a lipid extract from Cuban royal palm fruit, on histological changes of prostate hyperplasia induced with testosterone in rats.

    PubMed

    Noa, M; Arruzazabala, M L; Carbajal, D; Más, R; Molina, V

    2005-01-01

    Benign prostatic hyperplasia (BPH) is the nonmalignant, uncontrolled growth of prostate gland cells and stroma leading to difficulty in urinating. Lipid extracts from Saw palmetto (Arecaceae) fruits are used to treat BPH. The Cuban royal palm (Roystonea regia) is a member of this family and D-004, a lipid extract from its fruits, prevents prostate hyperplasia (PH) induced with testosterone, as opposed to dihydrotestosterone, in rodents. This study investigated whether D-004 could prevent the histological features of testosterone-induced PH in rats. Rats were distributed into six groups (10 rats per group): A negative control group receiving subcutaneous injections of soy oil and treated with vehicle, and five groups injected subcutaneously with testosterone and treated with the vehicle (positive control), D-004 (100, 200 and 400 mg/kg) or Saw palmetto (400 mg/kg). Treatments were given orally for 14 days. At sacrifice, prostates were removed and processed for light microscopy. The histopathological findings of PH were assessed according to a score-chart protocol. D-004 200 and 400 mg/kg, but not 100 mg/kg, significantly and moderately in a dose-dependent manner prevented prostate enlargement and the testosterone-induced histological changes. Compared with positive controls, D-004 200 and 400 mg/kg inhibited prostate size increases and the histological score up to 56.1% and 60.7%, respectively, while Saw palmetto 400 mg/kg reduced such variables by 45.8% and 49.0%, respectively. The effects of D-004 400 mg/kg on the histological changes, not on prostate size, were greater (p < 0.05) than those of Saw palmetto. D-004 and Saw palmetto did not affect body weight values. In conclusion, D-004 200 and 400 mg/kg administered orally for 14 days prevented the increase of prostate size and the testosterone-induced histological changes in rats, its effects being comparable or mildly better than those of Saw palmetto. These results extend previous data showing preventive

  12. Do Environmental Factors Modify the Genetic Risk of Prostate Cancer?

    PubMed Central

    Loeb, Stacy; Peskoe, Sarah B.; Joshu, Corinne E.; Huang, Wen-Yi; Hayes, Richard B.; Carter, H. Ballentine; Isaacs, William B.; Platz, Elizabeth A.

    2015-01-01

    Background Many SNPs influence prostate cancer risk. To what extent genetic risk can be reduced by environmental factors is unknown. Methods We evaluated effect modification by environmental factors of the association between susceptibility SNPs and prostate cancer in 1,230 incident prostate cancer cases and 1,361 controls, all white and similar ages, nested in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Trial. Genetic risk scores were calculated as number of risk alleles for 20 validated SNPs. We estimated the association between higher genetic risk (≥ 12 SNPs) and prostate cancer within environmental factor strata and tested for interaction. Results Men with ≥12 risk alleles had 1.98, 2.04, and 1.91 times the odds of total, advanced, and nonadvanced prostate cancer, respectively. These associations were attenuated with the use of selenium supplements, aspirin, ibuprofen, and higher vegetable intake. For selenium, the attenuation was most striking for advanced prostate cancer: compared with <12 alleles and no selenium, the OR for ≥12 alleles was 2.06 [95% confidence interval (CI), 1.67–2.55] in nonusers and 0.99 (0.38–2.58) in users (Pinteraction = 0.031). Aspirin had the most marked attenuation for nonadvanced prostate cancer: compared with <12 alleles and nonusers, the OR for ≥12 alleles was 2.25 (1.69–3.00) in nonusers and 1.70 (1.25–2.32) in users (Pinteraction = 0.009). This pattern was similar for ibuprofen (Pinteraction = 0.023) and vegetables (Pinteraction = 0.010). Conclusions This study suggests that selenium supplements may reduce genetic risk of advanced prostate cancer, whereas aspirin, ibuprofen, and vegetables may reduce genetic risk of nonadvanced prostate cancer. PMID:25342390

  13. The Prostate Exam

    ERIC Educational Resources Information Center

    Romero, Frederico R.; Romero, Antonio W.; Filho, Thadeu Brenny; Kulysz, David; Oliveira, Fernando C., Jr.; Filho, Renato Tambara

    2012-01-01

    Objective: To help students, residents, and general practitioners to improve the technique, skills, and reproducibility of their prostate examination. Methods: We developed a comprehensive guideline outlining prostate anatomy, indications, patient preparation, positioning, technique, findings, and limitations of this ancient art of urological…

  14. A population-based analysis of clustering identifies a strong genetic contribution to lethal prostate cancer

    PubMed Central

    Nelson, Quentin; Agarwal, Neeraj; Stephenson, Robert; Cannon-Albright, Lisa A.

    2013-01-01

    Background: Prostate cancer is a common and often deadly cancer. Decades of study have yet to identify genes that explain much familial prostate cancer. Traditional linkage analysis of pedigrees has yielded results that are rarely validated. We hypothesize that there are rare segregating variants responsible for high-risk prostate cancer pedigrees, but recognize that within-pedigree heterogeneity is responsible for significant noise that overwhelms signal. Here we introduce a method to identify homogeneous subsets of prostate cancer, based on cancer characteristics, which show the best evidence for an inherited contribution. Methods: We have modified an existing method, the Genealogical Index of Familiality (GIF) used to show evidence for significant familial clustering. The modification allows a test for excess familial clustering of a subset of prostate cancer cases when compared to all prostate cancer cases. Results: Consideration of the familial clustering of eight clinical subsets of prostate cancer cases compared to the expected familial clustering of all prostate cancer cases identified three subsets of prostate cancer cases with evidence for familial clustering significantly in excess of expected. These subsets include prostate cancer cases diagnosed before age 50 years, prostate cancer cases with body mass index (BMI) greater than or equal to 30, and prostate cancer cases for whom prostate cancer contributed to death. Conclusions: This analysis identified several subsets of prostate cancer cases that cluster significantly more than expected when compared to all prostate cancer familial clustering. A focus on high-risk prostate cancer cases or pedigrees with these characteristics will reduce noise and could allow identification of the rare predisposition genes or variants responsible. PMID:23970893

  15. Cryosurgery for prostate cancer.

    PubMed

    Fahmy, W E; Bissada, N K

    2003-01-01

    Choice of management for patients with prostate cancer is influenced by patient and disease characteristics and life expectancy. Management options include expectance (watchful waiting), radical prostatectomy, external beam radiotherapy, brachytherapy, and cryosurgical ablation of the prostate (CSAP). The role of cryotherapy in the management of prostate cancer is still evolving. Continued research has allowed the introduction of efficient and safe cryosurgical equipment exemplified by the current third-generation cryosurgical machines. CSAP can be performed in an ambulatory surgery setting or as inpatient surgery with overnight stay. The procedure is performed under continuous ultrasonic monitoring. Mature data from the use of second-generation cryosurgical equipment indicate that CSAP is an effective therapeutic modality for managing patients with prostate cancer. Current data with the third-generation cryosurgical equipment are not mature. However, the favorable side effect profile and the good early responses seem to indicate that this modality will have a prominent role in the management of patients with prostate cancer.

  16. Current status of 5α-reductase inhibitors in prostate disease management.

    PubMed

    Kang, Dong Il; Chung, Jae Il

    2013-04-01

    The key enzyme in the androgen synthesis and androgen receptor pathways is 5α-reductase (5-AR), which occurs as three isoenzymes. Types I and II 5-ARs the most important clinically, and two different 5-AR inhibitors (5-ARIs), finasteride and dutasteride, have been developed. Several urology associations have recommended and upgraded the use of 5-ARIs for an enlarged prostate with lower urinary tract symptoms. In the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events Trial, 5-ARIs reduced the incidence of low-grade prostate cancer. However, despite the documented reductions in the overall incidence of prostate cancer, 5-ARIs are at the center of a dispute. The American Society of Clinical Oncology (ASCO) and the American Urology Association (AUA) presented clinical guidelines for the use of 5-ARIs for chemoprevention of prostate cancer in 2008. However, ASCO/AUA has eliminated these from the main "Clinical Guidelines" in 2012, because the U.S. Food and Drug Administration denied a supplemental New Drug Application for the use of dutasteride for prostate cancer chemoprevention. The 5-ARIs can also be used to manage hemospermia and prostatic hematuria, and to prevent intraoperative bleeding, although there is insufficient evidence for a standard strategy. This review summarizes the current use of 5-ARIs for prostate disease, including benign prostate hyperplasia, prostate cancer, prostate-related bleeding, and hemospermia. PMID:23614056

  17. Real-Time Study of Prostate Intrafraction Motion During External Beam Radiotherapy With Daily Endorectal Balloon

    SciTech Connect

    Both, Stefan; Wang, Ken Kang-Hsin; Plastaras, John P.; Deville, Curtiland; Bar Ad, Voika; Tochner, Zelig; Vapiwala, Neha

    2011-12-01

    Purpose: To prospectively investigate intrafraction prostate motion during radiofrequency-guided prostate radiotherapy with implanted electromagnetic transponders when daily endorectal balloon (ERB) is used. Methods and Materials: Intrafraction prostate motion from 24 patients in 787 treatment sessions was evaluated based on three-dimensional (3D), lateral, cranial-caudal (CC), and anterior-posterior (AP) displacements. The mean percentage of time with 3D, lateral, CC, and AP prostate displacements >2, 3, 4, 5, 6, 7, 8, 9, and 10 mm in 1 minute intervals was calculated for up to 6 minutes of treatment time. Correlation between the mean percentage time with 3D prostate displacement >3 mm vs. treatment week was investigated. Results: The percentage of time with 3D prostate movement >2, 3, and 4 mm increased with elapsed treatment time (p < 0.05). Prostate movement >5 mm was independent of elapsed treatment time (p = 0.11). The overall mean time with prostate excursions >3 mm was 5%. Directional analysis showed negligible lateral prostate motion; AP and CC motion were comparable. The fraction of time with 3D prostate movement >3 mm did not depend on treatment week of (p > 0.05) over a 4-minute mean treatment time. Conclusions: Daily endorectal balloon consistently stabilizes the prostate, preventing clinically significant displacement (>5 mm). A 3-mm internal margin may sufficiently account for 95% of intrafraction prostate movement for up to 6 minutes of treatment time. Directional analysis suggests that the lateral internal margin could be further reduced to 2 mm.

  18. Optimizing Monoscopic kV Fluoro Acquisition for Prostate Intrafraction Motion Evaluation

    PubMed Central

    Adamson, Justus; Wu, Qiuwen

    2008-01-01

    Monoscopic kV imaging during radiotherapy has been recently implemented for prostate intrafraction motion evaluation. However, the accuracy of 3D localization techniques from monoscopic imaging of prostate and the effect of acquisition parameters on the 3D accuracy have not been studied in detail, with imaging dose remaining a concern. In this paper we investigate methods to optimize the kV acquisition parameters and imaging protocol to achieve improved 3D localization and 2D image registration accuracy for minimal imaging dose. Prostate motion during radiotherapy was simulated using existing cine-MRI measurements, and was used to investigate the accuracy of various 3D localization techniques and the effect of kV acquisition protocol. We also investigated the relationship between mAs and the accuracy of the 2D image registration for localization of fiducial markers, and we measured imaging dose for a 30-cm diameter phantom to evaluate the necessary dose to achieve acceptable image registration accuracy. Simulations showed that the error in assuming the shortest path to localize the prostate in 3D using monoscopic imaging during a typical IMRT fraction will be less than ~1.5 mm for 95% of localizations, but will also depend on prostate motion distribution, treatment duration, and image acquisition and treatment protocol. Most uncertainty cannot be reduced from higher imaging frequency or acquiring during gantry rotation between beams. Measured maximum surface dose to the cylindrical phantom from monoscopic kV intrafraction acquisitions varied between 0.4–5.5 mGy, depending on acquisition protocol, and was lower than the required dose for CBCT (21.1 mGy). Imaging dose can be lowered by ~15–40% when mAs is optimized with acquisition angle. Images acquired during MV beam delivery require increased mAs to obtain the same level of registration accuracy, with mAs/registration increasing roughly linearly with field size and dose rate. PMID:19075358

  19. The evolution of size of the uropygial gland: mutualistic feather mites and uropygial secretion reduce bacterial loads of eggshells and hatching failures of European birds.

    PubMed

    Soler, J J; Peralta-Sánchez, J M; Martín-Platero, A M; Martín-Vivaldi, M; Martínez-Bueno, M; Møller, A P

    2012-09-01

    Potentially, pathogenic bacteria are one of the main infective agents against which a battery of chemical and physical barriers has evolved in animals. Among these are the secretions by the exocrine uropygial gland in birds. The antimicrobial properties of uropygial secretions may prevent colonization and growth of microorganisms on feathers, skin and eggshells. However, uropygial gland secretions also favour the proliferation of feather mites that feed on secretions and microorganisms living on feathers that would otherwise reach eggshells during incubation if not consumed by feather mites. Therefore, at the interspecific level, uropygial gland size (as an index of volume of uropygial secretion) should be positively related to eggshell bacterial load (i.e. the risk of egg infection), whereas eggshell bacterial loads may be negatively related to abundance of feather mites eating bacteria. Here, we explore these previously untested predictions in a comparative framework using information on eggshell bacterial loads, uropygial gland size, diversity and abundance of feather mites and hatching success of 22 species of birds. The size of the uropygial gland was positively related to eggshell bacterial loads (mesophilic bacteria and Enterobacteriaceae), and bird species with higher diversity and abundance of feather mites harboured lower bacterial density on their eggshells (Enterococcus and Staphylococcus), in accordance with the hypothesis. Importantly, eggshell bacterial loads of mesophilic bacteria, Enterococcus and Enterobacteriaceae were negatively associated with hatching success, allowing us to interpret these interspecific relationships in a functional scenario, where both uropygial glands and mutualistic feather mites independently reduce the negative effects of pathogenic bacteria on avian fitness.

  20. Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure.

