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Sample records for 3d prostate cancer

  1. Factors Essential for Prostate Cancer Metastasis Revealed Through a Novel 3D Microtissue Assay

    DTIC Science & Technology

    2016-06-01

    AWARD NUMBER: W81XWH-15-1-0058 TITLE: Factors Essential for Prostate Cancer Metastasis Revealed Through a Novel 3D Microtissue Assay PRINCIPAL...6 1 Introduction In the United States, prostate cancer is the most frequently diagnosed cancer in men and the second leading...cause of cancer -related death. Skeletal metastasis is a highly common route of prostate cancer dissemination that greatly diminishes the chance of cure

  2. In vivo biomarker expression patterns are preserved in 3D cultures of Prostate Cancer

    SciTech Connect

    Windus, Louisa C.E.; Kiss, Debra L.; Glover, Tristan; Avery, Vicky M.

    2012-11-15

    Here we report that Prostate Cancer (PCa) cell-lines DU145, PC3, LNCaP and RWPE-1 grown in 3D matrices in contrast to conventional 2D monolayers, display distinct differences in cell morphology, proliferation and expression of important biomarker proteins associated with cancer progression. Consistent with in vivo growth rates, in 3D cultures, all PCa cell-lines were found to proliferate at significantly lower rates in comparison to their 2D counterparts. Moreover, when grown in a 3D matrix, metastatic PC3 cell-lines were found to mimic more precisely protein expression patterns of metastatic tumour formation as found in vivo. In comparison to the prostate epithelial cell-line RWPE-1, metastatic PC3 cell-lines exhibited a down-regulation of E-cadherin and {alpha}6 integrin expression and an up-regulation of N-cadherin, Vimentin and {beta}1 integrin expression and re-expressed non-transcriptionally active AR. In comparison to the non-invasive LNCaP cell-lines, PC3 cells were found to have an up-regulation of chemokine receptor CXCR4, consistent with a metastatic phenotype. In 2D cultures, there was little distinction in protein expression between metastatic, non-invasive and epithelial cells. These results suggest that 3D cultures are more representative of in vivo morphology and may serve as a more biologically relevant model in the drug discovery pipeline. -- Highlights: Black-Right-Pointing-Pointer We developed and optimised 3D culturing techniques for Prostate Cancer cell-lines. Black-Right-Pointing-Pointer We investigated biomarker expression in 2D versus 3D culture techniques. Black-Right-Pointing-Pointer Metastatic PC3 cells re-expressed non-transcriptionally active androgen receptor. Black-Right-Pointing-Pointer Metastatic PCa cell lines retain in vivo-like antigenic profiles in 3D cultures.

  3. Guided Interventions for Prostate Cancer Using 3D-Transurethral Ultrasound and MRI Fusion

    DTIC Science & Technology

    2015-10-01

    prostate may be visualized at once; improving image registration and reducing motion errors. 3D TUUS imaging has been demonstrated in a phantom setting... registration error 10-21 UCLA Milestone(s) Achieved: Validation of MR-TUUS image registration error with MRI and compared to 3D TRUS 21...TRUS ultrasound images of prostate phantom with 20 deg urethra bend, (left) 2D prostate image, (right) 3D volume of prostate phantom. 6 image

  4. NOTE: Adaptation of a 3D prostate cancer atlas for transrectal ultrasound guided target-specific biopsy

    NASA Astrophysics Data System (ADS)

    Narayanan, R.; Werahera, P. N.; Barqawi, A.; Crawford, E. D.; Shinohara, K.; Simoneau, A. R.; Suri, J. S.

    2008-10-01

    Due to lack of imaging modalities to identify prostate cancer in vivo, current TRUS guided prostate biopsies are taken randomly. Consequently, many important cancers are missed during initial biopsies. The purpose of this study was to determine the potential clinical utility of a high-speed registration algorithm for a 3D prostate cancer atlas. This 3D prostate cancer atlas provides voxel-level likelihood of cancer and optimized biopsy locations on a template space (Zhan et al 2007). The atlas was constructed from 158 expert annotated, 3D reconstructed radical prostatectomy specimens outlined for cancers (Shen et al 2004). For successful clinical implementation, the prostate atlas needs to be registered to each patient's TRUS image with high registration accuracy in a time-efficient manner. This is implemented in a two-step procedure, the segmentation of the prostate gland from a patient's TRUS image followed by the registration of the prostate atlas. We have developed a fast registration algorithm suitable for clinical applications of this prostate cancer atlas. The registration algorithm was implemented on a graphical processing unit (GPU) to meet the critical processing speed requirements for atlas guided biopsy. A color overlay of the atlas superposed on the TRUS image was presented to help pick statistically likely regions known to harbor cancer. We validated our fast registration algorithm using computer simulations of two optimized 7- and 12-core biopsy protocols to maximize the overall detection rate. Using a GPU, patient's TRUS image segmentation and atlas registration took less than 12 s. The prostate cancer atlas guided 7- and 12-core biopsy protocols had cancer detection rates of 84.81% and 89.87% respectively when validated on the same set of data. Whereas the sextant biopsy approach without the utility of 3D cancer atlas detected only 70.5% of the cancers using the same histology data. We estimate 10-20% increase in prostate cancer detection rates

  5. Personalized Medicine Approaches in Prostate Cancer Employing Patient Derived 3D Organoids and Humanized Mice

    PubMed Central

    Bartucci, Monica; Ferrari, Anna C.; Kim, Isaac Yi; Ploss, Alexander; Yarmush, Martin; Sabaawy, Hatem E.

    2016-01-01

    Prostate cancer (PCa) is the most common malignancy and the second most common cause of cancer death in Western men. Despite its prevalence, PCa has proven very difficult to propagate in vitro. PCa represents a complex organ-like multicellular structure maintained by the dynamic interaction of tumoral cells with parenchymal stroma, endothelial and immune cells, and components of the extracellular matrix (ECM). The lack of PCa models that recapitulate this intricate system has hampered progress toward understanding disease progression and lackluster therapeutic responses. Tissue slices, monolayer cultures and genetically engineered mouse models (GEMM) fail to mimic the complexities of the PCa microenvironment or reproduce the diverse mechanisms of therapy resistance. Moreover, patient derived xenografts (PDXs) are expensive, time consuming, difficult to establish for prostate cancer, lack immune cell-tumor regulation, and often tumors undergo selective engraftments. Here, we describe an interdisciplinary approach using primary PCa and tumor initiating cells (TICs), three-dimensional (3D) tissue engineering, genetic and morphometric profiling, and humanized mice to generate patient-derived organoids for examining personalized therapeutic responses in vitro and in mice co-engrafted with a human immune system (HIS), employing adaptive T-cell- and chimeric antigen receptor- (CAR) immunotherapy. The development of patient specific therapies targeting the vulnerabilities of cancer, when combined with antiproliferative and immunotherapy approaches could help to achieve the full transformative power of cancer precision medicine. PMID:27446916

  6. Silk scaffolds connected with different naturally occurring biomaterials for prostate cancer cell cultivation in 3D.

    PubMed

    Bäcker, Anne; Erhardt, Olga; Wietbrock, Lukas; Schel, Natalia; Göppert, Bettina; Dirschka, Marian; Abaffy, Paul; Sollich, Thomas; Cecilia, Angelica; Gruhl, Friederike J

    2017-02-01

    In the present work, different biopolymer blend scaffolds based on the silk protein fibroin from Bombyx mori (BM) were prepared via freeze-drying method. The chemical, structural, and mechanical properties of the three dimensional (3D) porous silk fibroin (SF) composite scaffolds of gelatin, collagen, and chitosan as well as SF from Antheraea pernyi (AP) and the recombinant spider silk protein spidroin (SSP1) have been systematically investigated, followed by cell culture experiments with epithelial prostate cancer cells (LNCaP) up to 14 days. Compared to the pure SF scaffold of BM, the blend scaffolds differ in porous morphology, elasticity, swelling behavior, and biochemical composition. The new composite scaffold with SSP1 showed an increased swelling degree and soft tissue like elastic properties. Whereas, in vitro cultivation of LNCaP cells demonstrated an increased growth behavior and spheroid formation within chitosan blended scaffolds based on its remarkable porosity, which supports nutrient supply matrix. Results of this study suggest that silk fibroin matrices are sufficient and certain SF composite scaffolds even improve 3D cell cultivation for prostate cancer research compared to matrices based on pure biomaterials or synthetic polymers.

  7. Clinical Outcome of Patients Treated With 3D Conformal Radiation Therapy (3D-CRT) for Prostate Cancer on RTOG 9406

    SciTech Connect

    Michalski, Jeff; Winter, Kathryn; Roach, Mack; Markoe, Arnold; Sandler, Howard M.; Ryu, Janice; Parliament, Matthew; Purdy, James A.; Valicenti, Richard K.; Cox, James D.

    2012-07-01

    Purpose: Report of clinical cancer control outcomes on Radiation Therapy Oncology Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose escalation trial for localized adenocarcinoma of the prostate. Methods and Materials: RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer. Patients were registered on five sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8 Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society for Therapeutic Radiation Oncology (ASTRO), and Phoenix biochemical failure definitions are reported. Results: Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable. Median follow-up for levels I, II, III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty-six percent of patients received NHT. The 5-year overall survival was 90%, 87%, 88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease-free survival (excluding protocol prostate-specific antigen definition) for levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the 5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%, 52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease-free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%, and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for levels I-V, respectively. Conclusion: Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer. This multi-institutional experience allows comparison to other experiences with modern radiation therapy.

  8. Probing the invasiveness of prostate cancer cells in a 3D microfabricated landscape

    PubMed Central

    Liu, Liyu; Sun, Bo; Pedersen, Jonas N.; Aw Yong, Koh-Meng; Getzenberg, Robert H.; Stone, Howard A.; Austin, Robert H.

    2011-01-01

    The metastatic invasion of cancer cells from primary tumors to distant ecological niches, rather than the primary tumors, is the cause of much cancer mortality [Zhang QB, et al. (2010) Int J Cancer 126:2534–2541; Chambers AF, Goss PE (2008) Breast Cancer Res 10:114]. Metastasis is a three-dimensional invasion process where cells spread from their site of origin and colonize distant microenvironmental niches. It is critical to be able to assess quantitatively the metastatic potential of cancer cells [Harma V, et al. (2010) PLoS ONE 5:e10431]. We have constructed a microfabricated chip with a three-dimensional topology consisting of lowlands and isolated square highlands (Tepuis), which stand hundreds of microns above the lowlands, in order to assess cancer cell metastatic potential as they invade the highlands. As a test case, the invasive ascents of the Tepui by highly metastatic PC-3 and noninvasive LNCaP prostate cancer cells were used. The vertical ascent by prostate cancer cells from the lowlands to the tops of the Tepui was imaged using confocal microscopy and used as a measure of the relative invasiveness. The less-metastatic cells (LNCaP) never populated all available tops, leaving about 15% of them unoccupied, whereas the more metastatic PC-3 cells occupied all available Tepuis. We argue that this distinct difference in invasiveness is due to contact inhibition. PMID:21474778

  9. 3D Cultures of prostate cancer cells cultured in a novel high-throughput culture platform are more resistant to chemotherapeutics compared to cells cultured in monolayer.

    PubMed

    Chambers, Karen F; Mosaad, Eman M O; Russell, Pamela J; Clements, Judith A; Doran, Michael R

    2014-01-01

    Despite monolayer cultures being widely used for cancer drug development and testing, 2D cultures tend to be hypersensitive to chemotherapy and are relatively poor predictors of whether a drug will provide clinical benefit. Whilst generally more complicated, three dimensional (3D) culture systems often better recapitulate true cancer architecture and provide a more accurate drug response. As a step towards making 3D cancer cultures more accessible, we have developed a microwell platform and surface modification protocol to enable high throughput manufacture of 3D cancer aggregates. Herein we use this novel system to characterize prostate cancer cell microaggregates, including growth kinetics and drug sensitivity. Our results indicate that prostate cancer cells are viable in this system, however some non-cancerous prostate cell lines are not. This system allows us to consistently control for the presence or absence of an apoptotic core in the 3D cancer microaggregates. Similar to tumor tissues, the 3D microaggregates display poor polarity. Critically the response of 3D microaggregates to the chemotherapeutic drug, docetaxel, is more consistent with in vivo results than the equivalent 2D controls. Cumulatively, our results demonstrate that these prostate cancer microaggregates better recapitulate the morphology of prostate tumors compared to 2D and can be used for high-throughput drug testing.

  10. Accuracy of volume measurement using 3D ultrasound and development of CT-3D US image fusion algorithm for prostate cancer radiotherapy

    SciTech Connect

    Baek, Jihye; Huh, Jangyoung; Hyun An, So; Oh, Yoonjin; Kim, Myungsoo; Kim, DongYoung; Chung, Kwangzoo; Cho, Sungho; Lee, Rena

    2013-02-15

    Purpose: To evaluate the accuracy of measuring volumes using three-dimensional ultrasound (3D US), and to verify the feasibility of the replacement of CT-MR fusion images with CT-3D US in radiotherapy treatment planning. Methods: Phantoms, consisting of water, contrast agent, and agarose, were manufactured. The volume was measured using 3D US, CT, and MR devices. A CT-3D US and MR-3D US image fusion software was developed using the Insight Toolkit library in order to acquire three-dimensional fusion images. The quality of the image fusion was evaluated using metric value and fusion images. Results: Volume measurement, using 3D US, shows a 2.8 {+-} 1.5% error, 4.4 {+-} 3.0% error for CT, and 3.1 {+-} 2.0% error for MR. The results imply that volume measurement using the 3D US devices has a similar accuracy level to that of CT and MR. Three-dimensional image fusion of CT-3D US and MR-3D US was successfully performed using phantom images. Moreover, MR-3D US image fusion was performed using human bladder images. Conclusions: 3D US could be used in the volume measurement of human bladders and prostates. CT-3D US image fusion could be used in monitoring the target position in each fraction of external beam radiation therapy. Moreover, the feasibility of replacing the CT-MR image fusion to the CT-3D US in radiotherapy treatment planning was verified.

  11. New 3D-Culture Approaches to Study Interactions of Bone Marrow Adipocytes with Metastatic Prostate Cancer Cells.

    PubMed

    Herroon, Mackenzie Katheryn; Diedrich, Jonathan Driscoll; Podgorski, Izabela

    2016-01-01

    Adipocytes are a major component of the bone marrow that can critically affect metastatic progression in bone. Understanding how the marrow fat cells influence growth, behavior, and survival of tumor cells requires utilization of in vitro cell systems that can closely mimic the physiological microenvironment. Herein, we present two new three-dimensional (3D) culture approaches to study adipocyte-tumor cell interactions in vitro. The first is a transwell-based system composed of the marrow-derived adipocytes in 3D collagen I gels and reconstituted basement membrane-overlayed prostate tumor cell spheroids. Tumor cells cultured under these 3D conditions are continuously exposed to adipocyte-derived factors, and their response can be evaluated by morphological and immunohistochemical analyses. We show via immunofluorescence analysis of metabolism-associated proteins that under 3D conditions tumor cells have significantly different metabolic response to adipocytes than tumor cells grown in 2D culture. We also demonstrate that this model allows for incorporation of other cell types, such as bone marrow macrophages, and utilization of dye-quenched collagen substrates for examination of proteolysis-driven responses to adipocyte- and macrophage-derived factors. Our second 3D culture system is designed to study tumor cell invasion toward the adipocytes and the consequent interaction between the two cell types. In this model, marrow adipocytes are separated from the fluorescently labeled tumor cells by a layer of collagen I. At designated time points, adipocytes are stained with BODIPY and confocal z-stacks are taken through the depth of the entire culture to determine the distance traveled between the two cell types over time. We demonstrate that this system can be utilized to study effects of candidate factors on tumor invasion toward the adipocytes. We also show that immunohistochemical analyses can be performed to evaluate the impact of direct interaction of prostate

  12. Measuring the effects of fractionated radiation therapy in a 3D prostate cancer model system using SERS nanosensors.

    PubMed

    Camus, Victoria L; Stewart, Grant; Nailon, William H; McLaren, Duncan B; Campbell, Colin J

    2016-08-15

    Multicellular tumour spheroids (MTS) are three-dimensional cell cultures that possess their own microenvironments and provide a more meaningful model of tumour biology than monolayer cultures. As a result, MTS are becoming increasingly used as tumor models when measuring the efficiency of therapies. Monitoring the viability of live MTS is complicated by their 3D nature and conventional approaches such as fluorescence often require fixation and sectioning. In this paper we detail the use of Surface Enhanced Raman Spectroscopy (SERS) to measure the viability of MTS grown from prostate cancer (PC3) cells. Our results show that we can monitor loss of viability by measuring pH and redox potential in MTS and furthermore we demonstrate that SERS can be used to measure the effects of fractionation of a dose of radiotherapy in a way that has potential to inform treatment planning.

  13. 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 ...

  14. Enhanced enrichment of prostate cancer stem-like cells with miniaturized 3D culture in liquid core-hydrogel shell microcapsules

    PubMed Central

    Yu, Jianhua; Lu, Xiongbin; Zynger, Debra L.; He, Xiaoming

    2015-01-01

    Cancer stem-like cells (CSCs) are rare subpopulations of cancer cells that are reported to be responsible for cancer resistance and metastasis associated with conventional cancer therapies. Therefore, effective enrichment/culture of CSCs is of importance to both the understanding and treatment of cancer. However, it usually takes approximately 10 days for the widely used conventional approach to enrich CSCs through the formation of CSC-containing aggregates. Here we report the time can be shortened to 2 days while obtaining prostate CSC-containing aggregates with better quality based on the expression of surface receptor markers, dye exclusion, gene and protein expression, and in vivo tumorigenicity. This is achieved by encapsulating and culturing human prostate cancer cells in the miniaturized 3D liquid core of microcapsules with an alginate hydrogel shell. The miniaturized 3D culture in core–shell microcapsules is an effective strategy for enriching/culturing CSCs in vitro to facilitate cancer research and therapy development. PMID:24952981

  15. What is Prostate Cancer?

    MedlinePlus

    ... Research? Prostate Cancer About 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 ...

  16. Optimizing prostate needle biopsy through 3D simulation

    NASA Astrophysics Data System (ADS)

    Zeng, Jianchao; Kaplan, Charles; Xuan, Jian Hua; Sesterhenn, Isabell A.; Lynch, John H.; Freedman, Matthew T.; Mun, Seong K.

    1998-06-01

    Prostate needle biopsy is used for the detection of prostate cancer. The protocol of needle biopsy that is currently routinely used in the clinical environment is the systematic sextant technique, which defines six symmetric locations on the prostate surface for needle insertion. However, this protocol has been developed based on the long-term observation and experience of urologists. Little quantitative or scientific evidence supports the use of this biopsy technique. In this research, we aim at developing a statistically optimized new prostate needle biopsy protocol to improve the quality of diagnosis of prostate cancer. This new protocol will be developed by using a three-dimensional (3-D) computer- based probability map of prostate cancer. For this purpose, we have developed a computer-based 3-D visualization and simulation system with prostate models constructed from the digitized prostate specimens, in which the process of prostate needle biopsy can be simulated automatically by the computer. In this paper, we first develop an interactive biopsy simulation mode in the system, and evaluate the performance of the automatic biopsy simulation with the sextant biopsy protocol by comparing the results by the urologist using the interactive simulation mode with respect to 53 prostate models. This is required to confirm that the automatic simulation is accurate and reliable enough for the simulation with respect to a large number of prostate models. Then we compare the performance of the existing protocols using the automatic biopsy simulation system with respect to 107 prostate models, which will statistically identify if one protocol is better than another. Since the estimation of tumor volume is extremely important in determining the significance of a tumor and in deciding appropriate treatment methods, we further investigate correlation between the tumor volume and the positive core volume with 89 prostate models. This is done in order to develop a method to

  17. Prostate cancer

    SciTech Connect

    Murphy, G.P.; Kuss, R., Khoury, S.; Chatelain, C.; Denis, L.

    1987-01-01

    This book contains over 70 selections. Some of the titles are: Place of the Computed Tomography in the Staging of Prostatic Cancer; Magnetic Resonance Imaging (MRI) in Staging of the Prostatic Cancer; Magnetic Resonance Imaging of the Prostate; Long-Term Results in Radiotherapy of Prostatic Cancer; Interstitial Irradiation Using I-125 Seeds; and Treatment of Cancer of the Prostate by Use of Physiotherapy: Long-Term Results.

  18. A 3D in vitro model of patient-derived prostate cancer xenograft for controlled interrogation of in vivo tumor-stromal interactions.

    PubMed

    Fong, Eliza L S; Wan, Xinhai; Yang, Jun; Morgado, Micaela; Mikos, Antonios G; Harrington, Daniel A; Navone, Nora M; Farach-Carson, Mary C

    2016-01-01

    Patient-derived xenograft (PDX) models better represent human cancer than traditional cell lines. However, the complex in vivo environment makes it challenging to employ PDX models to investigate tumor-stromal interactions, such as those that mediate prostate cancer (PCa) bone metastasis. Thus, we engineered a defined three-dimensional (3D) hydrogel system capable of supporting the co-culture of PCa PDX cells and osteoblastic cells to recapitulate the PCa-osteoblast unit within the bone metastatic microenvironment in vitro. Our 3D model not only maintained cell viability but also preserved the typical osteogenic phenotype of PCa PDX cells. Additionally, co-culture cellularity was maintained over that of either cell type cultured alone, suggesting that the PCa-osteoblast cross-talk supports PCa progression in bone, as is hypothesized to occur in patients with prostatic bone metastasis. Strikingly, osteoblastic cells co-cultured with PCa PDX tumoroids organized around the tumoroids, closely mimicking the architecture of PCa metastases in bone. Finally, tumor-stromal signaling mediated by the fibroblast growth factor axis tightly paralleled that in the in vivo counterpart. Together, these findings indicate that this 3D PCa PDX model recapitulates important pathological properties of PCa bone metastasis, and validate the use of this model for controlled and systematic interrogation of complex in vivo tumor-stromal interactions.

  19. Needle segmentation using 3D Hough transform in 3D TRUS guided prostate transperineal therapy

    SciTech Connect

    Qiu Wu; Yuchi Ming; Ding Mingyue; Tessier, David; Fenster, Aaron

    2013-04-15

    Purpose: Prostate adenocarcinoma is the most common noncutaneous malignancy in American men with over 200 000 new cases diagnosed each year. Prostate interventional therapy, such as cryotherapy and brachytherapy, is an effective treatment for prostate cancer. Its success relies on the correct needle implant position. This paper proposes a robust and efficient needle segmentation method, which acts as an aid to localize the needle in three-dimensional (3D) transrectal ultrasound (TRUS) guided prostate therapy. Methods: The procedure of locating the needle in a 3D TRUS image is a three-step process. First, the original 3D ultrasound image containing a needle is cropped; the cropped image is then converted to a binary format based on its histogram. Second, a 3D Hough transform based needle segmentation method is applied to the 3D binary image in order to locate the needle axis. The position of the needle endpoint is finally determined by an optimal threshold based analysis of the intensity probability distribution. The overall efficiency is improved through implementing a coarse-fine searching strategy. The proposed method was validated in tissue-mimicking agar phantoms, chicken breast phantoms, and 3D TRUS patient images from prostate brachytherapy and cryotherapy procedures by comparison to the manual segmentation. The robustness of the proposed approach was tested by means of varying parameters such as needle insertion angle, needle insertion length, binarization threshold level, and cropping size. Results: The validation results indicate that the proposed Hough transform based method is accurate and robust, with an achieved endpoint localization accuracy of 0.5 mm for agar phantom images, 0.7 mm for chicken breast phantom images, and 1 mm for in vivo patient cryotherapy and brachytherapy images. The mean execution time of needle segmentation algorithm was 2 s for a 3D TRUS image with size of 264 Multiplication-Sign 376 Multiplication-Sign 630 voxels. Conclusions

  20. A comparison of needle tip localization accuracy using 2D and 3D trans-rectal ultrasound for high-dose-rate prostate cancer brachytherapy treatment planning

    NASA Astrophysics Data System (ADS)

    Hrinivich, W. Thomas; Hoover, Douglas A.; Surry, Kathleen; Edirisinghe, Chandima; Montreuil, Jacques; D'Souza, David; Fenster, Aaron; Wong, Eugene

    2016-03-01

    Background: High-dose-rate brachytherapy (HDR-BT) is a prostate cancer treatment option involving the insertion of hollow needles into the gland through the perineum to deliver a radioactive source. Conventional needle imaging involves indexing a trans-rectal ultrasound (TRUS) probe in the superior/inferior (S/I) direction, using the axial transducer to produce an image set for organ segmentation. These images have limited resolution in the needle insertion direction (S/I), so the sagittal transducer is used to identify needle tips, requiring a manual registration with the axial view. This registration introduces a source of uncertainty in the final segmentations and subsequent treatment plan. Our lab has developed a device enabling 3D-TRUS guided insertions with high S/I spatial resolution, eliminating the need to align axial and sagittal views. Purpose: To compare HDR-BT needle tip localization accuracy between 2D and 3D-TRUS. Methods: 5 prostate cancer patients underwent conventional 2D TRUS guided HDR-BT, during which 3D images were also acquired for post-operative registration and segmentation. Needle end-length measurements were taken, providing a gold standard for insertion depths. Results: 73 needles were analyzed from all 5 patients. Needle tip position differences between imaging techniques was found to be largest in the S/I direction with mean+/-SD of -2.5+/-4.0 mm. End-length measurements indicated that 3D TRUS provided statistically significantly lower mean+/-SD insertion depth error of -0.2+/-3.4 mm versus 2.3+/-3.7 mm with 2D guidance (p < .001). Conclusions: 3D TRUS may provide more accurate HDR-BT needle localization than conventional 2D TRUS guidance for the majority of HDR-BT needles.

  1. Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins.

    PubMed

    Edmondson, Rasheena; Adcock, Audrey F; Yang, Liju

    2016-01-01

    This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells. The cellular responses upon treatment with two common anti-cancer drugs, Docetaxel and Rapamycin, were examined. The expressions of epidermal growth factor receptor (EGFR) and β-III tubulin in DU145 cells and p53 in LNCaP cells were examined. The results showed that the proliferation rates of cells cultured on the three matrices varied, especially between the synthetic matrix and the biologically-derived matrices. The drug responses and the expressions of drug sensitivity-associated proteins differed between cells on various matrices as well. Among the 3D cultures on the three matrices, increased expression of β-III tubulin in DU145 cells was correlated with increased resistance to Docetaxel, and decreased expression of EGFR in DU145 cells was correlated with increased sensitivity to Rapamycin. Increased expression of a p53 dimer in 3D-cultured LNCaP cells was correlated with increased resistance to Docetaxel. Collectively, the results showed that the matrix of 3D cell culture models strongly influences cellular behaviors, which highlights the imperative need to achieve standardization of 3D cell culture technology in order to be used in drug screening and cell biology studies.

  2. Influence of Matrices on 3D-Cultured Prostate Cancer Cells' Drug Response and Expression of Drug-Action Associated Proteins

    PubMed Central

    Edmondson, Rasheena; Adcock, Audrey F.; Yang, Liju

    2016-01-01

    This study investigated the effects of matrix on the behaviors of 3D-cultured cells of two prostate cancer cell lines, LNCaP and DU145. Two biologically-derived matrices, Matrigel and Cultrex BME, and one synthetic matrix, the Alvetex scaffold, were used to culture the cells. The cell proliferation rate, cellular response to anti-cancer drugs, and expression levels of proteins associated with drug sensitivity/resistance were examined and compared amongst the 3D-cultured cells on the three matrices and 2D-cultured cells. The cellular responses upon treatment with two common anti-cancer drugs, Docetaxel and Rapamycin, were examined. The expressions of epidermal growth factor receptor (EGFR) and β-III tubulin in DU145 cells and p53 in LNCaP cells were examined. The results showed that the proliferation rates of cells cultured on the three matrices varied, especially between the synthetic matrix and the biologically-derived matrices. The drug responses and the expressions of drug sensitivity-associated proteins differed between cells on various matrices as well. Among the 3D cultures on the three matrices, increased expression of β-III tubulin in DU145 cells was correlated with increased resistance to Docetaxel, and decreased expression of EGFR in DU145 cells was correlated with increased sensitivity to Rapamycin. Increased expression of a p53 dimer in 3D-cultured LNCaP cells was correlated with increased resistance to Docetaxel. Collectively, the results showed that the matrix of 3D cell culture models strongly influences cellular behaviors, which highlights the imperative need to achieve standardization of 3D cell culture technology in order to be used in drug screening and cell biology studies. PMID:27352049

  3. 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 ...

  4. Jacaric acid and its octadecatrienoic acid geoisomers induce apoptosis selectively in cancerous human prostate cells: a mechanistic and 3-D structure-activity study.

    PubMed

    Gasmi, Jihane; Thomas Sanderson, J

    2013-06-15

    Plant-derived non-essential fatty acids are important dietary nutrients, and some are purported to have chemopreventive properties against various cancers, including that of the prostate. In this study, we determined the ability of seven dietary C-18 fatty acids to cause cytotoxicity and induce apoptosis in various types of human prostate cancer cells. These fatty acids included jacaric and punicic acid found in jacaranda and pomegranate seed oil, respectively, three octadecatrienoic geometric isomers (alpha- and beta-calendic and catalpic acid) and two mono-unsaturated C-18 fatty acids (trans- and cis-vaccenic acid). Jacaric acid and four of its octadecatrienoic geoisomers selectively induced apoptosis in hormone-dependent (LNCaP) and -independent (PC-3) human prostate cancer cells, whilst not affecting the viability of normal human prostate epithelial cells (RWPE-1). Jacaric acid induced concentration- and time-depedent LNCaP cell death through activation of intrinsic and extrinsic apoptotic pathways resulting in cleavage of PARP-1, modulation of pro- and antiapoptotic Bcl-2 family of proteins and increased cleavage of caspase-3, -8 and -9. Moreover, activation of a cell death-inducing signalling cascade involving death receptor 5 was observed. Jacaric acid induced apoptosis in PC-3 cells by activation of the intrinsic pathway only. The spatial conformation cis, trans, cis of jacaric and punicic acid was shown to play a key role in the increased potency and efficacy of these two fatty acids in comparison to the five other C-18 fatty acids tested. Three-dimensional conformational analysis using the PubChem Database (http://pubchem.ncbi.nlm.nih.gov) showed that the cytotoxic potency of the C-18 fatty acids was related to their degree of conformational similarity to our cytotoxic reference compound, punicic acid, based on optimized shape (ST) and feature (CT) similarity scores, with jacaric acid being most 'biosimilar' (ST(ST-opt)=0.81; CT(CT-opt)=0.45). This 3-D

  5. Identifying Clinically Significant Prostate Cancers using 3-D In Vivo Acoustic Radiation Force Impulse Imaging with Whole-Mount Histology Validation.

    PubMed

    Palmeri, Mark L; Glass, Tyler J; Miller, Zachary A; Rosenzweig, Stephen J; Buck, Andrew; Polascik, Thomas J; Gupta, Rajan T; Brown, Alison F; Madden, John; Nightingale, Kathryn R

    2016-06-01

    Overly aggressive prostate cancer (PCa) treatment adversely affects patients and places an unnecessary burden on our health care system. The inability to identify and grade clinically significant PCa lesions is a factor contributing to excessively aggressive PCa treatment, such as radical prostatectomy, instead of more focal, prostate-sparing procedures such as cryotherapy and high-dose radiation therapy. We have performed 3-D in vivo B-mode and acoustic radiation force impulse (ARFI) imaging using a mechanically rotated, side-fire endorectal imaging array to identify regions suspicious for PCa in 29 patients being treated with radical prostatectomies for biopsy-confirmed PCa. Whole-mount histopathology analyses were performed to identify regions of clinically significant/insignificant PCa lesions, atrophy and benign prostatic hyperplasia. Regions of suspicion for PCa were reader-identified in ARFI images based on boundary delineation, contrast, texture and location. These regions of suspicion were compared with histopathology identified lesions using a nearest-neighbor regional localization approach. Of all clinically significant lesions identified on histopathology, 71.4% were also identified using ARFI imaging, including 79.3% of posterior and 33.3% of anterior lesions. Among the ARFI-identified lesions, 79.3% corresponded to clinically significant PCa lesions, with these lesions having higher indices of suspicion than clinically insignificant PCa. ARFI imaging had greater sensitivity for posterior versus anterior lesions because of greater displacement signal-to-noise ratio and finer spatial sampling. Atrophy and benign prostatic hyperplasia can cause appreciable prostate anatomy distortion and heterogeneity that confounds ARFI PCa lesion identification; however, in general, ARFI regions of suspicion did not coincide with these benign pathologies.

  6. Imaging of prostate cancer: a platform for 3D co-registration of in-vivo MRI ex-vivo MRI and pathology

    NASA Astrophysics Data System (ADS)

    Orczyk, Clément; Mikheev, Artem; Rosenkrantz, Andrew; Melamed, Jonathan; Taneja, Samir S.; Rusinek, Henry

    2012-02-01

    Objectives: Multi-parametric MRI is emerging as a promising method for prostate cancer diagnosis. prognosis and treatment planning. However, the localization of in-vivo detected lesions and pathologic sites of cancer remains a significant challenge. To overcome this limitation we have developed and tested a system for co-registration of in-vivo MRI, ex-vivo MRI and histology. Materials and Methods: Three men diagnosed with localized prostate cancer (ages 54-72, PSA levels 5.1-7.7 ng/ml) were prospectively enrolled in this study. All patients underwent 3T multi-parametric MRI that included T2W, DCEMRI, and DWI prior to robotic-assisted prostatectomy. Ex-vivo multi-parametric MRI was performed on fresh prostate specimen. Excised prostates were then sliced at regular intervals and photographed both before and after fixation. Slices were perpendicular to the main axis of the posterior capsule, i.e., along the direction of the rectal wall. Guided by the location of the urethra, 2D digital images were assembled into 3D models. Cancer foci, extra-capsular extensions and zonal margins were delineated by the pathologist and included in 3D histology data. A locally-developed software was applied to register in-vivo, ex-vivo and histology using an over-determined set of anatomical landmarks placed in anterior fibro-muscular stroma, central. transition and peripheral zones. The mean root square distance across corresponding control points was used to assess co-registration error. Results: Two specimens were pT3a and one pT2b (negative margin) at pathology. The software successfully fused invivo MRI. ex-vivo MRI fresh specimen and histology using appropriate (rigid and affine) transformation models with mean square error of 1.59 mm. Coregistration accuracy was confirmed by multi-modality viewing using operator-guided variable transparency. Conclusion: The method enables successful co-registration of pre-operative MRI, ex-vivo MRI and pathology and it provides initial evidence

  7. Development of a Set of Nomograms to Predict Acute Lower Gastrointestinal Toxicity for Prostate Cancer 3D-CRT

    SciTech Connect

    Valdagni, Riccardo; Rancati, Tiziana Fiorino, Claudio; Fellin, Gianni; Magli, Alessandro; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Greco, Carlo; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Vavassori, Vittorio

    2008-07-15

    Purpose: To predict acute Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) and Subjective Objective Signs Management and Analysis/Late Effect of Normal Tissue (SOMA/LENT) toxicities of the lower gastrointestinal (LGI) syndrome in patients with prostate cancer undergoing three-dimensional conformal radiotherapy using a tool (nomogram) that takes into account clinical and dosimetric variables that proved to be significant in the Italian Association for Radiation Oncology (AIRO) Group on Prostate Cancer (AIROPROS) 0102 trial. Methods and Materials: Acute rectal toxicity was scored in 1,132 patients by using both the RTOG/EORTC scoring system and a 10-item self-assessed questionnaire. Correlation between clinical variables/dose-volume histogram constraints and rectal toxicity was investigated by means of multivariate logistic analyses. Multivariate logistic analyses results were used to create nomograms predicting the symptoms of acute LGI syndrome. Results: Mean rectal dose was a strong predictor of Grade 2-3 RTOG/EORTC acute LGI toxicity (p 0.0004; odds ratio (OR) = 1.035), together with hemorrhoids (p = 0.02; OR 1.51), use of anticoagulants/antiaggregants (p = 0.02; OR = 0.63), and androgen deprivation (AD) (p = 0.04; OR = 0.65). Diabetes (p = 0.34; OR 1.28) and pelvic node irradiation (p = 0.11; OR = 1.56) were significant variables to adjust toxicity prediction. Bleeding was related to hemorrhoids (p = 0.02; OR = 173), AD (p = 0.17; OR = 0.67), and mean rectal dose (p 0.009; OR = 1.024). Stool frequency was related to seminal vesicle irradiation (p = 0.07; OR = 6.46), AD administered for more than 3 months (p = 0.002; OR = 0.32), and the percent volume of rectum receiving more than 60 Gy (V60Gy) V60 (p = 0.02; OR = 1.02). Severe fecal incontinence depended on seminal vesicle irradiation (p = 0.14; OR = 4.5) and V70 (p = 0.033; OR 1.029). Conclusions: To the best of our knowledge, this work presents the

  8. Results and DVH analysis of late rectal bleeding in patients treated with 3D-CRT or IMRT for localized prostate cancer

    PubMed Central

    Someya, Masanori; Hori, Masakazu; Tateoka, Kunihiko; Nakata, Kensei; Takagi, Masaru; Saito, Masato; Hirokawa, Naoki; Hareyama, Masato; Sakata, Koh-ichi

    2015-01-01

    In patients undergoing radiotherapy for localized prostate cancer, dose–volume histograms and clinical variables were examined to search for correlations between radiation treatment planning parameters and late rectal bleeding. We analyzed 129 patients with localized prostate cancer who were managed from 2002 to 2010 at our institution. They were treated with 3D conformal radiation therapy (3D-CRT, 70 Gy/35 fractions, 55 patients) or intensity-modulated radiation therapy (IMRT, 76 Gy/38 fractions, 74 patients). All radiation treatment plans were retrospectively reconstructed, dose–volume histograms of the rectum were generated, and the doses delivered to the rectum were calculated. Time to rectal bleeding ranged from 9–53 months, with a median of 18.7 months. Of the 129 patients, 33 patients had Grade 1 bleeding and were treated with steroid suppositories, while 25 patients with Grade 2 bleeding received argon plasma laser coagulation therapy (APC). Three patients with Grade 3 bleeding required both APC and blood transfusion. The 5-year incidence rate of Grade 2 or 3 rectal bleeding was 21.8% for the 3D-CRT group and 21.6% for the IMRT group. Univariate analysis showed significant differences in the average values from V65 to V10 between Grades 0–1 and Grades 2–3. Multivariate analysis demonstrated that patients with V65 ≥ 17% had a significantly increased risk (P = 0.032) of Grade 2 or 3 rectal bleeding. Of the 28 patients of Grade 2 or 3 rectal bleeding, 17 patients (60.7%) were cured by a single session of APC, while the other 11 patients required two sessions. Thus, none of the patients had any further rectal bleeding after the second APC session. PMID:25212601

  9. Magnetic resonance imaging-targeted, 3D transrectal ultrasound-guided fusion biopsy for prostate cancer: Quantifying the impact of needle delivery error on diagnosis

    SciTech Connect

    Martin, Peter R.; Cool, Derek W.; Romagnoli, Cesare; Fenster, Aaron; Ward, Aaron D.

    2014-07-15

    tumor was consistently greater when using spherical tumor shapes as opposed to no shape assumption. However, an assumption of spherical tumor shape for RMSE = 3.5 mm led to a mean overestimation of tumor sampling probabilities of 3%, implying that assuming spherical tumor shape may be reasonable for many prostate tumors. The authors also determined that a biopsy system would need to have a RMS needle delivery error of no more than 1.6 mm in order to sample 95% of tumors with one core. The authors’ experiments also indicated that the effect of axial-direction error on the measured tumor burden was mitigated by the 18 mm core length at 3.5 mm RMSE. Conclusions: For biopsy systems with RMSE ≥ 3.5 mm, more than one biopsy core must be taken from the majority of tumors to achieveP ≥ 95%. These observations support the authors’ perspective that some tumors of clinically significant sizes may require more than one biopsy attempt in order to be sampled during the first biopsy session. This motivates the authors’ ongoing development of an approach to optimize biopsy plans with the aim of achieving a desired probability of obtaining a sample from each tumor, while minimizing the number of biopsies. Optimized planning of within-tumor targets for MRI-3D TRUS fusion biopsy could support earlier diagnosis of prostate cancer while it remains localized to the gland and curable.

  10. PCaAnalyser: A 2D-Image Analysis Based Module for Effective Determination of Prostate Cancer Progression in 3D Culture

    PubMed Central

    Lovitt, Carrie J.; Avery, Vicky M.

    2013-01-01

    Three-dimensional (3D) in vitro cell based assays for Prostate Cancer (PCa) research are rapidly becoming the preferred alternative to that of conventional 2D monolayer cultures. 3D assays more precisely mimic the microenvironment found in vivo, and thus are ideally suited to evaluate compounds and their suitability for progression in the drug discovery pipeline. To achieve the desired high throughput needed for most screening programs, automated quantification of 3D cultures is required. Towards this end, this paper reports on the development of a prototype analysis module for an automated high-content-analysis (HCA) system, which allows for accurate and fast investigation of in vitro 3D cell culture models for PCa. The Java based program, which we have named PCaAnalyser, uses novel algorithms that allow accurate and rapid quantitation of protein expression in 3D cell culture. As currently configured, the PCaAnalyser can quantify a range of biological parameters including: nuclei-count, nuclei-spheroid membership prediction, various function based classification of peripheral and non-peripheral areas to measure expression of biomarkers and protein constituents known to be associated with PCa progression, as well as defining segregate cellular-objects effectively for a range of signal-to-noise ratios. In addition, PCaAnalyser architecture is highly flexible, operating as a single independent analysis, as well as in batch mode; essential for High-Throughput-Screening (HTS). Utilising the PCaAnalyser, accurate and rapid analysis in an automated high throughput manner is provided, and reproducible analysis of the distribution and intensity of well-established markers associated with PCa progression in a range of metastatic PCa cell-lines (DU145 and PC3) in a 3D model demonstrated. PMID:24278197

  11. Validation of 3D ultrasound: CT registration of prostate images

    NASA Astrophysics Data System (ADS)

    Firle, Evelyn A.; Wesarg, Stefan; Karangelis, Grigoris; Dold, Christian

    2003-05-01

    All over the world 20% of men are expected to develop prostate cancer sometime in his life. In addition to surgery - being the traditional treatment for cancer - the radiation treatment is getting more popular. The most interesting radiation treatment regarding prostate cancer is Brachytherapy radiation procedure. For the safe delivery of that therapy imaging is critically important. In several cases where a CT device is available a combination of the information provided by CT and 3D Ultrasound (U/S) images offers advantages in recognizing the borders of the lesion and delineating the region of treatment. For these applications the CT and U/S scans should be registered and fused in a multi-modal dataset. Purpose of the present development is a registration tool (registration, fusion and validation) for available CT volumes with 3D U/S images of the same anatomical region, i.e. the prostate. The combination of these two imaging modalities interlinks the advantages of the high-resolution CT imaging and low cost real-time U/S imaging and offers a multi-modality imaging environment for further target and anatomy delineation. This tool has been integrated into the visualization software "InViVo" which has been developed over several years in Fraunhofer IGD in Darmstadt.

  12. Hyaluronan (HA) Interacting Proteins RHAMM and Hyaluronidase Impact Prostate Cancer Cell Behavior and Invadopodia Formation in 3D HA-Based Hydrogels

    PubMed Central

    Gurski, Lisa A.; Nguyen, Ngoc T.; Xiao, Longxi; van Golen, Kenneth L.; Jia, Xinqiao; Farach-Carson, Mary C.

    2012-01-01

    To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, “invadopodia”, consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of

  13. Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model

    NASA Astrophysics Data System (ADS)

    Tomatis, S.; Rancati, T.; Fiorino, C.; Vavassori, V.; Fellin, G.; Cagna, E.; Mauro, F. A.; Girelli, G.; Monti, A.; Baccolini, M.; Naldi, G.; Bianchi, C.; Menegotti, L.; Pasquino, M.; Stasi, M.; Valdagni, R.

    2012-03-01

    The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with

  14. Prostate cancer xenografts engineered from 3D precision-porous poly(2-hydroxyethyl methacrylate) hydrogels as models for tumorigenesis and dormancy escape

    PubMed Central

    Long, Thomas J.; Sprenger, Cynthia C.; Plymate, Stephen R.; Ratner, Buddy D.

    2014-01-01

    Synthetic biomaterial scaffolds show promise for in vitro and in vivo 3D cancer models. Tumors engineered in biomaterial scaffolds have shown evidence of being more physiologically relevant than some traditional preclinical model systems, and synthetic biomaterials provide the added benefit of defined and consistent microenvironmental control. Here, we examine sphere-templated poly(2-hydroxyethyl methacrylate) (pHEMA) scaffolds as the basis for engineering xenografts from multiple human prostate cancer cell lines. pHEMA scaffolds seeded and pre-cultured with tumorigenic M12 cells prior to implantation generated tumors in athymic nude mice, demonstrating the ability of the scaffolds to be used as a synthetic vehicle for xenograft generation. pHEMA scaffolds seeded with LNCaP C4-2 cells, which require Matrigel or stromal cell support for tumor formation, were poorly tumorigenic up to twelve weeks after implantation even when Matrigel was infused into the scaffold, demonstrating a lack of necessary pro-tumorigenic signaling within the scaffolds. Finally, M12mac25 cells, which are ordinarily rendered non-tumorigenic through the expression of the tumor suppressor insulin-like growth factor binding protein 7 (IGFBP7), displayed a tumorigenic response when implanted within porous pHEMA scaffolds. These M12mac25 tumors showed a significantly higher macrophage infiltration within the scaffolds driven by the foreign body response to the materials. These findings show the potential for this biomaterials-based model system to be used in the study of prostate cancer tumorigenesis and dormancy escape. PMID:24942815

  15. Development of transrectal diffuse optical tomography combined with 3D-transrectal ultrasound imaging to monitor the photocoagulation front during interstitial photothermal therapy of primary focal prostate cancer

    NASA Astrophysics Data System (ADS)

    He, Jie; Weersink, Robert; Veilleux, Israel; Mayo, Kenwrick; Zhang, Anqi; Piao, Daqing; Alam, Adeel; Trachtenberg, John; Wilson, Brian C.

    2013-03-01

    Interstitial near-infrared laser thermal therapy (LITT) is currently undergoing clinical trials as an alternative to watchful waiting or radical surgery in patients with low-risk focal prostate cancer. Currently, we use magnetic resonance image (MRI)-based thermography to monitor treatment delivery and determine indirectly the completeness of the target tissue destruction while avoiding damage to adjacent normal tissues, particularly the rectal wall. However, incomplete tumor destruction has occurred in a significant fraction of patients due to premature termination of treatment, since the photocoagulation zone is not directly observed. Hence, we are developing transrectal diffuse optical tomography (TRDOT), in combination with transrectal 3D ultrasound (3D-TRUS), to address his limitation. This is based on the large changes in optical scattering expected upon tissue coagulation. Here, we present forward simulations of a growing coagulated lesion with optical scattering contrast, using an established finite element analysis software platform (NIRFAST). The simulations were validated in tissue-simulating phantoms, with measurements acquired by a state-of-the-art continuous wave (CW) TRDOT system and a recently assembled bench-top CW-DOT system, with specific source-detector configurations. Two image reconstruction schemes were investigated and evaluated, specifically for the accurate delineation of the posterior boundary of the coagulation zone as the critical parameter for treatment guidance in this clinical application.

  16. Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study

    PubMed Central

    Larkin, S E T; Johnston, H E; Jackson, T R; Jamieson, D G; Roumeliotis, T I; Mockridge, C I; Michael, A; Manousopoulou, A; Papachristou, E K; Brown, M D; Clarke, N W; Pandha, H; Aukim-Hastie, C L; Cragg, M S; Garbis, S D; Townsend, P A

    2016-01-01

    Background: Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. Methods: We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. Results: We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an ‘interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. Conclusions: Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker. PMID:27685442

  17. Prostate cancer screening

    MedlinePlus

    Prostate cancer screening - PSA; Prostate cancer screening - digital rectal exam; Prostate cancer screening - DRE ... level of PSA could mean you have prostate cancer. But other conditions can also cause a high ...

  18. Image guided radiation therapy applications for head and neck, prostate, and breast cancers using 3D ultrasound imaging and Monte Carlo dose calculations

    NASA Astrophysics Data System (ADS)

    Fraser, Danielle

    In radiation therapy an uncertainty in the delivered dose always exists because anatomic changes are unpredictable and patient specific. Image guided radiation therapy (IGRT) relies on imaging in the treatment room to monitor the tumour and surrounding tissue to ensure their prescribed position in the radiation beam. The goal of this thesis was to determine the dosimetric impact on the misaligned radiation therapy target for three cancer sites due to common setup errors; organ motion, tumour tissue deformation, changes in body habitus, and treatment planning errors. For this purpose, a novel 3D ultrasound system (Restitu, Resonant Medical, Inc.) was used to acquire a reference image of the target in the computed tomography simulation room at the time of treatment planning, to acquire daily images in the treatment room at the time of treatment delivery, and to compare the daily images to the reference image. The measured differences in position and volume between daily and reference geometries were incorporated into Monte Carlo (MC) dose calculations. The EGSnrc (National Research Council, Canada) family of codes was used to model Varian linear accelerators and patient specific beam parameters, as well as to estimate the dose to the target and organs at risk under several different scenarios. After validating the necessity of MC dose calculations in the pelvic region, the impact of interfraction prostate motion, and subsequent patient realignment under the treatment beams, on the delivered dose was investigated. For 32 patients it is demonstrated that using 3D conformal radiation therapy techniques and a 7 mm margin, the prescribed dose to the prostate, rectum, and bladder is recovered within 0.5% of that planned when patient setup is corrected for prostate motion, despite the beams interacting with a new external surface and internal tissue boundaries. In collaboration with the manufacturer, the ultrasound system was adapted from transabdominal imaging to neck

  19. [Prostate cancer].