    PubMed

    Watanabe, Mitsuhiro; Horai, Yasushi; Houten, Sander M; Morimoto, Kohkichi; Sugizaki, Taichi; Arita, Eri; Mataki, Chikage; Sato, Hiroyuki; Tanigawara, Yusuke; Schoonjans, Kristina; Itoh, Hiroshi; Auwerx, Johan

    2011-07-29

    We evaluated the metabolic impact of farnesoid X receptor (FXR) activation by administering a synthetic FXR agonist (GW4064) to mice in which obesity was induced by a high fat diet. Administration of GW4064 accentuated body weight gain and glucose intolerance induced by the high fat diet and led to a pronounced worsening of the changes in liver and adipose tissue. Mechanistically, treatment with GW4064 decreased bile acid (BA) biosynthesis, BA pool size, and energy expenditure, whereas reconstitution of the BA pool in these GW4064-treated animals by BA administration dose-dependently reverted the metabolic abnormalities. Our data therefore suggest that activation of FXR with synthetic agonists is not useful for long term management of the metabolic syndrome, as it reduces the BA pool size and subsequently decreases energy expenditure, translating as weight gain and insulin resistance. In contrast, expansion of the BA pool size, which can be achieved by BA administration, could be an interesting strategy to manage the metabolic syndrome.

  1. Recent advances in image-guided targeted prostate biopsy.

    PubMed

    Brown, Anna M; Elbuluk, Osama; Mertan, Francesca; Sankineni, Sandeep; Margolis, Daniel J; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-08-01

    Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques. PMID:25596716

  2. A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats.

    PubMed

    Allan, George; Sbriscia, Tifanie; Linton, Olivia; Lai, Muh-Tsann; Haynes-Johnson, Donna; Bhattacharjee, Sheela; Ng, Raymond; Sui, Zhihua; Lundeen, Scott

    2008-06-01

    Androgens are required for the maintenance of normal sexual activity in adulthood and for enhancing muscle growth and lean body mass in adolescents and adults. Androgen receptor (AR) ligands with tissue selectivity (selective androgen receptor modulators, or SARMs) have potential for treating muscle wasting, hypogonadism of aging, osteoporosis, female sexual dysfunction, and other indications. JNJ-37654032 is a nonsteroidal AR ligand with mixed agonist and antagonist activity in androgen-responsive cell-based assays. It is an orally active SARM with muscle selectivity in orchidectomized rat models. It stimulated growth of the levator ani muscle with ED(50) 0.8 mg/kg, stimulating maximal growth at a dose of 3mg/kg. In contrast, it stimulated ventral prostate growth to 21% of its full size at 3mg/kg. At the same time, JNJ-37654032 reduced prostate weight in intact rats by 47% at 3mg/kg, while having no inhibitory effect on muscle. Using magnetic resonance imaging to monitor body composition, JNJ-37654032 restored about 20% of the lean body mass lost following orchidectomy in aged rats. JNJ-37654032 reduced follicle-stimulating hormone levels in orchidectomized rats and reduced testis size in intact rats. JNJ-37654032 is a potent prostate-sparing SARM with the potential for clinical benefit in muscle-wasting diseases.

  3. Low Prostate Concentration of Lycopene Is Associated with Development of Prostate Cancer in Patients with High-Grade Prostatic Intraepithelial Neoplasia

    PubMed Central

    Mariani, Simone; Lionetto, Luana; Cavallari, Michele; Tubaro, Andrea; Rasio, Debora; De Nunzio, Cosimo; Hong, Gena M.; Borro, Marina; Simmaco, Maurizio

    2014-01-01

    Prostate cancer (PC) is a frequent male malignancy and represents the second most diagnosed cancer in men. Since pre-cancerous lesions, i.e., the high-grade prostatic intraepithelial neoplasia (HGPIN), can be detected years before progression to PC, early diagnosis and chemoprevention are targeted strategies to reduce PC rates. Animal studies have shown that lycopene, a carotenoid contained in tomatoes, is a promising candidate for the chemoprevention of PC. However, its efficacy in humans remains controversial. The present study aimed to investigate the relevance of plasma and prostate concentration of lycopene after a lycopene-enriched diet in patients diagnosed with HGPIN. Thirty-two patients diagnosed with HGPIN were administered a lycopene-enriched diet (20–25 mg/day of lycopene; through 30 g/day of triple concentrated tomato paste) for 6 months. A 6-month follow-up prostate biopsy assessed progression to PC. Patients were classified into three groups according to the histopathological features of the 6-month follow-up biopsy results: prostatitis; HGPIN and PC. PSA and plasma lycopene levels were measured before and after the dietary lycopene supplementation. Prostatic lycopene concentration was only assessed after the supplementation diet. Only prostatic lycopene concentration showed significant differences between the three groups (p = 0.03). Prostatic lycopene concentration below a 1 ng/mg threshold was associated with PC at 6-month follow-up biopsy (p = 0.003). We observed no overall benefits from a 6-month lycopene supplementation, as the rate of HGPIN progression to PC in our population (9/32, 28%) was similar to rates reported in the literature. Baseline PSA levels also showed no significant changes after a lycopene-enriched diet. Our findings point to prostatic lycopene concentration as a promising biomarker of PC. Further prospective longitudinal studies are needed to assess the prognostic role of prostatic lycopene in PC. PMID:24451130

  4. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice

    PubMed Central

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y.; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W.; Kumar, Nagi; Park, Jong Y.

    2014-01-01

    Background Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in TRAMP mice. Methods 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of three doses of Polyphenon E (200, 500, 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed prior to treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22 and 32 weeks old. Results The number and size of tumors in treated TRAMP mice were significantly decreased compared to untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared to 13% of mice (2/16) treated with high dose Polyphenon E during the same period. Further, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P=0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Conclusion Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Impact Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of PCa. PMID:24501325

  5. Olaparib With or Without Cediranib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-09-08

    Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; Stage IV Prostate Adenocarcinoma

  6. Risk stratification of prostate cancer 2016.

    PubMed

    Reiter, Robert E

    2016-01-01

    Prostate cancer is a common malignancy in men, but its management is fraught with controversy owing to its variable biologic and clinical behavior. Despite evidence that PSA screening reduces prostate cancer specific metastasis and death, it has not gained acceptance by various health authorities. Nevertheless, recent advances in biomarker development potentially address many of the shortcomings of routine PSA testing alone, including improved specificity for the detection of clinically significant cancer, optimized risk stratification to aid clinical management decisions, and discovery of genetic variants that may guide optimized therapy of advanced disease. PMID:27533326

  7. Performance of a low cost MBT prior to landfilling: study of the biological treatment of size reduced MSW without mechanical sorting.

    PubMed

    Lornage, R; Redon, E; Lagier, T; Hébé, I; Carré, J

    2007-01-01

    In France, the interest in Mechanical Biological Treatment (MBT) prior to landfilling is actually growing. In the absence of acceptance criteria for the waste to be landfilled, an alternative to the intensive, high-technology MBT can only find its place in the French context if it shows substantial benefits from an environmental, economic or operational point of view. This paper presents an experiment of low-cost MBT of size reduced MSW without material splitting. The performance of an experimental, pilot-scale mechanical and biological treatment process has been studied on 37.5 Mg of raw municipal solid waste. The mechanical process has been kept simple with only coarse shredding and no material recovery. The biological treatment, which was a low-cost forced aeration process, was monitored for 25 weeks. The biogas production potential of the waste was reduced by 90% to 19 NL kgDM(-1). The initial AT4 index of 82.9 mg O2 gDM(-1) decreased to 16.0 mg O2 gDM(-1). After 25 weeks of aerobic treatment, the dry mass loss reached 37%, while the mass of waste going to landfill was reduced by 28%. The average performances of the process were explained by the biological process itself, which was not optimal, and also by the characteristics of the input waste. The high particle size of the treated waste and the high content of slowly biodegradable matter (such as paper and cardboard) may both be significant drawbacks for the biological stabilisation of waste.

  8. Prostate segmentation with local binary patterns guided active appearance models

    NASA Astrophysics Data System (ADS)

    Ghose, Soumya; Oliver, Arnau; Martí, Robert; Lladó, Xavier; Freixenet, Jordi; Vilanova, Joan C.; Meriaudeau, Fabrice

    2011-03-01

    Real-time fusion of Magnetic Resonance (MR) and Trans Rectal Ultra Sound (TRUS) images aid in the localization of malignant tissues in TRUS guided prostate biopsy. Registration performed on segmented contours of the prostate reduces computational complexity and improves the multimodal registration accuracy. However, accurate and computationally efficient segmentation of the prostate in TRUS images could be challenging in the presence of heterogeneous intensity distribution inside the prostate gland, and other imaging artifacts like speckle noise, shadow regions and low Signal to Noise Ratio (SNR). In this work, we propose to enhance the texture features of the prostate region using Local Binary Patterns (LBP) for the propagation of a shape and appearance based statistical model to segment the prostate in a multi-resolution framework. A parametric model of the propagating contour is derived from Principal Component Analysis (PCA) of the prior shape and texture information of the prostate from the training data. The estimated parameters are then modified with the prior knowledge of the optimization space to achieve an optimal segmentation. The proposed method achieves a mean Dice Similarity Coefficient (DSC) value of 0.94+/-0.01 and a mean segmentation time of 0.68+/-0.02 seconds when validated with 70 TRUS images of 7 datasets in a leave-one-patient-out validation framework. Our method performs computationally efficient and accurate prostate segmentation in the presence of intensity heterogeneities and imaging artifacts.

  9. Texture Guided Active Appearance Model Propagation for Prostate Segmentation

    NASA Astrophysics Data System (ADS)

    Ghose, Soumya; Oliver, Arnau; Martí, Robert; Lladó, Xavier; Freixenet, Jordi; Vilanova, Joan C.; Meriaudeau, Fabrice

    Fusion of Magnetic Resonance Imaging (MRI) and Trans Rectal Ultra Sound (TRUS) images during TRUS guided prostate biopsy improves localization of the malignant tissues. Segmented prostate in TRUS and MRI improve registration accuracy and reduce computational cost of the procedure. However, accurate segmentation of the prostate in TRUS images can be a challenging task due to low signal to noise ratio, heterogeneous intensity distribution inside the prostate, and imaging artifacts like speckle noise and shadow. We propose to use texture features from approximation coefficients of Haar wavelet transform for propagation of a shape and appearance based statistical model to segment the prostate in a multi-resolution framework. A parametric model of the propagating contour is derived from Principal Component Analysis of prior shape and texture informations of the prostate from the training data. The parameters are then modified with prior knowledge of the optimization space to achieve optimal prostate segmentation. The proposed method achieves a mean Dice Similarity Coefficient value of 0.95±0.01, and mean segmentation time of 0.72±0.05 seconds when validated on 25 TRUS images, grabbed from video sequences, in a leave-one-out validation framework. Our proposed model performs computationally efficient accurate prostate segmentation in presence of intensity heterogeneity and imaging artifacts.

  10. The novel Akt inhibitor Palomid 529 (P529) enhances the effect of radiotherapy in prostate cancer

    PubMed Central

    Diaz, R; Nguewa, P A; Diaz-Gonzalez, J A; Hamel, E; Gonzalez-Moreno, O; Catena, R; Serrano, D; Redrado, M; Sherris, D; Calvo, A

    2009-01-01

    Radiotherapy (RT) is a common treatment for localised prostate cancer, but can cause important side effects. The therapeutic efficacy of RT can be enhanced by pharmacological compounds that target specific pathways involved in cell survival. This would elicit a similar therapeutic response using lower doses of RT and, in turn, reducing side effects. This study describes the antitumour activity of the novel Akt inhibitor 8-(1-Hydroxy-ethyl)-2-methoxy-3-(4-methoxy-benzyloxy)-benzo[c]chromen-6-one (Palomid 529 or P529) as well as its ability to decrease radiation-activated phospho-Akt (p-Akt) signalling in a prostate cancer model. P529 showed a potent antiproliferative activity in the NCI-60 cell lines panel, with growth inhibitory 50 (GI50) <35 μM. In addition, P529 significantly enhanced the antiproliferative effect of radiation in prostate cancer cells (PC-3). Analysis of signalling pathways targeted by P529 exhibited a decrease in p-Akt, VEGF, MMP-2, MMP-9, and Id-1 levels after radiation treatment. Moreover, the Bcl-2/Bax ratio was also reduced. Treatment of PC-3 tumour-bearing mice with 20 mg kg−1 P529 or 6 Gy radiation dose decreased tumour size by 42.9 and 53%, respectively. Combination of both treatments resulted in 77.4% tumour shrinkage. Decreased tumour growth was due to reduced proliferation and increased apoptosis (as assessed by PCNA and caspase-3 immunostaining). Our results show the antitumour efficacy of P529 alone, and as a radiosensitiser, and suggest that this compound could be used in the future to treat human prostate cancer. PMID:19240717

  11. Optimization of prostate biopsy

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Weir, James; Zhang, Wei; Sesterhenn, Isabell A.; Connelly, Roger R.; Moul, Judd W.; Mun, Seong K.

    1999-05-01

    Urologists routinely use the systematic sextant needle biopsy technique to detect prostate cancer. However, recent evidence suggests that this technique has a significant sampling error. We have developed a novel 3D computer assisted prostate biopsy simulator based upon 201 whole- mounted step-sectioned radical prostatectomy specimens to compare the diagnostic accuracy of various prostate needle biopsy protocols. Computerized prostate models have been developed to accurately depict the anatomy of the prostate and all individual tumor foci. We obtained 18-biopsies of each prostate model to determine the detection rates of various biopsy protocols. As a result, the 10- and 12- pattern biopsy protocols had a 99.0 percent detection rate, while the traditional sextant biopsy protocol rate was only 72.6 percent. The 5-region biopsy protocol had a 90.5 percent detection rate. the lateral sextant pattern revealed a detection rate of 95.5 percent, whereas the 4-pattern lateral biopsy protocol had a 93.5 percent detection rate. Our results suggest that all the biopsy protocols that use laterally placed biopsies based upon the five region anatomical model are superior to the routinely used sextant prostate biopsy pattern. Lateral biopsies in the mid and apical zones of the gland are the most important.