    PubMed

    Bey, P; Beckendorf, V; Stinès, J

    2001-10-01

    Radiation therapy of prostate carcinoma with a curative intent implies to treat the whole prostate at high dose (at least 66 Gy). According to clinical stage, PSA level, Gleason's score, the clinical target volume may include seminal vesicles and less often pelvic lymph nodes. Microscopic extracapsular extension is found in 15 to 60% of T1-T2 operated on, specially in apex tumors. On contrary, cancers developing from the transitional zone may stay limited to the prostate even with a big volume and with a high PSA level. Zonal anatomy of the prostate identifies internal prostate, including the transitional zone (5% of the prostate in young people). External prostate includes central and peripheral zones. The inferior limit of the prostate is not lower than the inferior border of the pubic symphysis. Clinical and radiological examination: ultrasonography, nuclear magnetic resonance (NMR), CT-scan identify prognostic factors as tumor volume, capsule effraction, seminal vesicles invasion and lymph node extension. The identification of the clinical target volume is now done mainly by CT-Scan which identifies prostate and seminal vesicles. NMR could be helpful to identify more precisely prostate apex. The definition of margins around the clinical target volume has to take in account daily reproducibility and organ motion and of course the maximum tolerable dose for organs at risk.

  20. Synthesis and cytotoxic activities of some 2-arylnaphtho[2,3-d]oxazole-4,9-dione derivatives on androgen-dependent (LNCaP) and androgen-independent (PC3) human prostate cancer cell lines.

    PubMed

    Brandy, Yakini; Ononiwu, Innocent; Adedeji, Dolapo; Williams, Vonetta; Mouamba, Claudia; Kanaan, Yasmine; Copeland, Robert L; Wright, Dwayne A; Butcher, Ray J; Denmeade, Samuel R; Bakare, Oladapo

    2012-08-01

    The synthesis of five 2-arylnaphtho[2,3-d]oxazole-4,9-dione derivatives was accomplished by refluxing 2-amino-3-bromo-1,4-naphthoquinone with appropriate benzoyl chloride analogs at elevated temperatures. In vitro anticancer evaluation of these compounds was performed on androgen-dependent, LNCaP, and androgen-independent, PC3, human prostate cancer cell lines. In general, these compounds displayed slightly stronger cytotoxicity on the androgen-dependent LNCaP than on the androgen-independent PC3 prostate cancer cell lines. The meta-substituted 2-(3-Chloro-phenyl)-naphtho[2,3-d]oxazole-4,9-dione (10) appear to display the best cytotoxicity on both cell lines with an IC(50) of 0.03 μM on LNCaP and 0.08 μM on PC3 after 5 days of exposure.

  1. Prostate cancer

    PubMed Central

    Mazhar, D; Waxman, J

    2002-01-01

    It is a paradigm in cancer treatment that early detection and treatment improves survival. However, although screening measures lead to a higher rate of detection, for small bulk localised prostate cancer it remains unclear whether early detection and early treatment will lead to an overall decrease in mortality. The management options include surveillance, radiotherapy, and radical prostatectomy but there is no evidence base to evaluate the benefits of each approach. Advanced prostate cancer is managed by hormonal therapy. There have been major changes in treatment over the last two decades with the use of more humane treatment and developments in both chemotherapy and radiation. In this article we review the natural history and management of prostate cancer. PMID:12415080

  2. Prostate cancer

    MedlinePlus

    ... If the cancer has not spread outside the prostate gland, common treatments include: Surgery ( radical prostatectomy ) Radiation therapy , including brachytherapy and proton therapy If you are older, your doctor may recommend simply monitoring the cancer with PSA tests and biopsies. Hormone therapy is ...

  3. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    SciTech Connect

    Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van; Heemsbergen, Wilma D.

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  4. Development of a 3D ultrasound-guided prostate biopsy system

    NASA Astrophysics Data System (ADS)

    Cool, Derek; Sherebrin, Shi; Izawa, Jonathan; Fenster, Aaron

    2007-03-01

    Biopsy of the prostate using ultrasound guidance is the clinical gold standard for diagnosis of prostate adenocarinoma. However, because early stage tumors are rarely visible under US, the procedure carries high false-negative rates and often patients require multiple biopsies before cancer is detected. To improve cancer detection, it is imperative that throughout the biopsy procedure, physicians know where they are within the prostate and where they have sampled during prior biopsies. The current biopsy procedure is limited to using only 2D ultrasound images to find and record target biopsy core sample sites. This information leaves ambiguity as the physician tries to interpret the 2D information and apply it to their 3D workspace. We have developed a 3D ultrasound-guided prostate biopsy system that provides 3D intra-biopsy information to physicians for needle guidance and biopsy location recording. The system is designed to conform to the workflow of the current prostate biopsy procedure, making it easier for clinical integration. In this paper, we describe the system design and validate its accuracy by performing an in vitro biopsy procedure on US/CT multi-modal patient-specific prostate phantoms. A clinical sextant biopsy was performed by a urologist on the phantoms and the 3D models of the prostates were generated with volume errors less than 4% and mean boundary errors of less than 1 mm. Using the 3D biopsy system, needles were guided to within 1.36 +/- 0.83 mm of 3D targets and the position of the biopsy sites were accurately localized to 1.06 +/- 0.89 mm for the two prostates.

  5. 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/ ...

  6. 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 ...

  7. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  8. A compact robotic apparatus and method for 3-D ultrasound guided prostate therapy

    NASA Astrophysics Data System (ADS)

    Bax, Jeffrey; Gardi, Lori; Montreuil, Jacques; Smith, David; Fenster, Aaron

    2007-03-01

    Ultrasound imaging has revolutionized the treatment of prostate cancer by producing increasingly accurate models of the prostate and influencing sophisticated targeting procedures for the insertion of radioactive seeds during brachytherapy. Three-dimensional (3D) ultrasound imaging, which allows 3D models of the prostate to be constructed from a series of two-dimensional images, helps to accurately target and implant seeds into the prostate. We have developed a compact robotic apparatus, as well as an effective method for guiding and controlling the insertion of transperineal needles into the prostate. This device has been designed to accurately guide a needle in 3D space so that the needle can be inserted into the prostate at an angle that does not interfere with the pubic arch. The physician can adjust manually or automatically the position of the apparatus in order to place several radioactive seeds into the prostate at designated target locations. Because many physicians are wary of conducting robotic surgical procedures, the apparatus has been developed so that the physician can position the needle for manual insertion and apply a method for manually releasing the needle without damaging the apparatus or endangering the patient.

  9. Prostate Mechanical Imaging: 3-D Image Composition and Feature Calculations

    PubMed Central

    Egorov, Vladimir; Ayrapetyan, Suren; Sarvazyan, Armen P.

    2008-01-01

    We have developed a method and a device entitled prostate mechanical imager (PMI) for the real-time imaging of prostate using a transrectal probe equipped with a pressure sensor array and position tracking sensor. PMI operation is based on measurement of the stress pattern on the rectal wall when the probe is pressed against the prostate. Temporal and spatial changes in the stress pattern provide information on the elastic structure of the gland and allow two-dimensional (2-D) and three-dimensional (3-D) reconstruction of prostate anatomy and assessment of prostate mechanical properties. The data acquired allow the calculation of prostate features such as size, shape, nodularity, consistency/hardness, and mobility. The PMI prototype has been validated in laboratory experiments on prostate phantoms and in a clinical study. The results obtained on model systems and in vivo images from patients prove that PMI has potential to become a diagnostic tool that could largely supplant DRE through its higher sensitivity, quantitative record storage, ease-of-use and inherent low cost. PMID:17024836

  10. Prostate Cancer Symptoms

    MedlinePlus

    ... PCF? Featured Blue Jacket Fashion Show Contact Us Prostate Cancer Symptoms The conversation about PSA screening really applies ... That’s why screening is such an important topic. Prostate Cancer Basics About the Prostate Risk Factors Prevention Symptoms ...

  11. 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 ...

  12. Predictors for Rectal and Intestinal Acute Toxicities During Prostate Cancer High-Dose 3D-CRT: Results of a Prospective Multicenter Study

    SciTech Connect

    Vavassori, Vittorio; Fiorino, Claudio . E-mail: fiorino.claudio@hsr.it; Rancati, Tiziana; Magli, Alessandro; Fellin, Gianni; Baccolini, Michela; Bianchi, Carla; Cagna, Emanuela; Mauro, Flora A.; Monti, Angelo F.; Munoz, Fernando; Stasi, Michele; Franzone, Paola; Valdagni, Riccardo

    2007-04-01

    Purpose: To find predictors for rectal and intestinal acute toxicity in patients with prostate cancer treated with {>=}70 Gy conformal radiotherapy. Methods and Materials: Between July 2002 and March 2004, 1,132 patients were entered into a cooperative study (AIROPROS01-02). Toxicity was scored using the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale and by considering the changes (before and after treatment) of the scores of a self-administered questionnaire on rectal/intestinal toxicity. The correlation with a number of parameters was assessed by univariate and multivariate analyses. Concerning the questionnaire, only moderate/severe complications were considered. Results: Of 1,132 patients, 1,123 were evaluable. Of these patients, 375, 265, and 28 had Grade 1, 2, and 3 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity, respectively. The mean rectal dose was the most predictive parameter (p = 0.0004; odds ratio, 1.035) for Grade 2 or worse toxicity, and the use of anticoagulants/antiaggregants (p 0.02; odds ratio, 0.63) and hormonal therapy (p = 0.04, odds ratio, 0.65) were protective. The questionnaire-based scoring revealed that a greater mean rectal dose was associated with a greater risk of bleeding; larger irradiated volumes were associated with frequency, tenesmus, incontinence, and bleeding; hormonal therapy was protective against frequency and tenesmus; hemorrhoids were associated with a greater risk of tenesmus and bleeding; and diabetes associated highly with diarrhea. Conclusion: The mean rectal dose correlated with acute rectal/intestinal toxicity in three-dimensional conformal radiotherapy for prostate cancer, and hormonal therapy and the use of anticoagulants/antiaggregants were protective. According to the moderate/severe injury scores on the self-assessed questionnaire, several clinical and dose-volume parameters were independently predictive for

  13. Vaccine Treatment for Prostate Cancer

    MedlinePlus

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer 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 ...

  14. Comparison and Limitations of DVH-Based NTCP Models Derived From 3D-CRT and IMRT Data for Prediction of Gastrointestinal Toxicities in Prostate Cancer Patients by Using Propensity Score Matched Pair Analysis

    SciTech Connect

    Troeller, Almut; Yan, Di; Marina, Ovidiu; Schulze, Derek; Alber, Markus; Parodi, Katia; Belka, Claus; Söhn, Matthias

    2015-02-01

    Purpose: This study compared normal tissue complication probability (NTCP) modeling of chronic gastrointestinal toxicities following prostate cancer treatment for 2 treatment modalities. Possible factors causing discrepancies in optimal NTCP model parameters between 3-dimensional conformal radiation therapy (3D-CRT) and intensity modulated RT (IMRT) were analyzed and discussed, including the impact of patient characteristics, image guidance, toxicity scoring bias, and NTCP model limitations. Methods and Materials: Rectal wall dose-volume histograms of 1115 patients treated for prostate cancer under an adaptive radiation therapy protocol were used to model gastrointestinal toxicity grade ≥2 (according to Common Terminology Criteria for Adverse Events). A total of 457 patients were treated with 3D-CRT and 658 with IMRT. 3D-CRT patients were matched to IMRT patients based on various patient characteristics, using a propensity score–based algorithm. Parameters of the Lyman equivalent uniform dose and cut-off dose logistic regression NTCP models were estimated for the 2 matched treatment modalities and the combined group. Results: After they were matched, the 3D-CRT and IMRT groups contained 275 and 550 patients with a large discrepancy of 28.7% versus 7.8% toxicities, respectively (P<.001). For both NTCP models, optimal parameters found for the 3D-CRT groups did not fit the IMRT patients well and vice versa. Models developed for the combined data overestimated NTCP for the IMRT patients and underestimated NTCP for the 3D-CRT group. Conclusions: Our analysis did not reveal a single definitive cause for discrepancies of model parameters between 3D-CRT and IMRT. Patient characteristics and bias in toxicity scoring, as well as image guidance alone, are unlikely causes of the large discrepancy of toxicities. Whether the cause was inherent to the specific NTCP models used in this study needs to be verified by future investigations. Because IMRT is increasingly used

  15. 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 ...

  16. Cryotherapy for prostate cancer

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000907.htm Cryotherapy for prostate cancer To use the sharing features ... first treatment for prostate cancer. What Happens During Cryotherapy Before the procedure, you will be given medicine ...

  17. Systematic review of the effect of radiation dose on tumor control and morbidity in the treatment of prostate cancer by 3D-CRT

    SciTech Connect

    Tol-Geerdink, Julia J. van . E-mail: J.vanTol@rther.umcn.nl; Stalmeier, Peep F.M.; Pasker-de Jong, Pieternel C.M.; Huizenga, Henk; Lin, Emile N.J.T. van; Schimmel, Erik C.; Leer, Jan Willem; Daal, Willem A.J. van

    2006-02-01

    Purpose: A higher radiation dose is believed to result in a larger probability of tumor control and a higher risk of side effects. To make an evidence-based choice of dose, the relation between dose and outcome needs to be known. This study focuses on the dose-response relation for prostate cancer. Methods and Materials: A systematic review was carried out on the literature from 1990 to 2003. From the selected studies, the radiation dose, the associated 5-year survival, 5-year bNED (biochemical no evidence of disease), acute and late gastrointestinal (GI) and genitourinary (GU) morbidity Grade 2 or more, and sexual dysfunction were extracted. With logistic regression models, the relation between dose and outcome was described. Results: Thirty-eight studies met our criteria, describing 87 subgroups and involving up to 3000 patients per outcome measure. Between the (equivalent) dose of 70 and 80 Gy, various models estimated an increase in 5-year survival (ranging from 10% to 11%), 5-year bNED for low-risk patients (5-7%), late GI complications (12-16%), late GU complications (8-10%), and erectile dysfunction (19-24%). Only for the overall 5-year bNED, results were inconclusive (range, 0-18%). Conclusions: The data suggest a relationship between dose and outcome measures, including survival. However, the strength of these conclusions is limited by the sometimes small number of studies, the incompleteness of the data, and above all, the correlational nature of the data. Unambiguous proof for the dose-response relationships can, therefore, only be obtained by conducting randomized trials.

  18. Living with Prostate Cancer

    MedlinePlus

    ... cancer treatment and can improve many aspects of health, including muscle strength, balance, fatigue, cardiovascular fitness, and depression. Physical activity after a prostate cancer diagnosis is linked to ...

  19. Effects of a novel carbocyclic analog of pyrrolo[2,3-d]pyrimidine nucleoside on pleiotropic induction of cell death in prostate cancer cells with different androgen responsiveness.

    PubMed

    Suh, Hyewon; Choi, Ko-woon; Lee, Jongbok; Ryou, Chongsuk; Rhee, Hakjune; Lee, Chul-Hoon

    2016-02-15

    Prostate cancer is the most frequently diagnosed cancer and is one of the leading causes of male cancer death in the world. Recently, in the course of our screening for a novel anticancer compound, we synthesized carbocyclic analogs of pyrrolo[2,3-d]pyrimidine nucleoside; compounds 5, and 6. In the current study, we report the effects of compound 5 on pleiotropic induction of cell death via up-regulation of AR-associated p21(Cip1) protein in prostate cancer cells with different androgen responsiveness, such as LNCaP (androgen-dependent and -sensitive), LNCaP(C4-2) (androgen-independent and -sensitive; androgen-refractory), and DU145 (androgen-independent and -insensitive) cells. The treatment of LNCaP cells with 6 μM compound 5 for 24 h stimulated the androgen receptor (AR) activity and dramatically up-regulated transcription (56-fold) of p21(Cip1), which, in turn, induces typical apoptosis in the cells. However, induction of apoptosis through up-regulation (23-fold) of AR-associated p21(Cip1) achieved in LNCaP(C4-2) cells was possible by intensive cell treatment with compound 5 (9 μM, 48 h), because the cells are less sensitive and independent to androgen than LNCaP cells. Furthermore, 6 μM compound 5-treated DU145 cells, which exhibit extremely low AR activation due to no androgen responsiveness and dependency, showed neither up-regulation of p21(Cip1) nor apoptotic induction. Instead, a different type of cell death, autophagy-like death through the LC3B-associated autophagosome formation, was obviously induced in DU145 cells. Taken together, our results suggest that pleiotropic induction of prostate cancer cell death by compound 5 is determined by how efficiently and how abundantly androgen-dependent activation of the AR occurs, whereas compound 6 shows no induction of apoptosis in LNCaP cells.

  20. Clinical and Dosimetric Predictors of Late Rectal Syndrome After 3D-CRT for Localized Prostate Cancer: Preliminary Results of a Multicenter Prospective Study

    SciTech Connect

    Fiorino, Claudio Fellin, Gianni; Rancati, Tiziana; Vavassori, Vittorio; Bianchi, Carla; Borca, Valeria Casanova; Girelli, Giuseppe; Mapelli, Marco; Menegotti, Loris; Nava, Simona; Valdagni, Riccardo

    2008-03-15

    Purpose: To assess the predictors of late rectal toxicity in a prospectively investigated group of patients treated at 70-80 Gy for prostate cancer (1.8-2 Gy fractions) with three-dimensional conformal radiotherapy. Methods and Materials: A total of 1,132 patients were entered into the study between 2002 and 2004. Three types of rectal toxicity, evaluated by a self-administered questionnaire, mainly based on the subjective objective management, analytic late effects of normal tissue system, were considered: stool frequency/tenesmus/pain, fecal incontinence, and bleeding. The data from 506 patients with a follow-up of 24 months were analyzed. The correlation between a number of clinical and dosimetric parameters and Grade 2 or greater toxicity was investigated by univariate and multivariate (MVA) logistic analyses. Results: Of the 1,132 patients, 21, 15, and 30 developed stool frequency/tenesmus/pain, fecal incontinence, and bleeding, respectively. Stool frequency/tenesmus/pain correlated with previous abdominal/pelvic surgery (MVA, p = 0.05, odds ratio [OR], 3.3). With regard to incontinence, MVA showed the volume receiving {>=}40 Gy (V{sub 40}) (p = 0.035, OR, 1.037) and surgery (p = 0.02, OR, 4.4) to be the strongest predictors. V{sub 40} to V{sub 70} were highly predictive of bleeding; V{sub 70} showed the strongest impact on MVA (p = 0.03), together with surgery (p = 0.06, OR, 2.5), which was also the main predictor of Grade 3 bleeding (p = 0.02, OR, 4.2). Conclusions: The predictive value of the dose-volume histogram was confirmed for bleeding, consistent with previously suggested constraints (V{sub 50} <55%, V{sub 60} <40%, V{sub 70} <25%, and V{sub 75} <5%). A dose-volume histogram constraint for incontinence can be suggested (V{sub 40} <65-70%). Previous abdominal/pelvic surgery correlated with all toxicity types; thus, a modified constraint for bleeding (V{sub 70} <15%) can be suggested for patients with a history of abdominal/pelvis surgery, although

  1. Can Prostate Cancer Be Found Early?

    MedlinePlus

    ... Prostate Cancer Early Detection, Diagnosis, and Staging Can Prostate Cancer Be Found Early? Screening is testing to find ... Health Care Team About Prostate Cancer? More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  2. 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.

  3. Prostate cancer - treatment

    MedlinePlus

    ... well. Proton therapy is another kind of radiation therapy used to treat prostate cancer. Proton beams target the tumor precisely, so there is less damage to the surrounding tissue. This therapy is not widely accepted or used. Prostate Brachytherapy ...

  4. Deformable segmentation of 3D MR prostate images via distributed discriminative dictionary and ensemble learning

    SciTech Connect

    Guo, Yanrong; Shao, Yeqin; Gao, Yaozong; Price, True; Oto, Aytekin; Shen, Dinggang

    2014-07-15

    patches of the prostate surface and trained to adaptively capture the appearance in different prostate zones, thus achieving better local tissue differentiation. For each local region, multiple classifiers are trained based on the randomly selected samples and finally assembled by a specific fusion method. In addition to this nonparametric appearance model, a prostate shape model is learned from the shape statistics using a novel approach, sparse shape composition, which can model nonGaussian distributions of shape variation and regularize the 3D mesh deformation by constraining it within the observed shape subspace. Results: The proposed method has been evaluated on two datasets consisting of T2-weighted MR prostate images. For the first (internal) dataset, the classification effectiveness of the authors' improved dictionary learning has been validated by comparing it with three other variants of traditional dictionary learning methods. The experimental results show that the authors' method yields a Dice Ratio of 89.1% compared to the manual segmentation, which is more accurate than the three state-of-the-art MR prostate segmentation methods under comparison. For the second dataset, the MICCAI 2012 challenge dataset, the authors' proposed method yields a Dice Ratio of 87.4%, which also achieves better segmentation accuracy than other methods under comparison. Conclusions: A new magnetic resonance image prostate segmentation method is proposed based on the combination of deformable model and dictionary learning methods, which achieves more accurate segmentation performance on prostate T2 MR images.

  5. Lipids and Prostate Cancer

    PubMed Central

    Suburu, Janel; Chen, Yong Q.

    2012-01-01

    The role of lipid metabolism has gained particular interest in prostate cancer research. A large body of literature has outlined the unique upregulation of de novo lipid synthesis in prostate cancer. Concordant with this lipogenic phenotype is a metabolic shift, in which cancer cells use alternative enzymes and pathways to facilitate the production of fatty acids. These newly synthesized lipids may support a number of cellular processes to promote cancer cell proliferation and survival. Hence, de novo lipogenesis is under intense investigation as a therapeutic target. Epidemiologic studies suggest dietary fat may also contribute to prostate cancer; however, whether dietary lipids and de novo synthesized lipids are differentially metabolized remains unclear. Here, we highlight the lipogenic nature of prostate cancer, especially the promotion of de novo lipid synthesis, and the significance of various dietary lipids in prostate cancer development and progression. PMID:22503963

  6. Prostate Cancer

    MedlinePlus

    ... cancers that don't respond to hormone therapy. Biological therapy Biological therapy (immunotherapy) uses your body's immune system to fight cancer cells. One type of biological therapy called sipuleucel-T (Provenge) has been developed ...

  7. Statistical 3D prostate imaging atlas construction via anatomically constrained registration

    NASA Astrophysics Data System (ADS)

    Rusu, Mirabela; Bloch, B. Nicolas; Jaffe, Carl C.; Rofsky, Neil M.; Genega, Elizabeth M.; Feleppa, Ernest; Lenkinski, Robert E.; Madabhushi, Anant

    2013-03-01

    Statistical imaging atlases allow for integration of information from multiple patient studies collected across different image scales and modalities, such as multi-parametric (MP) MRI and histology, providing population statistics regarding a specific pathology within a single canonical representation. Such atlases are particularly valuable in the identification and validation of meaningful imaging signatures for disease characterization in vivo within a population. Despite the high incidence of prostate cancer, an imaging atlas focused on different anatomic structures of the prostate, i.e. an anatomic atlas, has yet to be constructed. In this work we introduce a novel framework for MRI atlas construction that uses an iterative, anatomically constrained registration (AnCoR) scheme to enable the proper alignment of the prostate (Pr) and central gland (CG) boundaries. Our current implementation uses endorectal, 1.5T or 3T, T2-weighted MRI from 51 patients with biopsy confirmed cancer; however, the prostate atlas is seamlessly extensible to include additional MRI parameters. In our cohort, radical prostatectomy is performed following MP-MR image acquisition; thus ground truth annotations for prostate cancer are available from the histological specimens. Once mapped onto MP-MRI through elastic registration of histological slices to corresponding T2-w MRI slices, the annotations are utilized by the AnCoR framework to characterize the 3D statistical distribution of cancer per anatomic structure. Such distributions are useful for guiding biopsies toward regions of higher cancer likelihood and understanding imaging profiles for disease extent in vivo. We evaluate our approach via the Dice similarity coefficient (DSC) for different anatomic structures (delineated by expert radiologists): Pr, CG and peripheral zone (PZ). The AnCoR-based atlas had a CG DSC of 90.36%, and Pr DSC of 89.37%. Moreover, we evaluated the deviation of anatomic landmarks, the urethra and

  8. Theoretical Analysis of the Accuracy and Safety of MRI-Guided Transurethral 3-D Conformal Ultrasound Prostate Therapy

    NASA Astrophysics Data System (ADS)

    Burtnyk, Mathieu; Chopra, Rajiv; Bronskill, Michael

    2009-04-01

    MRI-guided transurethral ultrasound therapy is a promising new approach for the treatment of localized prostate cancer. Several studies have demonstrated the feasibility of producing large regions of thermal coagulation adequate for prostate therapy; however, the quantitative assessment of shaping these regions to complex 3-D human prostate geometries has not been fully explored. This study used numerical simulations and twenty manually-segmented pelvic anatomical models derived from high-quality MR images of prostate cancer patients to evaluate the treatment accuracy and safety of 3-D conformal MRI-guided transurethral ultrasound therapy. The simulations incorporated a rotating multi-element planar dual-frequency ultrasound transducer (seventeen 4×3 mm elements) operating at 4.7/9.7 MHz and 10 W/cm2 maximum acoustic power. Results using a novel feedback control algorithm which modulated the ultrasound frequency, power and device rate of rotation showed that regions of thermal coagulation could be shaped to predefined prostate volumes within 1.0 mm across the vast majority of these glands. Treatment times were typically 30 min and remained below 60 min for large 60 cc prostates. With a rectal cooling temperature of 15° C, the rectal wall did not exceed 30EM43 in half of the twenty patient models with only a few 1 mm3 voxels above this threshold in the other cases. At 4.7 MHz, heating of the pelvic bone can become significant when it is located less than 10 mm from the prostate. Numerical simulations show that MRI-guided transurethral ultrasound therapy can thermally coagulate whole prostate glands accurately and safely in 3-D.

  9. Thermal analysis of the surrounding anatomy during 3-D MRI-guided transurethral ultrasound prostate therapy

    NASA Astrophysics Data System (ADS)

    Burtnyk, Mathieu; Chopra, Rajiv; Bronskill, Michael

    2010-03-01

    Previous numerical simulations have shown that MRI-guided transurethral ultrasound therapy can generate highly accurate volumes of thermal coagulation conforming to 3-D human prostate geometries. The goal of this work is to simulate, quantify and evaluate the thermal impact of these treatments on the rectum, pelvic bone, neurovascular bundles (NVB) and urinary sphincters. This study used twenty 3-D anatomical models of prostate cancer patients and detailed bio-acoustic simulations incorporating an active feedback algorithm which controlled a rotating, planar ultrasound transducer (17-4×3 mm elements, 4.7/9.7 MHz, 10 Wac/cm2). Heating of the adjacent surrounding anatomy was evaluated using thermal tolerances reported in the literature. Heating of the rectum poses the most important safety concern and is influenced largely by the water temperature flowing through an endorectal cooling device; temperatures of 7-37° C are required to limit potential damage to less than 10 mm3 on the outer 1 mm layer of rectum. Significant heating of the pelvic bone was predicted in 30% of the patient models with an ultrasound frequency of 4.7 MHz; setting the frequency to 9.7 MHz when the bone is less than 10 mm away from the prostate reduced heating in all cases below the threshold for irreversible damage. Heating of the NVB was significant in 75% of the patient models in the absence of treatment planning; this proportion was reduced to 5% by using treatment margins of up to 4 mm. To avoid damaging the urinary sphincters, margins from the transducer of 2-4 mm should be used, depending on the transurethral cooling temperature. Simulations show that MRI-guided transurethral therapy can treat the entire prostate accurately. Strategies have been developed which, along with careful treatment planning, can be used to avoid causing thermal injury to the rectum, pelvic bone, NVB and urinary sphincters.

  10. Screening for Prostate Cancer

    MedlinePlus

    ... for prostate cancer. It concluded that the expected harms of PSA screening are greater than the potential ... exam or other screening tests. Potential Benefits and Harms The main goal of a cancer screening test ...

  11. 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 ...

  12. Cancer3D: understanding cancer mutations through protein structures.

    PubMed

    Porta-Pardo, Eduard; Hrabe, Thomas; Godzik, Adam

    2015-01-01

    The new era of cancer genomics is providing us with extensive knowledge of mutations and other alterations in cancer. The Cancer3D database at http://www.cancer3d.org gives an open and user-friendly way to analyze cancer missense mutations in the context of structures of proteins in which they are found. The database also helps users analyze the distribution patterns of the mutations as well as their relationship to changes in drug activity through two algorithms: e-Driver and e-Drug. These algorithms use knowledge of modular structure of genes and proteins to separately study each region. This approach allows users to find novel candidate driver regions or drug biomarkers that cannot be found when similar analyses are done on the whole-gene level. The Cancer3D database provides access to the results of such analyses based on data from The Cancer Genome Atlas (TCGA) and the Cancer Cell Line Encyclopedia (CCLE). In addition, it displays mutations from over 14,700 proteins mapped to more than 24,300 structures from PDB. This helps users visualize the distribution of mutations and identify novel three-dimensional patterns in their distribution.

  13. A comparison of US- versus MR-based 3-D Prostate Shapes Using Radial Basis Function Interpolation and Statistical Shape Models.

    PubMed

    Tao, Ran; Tavakoli, Mahdi; Sloboda, Ron; Usmani, Nawaid

    2015-03-01

    This paper presents a comparison of three-dimensional (3-D) segmentations of the prostate, based on two-dimensional (2-D) manually segmented contours, obtained using ultrasound (US) and magnetic resonance (MR) imaging data collected from 40 patients diagnosed with localized prostate cancer and scheduled to receive brachytherapy treatment. The approach we propose here for 3-D prostate segmentation first uses radial basis function interpolation to construct a 3-D point distribution model for each prostate. Next, a modified principal axis transformation is utilized for rigid registration of the US and MR images of the same prostate in preparation for the following shape comparison. Then, statistical shape models are used to capture the segmented 3-D prostate geometries for the subsequent cross-modality comparison. Our study includes not only cross-modality geometric comparisons in terms of prostate volumes and dimensions, but also an investigation of interchangeability of the two imaging modalities in terms of automatic contour segmentation at the pre-implant planning stage of prostate brachytherapy treatment. By developing a new scheme to compare the two imaging modalities in terms of the segmented 3-D shapes, we have taken a first step necessary for building coupled US-MR segmentation strategies for prostate brachytherapy pre-implant planning, which at present is predominantly informed by US images only.

  14. Simulated prostate biopsy: prostate cancer distribution and clinical correlation

    NASA Astrophysics Data System (ADS)

    Bauer, John J.; Zeng, Jianchao; Zhang, Wei; Sesterhenn, Isabell A.; Dean, Robert; Moul, Judd W.; Mun, Seong K.

    2000-04-01

    Our group has recently obtained data based upon whole- mounted step-sectioned radical prostatectomy specimens using a 3D computer assisted prostate biopsy simulator that suggests an increased detection rate is possible using laterally placed biopsies. A new 10-core biopsy pattern was demonstrated to be superior to the traditional sextant biopsy. This patter includes the traditional sextant biopsy cores and four laterally placed biopsies in the right and left apex and mid portion of the prostate gland. The objective of this study is to confirm the higher prostate cancer defection rate obtained using our simulated 10-core biopsy pattern in a small clinical trial. We retrospectively reviewed 35 consecutive patients with a pathologic diagnosis of prostate cancer biopsied by a single urologist using the 10-core prostate biopsy patterns were compared with respect to prostate cancer detection rate. Of the 35 patients diagnosed with prostate cancer, 54.3 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent were diagnosed when reviewing the sextant biopsy data only. Review of the 10-core pattern revealed that an additional 45.7 percent of patients were diagnosed solely with the laterally placed biopsies. Our results suggest that biopsy protocols that use laterally placed biopsies based upon a five region anatomical model are superior to the routinely used sextant prostate biopsy pattern.

  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.

  16. 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.

  17. 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 ...

  18. Chemoprevention of prostate cancer.

    PubMed

    Brand, Timothy C; Canby-Hagino, Edith D; Pratap Kumar, A; Ghosh, Rita; Leach, Robin J; Thompson, Ian M

    2006-08-01

    Prostate cancer is a common malignancy with multiple potential opportunities for cancer prevention. As the genetic basis of this malignancy is further understood, prevention strategies will be developed for individual patients based on specific risk factors and pathways of carcinogenesis. The PCPT has conclusively proven that prostate cancer prevention is possible. The results of the SELECT should be available within several years. An enormous challenge for the medical community will be the development of an efficient strategy to evaluate the substantial number of dietary, behavioral, and pharmacologic prevention opportunities. Ultimately, the goal of prostate can-cer prevention is to (1) identify men who are destined to develop clinically significant prostate cancer, and (2) provide individualized agents to prevent disease development.

  19. Interactive 3D segmentation of the prostate in magnetic resonance images using shape and local appearance similarity analysis

    NASA Astrophysics Data System (ADS)

    Shahedi, Maysam; Fenster, Aaron; Cool, Derek W.; Romagnoli, Cesare; Ward, Aaron D.

    2013-03-01

    3D segmentation of the prostate in medical images is useful to prostate cancer diagnosis and therapy guidance, but is time-consuming to perform manually. Clinical translation of computer-assisted segmentation algorithms for this purpose requires a comprehensive and complementary set of evaluation metrics that are informative to the clinical end user. We have developed an interactive 3D prostate segmentation method for 1.5T and 3.0T T2-weighted magnetic resonance imaging (T2W MRI) acquired using an endorectal coil. We evaluated our method against manual segmentations of 36 3D images using complementary boundary-based (mean absolute distance; MAD), regional overlap (Dice similarity coefficient; DSC) and volume difference (ΔV) metrics. Our technique is based on inter-subject prostate shape and local boundary appearance similarity. In the training phase, we calculated a point distribution model (PDM) and a set of local mean intensity patches centered on the prostate border to capture shape and appearance variability. To segment an unseen image, we defined a set of rays - one corresponding to each of the mean intensity patches computed in training - emanating from the prostate centre. We used a radial-based search strategy and translated each mean intensity patch along its corresponding ray, selecting as a candidate the boundary point with the highest normalized cross correlation along each ray. These boundary points were then regularized using the PDM. For the whole gland, we measured a mean+/-std MAD of 2.5+/-0.7 mm, DSC of 80+/-4%, and ΔV of 1.1+/-8.8 cc. We also provided an anatomic breakdown of these metrics within the prostatic base, mid-gland, and apex.

  20. Learning about Prostate Cancer

    MedlinePlus

    ... Gene Mapped To X Chromosome 1998 Researchers Link Gene to Hereditary Form of Prostate Cancer 2002 Get Email Updates Advancing human health through genomics research Privacy Copyright Contact Accessibility Plug-ins Site Map Staff Search FOIA Share Top

  1. Cholesterol and prostate cancer.

    PubMed

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R

    2012-12-01

    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  2. Advanced Prostate Cancer

    MedlinePlus

    ... if it has spread to: • Bones • Lungs • Liver • Brain • Lymph nodes outside the pelvis • Other organs You may be diagnosed with metastatic prostate cancer when you are first diagnosed, after having completed ...

  3. Random Walk Based Segmentation for the Prostate on 3D Transrectal Ultrasound Images.

    PubMed

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Nieh, Peter T; Master, Viraj V; Schuster, David M; Fei, Baowei

    2016-02-27

    This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37±0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications.

  4. Random walk based segmentation for the prostate on 3D transrectal ultrasound images

    NASA Astrophysics Data System (ADS)

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Nieh, Peter T.; Master, Viraj V.; Schuster, David M.; Fei, Baowei

    2016-03-01

    This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37+/-0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications.

  5. Random Walk Based Segmentation for the Prostate on 3D Transrectal Ultrasound Images

    PubMed Central

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Nieh, Peter T.; Master, Viraj V.; Schuster, David M.; Fei, Baowei

    2016-01-01

    This paper proposes a new semi-automatic segmentation method for the prostate on 3D transrectal ultrasound images (TRUS) by combining the region and classification information. We use a random walk algorithm to express the region information efficiently and flexibly because it can avoid segmentation leakage and shrinking bias. We further use the decision tree as the classifier to distinguish the prostate from the non-prostate tissue because of its fast speed and superior performance, especially for a binary classification problem. Our segmentation algorithm is initialized with the user roughly marking the prostate and non-prostate points on the mid-gland slice which are fitted into an ellipse for obtaining more points. Based on these fitted seed points, we run the random walk algorithm to segment the prostate on the mid-gland slice. The segmented contour and the information from the decision tree classification are combined to determine the initial seed points for the other slices. The random walk algorithm is then used to segment the prostate on the adjacent slice. We propagate the process until all slices are segmented. The segmentation method was tested in 32 3D transrectal ultrasound images. Manual segmentation by a radiologist serves as the gold standard for the validation. The experimental results show that the proposed method achieved a Dice similarity coefficient of 91.37±0.05%. The segmentation method can be applied to 3D ultrasound-guided prostate biopsy and other applications. PMID:27660383

  6. Zinc and prostatic cancer

    PubMed Central

    Song, Yang; Ho, Emily

    2014-01-01

    Purpose of review Aim to understand the connection between zinc and prostatic cancer, and to summarize the recent findings about the functions of zinc in the maintenance of prostate health. Recent findings Contradictory findings have been reported by epidemiologic studies examining the association between zinc intake and the risk of prostate cancer. However, a growing body of experimental evidence support that high zinc levels are essential for prostate health. The possible mechanisms include the effects of zinc on the inhibition of terminal oxidation, induction of mitochondrial apoptogenesis, and suppression of NFκB activity. The most recent finding is the effects of zinc in the maintenance of DNA integrity in normal prostate epithelial cells (PrEC) by modulating the expression and activity of DNA repair and damage response proteins, especially p53. Zinc depletion in PrEC increased p53 expression but compromised p53 DNA binding activity resulting an impaired DNA repair function. Moreover, recent findings support the role of zinc transporters as tumor suppressors in the prostate. Summary Future studies need to discover sensitive and specific zinc biomarkers and perform more in vivo studies on the effects of zinc on prostate functions in normal animals or prostate cancer models. PMID:19684515

  7. Understanding your prostate cancer risk

    MedlinePlus

    ... medlineplus.gov/ency/patientinstructions/000931.htm Understanding your prostate cancer risk To use the sharing features on this ... enable JavaScript. Are you at risk for developing prostate cancer in your lifetime? Learn about the risk factors ...

  8. 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.

  9. 3D-2D ultrasound feature-based registration for navigated prostate biopsy: a feasibility study.

    PubMed

    Selmi, Sonia Y; Promayon, Emmanuel; Troccaz, Jocelyne

    2016-08-01

    The aim of this paper is to describe a 3D-2D ultrasound feature-based registration method for navigated prostate biopsy and its first results obtained on patient data. A system combining a low-cost tracking system and a 3D-2D registration algorithm was designed. The proposed 3D-2D registration method combines geometric and image-based distances. After extracting features from ultrasound images, 3D and 2D features within a defined distance are matched using an intensity-based function. The results are encouraging and show acceptable errors with simulated transforms applied on ultrasound volumes from real patients.

  10. MYC and Prostate Cancer

    PubMed Central

    Koh, Cheryl M.; Bieberich, Charles J.; Dang, Chi V.; Nelson, William G.; Yegnasubramanian, Srinivasan; De Marzo, Angelo M.

    2010-01-01

    Prostate cancer, the majority of which is adenocarcinoma, is the most common epithelial cancer affecting a majority of elderly men in Western nations. Its manifestation, however, varies from clinically asymptomatic insidious neoplasms that progress slowly and do not threaten life to one that is highly aggressive with a propensity for metastatic spread and lethality if not treated in time. A number of somatic genetic and epigenetic alterations occur in prostate cancer cells. Some of these changes, such as loss of the tumor suppressors PTEN and p53, are linked to disease progression. Others, such as ETS gene fusions, appear to be linked more with early phases of the disease, such as invasion. Alterations in chromosome 8q24 in the region of MYC have also been linked to disease aggressiveness for many years. However, a number of recent studies in human tissues have indicated that MYC appears to be activated at the earliest phases of prostate cancer (e.g., in tumor-initiating cells) in prostatic intraepithelial neoplasia, a key precursor lesion to invasive prostatic adenocarcinoma. The initiation and early progression of prostate cancer can be recapitulated in genetically engineered mouse models, permitting a richer understanding of the cause and effects of loss of tumor suppressors and activation of MYC. The combination of studies using human tissues and mouse models paints an emerging molecular picture of prostate cancer development and early progression. This picture reveals that MYC contributes to disease initiation and progression by stimulating an embryonic stem cell–like signature characterized by an enrichment of genes involved in ribosome biogenesis and by repressing differentiation. These insights pave the way to potential novel therapeutic concepts based on MYC biology. PMID:21779461

  11. [Sexuality and prostate cancer].

    PubMed

    Colson, M-H; Lechevallier, E; Rambeaud, J-J; Alimi, J-C; Faix, A; Gravis, G; Hannoun-Levi, J-M; Quintens, H; Rébillard, X; Droupy, S

    2012-09-01

    All treatments of prostate cancer have a negative effect on both sexuality and male fertility. There is a specific profile of changes in the fields of quality of life, sexual, urinary, bowel and vitality according to the treatment modalities chosen. Maintain a satisfying sex is the main concern of a majority of men facing prostate cancer and its treatment. It is essential to assess the couple's sexuality before diagnosis of prostate cancer in order to deliver complete information and to consider early and appropriate treatment options at the request of the couple. Forms of sexuality sexual preference settings stored (orgasm) may, when the erection is not yet recovered, be an alternative to the couple to maintain intimacy and complicity. In all cases, a specific management and networking will in many cases to find a satisfactory sexuality. Consequences of the treatment on male fertility should be part of the information of patients with prostate cancer and their partners. The choice of treatment must take into account the desire of paternity of the couple. A semen analysis with sperm cryopreservation before any therapy should be routinely offered in men with prostate cancer, particularly among men under 55, with a partner under 43 years old or without children. If the desire for parenthood among couples, sperm cryopreservation before treatment and medical assisted reproduction are recommended.

  12. Promoter Hypermethylation in Prostate Cancer

    PubMed Central

    Park, Jong Y.

    2011-01-01

    Background The prostate gland is the most common site of cancer and the second leading cause of cancer mortality in American men. It is well known that epigenetic alterations such as DNA methylation within the regulatory (promoter) regions of genes are associated with transcriptional silencing in cancer. Promoter hypermethylation of critical pathway genes could be potential biomarkers and therapeutic targets for prostate cancer. Methods This review discusses current information on methylated genes associated with prostate cancer development and progression. Results Over 30 genes have been investigated for promoter methylation in prostate cancer. These methylated genes are involved in critical pathways, such as DNA repair, metabolism, and invasion/metastasis. The role of hypermethylated genes in regulation of critical pathways in prostate cancer is reviewed. Conclusions These findings may provide new information of the pathogenesis of prostate cancer. Certain epigenetic alterations in prostate tumors are being translated into clinical practice for therapeutic use. PMID:20861812

  13. Prostate Cancer Rates by Race and Ethnicity

    MedlinePlus

    ... HPV-Associated Lung Ovarian Skin Uterine Cancer Home Prostate Cancer Rates by Race and Ethnicity Language: English Español ( ... Tweet Share Compartir The rate of men getting prostate cancer or dying from prostate cancer varies by race ...

  14. Disruption of the 3D cancer genome blueprint.

    PubMed

    Achinger-Kawecka, Joanna; Clark, Susan J

    2017-01-01

    Recent advances in chromosome conformation capture technologies are improving the current appreciation of how 3D genome architecture affects its function in different cell types and disease. Long-range chromatin interactions are organized into topologically associated domains, which are known to play a role in constraining gene expression patterns. However, in cancer cells there are alterations in the 3D genome structure, which impacts on gene regulation. Disruption of topologically associated domains architecture can result in alterations in chromatin interactions that bring new regulatory elements and genes together, leading to altered expression of oncogenes and tumor suppressor genes. Here, we discuss the impact of genetic and epigenetic changes in cancer and how this affects the spatial organization of chromatin. Understanding how disruptions to the 3D architecture contribute to the cancer genome will provide novel insights into the principles of epigenetic gene regulation in cancer and mechanisms responsible for cancer associated mutations and rearrangements.

  15. American Cancer Society Recommendations for Prostate Cancer Early Detection

    MedlinePlus

    ... Prostate Cancer Prevention and Early Detection American Cancer Society Recommendations for Prostate Cancer Early Detection The American Cancer Society (ACS) recommends that men have a chance to ...

  16. SU-D-9A-06: 3D Localization of Neurovascular Bundles Through MR-TRUS Registration in Prostate Radiotherapy

    SciTech Connect

    Yang, X; Rossi, P; Ogunleye, T; Jani, A; Curran, W; Liu, T

    2014-06-01

    Purpose: Erectile dysfunction (ED) is the most common complication of prostate-cancer radiotherapy (RT) and the major mechanism is radiation-induced neurovascular bundle (NVB) damage. However, the localization of the NVB remains challenging. This study's purpose is to accurately localize 3D NVB by integrating MR and transrectal ultrasound (TRUS) images through MR-TRUS fusion. Methods: T1 and T2-weighted MR prostate images were acquired using a Philips 1.5T MR scanner and a pelvic phase-array coil. The 3D TRUS images were captured with a clinical scanner and a 7.5 MHz biplane probe. The TRUS probe was attached to a stepper; the B-mode images were captured from the prostate base to apex at a 1-mm step and the Doppler images were acquired in a 5-mm step. The registration method modeled the prostate tissue as an elastic material, and jointly estimated the boundary condition (surface deformation) and the volumetric deformations under elastic constraint. This technique was validated with a clinical study of 7 patients undergoing RT treatment for prostate cancer. The accuracy of our approach was assessed through the locations of landmarks, as well as previous ultrasound Doppler images of patients. Results: MR-TRUS registration was successfully performed for all patients. The mean displacement of the landmarks between the post-registration MR and TRUS images was 1.37±0.42 mm, which demonstrated the precision of the registration based on the biomechanical model; and the NVB volume Dice Overlap Coefficient was 92.1±3.2%, which demonstrated the accuracy of the NVB localization. Conclusion: We have developed a novel approach to improve 3D NVB localization through MR-TRUS fusion for prostate RT, demonstrated its clinical feasibility, and validated its accuracy with ultrasound Doppler data. This technique could be a useful tool as we try to spare the NVB in prostate RT, monitor NBV response to RT, and potentially improve post-RT potency outcomes.

  17. 3D printing of biomimetic microstructures for cancer cell migration.

    PubMed

    Huang, Tina Qing; Qu, Xin; Liu, Justin; Chen, Shaochen

    2014-02-01

    To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10 T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10 T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10 T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10 T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies.

  18. 3D printing of biomimetic microstructures for cancer cell migration

    PubMed Central

    Huang, Tina Qing; Qu, Xin; Liu, Justin; Chen, Shaochen

    2013-01-01

    To understand the physical behavior and migration of cancer cells, a 3D in vitro micro-chip in hydrogel was created using 3D projection printing. The micro-chip has a honeycomb branched structure, aiming to mimic 3D vascular morphology to test, monitor, and analyze differences in the behavior of cancer cells (i.e. HeLa) vs. non-cancerous cell lines (i.e. 10T1/2). The 3D Projection Printing system can fabricate complex structures in seconds from user-created designs. The fabricated microstructures have three different channel widths of 25, 45, and 120 microns wide to reflect a range of blood vessel diameters. HeLa and 10T1/2 cells seeded within the micro-chip were then analyzed for morphology and cell migration speed. 10T1/2 cells exhibited greater changes in morphology due to channel size width than HeLa cells; however, channel width had a limited effect on 10T1/2 cell migration while HeLa cancer cell migration increased as channel width decreased. This physiologically relevant 3D cancer tissue model has the potential to be a powerful tool for future drug discoveries and cancer migration studies PMID:24150602

  19. Expectant Management (Watchful Waiting) and Active Surveillance for Prostate Cancer

    MedlinePlus

    ... Prostate Cancer Watchful Waiting or Active Surveillance for Prostate Cancer Because prostate cancer often grows very slowly, some ... Away or Comes Back After Treatment More In Prostate Cancer About Prostate Cancer Causes, Risk Factors, and Prevention ...

  20. What Are the Key Statistics for Prostate Cancer?

    MedlinePlus

    ... Cancer Research? Prostate Cancer About Prostate Cancer Key Statistics for Prostate Cancer How common is prostate cancer? ... at some point are still alive today. For statistics related to survival, see Survival Rates for Prostate ...

  1. Vitamin E and Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vitamin E, its metabolites or its analogs, might help prevent prostate cancer initiation or progression. Prostate cancer is the most common non-skin malignancy and the second leading cause of cancer deaths among men in the United States, exceeded only by lung cancer. About 218,890 new cases of prost...

  2. [Grading of prostate cancer].

    PubMed

    Kristiansen, G; Roth, W; Helpap, B

    2016-07-01

    The current grading of prostate cancer is based on the classification system of the International Society of Urological Pathology (ISUP) following a consensus conference in Chicago in 2014. The foundations are based on the frequently modified grading system of Gleason. This article presents a brief description of the development to the current ISUP grading system.

  3. 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

  4. Tuberculous prostatitis: mimicking a cancer.

    PubMed

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions.

  5. Cholesterol and prostate cancer.

    PubMed

    Freeman, Michael R; Solomon, Keith R

    2004-01-01

    Cholesterol is a neutral lipid that accumulates in liquid-ordered, detergent-resistant membrane domains called lipid rafts. Lipid rafts serve as membrane platforms for signal transduction mechanisms that mediate cell growth, survival, and a variety of other processes relevant to cancer. A number of studies, going back many years, demonstrate that cholesterol accumulates in solid tumors and that cholesterol homeostasis breaks down in the prostate with aging and with the transition to the malignant state. This review summarizes the established links between cholesterol and prostate cancer (PCa), with a focus on how accumulation of cholesterol within the lipid raft component of the plasma membrane may stimulate signaling pathways that promote progression to hormone refractory disease. We propose that increases in cholesterol in prostate tumor cell membranes, resulting from increases in circulating levels or from dysregulation of endogenous synthesis, results in the coalescence of raft domains. This would have the effect of sequestering positive regulators of oncogenic signaling within rafts, while maintaining negative regulators in the liquid-disordered membrane fraction. This approach toward examining the function of lipid rafts in prostate cancer cells may provide insight into the role of circulating cholesterol in malignant growth and on the potential relationship between diet and aggressive disease. Large-scale characterization of proteins that localize to cholesterol-rich domains may help unveil signaling networks and pathways that will lead to identification of new biomarkers for disease progression and potentially to novel targets for therapeutic intervention.