  12. Serenoa repens extract in the treatment of benign prostatic hyperplasia.

    PubMed

    Geavlete, Petrisor; Multescu, Razvan; Geavlete, Bogdan

    2011-08-01

    We are experiencing a revival of interest in phytotherapeutic agents, both in Europe and North America, especially as a consequence of patients' dissatisfaction with the adverse effects of the medical alternatives. One of the most frequently prescribed and studied such agents is Serenoa repens extract, derived from the berry of the dwarf palm tree. We aimed to review the most important published data regarding this type of treatment for benign prostatic hyperplasia. A review of the existing articles regarding the use of Serenoa repens extracts for benign prostatic hyperplasia was performed. The articles were analysed with regard to their relevance, scientific value and the size of the evaluated series. Multiple mechanisms of action have been attributed to this extract, including antiandrogenic action, an anti-inflammatory/anti-oedematous effect, prolactin signal modulation, and an antiproliferative effect exerted through the inhibition of growth factors. Regarding efficacy, European Association of Urology guidelines state that Serenoa repens extracts significantly reduce nocturia in comparison with placebo. However, the guideline committee is unable to make specific recommendations about phytotherapy of male lower urinary tract symptoms owing to the heterogeneity of the products and the methodological problems associated with meta-analyses. Most of the published trials regarding Serenoa repens phytotherapy demonstrate a significant improvement of urinary status and a favourable safety profile. Also, some authors have credited it with giving a significant improvement in erectile function and decreasing complications following transurethral resection of the prostate, especially bleeding. The results of phytotherapy with Serenoa repens extracts are very promising. More high-quality, randomized, placebo-controlled studies are required in order to demonstrate without doubt the true therapeutic value of these products. Particular attention must be focused on

  13. Combined image-processing algorithms for improved optical coherence tomography of prostate nerves

    NASA Astrophysics Data System (ADS)

    Chitchian, Shahab; Weldon, Thomas P.; Fiddy, Michael A.; Fried, Nathaniel M.

    2010-07-01

    Cavernous nerves course along the surface of the prostate gland and are responsible for erectile function. These nerves are at risk of injury during surgical removal of a cancerous prostate gland. In this work, a combination of segmentation, denoising, and edge detection algorithms are applied to time-domain optical coherence tomography (OCT) images of rat prostate to improve identification of cavernous nerves. First, OCT images of the prostate are segmented to differentiate the cavernous nerves from the prostate gland. Then, a locally adaptive denoising algorithm using a dual-tree complex wavelet transform is applied to reduce speckle noise. Finally, edge detection is used to provide deeper imaging of the prostate gland. Combined application of these three algorithms results in improved signal-to-noise ratio, imaging depth, and automatic identification of the cavernous nerves, which may be of direct benefit for use in laparoscopic and robotic nerve-sparing prostate cancer surgery.

  14. Assessment of Prostatism

    PubMed Central

    Barrett, Peter H.

    1978-01-01

    Prostatism is a syndrome associated with outlet obstruction at the bladder neck and the commonest cause is benign prostatic hypertrophy. The main indications for investigation and treatment are these symptoms (especially nocturia). The diagnosis should then be confirmed by the physical signs such as an enlarged gland or palpable bladder. If other causes of these symptoms are eliminated, the patient should be referred to a urologist to confirm, through cystoscopy, signs of an obstructing prostate and bladder trabeculation. The surgery (TUR or open) for benign disease leaves the capsules behind and the patient should still be followed with routine rectal examinations for early detection of malignancy. PMID:21301523

  15. Prevention of sepsis prior to prostate biopsy

    PubMed Central

    Toner, Liam; Bolton, Damien M

    2016-01-01

    Purpose Urosepsis is the most feared complication of transrectal prostate biopsy. The incidence may be increasing from <1% to 2%–3% in contemporary series. Historically, fluoroquinolones have been effective antibiotic prophylaxis to prevent infective complications but antibiotic resistance is increasing. The increase in antibiotic resistance may contribute to reported increases in urosepsis and hospitalization after transrectal biopsy. This article will review other methods clinicians may employ to reduce the incidence of infective complications after prostate biopsy. Materials and Methods A systematic review of the literature was conducted using literature databases PubMed and Ovid MEDLINE in August 2015 in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) criteria. Results Effective strategies to reduce infective complications after transrectal prostate biopsy include augmented prophylaxis with other antibiotics, rectal swab culture directed antibiotic prophylaxis or a transperineal biopsy approach. Needle disinfection, minimizing the number of biopsy needles and rectal disinfectants may also be of use. These methods may be of particular utility in patients with risk factors for developing urosepsis such as recent antibiotic use and overseas travel. Conclusions The scientific literature describes various techniques designed to reduce infective complications caused by prostate biopsy. Clinicians should consider incorporating these novel techniques into their contemporary practice. PMID:26981590

  16. Potential Activity, Size, and Structure of Sulfate-Reducing Microbial Communities in an Exposed, Grazed and a Sheltered, Non-Grazed Mangrove Stand at the Red Sea Coast

    PubMed Central

    Balk, Melike; Keuskamp, Joost A.; Laanbroek, Hendrikus J.

    2015-01-01

    After oxygen, sulfate is the most important oxidant for the oxidation of organic matter in mangrove forest soils. As sulfate reducers are poor competitors for common electron donors, their relative success depends mostly on the surplus of carbon that is left by aerobic organisms due to oxygen depletion. We therefore hypothesized that sulfate-cycling in mangrove soils is influenced by the size of net primary production, and hence negatively affected by mangrove degradation and exploitation, as well as by carbon-exporting waves. To test this, we compared quantitative and qualitative traits of sulfate-reducing communities in two Saudi-Arabian mangrove stands near Jeddah, where co-occurring differences in camel-grazing pressure and tidal exposure led to a markedly different stand height and hence primary production. Potential sulfate reduction rates measured in anoxic flow-through reactors in the absence and presence of additional carbon sources were significantly higher in the samples from the non-grazed site. Near the surface (0–2 cm depth), numbers of dsrB gene copies and culturable cells also tended to be higher in the non-grazed sites, while these differences were not detected in the sub-surface (4–6 cm depth). It was concluded that sulfate-reducing microbes at the surface were indeed repressed at the low-productive site as could be expected from our hypothesis. At both sites, sulfate reduction rates as well as numbers of the dsrB gene copies and viable cells increased with depth suggesting repression of sulfate reduction near the surface in both irrespective of production level. Additionally, sequence analysis of DNA bands obtained from DGGE gels based on the dsrB gene, showed a clear difference in dominance of sulfate-reducing genera belonging to the Deltaproteobacteria and the Firmicutes between sampling sites and depths. PMID:26733999

  17. Potential Activity, Size, and Structure of Sulfate-Reducing Microbial Communities in an Exposed, Grazed and a Sheltered, Non-Grazed Mangrove Stand at the Red Sea Coast.

    PubMed

    Balk, Melike; Keuskamp, Joost A; Laanbroek, Hendrikus J

    2015-01-01

    After oxygen, sulfate is the most important oxidant for the oxidation of organic matter in mangrove forest soils. As sulfate reducers are poor competitors for common electron donors, their relative success depends mostly on the surplus of carbon that is left by aerobic organisms due to oxygen depletion. We therefore hypothesized that sulfate-cycling in mangrove soils is influenced by the size of net primary production, and hence negatively affected by mangrove degradation and exploitation, as well as by carbon-exporting waves. To test this, we compared quantitative and qualitative traits of sulfate-reducing communities in two Saudi-Arabian mangrove stands near Jeddah, where co-occurring differences in camel-grazing pressure and tidal exposure led to a markedly different stand height and hence primary production. Potential sulfate reduction rates measured in anoxic flow-through reactors in the absence and presence of additional carbon sources were significantly higher in the samples from the non-grazed site. Near the surface (0-2 cm depth), numbers of dsrB gene copies and culturable cells also tended to be higher in the non-grazed sites, while these differences were not detected in the sub-surface (4-6 cm depth). It was concluded that sulfate-reducing microbes at the surface were indeed repressed at the low-productive site as could be expected from our hypothesis. At both sites, sulfate reduction rates as well as numbers of the dsrB gene copies and viable cells increased with depth suggesting repression of sulfate reduction near the surface in both irrespective of production level. Additionally, sequence analysis of DNA bands obtained from DGGE gels based on the dsrB gene, showed a clear difference in dominance of sulfate-reducing genera belonging to the Deltaproteobacteria and the Firmicutes between sampling sites and depths.

  18. Potential Activity, Size, and Structure of Sulfate-Reducing Microbial Communities in an Exposed, Grazed and a Sheltered, Non-Grazed Mangrove Stand at the Red Sea Coast.

    PubMed

    Balk, Melike; Keuskamp, Joost A; Laanbroek, Hendrikus J

    2015-01-01

    After oxygen, sulfate is the most important oxidant for the oxidation of organic matter in mangrove forest soils. As sulfate reducers are poor competitors for common electron donors, their relative success depends mostly on the surplus of carbon that is left by aerobic organisms due to oxygen depletion. We therefore hypothesized that sulfate-cycling in mangrove soils is influenced by the size of net primary production, and hence negatively affected by mangrove degradation and exploitation, as well as by carbon-exporting waves. To test this, we compared quantitative and qualitative traits of sulfate-reducing communities in two Saudi-Arabian mangrove stands near Jeddah, where co-occurring differences in camel-grazing pressure and tidal exposure led to a markedly different stand height and hence primary production. Potential sulfate reduction rates measured in anoxic flow-through reactors in the absence and presence of additional carbon sources were significantly higher in the samples from the non-grazed site. Near the surface (0-2 cm depth), numbers of dsrB gene copies and culturable cells also tended to be higher in the non-grazed sites, while these differences were not detected in the sub-surface (4-6 cm depth). It was concluded that sulfate-reducing microbes at the surface were indeed repressed at the low-productive site as could be expected from our hypothesis. At both sites, sulfate reduction rates as well as numbers of the dsrB gene copies and viable cells increased with depth suggesting repression of sulfate reduction near the surface in both irrespective of production level. Additionally, sequence analysis of DNA bands obtained from DGGE gels based on the dsrB gene, showed a clear difference in dominance of sulfate-reducing genera belonging to the Deltaproteobacteria and the Firmicutes between sampling sites and depths. PMID:26733999

  19. Machine Learning classification of MRI features of Alzheimer's disease and mild cognitive impairment subjects to reduce the sample size in clinical trials.

    PubMed

    Escudero, Javier; Zajicek, John P; Ifeachor, Emmanuel

    2011-01-01

    There is a need for objective tools to help clinicians to diagnose Alzheimer's Disease (AD) early and accurately and to conduct Clinical Trials (CTs) with fewer patients. Magnetic Resonance Imaging (MRI) is a promising AD biomarker but no single MRI feature is optimal for all disease stages. Machine Learning classification can address these challenges. In this study, we have investigated the classification of MRI features from AD, Mild Cognitive Impairment (MCI), and control subjects from ADNI with four techniques. The highest accuracy rates for the classification of controls against ADs and MCIs were 89.2% and 72.7%, respectively. Moreover, we used the classifiers to select AD and MCI subjects who are most likely to decline for inclusion in hypothetical CTs. Using the hippocampal volume as an outcome measure, we found that the required group sizes for the CTs were reduced from 197 to 117 AD patients and from 366 to 215 MCI subjects. PMID:22256186

  20. A reduced-order integral formulation to account for the finite size effect of isotropic square panels using the transfer matrix method.

    PubMed

    Bonfiglio, Paolo; Pompoli, Francesco; Lionti, Riccardo

    2016-04-01

    The transfer matrix method is a well-established prediction tool for the simulation of sound transmission loss and the sound absorption coefficient of flat multilayer systems. Much research has been dedicated to enhancing the accuracy of the method by introducing a finite size effect of the structure to be simulated. The aim of this paper is to present a reduced-order integral formulation to predict radiation efficiency and radiation impedance for a panel with equal lateral dimensions. The results are presented and discussed for different materials in terms of radiation efficiency, sound transmission loss, and the sound absorption coefficient. Finally, the application of the proposed methodology for rectangular multilayer systems is also investigated and validated against experimental data. PMID:27106325

  1. A reduced-order integral formulation to account for the finite size effect of isotropic square panels using the transfer matrix method.

    PubMed

    Bonfiglio, Paolo; Pompoli, Francesco; Lionti, Riccardo

    2016-04-01

    The transfer matrix method is a well-established prediction tool for the simulation of sound transmission loss and the sound absorption coefficient of flat multilayer systems. Much research has been dedicated to enhancing the accuracy of the method by introducing a finite size effect of the structure to be simulated. The aim of this paper is to present a reduced-order integral formulation to predict radiation efficiency and radiation impedance for a panel with equal lateral dimensions. The results are presented and discussed for different materials in terms of radiation efficiency, sound transmission loss, and the sound absorption coefficient. Finally, the application of the proposed methodology for rectangular multilayer systems is also investigated and validated against experimental data.

  2. DNA damage phenotype and prostate cancer risk

    PubMed Central

    Kosti, O.; Goldman, L.; Saha, D.T.; Orden, R.A.; Pollock, A.J.; Madej, H.L.; Hsing, A.W.; Chu, L.W.; Lynch, J.H.; Goldman, R.

    2010-01-01

    The capacity of an individual to process DNA damage is considered a crucial factor in carcinogenesis. The comet assay is a phenotypic measure of the combined effects of sensitivity to a mutagen exposure and repair capacity. In this paper, we evaluate the association of the DNA repair kinetics, as measured by the comet assay, with prostate cancer risk. In a pilot study of 55 men with prostate cancer, 53 men without the disease, and 71 men free of cancer at biopsy, we investigated the association of DNA damage with prostate cancer risk at early (0-15 min) and later (15-45 min) stages following gamma-radiation exposure. Although residual damage within 45 min was the same for all groups (65% of DNA in comet tail disappeared), prostate cancer cases had a slower first phase (38% vs 41%) and faster second phase (27% vs 22%) of the repair response compared to controls. When subjects were categorized into quartiles, according to efficiency of repairing DNA damage, high repair-efficiency within the first 15 min after exposure was not associated with prostate cancer risk while higher at the 15-45 min period was associated with increased risk (OR for highest-to-lowest quartiles = 3.24, 95% CI=0.98-10.66, p-trend =0.04). Despite limited sample size, our data suggest that DNA repair kinetics marginally differ between prostate cancer cases and controls. This small difference could be associated with differential responses to DNA damage among susceptible individuals. PMID:21095241

  3. The investigation of prostatic calcifications using μ-PIXE analysis and their dosimetric effect in low dose rate brachytherapy treatments using Geant4.