  6. 3D MR-Spectroscopic Imaging Assessment of Metabolic Activity in the Prostate During the PSA 'Bounce' Following {sup 125}Iodine Brachytherapy

    SciTech Connect

    Kirilova, Anna; Damyanovich, Andrei; Crook, Juanita; Jezioranski, John; Wallace, Kris; Pintilie, Melania

    2011-02-01

    Purpose: A temporary increase in prostate-specific antigen (PSA) values is observed in 30%-40% of men following {sup 125} I brachytherapy (BT) for prostate cancer. We present the results of a study to characterize prostate metabolic activity during the PSA 'bounce' and to correlate metabolic changes with PSA levels using three-dimensional magnetic resonance spectroscopic imaging (3D-MRSI). Methods and Materials: 3D-MRSI was performed in 24 patients during the PSA bounce. Eight of these had also had a baseline 3D-MRSI scan before BT for the purpose of tumor mapping. The 3D-MRSI was repeated at 6- and 12-month intervals, and PSA levels were monitored every 3 months. Twenty-one of the patients had favorable-risk prostate cancer, and 3 had intermediate risk. Results: The choline+creatine signal intensity, although markedly reduced, was observable following BT. Diffuse activity not corresponding to original biopsy-positive sites was observed in 22 cases, and 2 cases were documented to have local recurrence. No statistically significant correlation between metabolic activity and PSA levels at each interval was found. Conclusion: Post-BT prostate 3D-MRSI shows evidence of diffuse metabolic activity unrelated to residual malignancy. This supports the benign nature of the PSA bounce and suggests an inflammatory etiology. In the situation of a rising PSA, observation of focal activity on MRI/3D-MRSI could be a useful adjunct to suggest local recurrence at an earlier interval after brachytherapy when prostate biopsies would still be unhelpful. Longer follow-up is necessary to confirm the complex relationship between metabolic activity and PSA levels.

  7. Testosterone Therapy and Prostate Cancer.

    PubMed

    Davidson, Emily; Morgentaler, Abraham

    2016-05-01

    Changes in understanding regarding the relationship of androgens and prostate cancer have led to changes in the use of testosterone therapy. The evidence supports a finite ability of androgens to stimulate prostate cancer growth, with a maximum achieved at low testosterone concentrations, called the saturation model. The saturation point corresponds with maximal androgenic stimulation at 250 ng/dL. Evidence is reviewed herein regarding the relationship of testosterone to prostate cancer and the relatively new practice of offering testosterone therapy to men with a history of prostate cancer. Although no prospective controlled trials have been performed, results have been reassuring.

  8. Prostate Cancer MR Imaging

    NASA Astrophysics Data System (ADS)

    Fütterer, Jurgen J.

    With a total of 192,280 new cases predicted for 2009, prostate cancer (PC) now accounts for 25% of all new male cancers diagnosed in the United States [1]. Furthermore, in their lifetime, one in six men will be clinically diagnosed with having PC, although many more men are found to have histological evidence of PC at autopsy [2,3,4]. Presently, approximately 1 in 10 men will die of PC [5,6]. The ever-aging population and wider spread use of the blood prostate-specific antigen (PSA) test [7,8], as well as the tendency to apply lower cut-off levels for this test [9], will further increase the diagnosis of this disease [10].

  9. Tocotrienols and Prostate Cancer

    DTIC Science & Technology

    2005-09-01

    factors [1-3]. Some evidence supports the protective effects of tomato products ( lycopene ), soy products (isoflavonoids) and fruits. Secondary...tocopherols and tocotrienols, have variable growth inhibitory effects on both types of prostate cancer cell line models. The gamma isoforms are more... effective than the alpha isoforms and the tocotrienols are more effective than the tocopherols. This study further showed that the vitamin E-mediated

  10. Prostate Cancer Prevention

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . The prostate is just below the bladder (the ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  11. IMRT versus 3D-CRT for thyroid cancer

    NASA Astrophysics Data System (ADS)

    Gizynska, Marta K.; Zawadzka, Anna

    2008-01-01

    A 3D-CRT involving a 4-field (5-field, 6-field, etc.) technique (photon and electron beams) and an alternative IMRT 7-field technique with 6 MV photon fields for thyroid cancer were compared. The IMRT allows reduction in the dose to the spinal cord of about 12 Gy and permits better coverage of the target volume with smaller standard deviation (average 4.65% for 3D-CRT as compared with 1.81% for IMRT). The time needed to prepare therapy (TPS, dosimetry, preparing boluses and electron aperture) and the session time are about the same for both techniques.

  12. Genomic Rearrangements in Prostate Cancer

    PubMed Central

    Barbieri, Christopher E.; Rubin, Mark A.

    2014-01-01

    Purpose of review Genomic instability is a fundamental feature of human cancer, leading to the activation of oncogenes and inactivation of tumor suppressors. In prostate cancer, structural genomic rearrangements, resulting in gene fusions, amplifications and deletions, are a critical mechanism effecting these alterations. Here we review recent literature regarding the importance of genomic rearrangements in the pathogenesis of prostate cancer and the potential impact on patient care. Recent findings Next generation sequencing has revealed a striking abundance, complexity, and heterogeneity of genomic rearrangements in prostate cancer. These recent studies have nominated a number of processes in predisposing prostate cancer to genomic rearrangements, including androgen-induced transcription. Summary Structural rearrangements are the critical mechanism resulting in the characteristic genomic changes associated with prostate cancer pathogenesis and progression. Future studies will determine if the impact of these events on tumor phenotypes can be translated to clinical utility for patient prognosis and choices of management strategies. PMID:25393273

  13. Segmentation of Image Data from Complex Organotypic 3D Models of Cancer Tissues with Markov Random Fields

    PubMed Central

    Robinson, Sean; Guyon, Laurent; Nevalainen, Jaakko; Toriseva, Mervi

    2015-01-01

    Organotypic, three dimensional (3D) cell culture models of epithelial tumour types such as prostate cancer recapitulate key aspects of the architecture and histology of solid cancers. Morphometric analysis of multicellular 3D organoids is particularly important when additional components such as the extracellular matrix and tumour microenvironment are included in the model. The complexity of such models has so far limited their successful implementation. There is a great need for automatic, accurate and robust image segmentation tools to facilitate the analysis of such biologically relevant 3D cell culture models. We present a segmentation method based on Markov random fields (MRFs) and illustrate our method using 3D stack image data from an organotypic 3D model of prostate cancer cells co-cultured with cancer-associated fibroblasts (CAFs). The 3D segmentation output suggests that these cell types are in physical contact with each other within the model, which has important implications for tumour biology. Segmentation performance is quantified using ground truth labels and we show how each step of our method increases segmentation accuracy. We provide the ground truth labels along with the image data and code. Using independent image data we show that our segmentation method is also more generally applicable to other types of cellular microscopy and not only limited to fluorescence microscopy. PMID:26630674

  14. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  15. What's New in Prostate Cancer Research and Treatment?

    MedlinePlus

    ... Cancer Research? Prostate Cancer About Prostate Cancer What’s New in Prostate Cancer Research? Research into the causes, ... in many medical centers throughout the world. Genetics New research on gene changes linked to prostate cancer ...

  16. 3D cancer cell migration in a confined matrix

    NASA Astrophysics Data System (ADS)

    Alobaidi, Amani; Sun, Bo

    Cancer cell migration is widely studied in 2D motion, which does not mimic the invasion processes in vivo. More recently, 3D cell migration studies have been performed. The ability of cancer cells to migrate within the extracellular matrix depends on the physical and biochemical features of the extracellular matrix. We present a model of cell motility in confined matrix geometry. The aim of the study is to study cancer migration in collagen matrix, as a soft tissue, to investigate their motility within the confined and surrounding collagen environment. Different collagen concentrations have been used to show the ability of these cancer cells to move through such a complex structure by measuring Cancer cell migration velocity as well as the displacement. Graduate student physics department.

  17. National Cancer Institute Prostate Cancer Genetics Workshop.

    PubMed

    Catalona, William J; Bailey-Wilson, Joan E; Camp, Nicola J; Chanock, Stephen J; Cooney, Kathleen A; Easton, Douglas F; Eeles, Rosalind A; FitzGerald, Liesel M; Freedman, Matthew L; Gudmundsson, Julius; Kittles, Rick A; Margulies, Elliott H; McGuire, Barry B; Ostrander, Elaine A; Rebbeck, Timothy R; Stanford, Janet L; Thibodeau, Stephen N; Witte, John S; Isaacs, William B

    2011-05-15

    Compelling evidence supports a genetic component to prostate cancer susceptibility and aggressiveness. Recent genome-wide association studies have identified more than 30 single-nucleotide polymorphisms associated with prostate cancer susceptibility. It remains unclear, however, whether such genetic variants are associated with disease aggressiveness--one of the most important questions in prostate cancer research today. To help clarify this and substantially expand research in the genetic determinants of prostate cancer aggressiveness, the first National Cancer Institute Prostate Cancer Genetics Workshop assembled researchers to develop plans for a large new research consortium and patient cohort. The workshop reviewed the prior work in this area and addressed the practical issues in planning future studies. With new DNA sequencing technology, the potential application of sequencing information to patient care is emerging. The workshop, therefore, included state-of-the-art presentations by experts on new genotyping technologies, including sequencing and associated bioinformatics issues, which are just beginning to be applied to cancer genetics.

  18. Biomarkers in localized prostate cancer.

    PubMed

    Ferro, Matteo; Buonerba, Carlo; Terracciano, Daniela; Lucarelli, Giuseppe; Cosimato, Vincenzo; Bottero, Danilo; Deliu, Victor M; Ditonno, Pasquale; Perdonà, Sisto; Autorino, Riccardo; Coman, Ioman; De Placido, Sabino; Di Lorenzo, Giuseppe; De Cobelli, Ottavio

    2016-02-01

    Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

  19. Combining Population and Patient-Specific Characteristics for Prostate Segmentation on 3D CT Images.

    PubMed

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M; Fei, Baowei

    2016-02-27

    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

  20. Combining population and patient-specific characteristics for prostate segmentation on 3D CT images

    NASA Astrophysics Data System (ADS)

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei

    2016-03-01

    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy.

  1. Combining Population and Patient-Specific Characteristics for Prostate Segmentation on 3D CT Images

    PubMed Central

    Ma, Ling; Guo, Rongrong; Tian, Zhiqiang; Venkataraman, Rajesh; Sarkar, Saradwata; Liu, Xiabi; Tade, Funmilayo; Schuster, David M.; Fei, Baowei

    2016-01-01

    Prostate segmentation on CT images is a challenging task. In this paper, we explore the population and patient-specific characteristics for the segmentation of the prostate on CT images. Because population learning does not consider the inter-patient variations and because patient-specific learning may not perform well for different patients, we are combining the population and patient-specific information to improve segmentation performance. Specifically, we train a population model based on the population data and train a patient-specific model based on the manual segmentation on three slice of the new patient. We compute the similarity between the two models to explore the influence of applicable population knowledge on the specific patient. By combining the patient-specific knowledge with the influence, we can capture the population and patient-specific characteristics to calculate the probability of a pixel belonging to the prostate. Finally, we smooth the prostate surface according to the prostate-density value of the pixels in the distance transform image. We conducted the leave-one-out validation experiments on a set of CT volumes from 15 patients. Manual segmentation results from a radiologist serve as the gold standard for the evaluation. Experimental results show that our method achieved an average DSC of 85.1% as compared to the manual segmentation gold standard. This method outperformed the population learning method and the patient-specific learning approach alone. The CT segmentation method can have various applications in prostate cancer diagnosis and therapy. PMID:27660382

  2. Critical assessment of intramodality 3D ultrasound imaging for prostate IGRT compared to fiducial markers

    SciTech Connect

    Meer, Skadi van der; Bloemen-van Gurp, Esther; Hermans, Jolanda; Voncken, Robert; Heuvelmans, Denys; Gubbels, Carol; Fontanarosa, Davide; Visser, Peter; Lutgens, Ludy; Gils, Francis van; Verhaegen, Frank

    2013-07-15

    Purpose: A quantitative 3D intramodality ultrasound (US) imaging system was verified for daily in-room prostate localization, and compared to prostate localization based on implanted fiducial markers (FMs).Methods: Thirteen prostate patients underwent multiple US scans during treatment. A total of 376 US-scans and 817 matches were used to determine the intra- and interoperator variability. Additionally, eight other patients underwent daily prostate localization using both US and electronic portal imaging (EPI) with FMs resulting in 244 combined US-EPI scans. Scanning was performed with minimal probe pressure and a correction for the speed of sound aberration was performed. Uncertainties of both US and FM methods were assessed. User variability of the US method was assessed.Results: The overall US user variability is 2.6 mm. The mean differences between US and FM are: 2.5 {+-} 4.0 mm (LR), 0.6 {+-} 4.9 mm (SI), and -2.3 {+-} 3.6 mm (AP). The intramodality character of this US system mitigates potential errors due to transducer pressure and speed of sound aberrations.Conclusions: The overall accuracy of US (3.0 mm) is comparable to our FM workflow (2.2 mm). Since neither US nor FM can be considered a gold standard no conclusions can be drawn on the superiority of either method. Because US imaging captures the prostate itself instead of surrogates no invasive procedure is required. It requires more effort to standardize US imaging than FM detection. Since US imaging does not involve a radiation burden, US prostate imaging offers an alternative for FM EPI positioning.

  3. Stages of Prostate Cancer

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  4. Prostate Cancer Screening

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system located just below the bladder (the organ that ... up part of semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  5. Human Prostate Cancer Hallmarks Map.

    PubMed

    Datta, Dipamoy; Aftabuddin, Md; Gupta, Dinesh Kumar; Raha, Sanghamitra; Sen, Prosenjit

    2016-08-01

    Human prostate cancer is a complex heterogeneous disease that mainly affects elder male population of the western world with a high rate of mortality. Acquisitions of diverse sets of hallmark capabilities along with an aberrant functioning of androgen receptor signaling are the central driving forces behind prostatic tumorigenesis and its transition into metastatic castration resistant disease. These hallmark capabilities arise due to an intense orchestration of several crucial factors, including deregulation of vital cell physiological processes, inactivation of tumor suppressive activity and disruption of prostate gland specific cellular homeostasis. The molecular complexity and redundancy of oncoproteins signaling in prostate cancer demands for concurrent inhibition of multiple hallmark associated pathways. By an extensive manual curation of the published biomedical literature, we have developed Human Prostate Cancer Hallmarks Map (HPCHM), an onco-functional atlas of human prostate cancer associated signaling and events. It explores molecular architecture of prostate cancer signaling at various levels, namely key protein components, molecular connectivity map, oncogenic signaling pathway map, pathway based functional connectivity map etc. Here, we briefly represent the systems level understanding of the molecular mechanisms associated with prostate tumorigenesis by considering each and individual molecular and cell biological events of this disease process.

  6. Multimodal 3D cancer-mimicking optical phantom

    PubMed Central

    Smith, Gennifer T.; Lurie, Kristen L.; Zlatev, Dimitar V.; Liao, Joseph C.; Ellerbee Bowden, Audrey K.

    2016-01-01

    Three-dimensional (3D) organ-mimicking phantoms provide realistic imaging environments for testing various aspects of optical systems, including for evaluating new probe designs, characterizing the diagnostic potential of new technologies, and assessing novel image processing algorithms prior to validation in real tissue. We introduce and characterize the use of a new material, Dragon Skin (Smooth-On Inc.), and fabrication technique, air-brushing, for fabrication of a 3D phantom that mimics the appearance of a real organ under multiple imaging modalities. We demonstrate the utility of the material and technique by fabricating the first 3D, hollow bladder phantom with realistic normal and multi-stage pathology features suitable for endoscopic detection using the gold standard imaging technique, white light cystoscopy (WLC), as well as the complementary imaging modalities of optical coherence tomography and blue light cystoscopy, which are aimed at improving the sensitivity and specificity of WLC to bladder cancer detection. The flexibility of the material and technique used for phantom construction allowed for the representation of a wide range of diseased tissue states, ranging from inflammation (benign) to high-grade cancerous lesions. Such phantoms can serve as important tools for trainee education and evaluation of new endoscopic instrumentation. PMID:26977369

  7. Polyphenols and Prostate Cancer Chemoprevention

    DTIC Science & Technology

    2005-03-01

    prostate chemoprevention are the soy isoflavone, genistein, and the tea catechin , (-)- epigallocatechin-3-gallate (EGCG). Another polyphenol that has...diet high in soy products have reduced incidence of clinically manifested prostate cancers. Likewise, Asians have a long history of drinking tea

  8. Toward 3D-guided prostate biopsy target optimization: an estimation of tumor sampling probabilities

    NASA Astrophysics Data System (ADS)

    Martin, Peter R.; Cool, Derek W.; Romagnoli, Cesare; Fenster, Aaron; Ward, Aaron D.

    2014-03-01

    Magnetic resonance imaging (MRI)-targeted, 3D transrectal ultrasound (TRUS)-guided "fusion" prostate biopsy aims to reduce the ~23% false negative rate of clinical 2D TRUS-guided sextant biopsy. Although it has been reported to double the positive yield, MRI-targeted biopsy still yields false negatives. Therefore, we propose optimization of biopsy targeting to meet the clinician's desired tumor sampling probability, optimizing needle targets within each tumor and accounting for uncertainties due to guidance system errors, image registration errors, and irregular tumor shapes. We obtained multiparametric MRI and 3D TRUS images from 49 patients. A radiologist and radiology resident contoured 81 suspicious regions, yielding 3D surfaces that were registered to 3D TRUS. We estimated the probability, P, of obtaining a tumor sample with a single biopsy. Given an RMS needle delivery error of 3.5 mm for a contemporary fusion biopsy system, P >= 95% for 21 out of 81 tumors when the point of optimal sampling probability was targeted. Therefore, more than one biopsy core must be taken from 74% of the tumors to achieve P >= 95% for a biopsy system with an error of 3.5 mm. Our experiments indicated that the effect of error along the needle axis on the percentage of core involvement (and thus the measured tumor burden) was mitigated by the 18 mm core length.

  9. Prostate Cancer Skeletal Metastases: Pathobiology and Interventions

    DTIC Science & Technology

    2005-02-01

    in higher levels in prostate carcinoma than in benign prostatic hyperplasia [35, 36], and is found in human metastatic lesions in bone [37]. However...compared to normal controls, benign prostatic hyperplasia , prostatitis, and localized or recurrent disease. In an animal model, prostate tumor cells...Malakouti S, Antar S, Kukreja S. Enhanced expression of parathyroid hormone-related protein in prostate cancer as compared with benign prostatic hyperplasia . Hum

  10. Urinary Biomarkers for Prostate Cancer.

    PubMed

    Tosoian, Jeffrey J; Ross, Ashley E; Sokoll, Lori J; Partin, Alan W; Pavlovich, Christian P

    2016-02-01

    In light of the overdiagnosis and overtreatment associated with widespread prostate-specific antigen-based screening, controversy persists surrounding the detection and diagnosis of prostate cancer (PCa). Given its anatomic proximity to the prostate, urine has been proposed as a noninvasive substrate for prostatic biomarkers. With greater understanding of the molecular pathways of carcinogenesis and significant technological advances, the breadth of potential biomarkers is substantial. In this review, the authors aim to provide an evidence-based assessment of current and emerging urinary biomarkers used in the detection and prognostication of PCa and high-grade PCa, with particular attention on clinically relevant findings.

  11. Genetics Home Reference: prostate cancer

    MedlinePlus

    ... genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence ...

  12. Tuberculous prostatitis: mimicking a cancer

    PubMed Central

    Aziz, El Majdoub; Abdelhak, Khallouk; Hassan, Farih Moulay

    2016-01-01

    Genitourinary tuberculosis is a common type of extra-pulmonary tuberculosis . The kidneys, ureter, bladder or genital organs are usually involved. Tuberculosis of the prostate has mainly been described in immune-compromised patients. However, it can exceptionally be found as an isolated lesion in immune-competent patients. Tuberculosis of the prostate may be difficult to differentiate from carcinoma of the prostate and the chronic prostatitis when the prostate is hard and nodular on digital rectal examination and the urine is negative for tuberculosis bacilli. In many cases, a diagnosis of tuberculous prostatitis is made by the pathologist, or the disease is found incidentally after transurethral resection. Therefore, suspicion of tuberculous prostatitis requires a confirmatory biopsy of the prostate. We report the case of 60-year-old man who presented a low urinary tract syndrome. After clinical and biological examination, and imaging, prostate cancer was highly suspected. Transrectal needle biopsy of the prostate was performed and histological examination showed tuberculosis lesions. PMID:28292092

  13. Hyaluronan Biosynthesis in Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    SUPPLEMENTARY NOTES 14. ABSTRACT: Despite advances in the diagnosis and treatment of prostate cancer in the last several years, metastasis represents the... metastasis to lymph nodes and bone. Metastasis to bone is especially noteworthy, not only because it reflects more advanced tumors, but also because of the...the growth and metastasis of androgen-independent tumors, it may be possible to better diagnose and treat prostate cancers by inhibiting growth of

  14. Cancer Cytokines and the Relevance of 3D Cultures for Studying those Implicated in Human Cancers.

    PubMed

    Maddaly, Ravi; Subramaniyan, Aishwarya; Balasubramanian, Harini

    2017-03-06

    Cancers are complex conditions and involving several factors for oncogenesis and progression. Of the various factors influencing the physiology of cancers, cytokines are known to play significant roles as mediators of functions. Intricate cytokine networks have been identified in cancers and interest in cytokines associated with cancers has been gaining ground. Of late, some of these cytokines are even identified as potential targets for cancer therapy apart from a few others such as IL-6 being identified as markers for disease prognosis. Of the major contributors to cancer research, cancer cell lines occupy the top slot as the most widely used material in vitro. In vitro cell cultures have seen significant evolution by the introduction of 3 dimensional (3D) culture systems. 3D cell cultures are now widely accepted as excellent material for cancer research which surpasses the traditional monolayer cultures. Cancer research has benefitted from 3D cell cultures for understanding the various hallmarks of cancers. However, the potential of these culture systems are still unexploited for cancer cytokine research compared to the other aspects of cancers such as gene expression changes, drug-induced toxicity, morphology, angiogenesis and invasion. Considering the importance of cancer cytokines, 3D cell cultures can be better utilized in understanding their roles and functions. Some of the possibilities where 3D cell cultures can contribute to cancer cytokine research arise from the distinct morphology of the tumor spheroids, the extracellular matrix (ECM), and the spontaneous occurrence of nutrient and oxygen gradients. Also, the 3D culture models enable one to co-culture different types of cells as a simulation of in vivo conditions, enhancing their utility to study cancer cytokines. We review here the cancer associated cytokines the contributions of 3D cancer cell cultures for studying cancer cytokines. This article is protected by copyright. All rights reserved.

  15. Immunotherapy in metastatic prostate cancer

    PubMed Central

    Slovin, Susan F.

    2016-01-01

    Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit. PMID:27843208

  16. Lycopene: redress for prostate cancer.

    PubMed

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

    2012-03-01

    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.

  17. 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

  18. Microfabricated polymeric vessel mimetics for 3-D cancer cell culture

    PubMed Central

    Jaeger, Ashley A.; Das, Chandan K.; Morgan, Nicole Y.; Pursley, Randall H.; McQueen, Philip G.; Hall, Matthew D.; Pohida, Thomas J.; Gottesman, Michael M.

    2013-01-01

    Modeling tumor growth in vitro is essential for cost-effective testing of hypotheses in preclinical cancer research. 3-D cell culture offers an improvement over monolayer culture for studying cellular processes in cancer biology because of the preservation of cell-cell and cell-ECM interactions. Oxygen transport poses a major barrier to mimicking in vivo environments and is not replicated in conventional cell culture systems. We hypothesized that we can better mimic the tumor microenvironment using a bioreactor system for controlling gas exchange in cancer cell cultures with silicone hydrogel synthetic vessels. Soft-lithography techniques were used to fabricate oxygen-permeable silicone hydrogel membranes containing arrays of micropillars. These membranes were inserted into a bioreactor and surrounded by basement membrane extract (BME) within which fluorescent ovarian cancer (OVCAR8) cells were cultured. Cell clusters oxygenated by synthetic vessels showed a ∼100um drop-off to anoxia, consistent with in vivo studies of tumor nodules fed by the microvasculature. We showed oxygen tension gradients inside the clusters oxygenated by synthetic vessels had a ∼100 µm drop-off to anoxia, which is consistent with in vivo studies. Oxygen transport in the bioreactor system was characterized by experimental testing with a dissolved oxygen probe and finite element modeling of convective flow. Our study demonstrates differing growth patterns associated with controlling gas distributions to better mimic in vivo conditions. PMID:23911071

  19. Sirolimus, Docetaxel, and Carboplatin in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2016-11-10

    Castration Levels of Testosterone; Hormone-Resistant Prostate Cancer; Metastatic Prostate Carcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  20. Microfabricated electrospun collagen membranes for 3-D cancer models and drug screening applications

    PubMed Central

    Hartman, Olga; Zhang, Chu; Adams, Elizabeth L.; Farach-Carson, Mary C.; Petrelli, Nicholas J.; Chase, Bruce D.; Rabolt, John F.