    PubMed

    Pope, D J; Cutajar, D L; George, S P; Guatelli, S; Bucci, J A; Enari, K E; Miller, S; Siegele, R; Rosenfeld, A B

    2015-06-01

    Low dose rate brachytherapy is a widely used modality for the treatment of prostate cancer. Most clinical treatment planning systems currently in use approximate all tissue to water, neglecting the existence of inhomogeneities, such as calcifications. The presence of prostatic calcifications may perturb the dose due to the higher photoelectric effect cross section in comparison to water. This study quantitatively evaluates the effect of prostatic calcifications on the dosimetric outcome of brachytherapy treatments by means of Monte Carlo simulations and its potential clinical consequences.Four pathological calcification samples were characterised with micro-particle induced x-ray emission (μ-PIXE) to determine their heavy elemental composition. Calcium, phosphorus and zinc were found to be the predominant heavy elements in the calcification composition. Four clinical patient brachytherapy treatments were modelled using Geant4 based Monte Carlo simulations, in terms of the distribution of brachytherapy seeds and calcifications in the prostate. Dose reductions were observed to be up to 30% locally to the calcification boundary, calcification size dependent. Single large calcifications and closely placed calculi caused local dose reductions of between 30-60%. Individual calculi smaller than 0.5 mm in diameter showed minimal dosimetric impact, however, the effects of small or diffuse calcifications within the prostatic tissue could not be determined using the methods employed in the study. The simulation study showed a varying reduction on common dosimetric parameters. D90 showed a reduction of 2-5%, regardless of calcification surface area and volume. The parameters V100, V150 and V200 were also reduced by as much as 3% and on average by 1%. These reductions were also found to relate to the surface area and volume of calcifications, which may have a significant dosimetric impact on brachytherapy treatment, however, such impacts depend strongly on specific factors

  4. Engineering chemically modified viruses for prostate cancer cell recognition.

    PubMed

    Mohan, K; Weiss, G A

    2015-12-01

    Specific detection of circulating tumor cells and characterization of their aggressiveness could improve cancer diagnostics and treatment. Metastasis results from such tumor cells, and causes the majority of cancer deaths. Chemically modified viruses could provide an inexpensive and efficient approach to detect tumor cells and quantitate their cell surface biomarkers. However, non-specific adhesion between the cell surface receptors and the virus surface presents a challenge. This report describes wrapping the virus surface with different PEG architectures, including as fusions to oligolysine, linkers, spacers and scaffolded ligands. The reported PEG wrappers can reduce by >75% the non-specific adhesion of phage to cell surfaces. Dynamic light scattering verified the non-covalent attachment by the reported wrappers as increased sizes of the virus particles. Further modifications resulted in specific detection of prostate cancer cells expressing PSMA, a key prostate cancer biomarker. The approach allowed quantification of PSMA levels on the cell surface, and could distinguish more aggressive forms of the disease. PMID:26463253

  5. MRI-Safe Robot for Endorectal Prostate Biopsy

    PubMed Central

    Stoianovici, Dan; Kim, Chunwoo; Srimathveeravalli, Govindarajan; Sebrecht, Peter; Petrisor, Doru; Coleman, Jonathan; Solomon, Stephen B.; Hricak, Hedvig

    2014-01-01

    This paper reports the development of an MRI-Safe robot for direct (interventional) MRI-guided endorectal prostate biopsy. The robot is constructed of nonmagnetic and electrically nonconductive materials, and is electricity free, using pneumatic actuation and optical sensors. Targeting biopsy lesions of MRI abnormality presents substantial clinical potential for the management of prostate cancer. The paper describes MRI-Safe requirements, presents the kinematic architecture, design and construction of the robot, and a comprehensive set of preclinical tests for MRI compatibility and needle targeting accuracy. The robot has a compact and simple 3 degree-of-freedom (DoF) structure, two for orienting a needle-guide and one to preset the depth of needle insertion. The actual insertion is performed manually through the guide and up to the preset depth. To reduce the complexity and size of the robot next to the patient, the depth setting DoF is remote. Experimental results show that the robot is safe to use in any MRI environment (MRI-Safe). Comprehensive MRI tests show that the presence and motion of the robot in the MRI scanner cause virtually no image deterioration or signal to noise ratio (SNR) change. Robot’s accuracy in bench test, CT-guided in-vitro, MRI-guided in-vitro and animal tests are 0.37mm, 1.10mm, 2.09mm, and 2.58mm respectively. These values are acceptable for clinical use. PMID:25378897

  6. Gastric adenocarcinoma with prostatic metastasis.

    PubMed

    Roshni, S; Anoop, Tm; Preethi, Tr; Shubanshu, G; Lijeesh, Al

    2014-06-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  7. Gastric Adenocarcinoma with Prostatic Metastasis

    PubMed Central

    Roshni, S; Preethi, TR; Shubanshu, G; Lijeesh, AL

    2014-01-01

    Metastasis of gastric adenocarcinoma to the prostate gland is extremely rare. Herein, we report a case of gastric adenocarcinoma in a 56-year-old man with prostatic metastasis diagnosed through the analysis of biopsy specimens from representative lesions in the stomach and prostate gland. Immunohistochemistry of the prostatic tissue showed positive staining for cytokeratin 7 and negative staining for prostate-specific antigen (PSA), whereas the serum PSA level was normal, confirming the diagnosis of prostatic metastasis from carcinoma of the stomach. PMID:25061542

  8. MRI of the Prostate

    MedlinePlus

    ... The images can then be examined on a computer monitor, transmitted electronically, printed or copied to a CD. The prostate gland is part of the male reproductive system. It is located in front of the rectum ...

  9. Prostate Cancer Foundation

    MedlinePlus

    ... Close About Us Our Story A Legacy of Leadership About the Prostate Cancer Foundation CEO Message Why ... Cancer Board of Directors Annual Report & Financials Our Leadership Leadership Team A Legacy of Leadership Featured Take ...

  10. Chronic prostatitis: management strategies.

    PubMed

    Murphy, Adam B; Macejko, Amanda; Taylor, Aisha; Nadler, Robert B

    2009-01-01

    The National Institutes of Health (NIH) has redefined prostatitis into four distinct entities. Category I is acute bacterial prostatitis. It is an acute prostatic infection with a uropathogen, often with systemic symptoms of fever, chills and hypotension. The treatment hinges on antimicrobials and drainage of the bladder because the inflamed prostate may block urinary flow. Category II prostatitis is called chronic bacterial prostatitis. It is characterized by recurrent episodes of documented urinary tract infections with the same uropathogen and causes pelvic pain, urinary symptoms and ejaculatory pain. It is diagnosed by means of localization cultures that are 90% accurate in localizing the source of recurrent infections within the lower urinary tract. Asymptomatic inflammatory prostatitis comprises NIH category IV. This entity is, by definition, asymptomatic and is often diagnosed incidentally during the evaluation of infertility or prostate cancer. The clinical significance of category IV prostatitis is unknown and it is often left untreated. Category III prostatitis is called chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). It is characterized by pelvic pain for more than 3 of the previous 6 months, urinary symptoms and painful ejaculation, without documented urinary tract infections from uropathogens. The syndrome can be devastating, affecting 10-15% of the male population, and results in nearly 2 million outpatient visits each year. The aetiology of CP/CPPS is poorly understood, but may be the result of an infectious or inflammatory initiator that results in neurological injury and eventually results in pelvic floor dysfunction in the form of increased pelvic muscle tone. The diagnosis relies on separating this entity from chronic bacterial prostatitis. If there is no history of documented urinary tract infections with a urinary tract pathogen, then cultures should be taken when patients are symptomatic. Prostatic localization cultures, called the

  11. Prostate cancer (image)

    MedlinePlus

    Treatment of prostate cancer varies depending on the stage of the cancer (i.e., spread) and may include surgical removal, radiation, chemotherapy, hormonal manipulation or a combination of these treatments.

  12. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  13. What Is Prostate Cancer?

    MedlinePlus Videos and Cool Tools

    ... the more likely he is to develop the disease. Physician: Come on back, first room. Narrator: Most ... cancer. Prostate cancer is really a spectrum of diseases where on one end of the spectrum there ...

  14. Detecting Prostate Cancer

    MedlinePlus Videos and Cool Tools

    ... abnormal and raises the index of suspicion that cancer may be present. Narrator: While the use of ... examination does not mean that they have prostate cancer. It means that we're concerned about it ...

  15. Phosphodiesterase 4D Inhibitors Limit Prostate Cancer Growth Potential

    PubMed Central

    Powers, Ginny L.; Hammer, Kimberly D.P.; Domenech, Maribella; Frantskevich, Katsiaryna; Malinowski, Rita L.; Bushman, Wade; Beebe, David J.; Marker, Paul C.

    2014-01-01

    Phosphodiesterase 4D (PDE4D) has recently been implicated as a proliferation-promoting factor in prostate cancer and is over-expressed in human prostate carcinoma. However, the effects of PDE4D inhibition using pharmacological inhibitors have not been examined in prostate cancer. These studies examined the effects of selective PDE4D inhibitors, NVP-ABE171 and cilomilast, as anti-prostate cancer therapies in both in vitro and in vivo models. The effects of PDE4D inhibitors on pathways that are critical in prostate cancer and/or downstream of cyclic AMP (cAMP) were examined. Both NVP-ABE171 and cilomilast decreased cell growth. In vitro, PDE4D inhibitors lead to decreased signaling of the sonic hedgehog (SHH), Androgen Receptor (AR), and MAPK pathways, but growth inhibition was best correlated to the sonic hedgehog pathway. PDE4D inhibition also reduced proliferation of epithelial cells induced by paracrine signaling from co-cultured stromal cells that had activated hedgehog signaling. In addition, PDE4D inhibitors decreased the weight of the prostate in wild-type mice. Prostate cancer xenografts grown in nude mice that were treated with cilomilast or NVP-ABE171 had decreased wet weight and increased apoptosis compared to vehicle treated controls. These studies suggest the pharmacological inhibition of PDE4D using small molecule inhibitors is an effective option for prostate cancer therapy. Implications PDE4D inhibitors decrease the growth of prostate cancer cells in vivo and in vitro, and PDE4D inhibition has therapeutic potential in prostate cancer. PMID:25149359

  16. Sanguinarine suppresses prostate tumor growth and inhibits survivin expression.

    PubMed

    Sun, Meng; Lou, Wei; Chun, Jae Yeon; Cho, Daniel S; Nadiminty, Nagalakshmi; Evans, Christopher P; Chen, Jun; Yue, Jiao; Zhou, Qinghua; Gao, Allen C

    2010-03-01

    Prostate cancer is a frequently occurring disease and is the second leading cause of cancer-related deaths of men in the United States. Current treatments have proved inadequate in curing or controlling prostate cancer, and a search for agents for the management of this disease is urgently needed. Survivin plays an important role in both progression of castration-resistant prostate cancer and resistance to chemotherapy. Altered expression of survivin in prostate cancer cells is associated with cancer progression, drug/radiation resistance, poor prognosis, and short patient survival. In the present study, the authors performed a cell-based rapid screen of the Prestwick Chemical Library consisting of 1120 Food and Drug Administration-approved compounds with known safety and bioavailability in humans to identify potential inhibitors of survivin and anticancer agents for prostate cancer. Sanguinarine, a benzophenanthridine alkaloid derived primarily from the bloodroot plant, was identified as a novel inhibitor of survivin that selectively kills prostate cancer cells over "normal" prostate epithelial cells. The authors found that sanguinarine inhibits survivin protein expression through protein degradation via the ubiquitin-proteasome system. Sanguinarine induces apoptosis and inhibits growth of human prostate cancer cells and in vivo tumor formation. Administration of sanguinarine, beginning 3 days after ectopic implantation of DU145 human prostate cancer cells, reduces both tumor weight and volume. In addition, sanguinarine sensitized paclitaxel-mediated growth inhibition and apoptosis, offering a potential therapeutic strategy for overcoming taxol resistance. These results suggest that sanguinarine may be developed as an agent either alone or in combination with taxol for treatment of prostate cancer overexpressing survivin. PMID:21318089

  17. Polymeric Nanoparticles for Targeted Radiosensitization of Prostate Cancer Cells

    PubMed Central

    Menon, Jyothi U.; Tumati, Vasu; Hsieh, Jer-Tsong; Nguyen, Kytai T.; Saha, Debabrata

    2014-01-01

    One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle system consisting of poly (lactic-co-glycolic acid) (PLGA) nanoparticles conjugated with prostate cancer cell penetrating peptide-R11 and encapsulated with a potent radio-sensitizer 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) to allow prostate cancer-specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11-conjugated nanoparticles (R11-NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in de-ionized water and serum. The nanoparticles were cytocompatible with immortalized prostate cells (PZ-HPV-7). Further, the particles showed a bi-phasic release of encapsulated NU7441 and were taken up by PC3 prostate cancer cells in a dose- and magnetic field-dependent manner while not being taken up in non-prostate cancer cell lines. In addition, R11-NU7441 NPs were effective radiation sensitizers of prostate cancer cell lines in vitro. These results thus demonstrate the potential of R11-conjugated PLGA NPs as novel platforms for targeted radiosensitization of prostate cancer cells. PMID:25088162

  18. LIGA20, a lyso derivative of ganglioside GM1, given orally after cortical thrombosis reduces infarct size and associated cognition deficit.