    2009-01-01

    Invasive epithelial tumors form from cells that are released from their natural basement membrane and form 3-D structures that interact with each other and with the microenvironment of the stromal tissues around the tumor, which often contains collagen. Cancer cells, growing as monolayers on tissue culture plastic, do not reflect many of the properties of whole tumors. This shortcoming limits their ability to serve as models for testing of pharmacologically active compounds, including those that are being tested as anti-neoplastics. This work seeks to create new 3-D cellular materials possessing properties similar to those in native tissues surrounding cancers, specifically electrospun micro- and nanofibrous collagen scaffolds that support tumor growth in 3-D. We hypothesize that a 3-D culture system will provide a better replica of tumor growth in a native environment, and thus better report the bioactivity of anti-neoplastic agents. In addition, we optimized conditions, and identified physical characteristics that support growth of the highly invasive, prostate cancer bone metastatic cell line C4-2B on these matrices for use in anti-cancer drug studies. The effects of matrix porosity, fiber diameter, elasticity and surface roughness on growth of cancer cells were evaluated. Data indicates that while cells attach and grow well on both nano- and microfibrous electrospun membranes, the microfibrous membrane represented a better approximation of the tumor microenvironemt. It was also observed that C4-2B non-adherent cells migrated through the depth of two electrospun membranes and formed colonies resembling tumors on day 3. An apoptosis study revealed that cells on electrospun substrates were more resistant to both anti-neoplastic agents, docetaxel (DOC) and camptothecin (CAM), compared to the cells grown on standard collagen-coated tissue culture polystyrene (TCP). Growth, survival, and apoptosis were measured, as well as the differences in the apoptotic

  1. The Danish Prostate Cancer Database

    PubMed Central

    Nguyen-Nielsen, Mary; Høyer, Søren; Friis, Søren; Hansen, Steinbjørn; Brasso, Klaus; Jakobsen, Erik Breth; Moe, Mette; Larsson, Heidi; Søgaard, Mette; Nakano, Anne; Borre, Michael

    2016-01-01

    Aim of database The Danish Prostate Cancer Database (DAPROCAdata) is a nationwide clinical cancer database that has prospectively collected data on patients with incident prostate cancer in Denmark since February 2010. The overall aim of the DAPROCAdata is to improve the quality of prostate cancer care in Denmark by systematically collecting key clinical variables for the purposes of health care monitoring, quality improvement, and research. Study population All Danish patients with histologically verified prostate cancer are included in the DAPROCAdata. Main variables The DAPROCAdata registers clinical data and selected characteristics for patients with prostate cancer at diagnosis. Data are collected from the linkage of nationwide health registries and supplemented with online registration of key clinical variables by treating physicians at urological and oncological departments. Main variables include Gleason scores, cancer staging, prostate-specific antigen values, and therapeutic measures (active surveillance, surgery, radiotherapy, endocrine therapy, and chemotherapy). Descriptive data In total, 22,332 patients with prostate cancer were registered in DAPROCAdata as of April 2015. A key feature of DAPROCAdata is the routine collection of patient-reported outcome measures (PROM), including data on quality-of-life (pain levels, physical activity, sexual function, depression, urine and fecal incontinence) and lifestyle factors (smoking, alcohol consumption, and body mass index). PROM data are derived from questionnaires distributed at diagnosis and at 1-year and 3-year follow-up. Hitherto, the PROM data have been limited by low completeness (26% among newly diagnosed patients in 2014). Conclusion DAPROCAdata is a comprehensive, yet still young clinical database. Efforts to improve data collection, data validity, and completeness are ongoing and of high priority. PMID:27843346

  2. Strategies to evaluate the impact of rectal volume on prostate motion during three-dimensional conformal radiotherapy for prostate cancer*

    PubMed Central

    Poli, Ana Paula Diniz Fortuna; Dias, Rodrigo Souza; Giordani, Adelmo José; Segreto, Helena Regina Comodo; Segreto, Roberto Araujo

    2016-01-01

    Objective To evaluate the rectal volume influence on prostate motion during three-dimensional conformal radiotherapy (3D-CRT) for prostate cancer. Materials and Methods Fifty-one patients with prostate cancer underwent a series of three computed tomography scans including an initial planning scan and two subsequent scans during 3D-CRT. The organs of interest were outlined. The prostate contour was compared with the initial CT images considering the anterior, posterior, superior, inferior and lateral edges of the organ. Variations in the anterior limits and volume of the rectum were assessed and correlated with prostate motion in the anteroposterior direction. Results The maximum range of prostate motion was observed in the superoinferior direction, followed by the anteroposterior direction. A significant correlation was observed between prostate motion and rectal volume variation (p = 0.037). A baseline rectal volume superior to 70 cm3 had a significant influence on the prostate motion in the anteroposterior direction (p = 0.045). Conclusion The present study showed a significant interfraction motion of the prostate during 3D-CRT with greatest variations in the superoinferior and anteroposterior directions, and that a large rectal volume influences the prostate motion with a cutoff value of 70 cm3. Therefore, the treatment of patients with a rectal volume > 70 cm3 should be re-planned with appropriate rectal preparation. PMID:26929456

  3. What Tests Can Detect Prostate Cancer?

    MedlinePlus

    ... Prevention and Early Detection What Tests Can Detect Prostate Cancer Early? The tests discussed below are used to ... also found in the blood. Most men without prostate cancer have PSA levels under 4 nanograms per milliliter ( ...

  4. Epigenetics of prostate cancer.

    PubMed

    McKee, Tawnya C; Tricoli, James V

    2015-01-01

    The introduction of novel technologies that can be applied to the investigation of the molecular underpinnings of human cancer has allowed for new insights into the mechanisms associated with tumor development and progression. They have also advanced the diagnosis, prognosis and treatment of cancer. These technologies include microarray and other analysis methods for the generation of large-scale gene expression data on both mRNA and miRNA, next-generation DNA sequencing technologies utilizing a number of platforms to perform whole genome, whole exome, or targeted DNA sequencing to determine somatic mutational differences and gene rearrangements, and a variety of proteomic analysis platforms including liquid chromatography/mass spectrometry (LC/MS) analysis to survey alterations in protein profiles in tumors. One other important advancement has been our current ability to survey the methylome of human tumors in a comprehensive fashion through the use of sequence-based and array-based methylation analysis (Bock et al., Nat Biotechnol 28:1106-1114, 2010; Harris et al., Nat Biotechnol 28:1097-1105, 2010). The focus of this chapter is to present and discuss the evidence for key genes involved in prostate tumor development, progression, or resistance to therapy that are regulated by methylation-induced silencing.

  5. Proton therapy for prostate cancer.

    PubMed

    Hoppe, Bradford; Henderson, Randal; Mendenhall, William M; Nichols, Romaine C; Li, Zuofeng; Mendenhall, Nancy P

    2011-06-01

    Proton therapy has been used in the treatment of cancer for over 50 years. Due to its unique dose distribution with its spread-out Bragg peak, proton therapy can deliver highly conformal radiation to cancers located adjacent to critical normal structures. One of the important applications of its use is in prostate cancer, since the prostate is located adjacent to the rectum and bladder. Over 30 years of data have been published on the use of proton therapy in prostate cancer; these data have demonstrated high rates of local and biochemical control as well as low rates of urinary and rectal toxicity. Although before 2000 proton therapy was available at only a couple of centers in the United States, several new proton centers have been built in the last decade. With the increased availability of proton therapy, research on its use for prostate cancer has accelerated rapidly. Current research includes explorations of dose escalation, hypofractionation, and patient-reported quality-of-life outcomes. Early results from these studies are promising and will likely help make proton therapy for the treatment of prostate cancer more cost-effective.

  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. 2D Ultrasound and 3D MR Image Registration of the Prostate for Brachytherapy Surgical Navigation

    PubMed Central

    Zhang, Shihui; Jiang, Shan; Yang, Zhiyong; Liu, Ranlu

    2015-01-01

    Abstract Two-dimensional (2D) ultrasound (US) images are widely used in minimally invasive prostate procedure for its noninvasive nature and convenience. However, the poor quality of US image makes it difficult to be used as guiding utility. To improve the limitation, we propose a multimodality image guided navigation module that registers 2D US images with magnetic resonance imaging (MRI) based on high quality preoperative models. A 2-step spatial registration method is used to complete the procedure which combines manual alignment and rapid mutual information (MI) optimize algorithm. In addition, a 3-dimensional (3D) reconstruction model of prostate with surrounding organs is employed to combine with the registered images to conduct the navigation. Registration accuracy is measured by calculating the target registration error (TRE). The results show that the error between the US and preoperative MR images of a polyvinyl alcohol hydrogel model phantom is 1.37 ± 0.14 mm, with a similar performance being observed in patient experiments. PMID:26448009

  8. Counseling the Client with Prostate Cancer.

    ERIC Educational Resources Information Center

    Curtis, Russell C.; Juhnke, Gerald A.

    2003-01-01

    Prostate cancer is prevalent in the United States and has a far-reaching effect on men and their relationships. Being diagnosed with and treated for prostate cancer often causes men to experience side effects that induce physical, emotional, and social change. Counselors need to be aware of prostate cancer's impact on men and their families.…

  9. Microtubule Control of Metabolism in Prostate Cancer

    DTIC Science & Technology

    2013-06-01

    Prostate Cancer PRINCIPAL INVESTIGATOR: Lynne Cassimeris CONTRACTING ORGANIZATION...Microtubule Control of Metabolism in Prostate Cancer 5b. GRANT NUMBER W81XWH-12-1-0071 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT...SUPPLEMENTARY NOTES 14. ABSTRACT The current standard chemotherapy treatment for metastatic castrate-resistant prostate cancer is the microtubule

  10. Microtubule Control of Metabolism in Prostate Cancer

    DTIC Science & Technology

    2013-11-01

    Prostate Cancer PRINCIPAL INVESTIGATOR: Lynne Cassimeris CONTRACTING ORGANIZATION: Lehigh University Bethlehem, PA 18015-3008 REPORT...Control of Metabolism in Prostate Cancer Dr. Lynne Cassimeris lc07@lehigh.edu Lehigh University 526 Brodhead Avenue Bethlehem, PA 18015-3008 U.S...tested whether metabolic inhibitors, metformin or 2-deoxy-glucose, function synergistically with docetaxel to block prostate cancer cell proliferation

  11. Reduction of Racial Disparities in Prostate Cancer

    DTIC Science & Technology

    2008-12-01

    JF, Levine AC. Inhibition of cyclooxygenase-2 suppresses angiogenesis and the growth of prostate cancer in vivo. J Urol 2000:164:820-5 10. Mahmud...Tzivony Y, Flescher E. Contrasting effects of aspirin on prostate cancer cells: suppression of proliferation and induction of drug resistance...TITLE: Reduction of Racial Disparities in Prostate Cancer PRINCIPAL INVESTIGATOR: Nicholas Daniels, MD MPH, Principal Investigator

  12. Prostate cancer brachytherapy: guidelines overview

    PubMed Central

    Białas, Brygida

    2012-01-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy. PMID:23349655

  13. Prostate cancer brachytherapy: guidelines overview.

    PubMed

    Wojcieszek, Piotr; Białas, Brygida

    2012-06-01

    Prostate cancer, due to wide availability of PSA tests, is very often diagnosed in early stage, nowadays. This makes management of this disease even harder in every day oncology care. There is a wide range of treatment options including surgery, radiotherapy and active surveillance, but essential question is which treatment patient and oncologist should decide for. Due to recent publication of Prostate Cancer Results Study Group, in which brachytherapy is one of supreme curative options for prostate cancer, we decided to overview most present european and north american recommendations. National Comprehensive Cancer Network, American Society for Radiation Oncology, American Brachytherapy Society, European Association of Urology and Groupe Européen de Curiethérapie of European Society for Therapeutic Radiation Oncology guidelines are overviewed, particularly focusing on HDR and LDR brachytherapy.

  14. The Relationship between Statins and Prostate Cancer Prevention

    DTIC Science & Technology

    2011-09-01

    In 2011, it is estimated that 240,890 men will be diagnosed with prostate cancer and 33,720 men will die from prostate cancer. Few prevention ...strategies for prostate cancer exist. HMG-CoA reductase inhibitors, statins, may prevent prostate cancer incidence and progression. We previously...prostate cancer in the Physicians’ Health Study and Early Stage Prostate Cancer Cohort study. Prostate cancer is commonly diagnosed and prevention

  15. Prostate Cancer Risk Prediction Models

    Cancer.gov

    Developing statistical models that estimate the probability of developing prostate cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  16. Detection of DNA viruses in prostate cancer.

    PubMed

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-04-28

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions.

  17. Targeting Prostate Cancer with Multifunctional Nanoparticles

    DTIC Science & Technology

    2015-10-01

    4 Fig 1. Characterization of three prostate cancer cell lines by western blot. COXIV is used as a loading control...characterize our three prostate cancer cell lines , LNCaP, DU145 and PC3, which are being used in this project. We showed that prostate specific antigen...PSA) is expressed in the LNCaP cells, but absent in the DU145 cells whereas AMACR (P504S) is expressed in all prostate cancer cell lines (Fig 1

  18. Metastatic Prostate Cancer of Hand

    PubMed Central

    Oshima, Koji; Ishimaru, Daichi; Nishimoto, Yutaka; Ohno, Yoshiyuki; Hirakawa, Akihiro; Miyazaki, Tatsuhiko; Akiyama, Haruhiko

    2016-01-01

    Soft tissue metastases of prostate cancer to other sites are extremely rare, and, to our best knowledge, there have been no reports of metastasis to soft tissue of the hand. A 63-year-old man was diagnosed with prostatic cancer. During treatment, bone and soft tissue metastases to the right hand, appearing in the first web space, were observed. The tumor was resected, along with both the first and second metacarpal bones. The thumb was reconstructed by pollicization of the remaining index finger, enabling the patient to use the pollicized thumb for activities of daily living. This is the first case report of prostate cancer metastasizing to the soft tissue in hand. After wide resection, pollicization was able to reconstruct a functional hand and thumb. PMID:27843661

  19. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  20. Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT.

    PubMed

    Gueorguiev, Gueorgui; Cotter, Christopher; Turcotte, Julie Catherine; Crawford, Bruce; Sharp, Gregory; Mah'D, Mufeed

    2015-09-08

    This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity-modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step-and-shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters 3%/3 mm DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors.

  1. Clinical implementation and error sensitivity of a 3D quality assurance protocol for prostate and thoracic IMRT.

    PubMed

    Gueorguiev, Gueorgui; Cotter, Christopher; Turcotte, Julie Catherine; Crawford, Bruce; Sharp, Gregory; Mah'D, Mufeed

    2015-09-01

    This work aims at three goals: first, to define a set of statistical parameters and plan structures for a 3D pretreatment thoracic and prostate intensity-modulated radiation therapy (IMRT) quality assurance (QA) protocol; secondly, to test if the 3D QA protocol is able to detect certain clinical errors; and third, to compare the 3D QA method with QA performed with single ion chamber and 2D gamma test in detecting those errors. The 3D QA protocol measurements were performed on 13 prostate and 25 thoracic IMRT patients using IBA's COMPASS system. For each treatment planning structure included in the protocol, the following statistical parameters were evaluated: average absolute dose difference (AADD), percent structure volume with absolute dose difference greater than 6% (ADD6), and 3D gamma test. To test the 3D QA protocol error sensitivity, two prostate and two thoracic step-and-shoot IMRT patients were investigated. Errors introduced to each of the treatment plans included energy switched from 6 MV to 10 MV, multileaf collimator (MLC) leaf errors, linac jaws errors, monitor unit (MU) errors, MLC and gantry angle errors, and detector shift errors. QA was performed on each plan using a single ion chamber and 2D array of ion chambers for 2D and 3D QA. Based on the measurements performed, we established a uniform set of tolerance levels to determine if QA passes for each IMRT treatment plan structure: maximum allowed AADD is 6%; maximum 4% of any structure volume can be with ADD6 greater than 6%, and maximum 4% of any structure volume may fail 3D gamma test with test parameters 3%/3 mm DTA. Out of the three QA methods tested the single ion chamber performed the worst by detecting 4 out of 18 introduced errors, 2D QA detected 11 out of 18 errors, and 3D QA detected 14 out of 18 errors. PACS number: 87.56.Fc.

  2. [Markers of prostate cancer stem cells: research advances].

    PubMed

    Wang, Shun-Qi; Huang, Sheng-Song

    2013-12-01

    Prostate cancer is one of the most seriously malignant diseases threatening men's health, and the mechanisms of its initiation and progression are not yet completely understood. Recent years have witnessed distinct advances in researches on prostate cancer stem cells in many aspects using different sources of materials, such as human prostate cancer tissues, human prostate cancer cell lines, and mouse models of prostate cancer. Prostate cancer stem cell study offers a new insight into the mechanisms of the initiation and progression of prostate cancer and contributes positively to its treatment. This article presents an overview on the prostate cancer stem cell markers utilized in the isolation and identification of prostate cancer stem cells.

  3. Prostate cancer immunotherapy: beyond immunity to curability.

    PubMed

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials.

  4. Fully automated prostate segmentation in 3D MR based on normalized gradient fields cross-correlation initialization and LOGISMOS refinement

    NASA Astrophysics Data System (ADS)

    Yin, Yin; Fotin, Sergei V.; Periaswamy, Senthil; Kunz, Justin; Haldankar, Hrishikesh; Muradyan, Naira; Cornud, François; Turkbey, Baris; Choyke, Peter

    2012-02-01

    Manual delineation of the prostate is a challenging task for a clinician due to its complex and irregular shape. Furthermore, the need for precisely targeting the prostate boundary continues to grow. Planning for radiation therapy, MR-ultrasound fusion for image-guided biopsy, multi-parametric MRI tissue characterization, and context-based organ retrieval are examples where accurate prostate delineation can play a critical role in a successful patient outcome. Therefore, a robust automated full prostate segmentation system is desired. In this paper, we present an automated prostate segmentation system for 3D MR images. In this system, the prostate is segmented in two steps: the prostate displacement and size are first detected, and then the boundary is refined by a shape model. The detection approach is based on normalized gradient fields cross-correlation. This approach is fast, robust to intensity variation and provides good accuracy to initialize a prostate mean shape model. The refinement model is based on a graph-search based framework, which contains both shape and topology information during deformation. We generated the graph cost using trained classifiers and used coarse-to-fine search and region-specific classifier training. The proposed algorithm was developed using 261 training images and tested on another 290 cases. The segmentation performance using mean DSC ranging from 0.89 to 0.91 depending on the evaluation subset demonstrates state of the art performance. Running time for the system is about 20 to 40 seconds depending on image size and resolution.

  5. Hormonal therapy of prostate cancer.

    PubMed

    Labrie, Fernand

    2010-01-01

    Of all cancers, prostate cancer is the most sensitive to hormones: it is thus very important to take advantage of this unique property and to always use optimal androgen blockade when hormone therapy is the appropriate treatment. A fundamental observation is that the serum testosterone concentration only reflects the amount of testosterone of testicular origin which is released in the blood from which it reaches all tissues. Recent data show, however, that an approximately equal amount of testosterone is made from dehydroepiandrosterone (DHEA) directly in the peripheral tissues, including the prostate, and does not appear in the blood. Consequently, after castration, the 95-97% fall in serum testosterone does not reflect the 40-50% testosterone (testo) and dihydrotestosterone (DHT) made locally in the prostate from DHEA of adrenal origin. In fact, while elimination of testicular androgens by castration alone has never been shown to prolong life in metastatic prostate cancer, combination of castration (surgical or medical with a gonadotropin-releasing hormone (GnRH) agonist) with a pure anti-androgen has been the first treatment shown to prolong life. Most importantly, when applied at the localized stage, the same combined androgen blockade (CAB) can provide long-term control or cure of the disease in more than 90% of cases. Obviously, since prostate cancer usually grows and metastasizes without signs or symptoms, screening with prostate-specific antigen (PSA) is absolutely needed to diagnose prostate cancer at an 'early' stage before metastasis occurs and the cancer becomes non-curable. While the role of androgens was believed to have become non-significant in cancer progressing under any form of androgen blockade, recent data have shown increased expression of the androgen receptor (AR) in treatment-resistant disease with a benefit of further androgen blockade. Since the available anti-androgens have low affinity for AR and cannot block androgen action completely

  6. Fast 3-d tomographic microwave imaging for breast cancer detection.

    PubMed

    Grzegorczyk, Tomasz M; Meaney, Paul M; Kaufman, Peter A; diFlorio-Alexander, Roberta M; Paulsen, Keith D

    2012-08-01

    Microwave breast imaging (using electromagnetic waves of frequencies around 1 GHz) has mostly remained at the research level for the past decade, gaining little clinical acceptance. The major hurdles limiting patient use are both at the hardware level (challenges in collecting accurate and noncorrupted data) and software level (often plagued by unrealistic reconstruction times in the tens of hours). In this paper we report improvements that address both issues. First, the hardware is able to measure signals down to levels compatible with sub-centimeter image resolution while keeping an exam time under 2 min. Second, the software overcomes the enormous time burden and produces similarly accurate images in less than 20 min. The combination of the new hardware and software allows us to produce and report here the first clinical 3-D microwave tomographic images of the breast. Two clinical examples are selected out of 400+ exams conducted at the Dartmouth Hitchcock Medical Center (Lebanon, NH). The first example demonstrates the potential usefulness of our system for breast cancer screening while the second example focuses on therapy monitoring.

  7. Special Section: New Ways to Detect Colon Cancer 3-D virtual screening now being used

    MedlinePlus

    ... New Ways to Detect Colon Cancer 3-D virtual screening now being used Past Issues / Spring 2009 ... showcases a 3-D image generated by the virtual colonoscopy software he invented with a team of ...

  8. Statistical modeling and visualization of localized prostate cancer

    NASA Astrophysics Data System (ADS)

    Wang, Yue J.; Xuan, Jianhua; Sesterhenn, Isabell A.; Hayes, Wendelin S.; Ebert, David S.; Lynch, John H.; Mun, Seong K.

    1997-05-01

    In this paper, a statistically significant master model of localized prostate cancer is developed with pathologically- proven surgical specimens to spatially guide specific points in the biopsy technique for a higher rate of prostate cancer detection and the best possible representation of tumor grade and extension. Based on 200 surgical specimens of the prostates, we have developed a surface reconstruction technique to interactively visualize in the clinically significant objects of interest such as the prostate capsule, urethra, seminal vesicles, ejaculatory ducts and the different carcinomas, for each of these cases. In order to investigate the complex disease pattern including the tumor distribution, volume, and multicentricity, we created a statistically significant master model of localized prostate cancer by fusing these reconstructed computer models together, followed by a quantitative formulation of the 3D finite mixture distribution. Based on the reconstructed prostate capsule and internal structures, we have developed a technique to align all surgical specimens through elastic matching. By labeling the voxels of localized prostate cancer by '1' and the voxels of other internal structures by '0', we can generate a 3D binary image of the prostate that is simply a mutually exclusive random sampling of the underlying distribution f cancer to gram of localized prostate cancer characteristics. In order to quantify the key parameters such as distribution, multicentricity, and volume, we used a finite generalized Gaussian mixture to model the histogram, and estimate the parameter values through information theoretical criteria and a probabilistic self-organizing mixture. Utilizing minimally-immersive and stereoscopic interactive visualization, an augmented reality can be developed to allow the physician to virtually hold the master model in one hand and use the dominant hand to probe data values and perform a simulated needle biopsy. An adaptive self- organizing

  9. SU-E-J-135: An Investigation of Ultrasound Imaging for 3D Intra-Fraction Prostate Motion Estimation

    SciTech Connect

    O'Shea, T; Harris, E; Bamber, J; Evans, P

    2014-06-01

    Purpose: This study investigates the use of a mechanically swept 3D ultrasound (US) probe to estimate intra-fraction motion of the prostate during radiation therapy using an US phantom and simulated transperineal imaging. Methods: A 3D motion platform was used to translate an US speckle phantom while simulating transperineal US imaging. Motion patterns for five representative types of prostate motion, generated from patient data previously acquired with a Calypso system, were using to move the phantom in 3D. The phantom was also implanted with fiducial markers and subsequently tracked using the CyberKnife kV x-ray system for comparison. A normalised cross correlation block matching algorithm was used to track speckle patterns in 3D and 2D US data. Motion estimation results were compared with known phantom translations. Results: Transperineal 3D US could track superior-inferior (axial) and anterior-posterior (lateral) motion to better than 0.8 mm root-mean-square error (RMSE) at a volume rate of 1.7 Hz (comparable with kV x-ray tracking RMSE). Motion estimation accuracy was poorest along the US probe's swept axis (right-left; RL; RMSE < 4.2 mm) but simple regularisation methods could be used to improve RMSE (< 2 mm). 2D US was found to be feasible for slowly varying motion (RMSE < 0.5 mm). 3D US could also allow accurate radiation beam gating with displacement thresholds of 2 mm and 5 mm exhibiting a RMSE of less than 0.5 mm. Conclusion: 2D and 3D US speckle tracking is feasible for prostate motion estimation during radiation delivery. Since RL prostate motion is small in magnitude and frequency, 2D or a hybrid (2D/3D) US imaging approach which also accounts for potential prostate rotations could be used. Regularisation methods could be used to ensure the accuracy of tracking data, making US a feasible approach for gating or tracking in standard or hypo-fractionated prostate treatments.

  10. Molecular Predictors of 3D Morphogenesis by Breast Cancer Cell Lines in 3D Culture

    SciTech Connect

    Han, Ju; Chang, Hang; Giricz, Orsi; Lee, Genee; Baehner, Frederick; Gray, Joe; Bissell, Mina; Kenny, Paraic; Parvin, Bahram

    2010-02-01

    Correlative analysis of molecular markers with phenotypic signatures is the simplest model for hypothesis generation. In this paper, a panel of 24 breast cell lines was grown in 3D culture, their morphology was imaged through phase contrast microscopy, and computational methods were developed to segment and represent each colony at multiple dimensions. Subsequently, subpopulations from these morphological responses were identified through consensus clustering to reveal three clusters of round, grape-like, and stellate phenotypes. In some cases, cell lines with particular pathobiological phenotypes clustered together (e.g., ERBB2 amplified cell lines sharing the same morphometric properties as the grape-like phenotype). Next, associations with molecular features were realized through (i) differential analysis within each morphological cluster, and (ii) regression analysis across the entire panel of cell lines. In both cases, the dominant genes that are predictive of the morphological signatures were identified. Specifically, PPAR? has been associated with the invasive stellate morphological phenotype, which corresponds to triple-negative pathobiology. PPAR? has been validated through two supporting biological assays.

  11. Infections and inflammation in prostate cancer.

    PubMed

    Sfanos, Karen S; Isaacs, William B; De Marzo, Angelo M

    2013-12-25

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an "enabling characteristic" of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections.

  12. Infections and inflammation in prostate cancer

    PubMed Central

    Sfanos, Karen S; Isaacs, William B; Marzo, Angelo M De

    2013-01-01

    The frequent observation of both acute and chronic inflammation of unknown stimulus in the adult prostate has motivated a large body of research aimed at identifying potential infectious agents that may elicit prostatic inflammation. The overarching hypothesis is that infection-induced inflammation may be associated with prostate cancer development or progression, as inflammation is known to serve as an “enabling characteristic” of cancer. With recent advances in molecular techniques for microorganism identification, a panoply of microorganisms has been scrutinized in prostate tissues and in relation to prostate carcinogenesis. The aim of this review is to summarize the current literature on the evidence for infectious agents as a contributing factor to prostatic inflammation and prostate cancer, and to highlight recent literature suggesting an infectious etiology to the biogenesis of prostatic corpora amylacea and on the development of mouse models of prostatic infections. PMID:25110720

  13. Biofunctionalization of electrospun PCL-based scaffolds with perlecan domain IV peptide to create a 3-D pharmacokinetic cancer model

    PubMed Central

    Hartman, Olga; Zhang, Chu; Adams, Elizabeth L.; Farach-Carson, Mary C.; Petrelli, Nicholas J.; Chase, Bruce D.; Rabolt, John F.

    2010-01-01

    Because prostate cancer cells metastasize to bone and exhibit osteoblastic features (osteomimicry), the interrelationships between bone-specific microenvironment and prostate cancer cells at sites of bone metastasis are critical to disease progression. In this work the bone marrow microenvironment in vitro was recreated both by tailoring scaffolds physical properties and by functionalizing electrospun polymer fibers with a bioactive peptide derived from domain IV of perlecan heparan sulfate proteoglycan. Electrospun poly (ε-caprolactone) (PCL) fibers and PCL/gelatin composite scaffolds were modified covalently with perlecan domain IV (PlnDIV) peptide. The expression of tight junction protein (E-cadherin) and focal adhesion kinase (FAK) phosphorylation on tyrosine 397 also were investigated. The described bioactive motif significantly enhanced adherence and infiltration of the metastatic prostate cancer cells on all modified electrospun substrates by day 5 post-seeding. Cells cultured on PlnDIV-modified matrices organized stress fibers and increased proliferation at statistically significant rates. Additional findings suggest that presence of PlnDIV peptide in the matrix reduced expression of tight junction protein and binding to PlnDIV peptide was accompanied by increased focal adhesion kinase (FAK) phosphorylation on tyrosine 397. We conclude that PlnDIV peptide supports key signaling events leading to proliferation, survival, and migration of C4-2B cancer cells; hence its incorporation into electrospun matrix is a key improvement to create a successful three-dimensional (3-D) pharmacokinetic cancer model. PMID:20417554

  14. Screening spectroscopy of prostate cancer

    NASA Astrophysics Data System (ADS)

    Yermolenko, S. B.; Voloshynskyy, D. I.; Fedoruk, O. S.

    2015-11-01

    The aim of the study was to establish objective parameters of the field of laser and incoherent radiation of different spectral ranges (UV, visible, IR) as a non-invasive optical method of interaction with different samples of biological tissues and fluids of patients to determine the state of prostate cancer and choosing the best personal treatment. The objects of study were selected venous blood plasma of patient with prostate cancer, histological sections of rat prostate gland in the postoperative period. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5-25 microns) dry residue of plasma by spectral diagnostic technique of thin histological sections of biological tissues.

  15. Particle radiotherapy for prostate cancer.

    PubMed

    Shioyama, Yoshiyuki; Tsuji, Hiroshi; Suefuji, Hiroaki; Sinoto, Makoto; Matsunobu, Akira; Toyama, Shingo; Nakamura, Katsumasa; Kudo, Sho

    2015-01-01

    Recent advances in external beam radiotherapy have allowed us to deliver higher doses to the tumors while decreasing doses to the surrounding tissues. Dose escalation using high-precision radiotherapy has improved the treatment outcomes of prostate cancer. Intensity-modulated radiation therapy has been widely used throughout the world as the most advanced form of photon radiotherapy. In contrast, particle radiotherapy has also been under development, and has been used as an effective and non-invasive radiation modality for prostate and other cancers. Among the particles used in such treatments, protons and carbon ions have the physical advantage that the dose can be focused on the tumor with only minimal exposure of the surrounding normal tissues. Furthermore, carbon ions also have radiobiological advantages that include higher killing effects on intrinsic radio-resistant tumors, hypoxic tumor cells and tumor cells in the G0 or S phase. However, the degree of clinical benefit derived from these theoretical advantages in the treatment of prostate cancer has not been adequately determined. The present article reviews the available literature on the use of particle radiotherapy for prostate cancer as well as the literature on the physical and radiobiological properties of this treatment, and discusses the role and the relative merits of particle radiotherapy compared with current photon-based radiotherapy, with a focus on proton beam therapy and carbon ion radiotherapy.

  16. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2010-05-01

    Center IRB, and the I owa City VA Medical Center Research and Development Committee. During the second and t hird years we have been recruiting pa...American Urologic Association (AUA). (3) Talks to prostate cancer survivor support groups in at the University of I owa , Mercy Medical Center in Cedar

  17. Sanguinarine: A Novel Agent Against Prostate Cancer

    DTIC Science & Technology

    2008-01-01

    surgical approaches have not been successful in the management of prostate cancer (CaP). Natural plant - based products have shown promise as anticancer...or treatment of prostate cancer . Several studies have shown that plant -derived alkaloids possess remarkable anticancer effects. Sanguinarine, an...Preclinical evaluation of plant alkaloid sanguinarine against prostate cancer development in a nude mice xenograft model. Proc Amer Assoc Cancer

  18. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2014-04-01

    epithelium , stroma, as well as immune system, and the fixed nature of the prostate model with expression of the large T antigen, which may have...prostate cancer glandular architecture formed (Figure 10). Figure 10. Subcutanous TRAMP Model to Recapitulate Prostate Cancer. TRAMP C2 cells...specifically modulate the TLR signaling pathway in prostate epithelium , stroma, and immune system. To parse out the role of TLR signaling in

  19. Association of multiparametric MRI quantitative imaging features with prostate cancer gene expression in MRI-targeted prostate biopsies

    PubMed Central

    Stoyanova, Radka; Pollack, Alan; Takhar, Mandeep; Lynne, Charles; Parra, Nestor; Lam, Lucia L.C.; Alshalalfa, Mohammed; Buerki, Christine; Castillo, Rosa; Jorda, Merce; Ashab, Hussam Al-deen; Kryvenko, Oleksandr N.; Punnen, Sanoj; Parekh, Dipen J.; Abramowitz, Matthew C.; Gillies, Robert J.; Davicioni, Elai; Erho, Nicholas; Ishkanian, Adrian

    2016-01-01

    Standard clinicopathological variables are inadequate for optimal management of prostate cancer patients. While genomic classifiers have improved patient risk classification, the multifocality and heterogeneity of prostate cancer can confound pre-treatment assessment. The objective was to investigate the association of multiparametric (mp)MRI quantitative features with prostate cancer risk gene expression profiles in mpMRI-guided biopsies tissues. Global gene expression profiles were generated from 17 mpMRI-directed diagnostic prostate biopsies using an Affimetrix platform. Spatially distinct imaging areas (‘habitats’) were identified on MRI/3D-Ultrasound fusion. Radiomic features were extracted from biopsy regions and normal appearing tissues. We correlated 49 radiomic features with three clinically available gene signatures associated with adverse outcome. The signatures contain genes that are over-expressed in aggressive prostate cancers and genes that are under-expressed in aggressive prostate cancers. There were significant correlations between these genes and quantitative imaging features, indicating the presence of prostate cancer prognostic signal in the radiomic features. Strong associations were also found between the radiomic features and significantly expressed genes. Gene ontology analysis identified specific radiomic features associated with immune/inflammatory response, metabolism, cell and biological adhesion. To our knowledge, this is the first study to correlate radiogenomic parameters with prostate cancer in men with MRI-guided biopsy. PMID:27438142

  20. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2014-05-01

    setting of cancer. Current efforts are focused on selecting RNA aptamers to receptors expressed on the surface of target cells with...institutions. A major project in the lab is targeted therapy of prostate cancer using PSMA-guided aptamers . Prabhat Goswami, PhD; Professor...participate. The Schultz lab also works to identify key cell-surface receptor residues as targets for novel peptide- and aptamer -based receptor

  1. Targeting prostate cancer stem cells.

    PubMed

    Crea, Francesco; Mathews, Lesley A; Farrar, William L; Hurt, Elaine M

    2009-12-01

    Cancer stem cells are the sub-population of cells present within tumors responsible for tumorigenesis. These cells have unique biological properties including self-renewal and the ability to differentiate. Furthermore, it is thought that these cells are more resistant to conventional chemotherapy and, as a result, are responsible for patient relapse. We will discuss the identification of prostate cancer stem cells, their unique properties and how these cells may be targeted for more efficacious therapies.

  2. Early Detection of Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    effective marker for diagnosis and detection of prostate cancer. Low concentrations of PSA would be detected using acoustic wave sensors because of...associated electrical field. For biological sensors, binding of a substance onto the resonating membrane surface causes a decrease in the acoustic...of diverse conditions and diseases including those that affect the thyroid, HIV, diabetes , pregnancy, and several types of cancer. In clinical

  3. Progress Against Prostate Cancer | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Progress Against Prostate Cancer Past Issues / Winter 2010 Table of Contents Click ... This can narrow the urethra, decreasing urine flow. Prostate cancer is made up of cells the body does ...

  4. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer.

    PubMed

    Białek, Waldemar; Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-12-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin.

  5. Granulomatous prostatitis after intravesical immunotherapy mimicking prostate cancer

    PubMed Central

    Rudzki, Sławomir; Iberszer, Paweł; Wronecki, Lech

    2016-01-01

    Intravesical immunotherapy with attenuated strains of Mycobacterium bovis is a widely used therapeutic option in patients with non-muscle-invasive transitional cell carcinoma of the bladder. A rare complication of intravesical therapy with the Bacillus Calmette-Guérin vaccine is granulomatous prostatitis, which due to increasing levels of prostate-specific antigen and abnormalities found in transrectal examination of the prostate may suggest concomitant prostate cancer. A case of extensive granulomatous prostatitis in a 61-year-old patient which occurred after the first course of a well-tolerated Bacillus Calmette-Guérin therapy is presented. Due to abnormalities found in rectal examination and an abnormal transrectal ultrasound image of the prostate with extensive infiltration mimicking neoplastic hyperplasia a core biopsy of the prostate was performed. Histopathological examination revealed inflammatory infiltration sites of tuberculosis origin. PMID:28138411

  6. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells.

    PubMed

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L; Han, Jessica H; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H; Bussey, Kimberly J; Meldrum, Deirdre R

    2016-08-09

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an 'epigenetic' drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat's differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action.

  7. Vorinostat differentially alters 3D nuclear structure of cancer and non-cancerous esophageal cells

    PubMed Central

    Nandakumar, Vivek; Hansen, Nanna; Glenn, Honor L.; Han, Jessica H.; Helland, Stephanie; Hernandez, Kathryn; Senechal, Patti; Johnson, Roger H.; Bussey, Kimberly J.; Meldrum, Deirdre R.

    2016-01-01

    The histone deacetylase (HDAC) inhibitor vorinostat has received significant attention in recent years as an ‘epigenetic’ drug used to treat solid tumors. However, its mechanisms of action are not entirely understood, particularly with regard to its interaction with the aberrations in 3D nuclear structure that accompany neoplastic progression. We investigated the impact of vorinostat on human esophageal epithelial cell lines derived from normal, metaplastic (pre-cancerous), and malignant tissue. Using a combination of novel optical computed tomography (CT)-based quantitative 3D absorption microscopy and conventional confocal fluorescence microscopy, we show that subjecting malignant cells to vorinostat preferentially alters their 3D nuclear architecture relative to non-cancerous cells. Optical CT (cell CT) imaging of fixed single cells showed that drug-treated cancer cells exhibit significant alterations in nuclear morphometry. Confocal microscopy revealed that vorinostat caused changes in the distribution of H3K9ac-marked euchromatin and H3K9me3-marked constitutive heterochromatin. Additionally, 3D immuno-FISH showed that drug-induced expression of the DNA repair gene MGMT was accompanied by spatial relocation toward the center of the nucleus in the nuclei of metaplastic but not in non-neoplastic cells. Our data suggest that vorinostat’s differential modulation of 3D nuclear architecture in normal and abnormal cells could play a functional role in its anti-cancer action. PMID:27503568

  8. 3-D photoacoustic and pulse echo imaging of prostate tumor progression in the mouse window chamber

    NASA Astrophysics Data System (ADS)

    Bauer, Daniel R.; Olafsson, Ragnar; Montilla, Leonardo G.; Witte, Russell S.

    2011-02-01

    Understanding the tumor microenvironment is critical to characterizing how cancers operate and predicting their response to treatment. We describe a novel, high-resolution coregistered photoacoustic (PA) and pulse echo (PE) ultrasound system used to image the tumor microenvironment. Compared to traditional optical systems, the platform provides complementary contrast and important depth information. Three mice are implanted with a dorsal skin flap window chamber and injected with PC-3 prostate tumor cells transfected with green fluorescent protein. The ensuing tumor invasion is mapped during three weeks or more using simultaneous PA and PE imaging at 25 MHz, combined with optical and fluorescent techniques. Pulse echo imaging provides details of tumor structure and the surrounding environment with 100-μm3 resolution. Tumor size increases dramatically with an average volumetric growth rate of 5.35 mm3/day, correlating well with 2-D fluorescent imaging (R = 0.97, p < 0.01). Photoacoustic imaging is able to track the underlying vascular network and identify hemorrhaging, while PA spectroscopy helps classify blood vessels according to their optical absorption spectrum, suggesting variation in blood oxygen saturation. Photoacoustic and PE imaging are safe, translational modalities that provide enhanced depth resolution and complementary contrast to track the tumor microenvironment, evaluate new cancer therapies, and develop molecular contrast agents in vivo.

  9. Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

    DTIC Science & Technology

    2005-10-01

    most widely used marker of prostate cancer - and prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated...Vigneron, D.B., Konety, B., Nelson, S.J., Narayan, P., and Hricak, H. Citrate as in vivo marker to discriminate prostate cancer from benign prostatic hyperplasia and

  10. [Prostate cancer brachytherapy].

    PubMed

    Pommier, P; Guérif, S; Peiffert, D; Créhange, G; Hannoun-Lévi, J-M; de Crevoisier, R

    2016-09-01

    Prostate brachytherapy techniques are described, concerning both Iodine 125 high dose rate brachytherapy. The following parts are presented: brachytherapy indications, technical description, immediate postoperative management and post-treatment evaluation, and 4 to 6 weeks as well as long-term follow-up.

  11. Targeting Discoidin Domain Receptors in Prostate Cancer

    DTIC Science & Technology

    2016-08-01

    1 AWARD NUMBER: W81XWH-15-1-0226 TITLE: Targeting Discoidin Domain Receptors in Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Rafael Fridman...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-15-1-0226 Targeting Discoidin Domain Receptors in Prostate Cancer 5b. GRANT NUMBER W81XWH-15...DDRs in prostate cancer . During the first funding period, we conducted immunohistochemical studies by staining a 200 case Grade/Stage tissue

  12. Imaging Prostate Cancer with Positron Emission Tomography

    DTIC Science & Technology

    2014-07-01

    AD_________________ Award Number: W81XWH-13-1-0125 TITLE: Imaging Prostate Cancer with Positron Emission Tomography...ABOVE ADDRESS. 1. REPORT DATE 2014 2. REPORT TYPE Annual 3. DATES COVERED 01 Sept 2013-31 Aug 2014 4. TITLE AND SUBTITLE Imaging Prostate Cancer ...proposal is to develop peptide based radiopharmaceuticals and evaluate them as PET imaging agents in preclinical animal models of prostate cancer

  13. Multifunctional Nanotherapeutic System for Advanced Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    therapy for drug resistant prostate cancer cells. In addition the findings from this study can be extended to the combinatorial therapy involving...AD_________________ Award Number: W81XWH-11-1-0571 TITLE: “Multifunctional Nanotherapeutic System for Advanced Prostate Cancer ...29September2013 4. TITLE AND SUBTITLE Multifunctional Nanotherapeutic System for Advanced Prostate Cancer 5a. CONTRACT NUMBER W81XWH-11-1-0571 5b

  14. Prostate Cancer Presenting with Parietal Bone Metastasis

    PubMed Central

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  15. Prostate Cancer Disparities in an Incarcerated Community

    DTIC Science & Technology

    2012-09-01

    Florida Department of Corrections (FDOC) as a model for elucidating the genetic, epigenetic , and socio-environmental etiologies of prostate cancer . 9 | P...TITLE: Prostate Cancer Disparities in an Incarcerated Community PRINCIPAL INVESTIGATOR: Meghan E. Borysova, Ph.D...1 Sep 2011 - 31 Aug 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Prostate Cancer Disparities in an Incarcerated Community 5b. GRANT NUMBER

  16. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    al. Plasma antibodies against Trichomonas vaginalis and subsequent risk of prostate cancer. Cancer Epidemiology Biomarkers and Prevention 2006;15...infectious agents with respect to prostate cancer: T vaginalis , the most common non-viral sexually transmitted infection, and the recently identified...To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is nested within the

  17. Roles of Eicosanoids in Prostate Cancer

    PubMed Central

    Nithipatikom, Kasem; Campbell, William B.

    2012-01-01

    Summary Eicosanoids, the metabolites of arachidonic acid, have diverse functions in the regulation of cancer including prostate cancer. This review will provide an overview of the roles of eicosanoids and endocannabinoids and their potential as therapeutic targets for prostate cancer treatment. PMID:24563660

  18. Radiation Induced Immune Response in Prostate Cancer

    DTIC Science & Technology

    2014-12-01

    trials of antibodies to TIP-1 in patients receiving radiotherapy for radiation. Publications, Abstracts, and Presentations none Inventions...therapy. Because radiotherapy is a primary mode of treatment of both localized prostate cancer and metastatic prostate cancer. These antigens are...antigens that are specifically over- expressed in cancer resulting in too few molecular targets and small percentages of patients who can be treated

  19. Vitamin D, Sunlight and Prostate Cancer Risk

    PubMed Central

    Donkena, Krishna Vanaja; Young, Charles Y. F.

    2011-01-01

    Prostate cancer is the second common cancer in men worldwide. The prevention of prostate cancer remains a challenge to researchers and clinicians. Here, we review the relationship of vitamin D and sunlight to prostate cancer risk. Ultraviolet radiation of the sunlight is the main stimulator for vitamin D production in humans. Vitamin D's antiprostate cancer activities may be involved in the actions through the pathways mediated by vitamin D metabolites, vitamin D metabolizing enzymes, vitamin D receptor (VDR), and VDR-regulated genes. Although laboratory studies including the use of animal models have shown that vitamin D has antiprostate cancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be inconclusive and an intensively studied subject. This review will provide up-to-date information regarding the recent outcomes of laboratory and epidemiology studies on the effects of vitamin D on prostate cancer prevention. PMID:21991434

  20. Prostate and Urologic Cancer | Division of Cancer Prevention

    Cancer.gov

    [[{"fid":"183","view_mode":"default","fields":{"format":"default","field_file_image_alt_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage Logo","field_file_image_title_text[und][0][value]":"Prostate and Urologic Cancer Research Group Homepage Logo","field_folder[und]":"15"},"type":"media","attributes":{"alt":"Prostate and Urologic Cancer Research Group Homepage Logo","title":"Prostate and Urologic Cancer Research Group Homepage Logo","height":"266","width":"400","clas | Conducts and supports research on the prevention and early detection of prostate, bladder, and skin cancers.

  1. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2010-03-01

    progression; 2-) To characterize the role of the infectious protozoa T. vaginalis in prostate carcinogenesis and progression. The current study is...understanding of the infectious pathogenesis of prostate cancer. Aim II. To characterize the role of the infectious protozoa T. vaginalis in prostate

  2. Microsatellite instability in prostate cancer

    SciTech Connect

    Shan, A.L.; Wick, M.J.; Persons, D.L.

    1994-09-01

    Microsatellite instability (MIN) has been documented in hereditary nonpolyposis colorectal cancer (HNPCC) as well as in sporadic forms of human cancers. Two of the genes which appear to be responsible for this particular tumor phenotype, hMSH2 and hMLH1, have now been identified. To determine the potential role of these mutator genes in prostate cancer, we have examined 95 prostate adenocarcinomas (40 paraffin embedded and 55 fresh frozen) for the presence of genetic instability at four microsatellite markers. The markers are localized to chromosome arms 5q(APC-CA1), 8p(Mfd 210Z), 15q(635/636), and 17q(p53-CA). Patients from whom paraffin embedded material was obtained were divided into short term (<3 years, n=18), and long term (>3 years, n=22) survivors. Of the 95 tumors examined, only four tumors (4%) demonstrated MIN: two tumors demonstrated MIN at 3 loci (p53-CA, APC-CA1, 635/636), one tumor demonstrated MIN at 2 loci (APC-CA1 and 635/636), and one tumor demonstrated instability at 635/636 only. All tumors exhibiting MIN had Gleason scores of {ge} 4+4. A correlation between MIN and survival was not observed. Information on family history was limited. However, of the two patients demonstrating MIN at three loci, one patient was diagnosed with a second malignancy (TCC of the ureter), but otherwise had a negative family history, while the second patient had one first degree relative with esophageal cancer. The patient demonstrating MIN at two loci had a negative family history, while the remaining patient had two first degree relatives with cancer (prostate and stomach). These results suggest that hMSH2 and hMLH1 (as reflected by the small percentage of tumors displaying MIN) do not play a prominent role in the process of prostate tumorigenesis.

  3. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    FAS activity in prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify key metabolic ...intermediates involved in lipid metabolism , mitochondrial function, inflammation, and apoptosis in the prostatectomy samples. 15. SUBJECT TERMS : none...vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism , and prostate cancer aggressiveness, our

  4. Mitochondria, prostate cancer, and biopsy sampling error.

    PubMed

    Parr, Ryan L; Mills, John; Harbottle, Andrew; Creed, Jennifer M; Crewdson, Gregory; Reguly, Brian; Guimont, François S

    2013-04-01

    Mitochondria and their associated genome are emerging as sophisticated indicators of prostate cancer biology. Alterations in the mitochondrial genome (mtgenome) have been implicated in cell proliferation, metastatic behavior, androgen independence, as a signal for apoptosis, and as a predictor of biochemical recurrence. Somatic mutation patterns in complete mtgenomes are associated with prostate specific antigen levels (PSA) in prostate cancer patients and a large-scale mtgenome deletion (3.4 kb) is consistent with a prostate "cancerization" field effect. This review will focus on the biological characteristics of mitochondria and their direct clinical application to prostate cancer. Mitochondrial science is currently influencing clinical prostate cancer diagnostics and the rapid progress in this area indicates future, break-through contributions in the general field of oncology.

  5. 3D prostate MR-TRUS non-rigid registration using dual optimization with volume-preserving constraint

    NASA Astrophysics Data System (ADS)

    Qiu, Wu; Yuan, Jing; Fenster, Aaron

    2016-03-01

    We introduce an efficient and novel convex optimization-based approach to the challenging non-rigid registration of 3D prostate magnetic resonance (MR) and transrectal ultrasound (TRUS) images, which incorporates a new volume preserving constraint to essentially improve the accuracy of targeting suspicious regions during the 3D TRUS guided prostate biopsy. Especially, we propose a fast sequential convex optimization scheme to efficiently minimize the employed highly nonlinear image fidelity function using the robust multi-channel modality independent neighborhood descriptor (MIND) across the two modalities of MR and TRUS. The registration accuracy was evaluated using 10 patient images by calculating the target registration error (TRE) using manually identified corresponding intrinsic fiducials in the whole prostate gland. We also compared the MR and TRUS manually segmented prostate surfaces in the registered images in terms of the Dice similarity coefficient (DSC), mean absolute surface distance (MAD), and maximum absolute surface distance (MAXD). Experimental results showed that the proposed method with the introduced volume-preserving prior significantly improves the registration accuracy comparing to the method without the volume-preserving constraint, by yielding an overall mean TRE of 2:0+/-0:7 mm, and an average DSC of 86:5+/-3:5%, MAD of 1:4+/-0:6 mm and MAXD of 6:5+/-3:5 mm.