    PubMed Central

    Kharlamov, A; Zivkovic, I; Polo, A; Armstrong, D M; Costa, E; Guidotti, A

    1994-01-01

    A bilateral photochemically induced thrombotic lesion of rat sensorimotor cortex (approximately 3 mm in diameter and 25 mm3 in volume) is associated with a persistent cognition (learning and memory) deficit, which was evaluated with water maze tasks. The N-dichloroacetylsphingosine derivative of lysoGM1 (LIGA20) administered after the lesion either i.v. or per or reduces the infarct size by 30-40% and attenuates the associated cognition deficits, presumably by limiting the extent of damage of neurons at risk located in the surroundings of the infarcted core (i.e., area penumbra). The LIGA20 protection is dose and time dependent. Maximal protection is afforded by a single dose of LIGA20 of 34 mumol/kg i.v. 1 hr after lesion or by a dose of 270 mumol/kg per os when administered 1 hr and 24 hr after the lesion. The protective effect of LIGA20 can be observed when the drug is administered i.v. up to 6 hr after the lesion. The protective efficacy of the oral administration of LIGA20 is related to its physiochemical properties, which, unlike those of GM1, allow absorption from the gastrointestinal tract. LIGA20 given orally reaches the brain promptly and rapidly inserts into the neuronal membranes. Here, by an unknown molecular mechanism, LIGA20 selectively reduces the pathological amplification of Ca2+ signaling elicited by persistent stimulation of ionotropic glutamate receptors in the area penumbra. PMID:8022776

  19. Prostate cancer. Foreword.

    PubMed

    Patel, Hiten R H

    2014-11-01

    Professor Hiten Patel is an expert in Laparoscopic and Robotic Surgery for treating prostate disease. He is also a leading researcher in basic science and `clinical research. His basic science research is focused on studying the pathways for improving prostate cancer diagnosis and prognosis through biomarker application, and his clinical research includes new technology applications for training surgeons and improving patient care outcome. Prof Patel is also Chairman of the Urology group for the Enhanced Recovery after Surgery Society.

  20. Monopolar versus bipolar transurethral resection of prostate for benign prostatic hyperplasia: Operative outcomes and surgeon preferences, a real-world scenario

    PubMed Central

    Madduri, Vijay Kumar Sarma; Bera, Malay Kumar; Pal, Dilip Kumar

    2016-01-01

    Context: Monopolar transurethral resection of prostate (M-TURP) is considered the gold standard for the management of bladder outlet obstruction due to benign prostatic hyperplasia. Its newly introduced modification, bipolar TURP (B-TURP), promises to overcome its most prominent shortcomings, namely bleeding and dilutional hyponatremia. Literature is conflicting regarding merits of B-TURP over M-TURP. Aims: To find a difference, if any, in perioperative outcomes between M-TURP and B-TURP in a real-wold setting. Settings and Design: Prospective nonrandomized study. Subjects and Methods: Operative outcomes of patients undergoing M-TURP and B-TURP from February 2014 to October 2015 were compared. Statistical Analysis Used: Categorical data were compared by Fischer exact test and numerical data were compared by independent samples Mann–Whitney U-test. P <0.05 was considered statistically significant. Results: The mean size of prostate operated by bipolar technology was significantly greater than those operated by monopolar technology (38.12 ± 9.59 cc vs. 66.49 ± 22.95 cc; P < 0.001). The mean fall in postoperative serum sodium concentration was 0.99 ± 0.76 mEq/L for the B-TURP group as compared to 3.60 ± 2.89 mEq/L for the M-TURP group (P < 0.001). The mean drop in postoperative hemoglobin concentration (P = 0.28) was statistically insignificant, even though larger glands were operated by B-TURP. There were three instances of the transurethral resection (TUR) syndrome in the M-TURP group whereas no TUR syndrome occurred in the B-TURP group. Conclusions: In spite of various contrary viewpoints in literature, surgeons prefer to operate on larger prostates using bipolar technology. B-TURP definitely reduces the incidence of bleeding and dilutional hyponatremia, making it a contender to replace M-TURP as the new gold standard. PMID:27453650

  1. Nanosecond pulse electric field activation of platelet-rich plasma reduces myocardial infarct size and improves left ventricular mechanical function in the rabbit heart.

    PubMed

    Hargrave, Barbara; Li, Francis

    2012-12-01

    In the current study, we used the novel, nonchemical method of nanosecond pulsed electric fields (nsPEF) to investigate the efficiency of a protocol involving the in vivo treatment of the ischemic and reperfused heart and heart cells in culture with platelet-rich plasma (PRP). Associated with the restoration of blood flow to the ischemic tissue is a phenomenon referred to as "ischemic reperfusion injury." Clinically a type of reperfusion injury occurs during coronary bypass surgery once blood perfusion to the heart is restarted. Although the restoration of oxygen to ischemic myocardial cells is critical for tissue survival, reperfusion causes myocardial oxidative stress, attributable in part to the increased production of reactive oxygen species (ROS). Enhanced ROS production is associated with mitochondrial damage. Adult female New Zealand white rabbits were anesthetized and a left thoracotomy performed to expose the heart. The distal segment of the left anterior descending coronary artery was occluded for 15 minutes and then released so reperfusion of the tissue could occur. PRP (.21 mg/heart) or saline was injected into the ischemic area of the myocardium. Mechanical function of the left ventricle was analyzed using a Millar catheter attached to a Micro-Med Analysis System. H9c2 cells in culture were treated with 1 mL of nsPEF activated PRP (1.05 mg/flask) for 24 hours before analysis for ROS production or mitochondrial depolarization damage). The left ventricle contracted and relaxed faster and infarct size was reduced in hearts treated with PRP compared with saline. ROS production and mitochondrial depolarization were reduced in H9c2 cells treated with PRP and stimulated with hydrogen peroxide. These results provide evidence that nsPEFs can successfully be used to prepare PRP and that the PRP is functional in heart protection possibly by reducing ROS generation and stabilizing the mitochondria of the ischemic/reperfused heart.

  2. [Effect of prostatilen AC suppositories on course of experimental prostatitis].

    PubMed

    Savateeva-Liubimova, T N; Sivak, K V; Malinin, V V

    2012-01-01

    The article presents the results of evaluation of efficacy of new drug prostatilen AC (rectal suppositories), containing regulatory peptides of the bovine prostate and zinc arginate-glycinate complex, in the treatment of prostatitis. The experiment was conducted on 40 Sprague-Dawley rats weighing 180-200 g. Chronic prostatitis was modeled by injection of 10% Dimexidum in combination with water, mixed with turpentine, a volumetric ratio of 4:1. It is shown that prostatilen AC has pronounced organotropic antiinflammatory effect, which manifests in reducing the weight of the prostate, reducing the protein level in the urine, activity of acid phosphatase, and levels of ceruloplasmin and C-reactive protein. In addition, this drug normalizes the act of urination and increases the diurnal diuresis, has antioxidant properties and increases the blood level of the male sex hormone testosterone.

  3. Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes

    PubMed Central

    Sundberg, Berit; Mattsson, Jonas; Henningsohn, Lars; Levitsky, Victor; Uhlin, Michael

    2016-01-01

    Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer. PMID:26993768

  4. Progression of benign prostatic hyperplasia is associated with pro-inflammatory mediators and chronic activation of prostate-infiltrating lymphocytes.

    PubMed

    Norström, Melissa M; Rådestad, Emelie; Sundberg, Berit; Mattsson, Jonas; Henningsohn, Lars; Levitsky, Victor; Uhlin, Michael

    2016-04-26

    Benign prostatic hyperplasia (BPH) is a common chronic non-malignant condition whose prevalence substantially increases with age. Immune cell infiltration and pro-inflammatory mediators have been implicated in the pathogenesis. Here, we characterized 21 extracellular markers on prostate-infiltrating lymphocytes (PILs) and analyzed expression of 26 soluble proteins in prostate tissue obtained from BPH patients (n = 31). These data were correlated with clinical parameters and compared with peripheral blood mononuclear cells (PBMCs) (n = 10). Increased frequencies of T cells expressing co-inhibitory receptors LAG-3, PD-1, TIM-3 or CTLA-4, and co-stimulatory receptors CD28, OX40 or 4-1BB were observed in BPH tissue compared to PBMCs. These findings are consistent with chronic activation and possible functional exhaustion of PILs that may be further augmented by several identified pro-inflammatory factors, such as IL-8 and MCP-1, promoting inflammation and chemotaxis of immune cells to the prostate. Prostate size and plasma prostate-specific antigen levels positively correlated with IL-8 and MCP-1 concentrations, and frequencies of T cells expressing CTLA-4 and TIM-3. It remains to be established whether the link between inflammation and BPH progression supported by our findings reflects a progressive failure of the immune system leading to decreased immune surveillance and development of prostate cancer. PMID:26993768

  5. Hypoxia-responsive miR-124 and miR-144 reduce hypoxia-induced autophagy and enhance radiosensitivity of prostate cancer cells via suppressing PIM1.

    PubMed

    Gu, Hao; Liu, Mingzhu; Ding, Changmao; Wang, Xin; Wang, Rui; Wu, Xinyu; Fan, Ruitai

    2016-06-01

    Cancer cells in hypoxia usually make adaptive changes in cellular metabolism, such as altered autophagy. This might be a cause of enhanced radioresistance in some types of cancer. In this study, we investigated hypoxia-responsive miRNAs in two prostate cancer cell lines (DU145 and PC3). This study firstly reported that hypoxia induces further downregulation of miR-124 and miR-144, which might be a result of impaired dicer expression. These two miRNAs can simultaneously target 3'UTR of PIM1. Functional study showed that miR-124 or miR-144 overexpression can inhibit hypoxia-induced autophagy and enhance radiosensitivity at least via downregulating PIM1. Therefore, hypoxia induced miR-124 and miR-144 downregulation may contribute to a prosurvival mechanism of prostate cancer cells to hypoxia and irradiation at least through attenuated suppressing of PIM1. This finding presents a potential therapeutic target for prostate cancer. PMID:26990493

  6. Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer.

    PubMed

    Yan, Judy; Ojo, Diane; Kapoor, Anil; Lin, Xiaozeng; Pinthus, Jehonathan H; Aziz, Tariq; Bismar, Tarek A; Wei, Fengxiang; Wong, Nicholas; De Melo, Jason; Cutz, Jean-Claude; Major, Pierre; Wood, Geoffrey; Peng, Hao; Tang, Damu

    2016-03-15

    Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P < 0.05). Collectively, our findings demonstrate that CNTN1 promotes prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.

  7. A novel approach for evaluation of prostate deformation and associated dosimetric implications in IGRT of the prostate

    SciTech Connect

    Mayyas, Essa E-mail: ortonc@comcast.net; Kim, Jinkoo; Kumar, Sanath; Liu, Chang; Wen, Ning; Movsas, Benjamin; Elshaikh, Mohamed A.; Chetty, Indrin J.

    2014-09-15

    Purpose: Prostate deformation is assumed to be a secondary correction and is typically ignored in the planning target volume (PTV) margin calculations. This assumption needs to be tested, especially when planning margins are reduced with daily image-guidance. In this study, deformation characteristics of the prostate and seminal vesicles were determined, and the dosimetric impact on treatment plans with different PTV margins was investigated. Methods: Ten prostate cancer patients were retrospectively selected for the study, each with three fiducial markers implanted in the prostate. Two hundred CBCT images were registered to respective planning CT images using a B-spline-based deformable image registration (DIR) software. A manual bony anatomy-based match was first applied based on the alignment of the pelvic bones and fiducial landmarks. DIR was then performed. For each registration, deformation vector fields (DVFs) of the prostate and seminal vesicles (SVs) were quantified using deformation-volume histograms. In addition, prostate rotation was evaluated and compared with prostate deformation. For a patient demonstrating small and large prostate deformations, target coverage degradation was analyzed in each of three treatment plans with PTV margins of 10 mm (6 mm at the prostate/rectum interface), as well as 5, and 3 mm uniformly. Results: Deformation of the prostate was most significant in the anterior direction. Maximum prostate deformation of greater than 10, 5, and 3 mm occurred in 1%, 17%, and 76% of the cases, respectively. Based on DVF-histograms, DVF magnitudes greater than 5 and 3 mm occurred in 2% and 27% of the cases, respectively. Deformation of the SVs was most significant in the posterior direction, and it was greater than 5 and 3 mm in 7.5% and 44.9% of the cases, respectively. Prostate deformation was found to be poorly correlated with rotation. Fifty percent of the cases showed rotation with negligible deformation and 7% of the cases showed

  8. Influence of volumes of prostate, rectum, and bladder on treatment planning CT on interfraction prostate shifts during ultrasound image-guided IMRT

    SciTech Connect

    Reddy, Nandanuri M. S.; Nori, Dattatreyudu; Sartin, William; Maiorano, Samuel; Modena, Jennifer; Mazur, Andrej; Osian, Adrian; Sood, Brijmohan; Ravi, Akkamma; Sampath, Seshadri; Lange, Christopher S.

    2009-12-15

    required for patients with distended or empty rectum on planning CT to reduce rectal toxicity in the case of empty rectum and to minimize geometric miss of prostate.

  9. Drugs Approved for Prostate Cancer

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Prostate Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Prostate Cancer Abiraterone Acetate Bicalutamide Cabazitaxel Casodex (Bicalutamide) Degarelix Docetaxel ...

  10. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... Wellness PCF Spotlight Glossary African American Men Understanding Prostate Cancer Newly Diagnosed Newly Diagnosed Staging the Disease Issues ... you care about has recently been diagnosed with prostate cancer, this section will help guide you through the ...

  11. New Prostate Cancer Treatment Target

    Cancer.gov

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  12. Ejaculatory Function After Permanent {sup 125}I Prostate Brachytherapy for Localized Prostate Cancer

    SciTech Connect

    Huyghe, Eric Delannes, Martine; Wagner, Fabien M.; Delaunay, Boris; Nohra, Joe; Thoulouzan, Matthieu; Shut-Yee, J. Yeung; Plante, Pierre; Soulie, Michel; Thonneau, Patrick; Bachaud, Jean Marc

    2009-05-01

    Purpose: Ejaculatory function is an underreported aspect of male sexuality in men treated for prostate cancer. We conducted the first detailed analysis of ejaculatory function in patients treated with permanent {sup 125}I prostate brachytherapy for localized prostate cancer. Patients and Methods: Of 270 sexually active men with localized prostate cancer treated with permanent {sup 125}I prostate brachytherapy, 241 (89%), with a mean age of 65 years (range, 43-80), responded to a mailed questionnaire derived from the Male Sexual Health Questionnaire regarding ejaculatory function. Five aspects of ejaculatory function were examined: frequency, volume, dry ejaculation, pleasure, and pain. Results: Of the 241 sexually active men, 81.3% had conserved ejaculatory function after prostate brachytherapy; however, the number of patients with rare/absent ejaculatory function was double the pretreatment number (p < .0001). The latter finding was correlated with age (p < .001) and the preimplant International Index of Erectile Function score (p < .001). However, 84.9% of patients with maintained ejaculatory function after implantation reported a reduced volume of ejaculate compared with 26.9% before (p < .001), with dry ejaculation accounting for 18.7% of these cases. After treatment, 30.3% of the patients experienced painful ejaculation compared with 12.9% before (p = .0001), and this was associated with a greater number of implanted needles (p = .021) and the existence of painful ejaculation before implantation (p < .0001). After implantation, 10% of patients who continued to be sexually active experienced no orgasm compared with only 1% before treatment. in addition, more patients experienced late/difficult or weak orgasms (p = .001). Conclusion: Most men treated with brachytherapy have conserved ejaculatory function after prostate brachytherapy. However, most of these men experience a reduction in volume and a deterioration in orgasm.

  13. Cultural sensitivity and informed decision making about prostate cancer screening.

    PubMed

    Chan, Evelyn C Y; Haynes, Michelle C; O'Donnell, Frederick T; Bachino, Carolyn; Vernon, Sally W

    2003-12-01

    Because informed consent for prostate cancer screening with prostate specific antigen (PSA) is recommended, we determined how African Americans, Hispanics, and Caucasians want information about screening with PSA and the digital rectal exam (DRE) presented in culturally sensitive brochures specific for each group. We analyzed focus group discussions using content analysis and compared themes across groups in a university outpatient internal medicine practice setting. The participants were twenty couples with men age 50 and older who participated in four focus groups. Main outcome measures were participants' views on the content and graphic design of culturally sensitive brochures promoting informed decision making about prostate cancer screening. There were content and graphic design differences in the way ethnic groups wanted information presented about the prostate, prostate cancer, risk, and screening. Caucasians likened the size of the prostate to a walnut; Hispanics, to a small lime. Hispanics emphasized how advanced prostate cancer can be symptomatic; Caucasians, how early prostate cancer can be asymptomatic. African Americans wanted risk information specific for them and the advantages and disadvantages of a PSA and DRE; Hispanics, did not. Caucasians and African Americans sought a more active role for men in informed decision making than Hispanics. Differences in the way African Americans, Hispanics, and Caucasians want information presented about prostate cancer screening suggest there may be cultural differences in the reasonable person standard of informed consent, in attitudes toward the physician-patient relationship, screening, and informed decision making. Physicians promoting informed decision making about controversial screening tests should take cultural sensitivity into account when designing educational interventions and using them. PMID:14620963

  14. Effect of Boerhaavia diffusa in experimental prostatic hyperplasia in rats

    PubMed Central

    Vyas, Bhavin A.; Desai, Niket Y.; Patel, Paras K.; Joshi, Shrikant V.; Shah, Dinesh R.

    2013-01-01

    Objective: Present investigation was undertaken to study the effectiveness of hydroalcoholic extract of roots of Boerhaavia diffusa in experimental benign prostatic hyperplasia (BPH) in rats using various animal models. Materials and Methods: BPH in rats was induced by subcutaneous injection of testosterone (5 mg/kg) daily for 28 days. Rats were divided in to five groups (six rats each). A negative control group received arachis oil (1 ml/kg s.c.) and four groups were injected testosterone. These four groups were further divided into reference group (finasteride 1 mg/kg), model group (testosterone), study group A (B. diffusa 100 mg/kg), and study group B (B. diffusa 250 mg/kg). On the 29th day, rats were sacrificed and body weight, prostate weight, bladder weight, and serum testosterone level were measured and histological studies were carried out. Further in vitro analysis of B. diffusa extract on contractility of isolated rat vas deferens and prostate gland, produced by exogenously administered agonists were carried out. All results were expressed as mean ± SEM. 0 Data were analyzed by one-way analysis of variance followed by Tukey's test. Results: B. diffusa (100 mg/kg) treatment for 28 days resulted in significant inhibition of prostate growth (P < 0.05). Drug extract did not have significant change on serum testosterone level. Histopathological analysis of prostate gland supported above results. Results of in vitro experiment suggest that extracts had attenuated the contractile responses of isolated vas deferens and prostate gland to exogenously applied agonists. Conclusion: The results suggested that treatment with B. diffusa may improve symptoms of disease and inhibit the increased prostate size. In vitro study implies that herbal extracts has the machinery to produce beneficial effect on prostatic smooth muscle, which would relieve the urinary symptoms of disease. B. diffusa could be a potential source of new treatment of prostatic hyperplasia. PMID

  15. Glial Restricted Precursor Cell Transplant with Cyclic Adenosine Monophosphate Improved Some Autonomic Functions but Resulted in a Reduced Graft Size after Spinal Cord Contusion Injury in Rats

    PubMed Central

    Nout, Yvette S.; Culp, Esther; Schmidt, Markus H.; Tovar, C. Amy; Pröschel, Christoph; Mayer-Pröschel, Margot; Noble, Mark D.; Beattie, Michael S.; Bresnahan, Jacqueline C.

    2010-01-01

    Transplantation of glial restricted precursor (GRP) cells has been shown to reduce glial scarring after spinal cord injury (SCI) and, in combination with neuronal restricted precursor (NRP) cells or enhanced expression of neurotrophins, to improve recovery of function after SCI. We hypothesized that combining GRP transplants with rolipram and cAMP would improve functional recovery, similar to that seen after combining Schwann cell transplants with increasing cAMP. A short term study, 1)uninjured control, 2)SCI+vehicle, and 3)SCI+cAMP, showed that spinal cord [cAMP] were increased 14 days after SCI. We used 51 male rats subjected to a thoracic SCI for a 12-week survival study: 1)SCI+vehicle, 2)SCI+GRP, 3)SCI+cAMP, 4)SCI+GRP+cAMP, and 5)uninjured endpoint age-matched control (AM). Rolipram was administered for 2 weeks after SCI. At 9 days after SCI, GRP transplantation and injection of dibutyryl-cAMP into the spinal cord were performed. GRP cells survived, differentiated, and formed extensive transplants that were well integrated with host tissue. Presence of GRP cells increased the amount of tissue in the lesion; however, cAMP reduced the graft size. White matter sparing at the lesion epicenter was not affected. Serotonergic input to the lumbosacral spinal cord was not affected by treatment, but the amount of serotonin immediately caudal to the lesion was reduced in the cAMP groups. Using telemetric monitoring of corpus spongiosum penis pressure we show that the cAMP groups regained the same number of micturitions per 24 hrs when compared to the AM group, however, the frequency of peak pressures was increased in these groups compared to the AM group. In contrast, the GRP groups had similar frequency of peak pressures compared to baseline and the AM group. Animals that received GRP cells regained the same number of erectile events per 24 hrs compared to baseline and the AM group. Since cAMP reduced the GRP transplant graft, and some modest positive effects were seen

  16. Antioxidant Treatment Promotes Prostate Epithelial Proliferation in Nkx3.1 Mutant Mice

    PubMed Central

    Martinez, Erin E.; Anderson, Philip D.; Logan, Monica; Abdulkadir, Sarki A.

    2012-01-01

    Discordant results in preclinical and clinical trials have raised questions over the effectiveness of antioxidants in prostate cancer chemoprevention. Results from the large-scale Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed that antioxidants failed to prevent, and in some cases promoted, prostate cancer formation in men without a history of the disease. One possible explanation for these alarming results is the notion that the effects of antioxidant treatment on the prostate are modified by specific, intrinsic genetic risk factors, causing some men to respond negatively to antioxidant treatment. Loss of expression of the homeobox transcription factor NKX3.1 in the prostate is frequently associated with human prostate cancer. Nkx3.1 mutant mice display prostatic hyperplasia and dysplasia and are used as a model of the early stages of prostate cancer initiation. While the mechanisms by which Nkx3.1 loss promotes prostate tumorigenicity are not completely understood, published data have suggested that elevated reactive oxygen species (ROS) associated with Nkx3.1 loss may be a causative factor. Here we have tested this hypothesis by treating Nkx3.1 mutant mice with the antioxidant N-acetylcysteine (NAC) for 13 weeks post-weaning. Surprisingly, while NAC treatment decreased ROS levels in Nkx3.1 mutant mouse prostates, it failed to reduce prostatic epithelial hyperplasia/dysplasia. Rather, NAC treatment increased epithelial cell proliferation and promoted the expression of a pro-proliferative gene signature. These results show that ROS do not promote proliferation in the Nkx3.1-null prostate, but instead inhibit proliferation, suggesting that antioxidant treatment may encourage prostate epithelial cell proliferation early in prostate tumorigenesis. Our findings provide new insight that may help explain the increased prostate cancer risk observed with vitamin E treatment in the SELECT trial and emphasize the need for preclinical studies using accurate

  17. Shrinkage of experimental benign prostatic hyperplasia and reduction of prostatic cell volume by a gastrin-releasing peptide antagonist

    PubMed Central

    Rick, Ferenc G.; Abi-Chaker, Andrew; Szalontay, Luca; Perez, Roberto; Jaszberenyi, Miklos; Jayakumar, Arumugam R.; Shamaladevi, Nagarajarao; Szepeshazi, Karoly; Vidaurre, Irving; Halmos, Gabor; Krishan, Awtar; Block, Norman L.; Schally, Andrew V.

    2013-01-01

    Gastrin releasing-peptide (GRP) is a potent growth factor in many malignancies. Benign prostatic hyperplasia (BPH) is a progressive age-related proliferation of glandular and stromal tissues; various growth factors and inflammatory processes are involved in its pathogenesis. We have demonstrated that potent antagonists of GRP inhibit growth of experimental human tumors including prostate cancer, but their effect on models of BPH has not been studied. Here, we evaluated the effects of GRP antagonist RC-3940-II on viability and cell volume of BPH-1 human prostate epithelial cells and WPMY-1 prostate stromal cells in vitro, and in testosterone-induced BPH in Wistar rats in vivo. RC-3940-II inhibited the proliferation of BPH-1 and WPMY-1 cells in a dose-dependent manner and reduced prostatic cell volume in vitro. Shrinkage of prostates was observed after 6 wk of treatment with RC-3940-II: a 15.9% decline with 25 μg/d; and a 18.4% reduction with 50 μg/d (P < 0.05 for all). Significant reduction in levels of proliferating cell nuclear antigen, NF-κβ/p50, cyclooxygenase-2, and androgen receptor was also seen. Analysis of transcript levels of genes related to growth, inflammatory processes, and signal transduction showed significant changes in the expression of more than 90 genes (P < 0.05). In conclusion, GRP antagonists reduce volume of human prostatic cells and lower prostate weight in experimental BPH through direct inhibitory effects on prostatic GRP receptors. GRP antagonists should be considered for further development as therapy for BPH. PMID:23359692

  18. Strategies for prevention of ultrasound-guided prostate biopsy infections

    PubMed Central

    Lu, Diane D; Raman, Jay D

    2016-01-01

    Prostate cancer is the most common cancer in male patients and the second leading cause of cancer-related mortality in males. To confirm the diagnosis of prostate cancer, an ultrasound-guided needle biopsy is necessary to obtain prostate tissue sufficient for histologic analysis by pathologists. Ultrasound-guided prostate needle biopsy can be accomplished via a transperineal or transrectal approach. The latter biopsy technique involves placing an ultrasound probe into the rectum, visualizing the prostate located just anterior to it, and then obtaining 12–14 biopsies. Each biopsy core requires piercing of the rectal mucosa which can inherently contribute to infection. The increasing infectious risk of prostate needle biopsy requires refinement and re-evaluation of the process in which the technique is performed. Such processes include (but are not limited to) prebiopsy risk stratification, antibiotic prophylaxis, use of rectal preparations, and equipment processing. In the subsequent review, we highlight the current available information on different strategies to reduce the risk of infection following prostate needle biopsy. PMID:27468242

  19. Prostatic adenoma of ductal origin.

    PubMed

    Min, K W; Gyorkey, F

    1980-07-01

    A case of prostatic adenoma believed to originate from the prostatic duct is described. There were morphologic similarities to basal cell adenomas of salivary glands, and it was concluded that the tumor is a benign counterpart of "salivary gland" carcinomas, rarely observed in the prostate.

  20. Steroid hormone receptors in prostatic hyperplasia and prostatic carcinoma.

    PubMed

    Khalid, B A; Nurshireen, A; Rashidah, M; Zainal, B Y; Roslan, B A; Mahamooth, Z

    1990-06-01

    One hundred and six prostatic tissue samples obtained from transurethral resection were analysed for androgen and estrogen receptors. In 62 of these, progesterone and glucocorticoid receptors were also assayed. Steroid receptors were assayed using single saturation dose 3H-labelled ligand assays. Ninety percent of the 97 prostatic hyperplasia tissues and six of the nine prostatic carcinoma tissues were positive for androgen receptors. Estrogen receptors were only present in 19% and 33% respectively. Progesterone receptors were present in 70% of the tissues, but glucocorticoid receptors were present in only 16% of prostatic hyperplasia and none in prostatic carcinoma. PMID:1725553

  1. Experience with prostate-specific antigen in prostatic carcinoma.

    PubMed

    Romics, I; Bach, D

    1991-01-01

    A total of 71 prostatic tumour patients and 45 prostatic adenoma patients were tested for prostate-specific antigen (PSA), immunological prostatic acid phosphatase (PAP) concentration as well as serum prostatic phosphatase (SPP) and enzymic serum phosphatase. It was found among untreated patients that PSA showed the highest percentage of pathologic affection in each stage. PSA, on the evidence of clearance test in the initial days of therapy and after a follow-up period of several months, gave a good picture of the course that the disease had taken.

  2. Reduction of prostate cancer mortality in Tyrol, Austria, after introduction of prostate-specific antigen testing.

    PubMed

    Oberaigner, Willi; Horninger, Wolfgang; Klocker, Helmut; Schönitzer, Dieter; Stühlinger, Wolf; Bartsch, Georg

    2006-08-15

    The objective of this study was to analyze in detail the time trend in prostate cancer mortality in the population of Tyrol, Austria. In Tyrol, prostate-specific antigen tests were introduced in 1988-1989 and, since 1993, have been offered to all men aged 45-74 years free of charge. More than three quarters of all men in this age group had at least one such test in the last decade. The authors applied the age-period-cohort model by Poisson regression to mortality data covering more than three decades, from 1970 to 2003. For Tyrol, the full model with age and period and cohort terms fit fairly well. Period terms showed a significant reduction in prostate cancer mortality in the last 5 years, with a risk ratio of 0.81 (95% confidence interval: 0.68, 0.98) for Tyrol; for Austria without Tyrol, no effect was seen, with a risk ratio of 1.00 (95% confidence interval: 0.95, 1.05). Each was compared with the mortality rate in the period 1989-1993. Although the results of randomized screening trials are not expected until 2008-2010, these findings support the evidence that prostate-specific antigen testing offered to a population free of charge can reduce prostate cancer mortality.

  3. Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study

    PubMed Central

    2016-01-01

    Introduction. The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods. Ten male SpA patients (mean ± SD age 39 ± 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis. Results. SpA patients presented with significantly lower appendicular lean body mass (LBM) (p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients (p = 0.03) with a parallel trend for specific strength (p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers (p = 0.04), but no difference in CSA type I fibers. Conclusions. Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA.

  4. Reduced Appendicular Lean Body Mass, Muscle Strength, and Size of Type II Muscle Fibers in Patients with Spondyloarthritis versus Healthy Controls: A Cross-Sectional Study

    PubMed Central

    2016-01-01

    Introduction. The purpose of this study was to investigate body composition, muscle function, and muscle morphology in patients with spondyloarthritis (SpA). Methods. Ten male SpA patients (mean ± SD age 39 ± 4.1 years) were compared with ten healthy controls matched for sex, age, body mass index, and self-reported level of physical exercise. Body composition was measured by dual energy X-ray absorptiometry. Musculus quadriceps femoris (QF) strength was assessed by maximal isometric contractions prior to test of muscular endurance. Magnetic resonance imaging of QF was used to measure muscle size and calculate specific muscle strength. Percutaneous needle biopsy samples were taken from m. vastus lateralis. Results. SpA patients presented with significantly lower appendicular lean body mass (LBM) (p = 0.02), but there was no difference in bone mineral density, fat mass, or total LBM. Absolute QF strength was significantly lower in SpA patients (p = 0.03) with a parallel trend for specific strength (p = 0.08). Biopsy samples from the SpA patients revealed significantly smaller cross-sectional area (CSA) of type II muscle fibers (p = 0.04), but no difference in CSA type I fibers. Conclusions. Results indicate that the presence of SpA disease is associated with reduced appendicular LBM, muscle strength, and type II fiber CSA. PMID:27672678

  5. Rotigaptide (ZP123) prevents spontaneous ventricular arrhythmias and reduces infarct size during myocardial ischemia/reperfusion injury in open-chest dogs.

    PubMed

    Hennan, James K; Swillo, Robert E; Morgan, Gwen A; Keith, James C; Schaub, Robert G; Smith, Robert P; Feldman, Hal S; Haugan, Ketil; Kantrowitz, Joel; Wang, Phil J; Abu-Qare, Aqel; Butera, John; Larsen, Bjarne D; Crandall, David L

    2006-04-01

    The antiarrhythmic and cardioprotective effect of increasing gap junction intercellular communication during ischemia/reperfusion injury has not been studied. The antiarrhythmic peptide rotigaptide (previously ZP123), which maintains gap junction intercellular communication, was tested in dogs subjected to a 60-min coronary artery occlusion and 4 h of reperfusion. Rotigaptide was administered i.v. 10 min before reperfusion as a bolus + i.v. infusion at doses of 1 ng/kg bolus + 10 ng/kg/h infusion (n = 6), 10 ng/kg bolus + 100 ng/kg/h infusion (n = 5), 100 ng/kg bolus + 1000 ng/kg/h infusion (n = 8), 1000 ng/kg bolus + 10 mug/kg/h infusion (n = 6), and vehicle control (n = 5). Premature ventricular complexes (PVCs) were quantified during reperfusion. A series of four or more consecutive PVCs was defined as ventricular tachycardia (VT). The total incidence of VT was reduced significantly with the two highest doses of rotigaptide (20.3 +/- 10.9 and 4.3 +/- 4.1 events; p < 0.05) compared with controls (48.7 +/- 6.0). Total PVCs were reduced significantly from 25.1 +/- 4.2% in control animals to 11.0 +/- 4.4 and 1.7 +/- 1.3% after the two highest doses of rotigaptide. Infarct size, expressed as a percentage of the left ventricle, was reduced significantly from 13.2 +/- 1.9 in controls to 7.1 +/- 1.0 (p < 0.05) at the highest dose of rotigaptide. Ultrastructural evaluation revealed no differences in myocardial injury in the infarct area, area at risk, border zone, or normal zone in vehicle and rotigaptide-treated animals. However, rotigaptide did increase the presence of gap junctions in the area at risk (p = 0.022, Fisher's exact test). Rotigaptide had no effect on heart rate, blood pressure, heart rate-corrected QT interval, or left ventricular end-diastolic pressure. In conclusion, these results demonstrate that rotigaptide is a potent antiarrhythmic compound with cardioprotective effects and desirable safety.

  6. Prostate Cancer Support Groups

    PubMed Central

    Chambers, Suzanne; Garrett, Bernie; Bottorff, Joan L.; McKenzie, Michael; Han, Christina S.; Ogrodniczuk, John S.

    2015-01-01

    To understand prostate cancer (PCa) specialists’ views about prostate cancer support groups (PCSGs), a volunteer sample of Canada-based PCa specialists (n = 150), including urologists (n = 100), radiation oncologists (n = 40), and medical oncologists (n = 10) were surveyed. The 56-item questionnaire used in this study included six sets of attitudinal items to measure prostate cancer specialists’ beliefs about positive and negative influences of PCSGs, reasons for attending PCSGs, the attributes of effective PCSGs, and the value of face-to-face and web-based PCSGs. In addition, an open-ended question was included to invite additional input from participants. Results showed that PCSGs were positively valued, particularly for information sharing, education and psychosocial support. Inclusivity, privacy, and accessibility were identified as potential barriers, and recommendations were made for better marketing PCSGs to increase engagement. Findings suggest prostate cancer specialists highly valued the role and potential benefits of face-to-face PCSGs. Information provision and an educational role were perceived as key benefits. Some concerns were expressed about the ability of web-based PCSGs to effectively engage and educate men who experience prostate cancer. PMID:25061087

  7. Precursors of prostate cancer.

    PubMed

    Bostwick, David G; Cheng, Liang

    2012-01-01

    High-grade prostatic intraepithelial neoplasia (PIN) is the only accepted precursor of prostatic adenocarcinoma, according to numerous studies of animal models and man; other proposed precursors include atrophy and malignancy-associated changes (with no morphologic changes). PIN is characterized by progressive abnormalities of phenotype and genotype that are intermediate between benign prostatic epithelium and cancer, indicating impairment of cell differentiation and regulatory control with advancing stages of prostatic carcinogenesis. The only method of detection of PIN is biopsy because it does not significantly elevate serum prostate-specific antigen concentration and cannot be detected by ultrasonography. The mean incidence of PIN in biopsies is 9% (range, 4%-16%), representing about 115,000 new cases of isolated PIN diagnosed each year in the United States. The clinical importance of PIN is its high predictive value as a marker for adenocarcinoma, and its identification warrants repeat biopsy for concurrent or subsequent carcinoma, especially when multifocal or observed in association with atypical small acinar proliferation (ASAP). Carcinoma develops in most patients with PIN within 10 years. Androgen deprivation therapy and radiation therapy decrease the prevalence and extent of PIN, suggesting that these forms of treatment may play a role in prevention of subsequent cancer. Multiple clinical trials to date of men with PIN have had modest success in delaying or preventing subsequent cancer. PMID:22212075

  8. The diet as a cause of human prostate cancer.

    PubMed

    Nelson, William G; Demarzo, Angelo M; Yegnasubramanian, Srinivasan

    2014-01-01

    Asymptomatic prostate inflammation and prostate cancer have reached epidemic proportions among men in the developed world. Animal model studies implicate dietary carcinogens, such as the heterocyclic amines from over-cooked meats and sex steroid hormones, particularly estrogens, as candidate etiologies for prostate cancer. Each acts by causing epithelial cell damage, triggering an inflammatory response that can evolve into a chronic or recurrent condition. This milieu appears to spawn proliferative inflammatory atrophy (PIA) lesions, a type of focal atrophy that represents the earliest of prostate cancer precursor lesions. Rare PIA lesions contain cells which exhibit high c-Myc expression, shortened telomere segments, and epigenetic silencing of genes such as GSTP1, encoding the π-class glutathione S-transferase, all characteristic of prostatic intraepithelial neoplasia (PIN) and prostate cancer. Subsequent genetic changes, such as the gene translocations/deletions that generate fusion transcripts between androgen-regulated genes (such as TMPRSS2) and genes encoding ETS family transcription factors (such as ERG1), arise in PIN lesions and may promote invasiveness characteristic of prostatic adenocarcinoma cells. Lethal prostate cancers contain markedly corrupted genomes and epigenomes. Epigenetic silencing, which seems to arise in response to the inflamed microenvironment generated by dietary carcinogens and/or estrogens as part of an epigenetic "catastrophe" affecting hundreds of genes, persists to drive clonal evolution through metastatic dissemination. The cause of the initial epigenetic "catastrophe" has not been determined but likely involves defective chromatin structure maintenance by over-exuberant DNA methylation or histone modification. With dietary carcinogens and estrogens driving pro-carcinogenic inflammation in the developed world, it is tempting to speculate that dietary components associated with decreased prostate cancer risk, such as intake of

  9. Treating benign prostatic hyperplasia with botulinum neurotoxin.

    PubMed

    Brisinda, G; Vanella, S; Marniga, G; Crocco, A; Maria, G

    2011-01-01

    Botulinum toxin (BoNT) has been increasingly used in the interventional treatment of several disorders; the use of this agent has extended to a plethora of conditions including focal dystonia, spasticity, inappropriate contraction in most gastrointestinal sphincters, eye movement disorders, hyperhidrosis, genitourinary disorders and aesthetically undesirable hyperfunctional facial lines. In addition, BoNT is being investigated for the control of pain, and for the management of tension or migraine headaches and myofascial pain syndrome. Benign prostatic hyperplasia (BPH) is a common condition in ageing men; the goal of therapy is to reduce the lower urinary tract symptoms (LUTS) associated with BPH and to improve the quality of life. However, medical treatment, including drugs that relax smooth muscle within the prostate and drugs that shrink the gland are not totally effective or without complications. The standard surgical treatment for BPH is progressively changing to minimally invasive therapies, but none of them has provided clear results. The use of BoNT-A to inhibit the autonomic efferent effects on prostate growth and contraction, and inhibit the abnormal afferent effects on prostate sensation, might be an alternative treatment for BPH. BoNT injections have several advantages over drugs and surgical therapies in the management of intractable or chronic disease; systemic pharmacologic effects are rare, permanent destruction of tissue does not occur, and graded degrees of relaxation may be achieved by varying the dose injected. In this paper, clinical experience over the last years with BoNT in BPH impaired patients will be illustrated.

  10. [Primary prevention of urologic tumors: prostate cancer].

    PubMed

    Schmitz-Dräger, B J; Lümmen, G; Bismarck, E; Fischer, C

    2011-10-01

    Assessment of the role of vitamins and micronutrients in the primary prevention of prostate cancer has changed dramatically in the past 10 years. Efforts to confirm the efficacy of a single substance have not yet succeeded. Therefore, such recommendations should at present no longer be given. Consideration could even be given to discussing whether additional large-scale interventional studies are expedient in this regard. There is still solid evidence that a well-balanced moderate diet, reduced consumption of milk products, and an Asian or Mediterranean diet are not only beneficial for general good health but can also prevent the development of prostate cancer. This should be the focus of further epidemiological studies. Thus, one can certainly speak of a paradigm shift in the prevention of prostate cancer. In contrast, available data on chemoprevention with 5α-reductase inhibitors is unequivocal: intake of finasteride as well as dutasteride correlates with significantly decreased evidence for prostate cancer. Converting this result into urologic practice remains the topic of extensive controversy. PMID:21927877

  11. Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer

    PubMed Central

    Zhang, Liangfen; Rimando, Agnes M.; Lage, Janice M.; Lewin, Jack R.; Atfi, Azeddine; Zhang, Xu; Levenson, Anait S.

    2016-01-01

    Overexpression of the epigenetic modifier metastasis-associated protein 1 (MTA1) is associated with aggressive human prostate cancer. The purpose of this study was to determine MTA1- targeted chemopreventive and therapeutic efficacy of pterostilbene, a natural potent analog of resveratrol, in pre-clinical models of prostate cancer. Here, we show that high levels of MTA1 expression in Pten-loss prostate cooperate with key oncogenes, including c-Myc and Akt among others, to promote prostate cancer progression. Loss-of-function studies using human prostate cancer cells indicated direct involvement of MTA1 in inducing inflammation and epithelial-to-mesenchymal transition. Importantly, pharmacological inhibition of MTA1 by pterostilbene resulted in decreased proliferation and angiogenesis and increased apoptosis. This restrained prostatic intraepithelial neoplasia (PIN) formation in prostate-specific Pten heterozygous mice and reduced tumor development and progression in prostate-specific Pten-null mice. Our findings highlight MTA1 as a key upstream regulator of prostate tumorigenesis and cancer progression. More significantly, it offers pre-clinical proof for pterostilbene as a promising lead natural agent for MTA1-targeted chemopreventive and therapeutic strategy to curb prostate cancer. PMID:26943043

  12. A Double Blind, Randomized, Neoadjuvant Study of the Tissue effects of POMx Pills in Men with Prostate Cancer Prior to Radical Prostatectomy

    PubMed Central

    Freedland, Stephen J.; Carducci, Michael; Kroeger, Nils; Partin, Alan; Rao, Jian-yu; Jin, Yusheng; Kerkoutian, Susan; Wu, Hong; Li, Yunfeng; Creel, Patricia; Mundy, Kelly; Gurganus, Robin; Fedor, Helen; King, Serina A.; Zhang, Yanjun; Heber, David; Pantuck, Allan J.

    2013-01-01

    Pomegranates slow prostate cancer xenograft growth and prolong PSA doubling times in single-arm human studies. Pomegranates’ effects on human prostate tissue are understudied. We hypothesized orally administered pomegranate extract (POMx; PomWonderful, Los Angeles, CA) would lower tissue 8-hydroxy-2-deoxyguanosine (8-OHdG), an oxidative stress biomarker. 70 men were randomized to 2 tablets POMx or placebo daily up to 4 weeks prior to radical prostatectomy. Tissue was analyzed for intra-prostatic Urolithin A, a pomegranate metabolite, benign and malignant 8-OHdG, and cancer pS6 kinase, NFκB, and Ki67. Primary end-point was differences in 8-OHdG powered to detect 30% reduction. POMx was associated with 16% lower benign tissue 8-OHdG (p=0.095), which was not statistically significant. POMx was well-tolerated with no treatment-related withdrawals. There were no differences in baseline clinicopathological features between arms. Urolithin A was detected in 21/33 patient in the POMx group vs. 12/35 in the placebo group (p=0.031). Cancer pS6 kinase, NFκB, Ki67, and serum PSA changes were similar between arms. POMx prior to surgery results in pomegranate metabolite accumulation in prostate tissues. Our primary end-point in this modest-sized short-term trial was negative. Future larger longer studies are needed to more definitely test whether POMx reduces prostate oxidative stress as well as further animal testing to better understand the multiple mechanisms through which POMx may alter prostate cancer biology. PMID:23985577

  13. Fatty acid activated PPARγ promotes tumorigenicity of prostate cancer cells by up regulating VEGF via PPAR responsive elements of the promoter

    PubMed Central

    Forootan, Farzad S.; Forootan, Shiva S.; Gou, Xiaojun; Yang, Jin; Liu, Bichong; Chen, Danqing; Fayi, Majed Saad Al; Al-Jameel, Waseem; Rudland, Philip S.; Hussain, Syed A.; Ke, Youqiang

    2016-01-01

    In previous work, it is suggested that the excessive amount of fatty acids transported by FABP5 may facilitate the malignant progression of prostate cancer cells through a FABP5-PPARγ-VEGF signal transduction axis to increase angiogenesis. To further functionally characterise the FABP5-PPARγ-VEGF signal transduction pathway, we have, in this work, investigated the molecular mechanisms involved in its tumorigenicity promoting role in prostate cancer. Suppression of PPARγ in highly malignant prostate cancer cells produced a significant reduction (up to 53%) in their proliferation rate, invasiveness (up to 89%) and anchorage-independent growth (up to 94%) in vitro. Knockdown of PPARγ gene in PC3-M cells by siRNA significantly reduced the average size of tumours formed in nude mice by 99% and tumour incidence by 90%, and significantly prolonged the latent period by 3.5 fold. Results in this study combined with some previous results suggested that FABP5 promoted VEGF expression and angiogenesis through PPARγ which was activated by fatty acids transported by FABP5. Further investigations showed that PPARγ up-regulated VEGF expression through acting with the PPAR-responsive elements in the promoter region of VEGF gene in prostate cancer cells. Although androgen can modulate VEGF expression through Sp1/Sp3 binding site on VEGF promoter in androgen-dependent prostate cancer cells, this route, disappeared as the cells gradually lost their androgen dependency; was replaced by the FABP5-PPARγ-VEGF signalling pathway. These results suggested that the FABP5-PPARγ-VEGF signal transduction axis, rather than androgen modulated route, may be a more important novel therapeutic target for angiogenesis-suppression treatment of castration resistant prostate cancer. PMID:26814431

  14. Effect of noise reducing components on nose landing gear stability for a mid-size aircraft coupled with vortex shedding and freeplay

    NASA Astrophysics Data System (ADS)

    Eret, Petr; Kennedy, John; Bennett, Gareth J.

    2015-10-01

    In the pursuit of quieter aircraft, significant effort has been dedicated to airframe noise identification and reduction. The landing gear is one of the main sources of airframe noise on approach. The addition of noise abatement technologies such as fairings or wheel hub caps is usually considered to be the simplest solution to reduce this noise. After touchdown, noise abatement components can potentially affect the inherently nonlinear and dynamically complex behaviour (shimmy) of landing gear. Moreover, fairings can influence the aerodynamic load on the system and interact with the mechanical freeplay in the torque link. This paper presents a numerical study of nose landing gear stability for a mid-size aircraft with low noise solutions, which are modelled by an increase of the relevant model structural parameters to address a hypothetical effect of additional fairings and wheel hub caps. The study shows that the wheel hub caps are not a threat to stability. A fairing has a destabilising effect due to the increased moment of inertia of the strut and a stabilising effect due to the increased torsional stiffness of the strut. As the torsional stiffness is dependent on the method of attachment, in situations where the fairing increases the torsional inertia with little increase to the torsional stiffness, a net destabilising effect can result. Alternatively, it is possible that for the case that if the fairing were to increase equally both the torsional stiffness and the moment of inertia of the strut, then their effects could be mutually negated. However, it has been found here that for small and simple fairings, typical of current landing gear noise abatement design, their implementation will not affect the dynamics and stability of the system in an operational range (Fz ≤ 50 000 N, V ≤ 100 m/s). This generalisation is strictly dependent on size and installation methods. The aerodynamic load, which would be influenced by the presence of fairings, was modelled

  15. The natural history of benign prostatic hyperplasia: what have we learned in the last decade?

    PubMed

    Kirby, R S

    2000-11-01

    Benign prostatic hyperplasia (BPH) frequently has a significant detrimental impact on a patient's quality of life. If the disease is left untreated, it may progress in severity, leading to recurrent bladder infections, bladder calculi, and acute urinary retention (AUR), necessitating surgical treatment. The Forth Valley, Scotland, study reported that 14% of men aged 40 to 50 years have BPH. This increases to 43% of men >60 years old. BPH has been shown to be nearly as prevalent as hypertension and diabetes among patients seeking treatment for erectile dysfunction. The effects of BPH on quality of life include lack of sleep, anxiety, reduced mobility, interference with leisure activities and usual daily activities, and a compromised sense of well-being. Three symptoms are associated with an increased risk of AUR in men with BPH: a reduction in the force of the urinary stream, a sensation of incomplete bladder emptying, and an enlarged prostate gland on digital rectal examination. Age is a strong independent risk factor for the development of AUR. Transurethral resection of the prostate was more effective than watchful waiting in preventing AUR, as shown in the Veteran's Affairs Cooperative Study. Data from the Olmsted County study revealed that urinary flow decreases and prostate size increases with advanced age. This study also showed that lower urinary tract symptoms have a negative impact on parameters of physical and mental aspects of health. More recently, studies have shown that medical treatment with 5alpha-reductase inhibitors and possibly also alpha-blockers may alter the natural history and progression of BPH.

  16. The significance of dynamin 2 expression for prostate cancer progression, prognostication, and therapeutic targeting.

    PubMed

    Xu, Bin; Teng, Liang Hong; Silva, Sabrina Daniela da; Bijian, Krikor; Al Bashir, Samir; Jie, Su; Dolph, Michael; Alaoui-Jamali, Moulay A; Bismar, Tarek A

    2014-02-01

    Dynamin 2 (Dyn2) is essential for intracellular vesicle formation and trafficking, cytokinesis, and receptor endocytosis. In this study, we investigated the implication of Dyn2 as a prognostic marker and therapeutic target for progressive prostate cancer (PCA). We evaluated Dyn2 protein expression by immunohistochemistry in two cohorts: men with localized PCA treated by retropubic radical prostatectomy (n = 226), and men with advanced/castrate-resistant PCA (CRPC) treated by transurethral resection of prostate (TURP) (n = 253). The role of Dyn2 in cell invasiveness was assessed by in vitro and in vivo experiments using androgen-responsive and refractory PCA preclinical models. Dyn2 expression was significantly increased across advanced stages of PCA compared to benign prostate tissue (P < 0.0001). In the CRPC cohort, high Dyn2 was associated with higher Gleason score (P = 0.004) and marginally with cancer-specific mortality (P = 0.052). In preclinical models, Dyn2 gene silencing significantly reduced cell migration and invasion in vitro, as well as tumor size and lymph node metastases in vivo. In isolated PCA cells, Dyn2 was found to regulate focal adhesion turnover, which is critical for cell migration; this mechanism requires full Dyn2 compared to mutants deficient in GTPase activity. In conclusion, Dyn2 overexpression is associated with neoplastic prostate epithelium and is associated with poor prognosis. Inhibition of Dyn2 prevents cell invasiveness in androgen-responsive and -refractory PCA models, supporting the potential benefit of Dyn2 to serve as a therapeutic target for advanced PCA.

  17. Prostatic abscess: Objective assessment of the treatment approach in the absence of guidelines

    PubMed Central

    Elshal, Ahmed M.; Abdelhalim, Ahmed; Barakat, Tamer S.; Shaaban, Atallah A.; Nabeeh, Adel; Ibrahiem, El-Housseiny

    2014-01-01

    Objective To assess the outcome of the drainage procedure used for treating a prostatic abscess, and to propose a treatment algorithm to reduce the morbidity and the need for re-treatment. Patients and methods We retrospectively reviewed patients who were admitted and received an interventional treatment for a prostatic abscess. All baseline relevant variables were reviewed. Details of the intervention, laboratory data, duration of hospital stay, follow-up data and re-admissions were recorded. Results A prostatic abscess was diagnosed in 42 patients; 30 were treated by transurethral deroofing and 12 by transrectal needle aspiration. The median (range) size of the abscess was 4.5 (2–23) mL and 2.7 (1.5–7.1) mL in the deroofing and aspiration groups, respectively (P = 0.2). In half of the cases multiple abscesses were evident on imaging before the intervention. The median (range) hospital stay after deroofing and aspiration was 2 (1–11) and 1 (1–19) days, respectively (P = 0.04). Perioperative complications occurred only in the deroofing group, in which two patients developed septic shock requiring intensive care (Clavien 4) and one developed epididymo-orchitis (Clavien 2). There were two late complications in the deroofing group, in which one patient developed a urethral stricture that required endoscopic urethrotomy (Clavien 3a) and one developed a urethral diverticulum and urinary incontinence that required diverticulectomy and a bulbo-urethral sling procedure (Clavien 3b). A urethro-rectal fistula developed after aspiration in one patient. Re-treatment for the abscess was indicated in two (7%) patients in the deroofing group, which was treated by aspiration. Conclusion Transrectal needle aspiration for a prostatic abscess, when done for properly selected cases, could minimise the morbidity of the drainage procedure. PMID:26019960

  18. The natural history of benign prostatic hyperplasia: what have we learned in the last decade?

    PubMed

    Kirby, R S

    2000-11-01

    Benign prostatic hyperplasia (BPH) frequently has a significant detrimental impact on a patient's quality of life. If the disease is left untreated, it may progress in severity, leading to recurrent bladder infections, bladder calculi, and acute urinary retention (AUR), necessitating surgical treatment. The Forth Valley, Scotland, study reported that 14% of men aged 40 to 50 years have BPH. This increases to 43% of men >60 years old. BPH has been shown to be nearly as prevalent as hypertension and diabetes among patients seeking treatment for erectile dysfunction. The effects of BPH on quality of life include lack of sleep, anxiety, reduced mobility, interference with leisure activities and usual daily activities, and a compromised sense of well-being. Three symptoms are associated with an increased risk of AUR in men with BPH: a reduction in the force of the urinary stream, a sensation of incomplete bladder emptying, and an enlarged prostate gland on digital rectal examination. Age is a strong independent risk factor for the development of AUR. Transurethral resection of the prostate was more effective than watchful waiting in preventing AUR, as shown in the Veteran's Affairs Cooperative Study. Data from the Olmsted County study revealed that urinary flow decreases and prostate size increases with advanced age. This study also showed that lower urinary tract symptoms have a negative impact on parameters of physical and mental aspects of health. More recently, studies have shown that medical treatment with 5alpha-reductase inhibitors and possibly also alpha-blockers may alter the natural history and progression of BPH. PMID:11074195

  19. Benign prostatic hyperplasia.

    PubMed Central

    Simpson, R J

    1997-01-01

    The clinical syndrome of benign prostatic hyperplasia reflects a complex interplay between benign prostatic enlargement, which will affect almost all men by the age of 80, and the resulting outlet obstruction and lower urinary tract symptoms. The disease is now known to adversely affect the quality of life of around one man in three over the age of 50. New medical treatments and new surgical interventions are challenging the previous standard treatment of transurethral resection of prostate, which continues to have a morbidity of 17% and some mortality. Primary care will be increasingly involved in shared care with particular emphasis on monitoring of patients on watchful waiting medical therapy- and following operative intervention. PMID:9196969

  20. ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer

    PubMed Central

    Holzmann, Christian; Kilch, Tatiana; Kappel, Sven; Armbrüster, Andrea; Jung, Volker; Stöckle, Michael; Bogeski, Ivan; Schwarz, Eva C.; Peinelt, Christine

    2013-01-01

    Labelled 5α-dihydrotestosterone (DHT) binding experiments have shown that expression levels of (yet unidentified) membrane androgen receptors (mAR) are elevated in prostate cancer and correlate with a negative prognosis. However, activation of these receptors which mediate a rapid androgen response can counteract several cancer hallmark functions such as unlimited proliferation, enhanced migration, adhesion and invasion and the inability to induce apoptosis. Here, we investigate the downstream signaling pathways of mAR and identify rapid DHT induced activation of store-operated Ca2+ entry (SOCE) in primary cultures of human prostate epithelial cells (hPEC) from non-tumorous tissue. Consequently, down-regulation of Orai1, the main molecular component of Ca2+ release-activated Ca2+ (CRAC) channels results in an almost complete loss of DHT induced SOCE. We demonstrate that this DHT induced Ca2+ influx via Orai1 is important for rapid androgen triggered prostate specific antigen (PSA) release. We furthermore identified alterations of the molecular components of CRAC channels in prostate cancer. Three lines of evidence indicate that prostate cancer cells down-regulate expression of the Orai1 homolog Orai3: First, Orai3 mRNA expression levels are significantly reduced in tumorous tissue when compared to non-tumorous tissue from prostate cancer patients. Second, mRNA expression levels of Orai3 are decreased in prostate cancer cell lines LNCaP and DU145 when compared to hPEC from healthy tissue. Third, the pharmacological profile of CRAC channels in prostate cancer cell lines and hPEC differ and siRNA based knock-down experiments indicate changed Orai3 levels are underlying the altered pharmacological profile. The cancer-specific composition and pharmacology of CRAC channels identifies CRAC channels as putative targets in prostate cancer therapy. PMID:24240085