  6. WITHDRAWN: Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, J M; Mouraviev, V; Sun, L; Madden, J F; Polascik, T J

    2008-05-13

    The authors hereby retract the e-publication dated 13 May 2008 and entitled, 'Can the conventional sextant prostate biopsy reliably diagnose unilateral prostate cancer in low-risk, localized, prostate cancer?' The authors are submitting a revised version with the same title. This article's statistics were performed for predicting bilateral prostate cancer outcomes. The article was written to help predict unilateral prostate cancer. Although the statistical numbers are correct, they are backwards. We apologize that the statistics indicate a contrary outcome (eg predicting bilateral cancer instead of unilateral disease).

  7. WE-EF-210-08: BEST IN PHYSICS (IMAGING): 3D Prostate Segmentation in Ultrasound Images Using Patch-Based Anatomical Feature

    SciTech Connect

    Yang, X; Rossi, P; Jani, A; Ogunleye, T; Curran, W; Liu, T

    2015-06-15

    Purpose: Transrectal ultrasound (TRUS) is the standard imaging modality for the image-guided prostate-cancer interventions (e.g., biopsy and brachytherapy) due to its versatility and real-time capability. Accurate segmentation of the prostate plays a key role in biopsy needle placement, treatment planning, and motion monitoring. As ultrasound images have a relatively low signal-to-noise ratio (SNR), automatic segmentation of the prostate is difficult. However, manual segmentation during biopsy or radiation therapy can be time consuming. We are developing an automated method to address this technical challenge. Methods: The proposed segmentation method consists of two major stages: the training stage and the segmentation stage. During the training stage, patch-based anatomical features are extracted from the registered training images with patient-specific information, because these training images have been mapped to the new patient’ images, and the more informative anatomical features are selected to train the kernel support vector machine (KSVM). During the segmentation stage, the selected anatomical features are extracted from newly acquired image as the input of the well-trained KSVM and the output of this trained KSVM is the segmented prostate of this patient. Results: This segmentation technique was validated with a clinical study of 10 patients. The accuracy of our approach was assessed using the manual segmentation. The mean volume Dice Overlap Coefficient was 89.7±2.3%, and the average surface distance was 1.52 ± 0.57 mm between our and manual segmentation, which indicate that the automatic segmentation method works well and could be used for 3D ultrasound-guided prostate intervention. Conclusion: We have developed a new prostate segmentation approach based on the optimal feature learning framework, demonstrated its clinical feasibility, and validated its accuracy with manual segmentation (gold standard). This segmentation technique could be a useful

  8. Olaparib With or Without Cediranib in Treating Patients With Metastatic Hormone-Resistant Prostate Cancer

    ClinicalTrials.gov

    2017-04-04

    Castration-Resistant Prostate Carcinoma; 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

  9. Functional Angiogenic Mediators in Prostate Cancer

    DTIC Science & Technology

    2000-08-01

    FUNDING NUMBERS Functional Angiogenic Mediators in Prostate Cancer DAMD17-99- 1 -9521 6. AUTHOR(S) Jennifer A. Doll, Ph.D. 7. PERFORMING ORGANIZATION NAME...transition in the prostate by 1 ) identifying the key angiogenic mediators , 2) investigating the clinical significance of mediator levels in prostatic fluid...our proposal, we set out to 1 ) identify such mediators in the prostate, 2) assess the clinical usefulness of measuring angiogenic mediator levels in

  10. [Medical treatment of prostate cancer].

    PubMed

    Lobel, B; Cipolla, B; Labrador, J

    1994-03-01

    Hormone dependence of prostate cancer is well known. In 80% of cases with metastases, hormone suppression leads to the reduction of tumour volume and related disorders. However the treatment is generally palliative because malignant process recurs after about around 16 months. Mean survival is less than 3 years in these forms. Lack of response come always together with a poor prognosis, and there is 90% mortality at 2 years. Advanced prostatic cancer should not be treated with hormones if the patient has few symptoms and his quality of life is satisfactory. Symptomatic forms require hormone manipulation. Orchidectomy or LH-RH are recommended. Total androgen ablation (combined treatment) leads rapidly to more relief of symptoms, but its drawbacks and especially high cost indicate that its use should be weighed individually. Estramustine is not a first-lune treatment. Presently, there is no criteria to predict response to treatment.

  11. Nebraska Prostate Cancer Research Program

    DTIC Science & Technology

    2014-07-01

    Effect of Metal Ion Chelators on Mannose 6-Phosphate/Insulin-like Growth Factor II Receptor in DU145 Prostate Cancer Cells. UNMC Summer Undergraduate...Lynnette Lefall Date Published: Friday, August 6, 2010 Keidra Bryant – Abstract Effect of Metal Ion Chelators on Mannose 6-Phosphate/Insulin...cleaved at the cell surface by a protease that is inhibited by metal ion chelators. This work was done in a human embryonic kidney cell line. The goal

  12. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2011-05-01

    this laboratory concentrates on the area of tumor immunology with an emphasis on immunotherapy. We have constructed microbial vaccines to be used...to the transgene product induced by the vaccine are underway. Additionally, we are carrying our "translational" research in the form of clinical...trials of our adenovirus vaccine in men with prostate cancer. Important in these trials is the safety of the vaccine and its ability to induce anti

  13. Prostate Cancer Research Training Program

    DTIC Science & Technology

    2012-05-01

    i mmunology with an emphasis on immunotherapy. We ha ve constructed microbial vaccines to be used for the investigation of gene and immunotherapy... vaccine are underway. Additionally, we are carrying our "translational" research in the fo rm of clinical trials of our adenovirus vaccine in men with...prostate cancer. Important in thes e trials is the safety of the vaccine and its ability to in duce anti-tumor immunity. We have recently completed

  14. Vaccine Immunotherapy for Prostate Cancer

    DTIC Science & Technology

    2006-07-01

    comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE...growth of androgen-dependent cancer cells, and result in clinical tumor control . After a median time of 2 years, patients progress into a clinical...calculogenesis. Finally, Bischoff and Goerttler (38) used Gelfoam in human prostate therapeutic embolization with success. Our laboratory, in collaboration

  15. Protease Profiling in Prostate Cancer

    DTIC Science & Technology

    2004-05-01

    acid synthase, which contains a serine hydrolase domain. We identified a lead inhibitor of this domain of fatty acid synthase, called Orlistat, which...SUBJECT TERMS 15. NUMBER OF PAGES Prostate cancer, tumor biology, protease, proteomics, transgenic, 20 animal model, fatty acid synthase, orlistat 16...the enzymes we identified is fatty acid synthase. Fatty acid synthase is the sole enzyme responsible for the cellular synthesis of fatty acids . This

  16. Utility of ADC measurement on diffusion-weighted MRI in differentiation of prostate cancer, normal prostate and prostatitis.

    PubMed

    Esen, Meltem; Onur, Mehmet Ruhi; Akpolat, Nusret; Orhan, Irfan; Kocakoc, Ercan

    2013-08-01

    To determine the utility of apparent diffusion coefficient (ADC) values in differentiation of prostate cancer from normal prostate parenchyma and prostatitis we obtained ADC values of 50 patients at b 100, 600 and 1,000 s/mm(2) diffusion gradients. The ADC values of prostate cancer group were significantly lower than normal prostate and prostatitis group at b 600 and 1,000 s/mm(2) gradients. The ADC values at high diffusion gradients may be used in differentiation prostate cancer from normal prostate and prostatitis.

  17. DNA Vaccines for Prostate Cancer

    PubMed Central

    McNeel, Douglas G.; Becker, Jordan T.; Johnson, Laura E.; Olson, Brian M.

    2013-01-01

    Delivery of plasmid DNA encoding an antigen of interest has been demonstrated to be an effective means of immunization, capable of eliciting antigen-specific T cells. Plasmid DNA vaccines offer advantages over other anti-tumor vaccine approaches in terms of simplicity, manufacturing, and possibly safety. The primary disadvantage is their poor transfection efficiency and subsequent lower immunogenicity relative to other genetic vaccine approaches. However, multiple preclinical models demonstrate anti-tumor efficacy, and many efforts are underway to improve the immunogenicity and anti-tumor effect of these vaccines. Clinical trials using DNA vaccines as treatments for prostate cancer have begun, and to date have demonstrated safety and immunological effect. This review will focus on DNA vaccines as a specific means of antigen delivery, advantages and disadvantages of this type of immunization, previous experience in preclinical models and human trials specifically conducted for the treatment of prostate cancer, and future directions for the application of DNA vaccines to prostate cancer immunotherapy. PMID:24587772

  18. 3-D Ultrasound Vascularity Assessment for Breast Cancer Diagnosis

    DTIC Science & Technology

    1999-09-01

    34truth" data in classifying a given case as benign or malignant. Discrimination thresholds are determined using a linear Baysian classifier for the two...somewhat intuitive. The diagonal line represents a Baysian discrimination line, equally weighing the cost of false-positive and false-negative...threshold is lowered to produce a sensitivity of 100%. Using a 3D linear Baysian discrimination scheme (which produces a threshold plane), the average

  19. Analyzing the roles of Rho GTPases in cancer cell migration with a live cell imaging 3D-morphology-based assay.

    PubMed

    Colomba, Audrey; Ridley, Anne J

    2014-01-01

    Rho GTPases are master regulators of cytoskeleton dynamics and therefore regulate cell motility. Rho GTPases, as well as their regulators and effectors, are often deregulated in cancers and thus contribute to tumor progression to metastasis. Cancer progression involves multiple steps, including invasion of the surrounding tissues. Several methods to investigate the invasion of tumors cells in 3D matrices in vitro have been developed. In this chapter we describe a 3D-based morphology assay that can be used for medium-throughput microscopy-based screening to identify regulators of cancer cell invasion. We use this method coupled to RNAi to investigate how Rho GTPases affect prostate cancer cell morphology in 3D Matrigel.

  20. Arachidonic acid metabolism in human prostate cancer

    PubMed Central

    YANG, PEIYING; CARTWRIGHT, CARRIE A.; LI, JIN; WEN, SIJIN; PROKHOROVA, INA N.; SHUREIQI, IMAD; TRONCOSO, PATRICIA; NAVONE, NORA M.; NEWMAN, ROBERT A.; KIM, JERI

    2012-01-01

    The arachidonic acid pathway is important in the development and progression of numerous malignant diseases, including prostate cancer. To more fully evaluate the role of individual cyclooxygenases (COXs), lipoxygenases (LOXs) and their metabolites in prostate cancer, we measured mRNA and protein levels of COXs and LOXs and their arachidonate metabolites in androgen-dependent (LNCaP) and androgen-independent (PC-3 and DU145) prostate cancer cell lines, bone metastasis-derived MDA PCa 2a and MDA PCa 2b cell lines and their corresponding xenograft models, as well as core biopsy specimens of primary prostate cancer and nonneoplastic prostate tissue taken ex vivo after prostatectomy. Relatively high levels of COX-2 mRNA and its product PGE2 were observed only in PC-3 cells and their xenografts. By contrast, levels of the exogenous 12-LOX product 12-HETE were consistently higher in MDA PCa 2b and PC-3 cells and their corresponding xenograft tissues than were those in LNCaP cells. More strikingly, the mean endogenous level of 12-HETE was significantly higher in the primary prostate cancers than in the nonneoplastic prostate tissue (0.094 vs. 0.010 ng/mg protein, respectively; p=0.019). Our results suggest that LOX metabolites such as 12-HETE are critical in prostate cancer progression and that the LOX pathway may be a target for treating and preventing prostate cancer. PMID:22895552

  1. Caveolin-1 and prostate cancer progression.

    PubMed

    Freeman, Michael R; Yang, Wei; Di Vizio, Dolores

    2012-01-01

    Caveolin-1 was identified in the 1990s as a marker of aggressive prostate cancer. The caveolin-1 protein localizes to vesicular structures called caveolae and has been shown to bind and regulate many signaling proteins involved in oncogenesis. Caveolin-1 also has lipid binding properties and mediates aspects of cholesterol and fatty acid metabolism and can elicit biological responses in a paracrine manner when secreted. Caveolin-1 is also present in the serum of prostate cancer patients and circulating levels correlate with extent of disease. Current evidence indicates that increased expression of caveolin-1 in prostate adenocarcinoma cells and commensurate downregulation of the protein in prostate stroma, mediate progression to the castration-resistant phase of prostate cancer through diverse pathways. This chapter summarizes the current state of our understanding of the cellular and physiologic mechanisms in which caveolin-1 participates in the evolution of prostate cancer cell phenotypes.

  2. Development of New Treatments for Prostate Cancer

    SciTech Connect

    DiPaola, R. S.; Abate-Shen, C.; Hait, W. N.

    2005-02-01

    The Dean and Betty Gallo Prostate Cancer Center (GPCC) was established with the goal of eradicating prostate cancer and improving the lives of men at risk for the disease through research, treatment, education and prevention. GPCC was founded in the memory of Dean Gallo, a beloved New Jersey Congressman who died tragically of prostate cancer diagnosed at an advanced stage. GPCC unites a team of outstanding researchers and clinicians who are committed to high-quality basic research, translation of innovative research to the clinic, exceptional patient care, and improving public education and awareness of prostate cancer. GPCC is a center of excellence of The Cancer Institute of New Jersey, which is the only NCI-designated comprehensive cancer center in the state. GPCC efforts are now integrated well as part of our Prostate Program at CINJ, in which Dr. Robert DiPaola and Dr. Cory Abate-Shen are co-leaders. The Prostate Program unites 19 investigators from 10 academic departments who have broad and complementary expertise in prostate cancer research. The overall goal and unifying theme is to elucidate basic mechanisms of prostate growth and oncogenesis, with the ultimate goal of promoting new and effective strategies for the eradication of prostate cancer. Members' wide range of research interests collectively optimize the chances of providing new insights into normal prostate biology and unraveling the molecular pathophysiology of prostate cancer. Cell culture and powerful animal models developed by program members recapitulate the various stages of prostate cancer progression, including prostatic intraepithelial neoplasia, adenocarcinoma, androgen-independence, invasion and metastases. These models promise to further strengthen an already robust program of investigator-initiated therapeutic clinical trials, including studies adopted by national cooperative groups. Efforts to translate laboratory results into clinical studies of early detection and chemoprevention

  3. Prevention and Early Detection of Prostate Cancer

    PubMed Central

    Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

    2014-01-01

    Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

  4. Linking Estrogens, Prostatitis and Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    provide the first direct evidence linking phy siologic estr ogen up- regulation an d pr ostate ma lignancy via inflammation. Ellem, Stuart J...inflammation and malignancy in the prostate. The identification of estr ogen as a cause of prostatitis, as well as a fac tor in the development of

  5. Genetic variation: effect on prostate cancer

    PubMed Central

    Sissung, Tristan M.; Price, Douglas K.; Del Re, Marzia; Ley, Ariel M.; Giovannetti, Elisa; Danesi, Romano

    2014-01-01

    Summary The crucial role of androgens in the development of prostate cancer is well established. The aim of this review is to examine the role of constitutional (germline) and tumor-specific (somatic) polymorphisms within important regulatory genes of prostate cancer. These include genes encoding enzymes of the androgen biosynthetic pathway, the androgen receptor gene, genes that encode proteins of the signal transduction pathways that may have a role in disease progression and survival, and genes involved in prostate cancer angiogenesis. Characterization of deregulated pathways critical to cancer cell growth have lead to the development of new treatments, including the CYP17 inhibitor abiraterone and clinical trials using novel drugs that are ongoing or recently completed [1]. The pharmacogenetics of the drugs used to treat prostate cancer will also be addressed. This review will define how germline polymorphisms are known affect a multitude of pathways, and therefore phenotypes, in prostate cancer etiology, progression, and treatment. PMID:25199985

  6. Review of selenium and prostate cancer prevention.

    PubMed

    Yang, Lei; Pascal, Mouracade; Wu, Xiao-Hou

    2013-01-01

    Prostate cancer is the most common malignancy in men in the United States. Surgery or radiation are sometimes unsatisfactory treatments because of the complications such as incontinence or erectile dysfunction. Selenium was found to be effective to prevent prostate cancer in the Nutritional Prevention of Cancer Trial (NPC), which motivated two other clinical trials: the Selenium and Vitamin E Cancer Prevention Trial (SELECT) and a Phase III trial of selenium to prevent prostate cancer in men with high-grade prostatic intraepithelial neoplasia. However, these two trials failed to confirm the results of the NPC trial and indicated that the selenium may not be preventive of prostate cancer. In this article we review the three clinical trials and discuss some different points which might be potential factors underlying variation in results obtained.

  7. Prognostic factors in prostate cancer.

    PubMed

    Braeckman, Johan; Michielsen, Dirk

    2007-01-01

    In the nineteenth century the main goal of medicine was predictive: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted to cure the disease. Since the twentieth century, the word prognosis has also been used in nonmedical contexts, for example in corporate finance or elections. The most accurate form of prognosis is achieved statistically. Based on different prognostic factors it should be possible to tell patients how they are expected to do after prostate cancer has been diagnosed and how different treatments may change this outcome. A prognosis is a prediction. The word prognosis comes from the Greek word (see text) and means foreknowing. In the nineteenth century this was the main goal of medicine: diagnose the disease and achieve a satisfying prognosis of the patient's chances. Today the effort has shifted towards seeking a cure. Prognostic factors in (prostate) cancer are defined as "variables that can account for some of the heterogeneity associated with the expected course and outcome of a disease". Bailey defined prognosis as "a reasoned forecast concerning the course, pattern, progression, duration, and end of the disease. Prognostic factors are not only essential to understand the natural history and the course of the disease, but also to predict possible different outcomes of different treatments or perhaps no treatment at all. This is extremely important in a disease like prostate cancer where there is clear evidence that a substantial number of cases discovered by prostate-specific antigen (PSA) testing are unlikely ever to become clinically significant, not to mention mortal. Furthermore, prognostic factors are of paramount importance for correct interpretation of clinical trials and for the construction of future trials. Finally, according to WHO national screening committee criteria for implementing a national screening programme, widely accepted prognostic factors must be defined before

  8. [Second cancer after starting treatment for prostate cancer].

    PubMed

    Mikata, Noriharu; Imao, Sadao; Fukasawa, Ritu

    2002-08-01

    The subjects for the present study were 270 patients with prostate cancer who underwent initial treatment at our hospital over the 14 years from 1986 to 1999. They were investigated to assess the relationship between their treatment and metachronous tumors. Sixteen patients (5.9%) developed cancer of other organs after starting treatment for prostate cancer. These metachronous tumors included gastric cancer in six patients as well as lung cancer, esophageal cancer, colorectal cancer, liver cancer, renal cancer, bladder cancer, skin cancer, leukemia, and mediastinal adenocarcinoma. Treatment for prostate cancer other than surgery included radiotherapy in eight patients, administration of estramustine phosphate sodium in nine patients, and LH-RH analogues in six patients. The chi-square test showed no significant difference in the incidence of metachronous cancer in relation to the presence/absence of these three therapies. The present study therefore ruled out the possible induction of other tumors by treatment for prostate cancer.

  9. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2013-04-01

    epithelium , stroma, as well as immune system, and the fixed nature of the prostate model with expression of the large T antigen, which may have limited...cancer glandular architecture formed (Figure 8). Figure 8. Subcutanous TRAMP Model to Recapitulate Prostate Cancer. TRAMP C2 cells with and...model to be able to alter the aggressiveness of the tumor and specifically modulate the TLR signaling pathway in prostate epithelium , stroma, and immune

  10. 4D analysis of influence of patient movement and anatomy alteration on the quality of 3D U/S-based prostate HDR brachytherapy treatment delivery

    SciTech Connect

    Milickovic, Natasa; Mavroidis, Panayiotis; Tselis, Nikolaos; Nikolova, Iliyana; Katsilieri, Zaira; Kefala, Vasiliki; Zamboglou, Nikolaos; Baltas, Dimos

    2011-09-15

    Purpose: Modern HDR brachytherapy treatment for prostate cancer based on the 3D ultrasound (U/S) plays increasingly important role. The purpose of this study is to investigate possible patient movement and anatomy alteration between the clinical image set acquisition, made after the needle implantation, and the patient irradiation and their influence on the quality of treatment. Methods: The authors used 3D U/S image sets and the corresponding treatment plans based on a 4D-treatment planning procedure: plans of 25 patients are obtained right after the needle implantation (clinical plan is based on this 3D image set) and just before and after the treatment delivery. The authors notice the slight decrease of treatment quality with increase of time gap between the clinical image set acquisition and the patient irradiation. 4D analysis of dose-volume-histograms (DVHs) for prostate: CTV1 = PTV, and urethra, rectum, and bladder as organs at risk (OARs) and conformity index (COIN) is presented, demonstrating the effect of prostate, OARs, and needles displacement. Results: The authors show that in the case that the patient body movement/anatomy alteration takes place, this results in modification of DVHs and radiobiological parameters, hence the plan quality. The observed average displacement of needles (1 mm) and of prostate (0.57 mm) is quite small as compared with the average displacement noted in several other reports [A. A. Martinez et al., Int. J. Radiat. Oncol., Biol., Phys. 49(1), 61-69 (2001); S. J. Damore et al., Int. J. Radiat. Oncol., Biol., Phys. 46(5), 1205-1211 (2000); P. J. Hoskin et al., Radiotherm. Oncol. 68(3), 285-288 (2003); E. Mullokandov et al., Int. J. Radiat. Oncol., Biol., Phys. 58(4), 1063-1071 (2004)] in the literature. Conclusions: Although the decrease of quality of dosimetric and radiobiological parameters occurs, this does not cause clinically unacceptable changes to the 3D dose distribution, according to our clinical protocol.

  11. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    a randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer... finasteride  (an inhibitor of androgen bioactivation) could  prevent prostate cancer. Included in our study are approximately 1,800 case‐control pairs

  12. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2011-09-01

    placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 3 of the...risk. Our study is nested within the Prostate Cancer Prevention Trial (PCPT), a randomized placebo-controlled clinical trial to determine if finasteride

  13. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2014-10-01

    developing cancer diagnostic biomarkers. Genome Research 22: 183-187, 2012. Sarah Hawley, Ladan Fazli , Jesse K. McKenney, Jeff Simko, Dean Troyer, Marlo...MUC1 in human prostate cancers. Prostate 74: 1059-1067, 2014. Troyer D, Jamaspishvili T, Wei W, Feng Z, Good J, Hawley S, Fazli L, McKenney J

  14. A history of prostate cancer treatment

    PubMed Central

    Denmeade, Samuel R.; Isaacs, John T.

    2014-01-01

    The increased incidence of prostate cancer has led to remarkable changes in diagnosis and treatment over the past century. What were the first ways in which prostate cancer was treated, and how did these evolve into the variety of therapeutic strategies from which patients have to choose today? PMID:12044015

  15. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2014-09-01

    receiving appropriate education, genetic counseling , and/or referral. During each interview the research coordinator identifies at risk family members...AD_________________ Award Number: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African...ADDRESS. 1. REPORT DATE 2. REPORT TYPE Annual 3. DATES COVERED 15 Aug 2013 – 14 Aug 2014 4. TITLE AND SUBTITLE Prostate Cancer Genetics in

  16. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2015-11-01

    AWARD NUMBER: W81XWH-11-1-0566 TITLE: Prostate Cancer Genetics in African Americans PRINCIPAL INVESTIGATOR: Henry T. Lynch, MD CONTRACTING...W81XWH-11-1-0566 November 2015 Final 15Aug2011 - 14Aug2015 Prostate Cancer Genetics in African Americans Henry T. Lynch Nothing listed 36

  17. Detection of DNA viruses in prostate cancer

    PubMed Central

    Smelov, Vitaly; Bzhalava, Davit; Arroyo Mühr, Laila Sara; Eklund, Carina; Komyakov, Boris; Gorelov, Andrey; Dillner, Joakim; Hultin, Emilie

    2016-01-01

    We tested prostatic secretions from men with and without prostate cancer (13 cases and 13 matched controls) or prostatitis (18 cases and 18 matched controls) with metagenomic sequencing. A large number (>200) of viral reads was only detected among four prostate cancer cases (1 patient each positive for Merkel cell polyomavirus, JC polyomavirus and Human Papillomavirus types 89 or 40, respectively). Lower numbers of reads from a large variety of viruses were detected in all patient groups. Our knowledge of the biology of the prostate may be furthered by the fact that DNA viruses are commonly shed from the prostate and can be readily detected by metagenomic sequencing of expressed prostate secretions. PMID:27121729

  18. Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer

    DTIC Science & Technology

    2007-09-01

    androgen -insensitive prostate cancer patients based upon our work. 15. SUBJECT TERMS Prostate Cancer , Neuroendocrine, Progression...two androgen - ines PC-3 and DU-145 by examining the status of publication. a Src kinase inhibitor AZ independent prostate cancer cell l...differentiation in prostate cancer . AR activation. Together with our studies in the chimeric growth of androgen -sensitive and androgen -insensitive cells,

  19. Prostate Cancer Genetics in African Americans

    DTIC Science & Technology

    2013-09-01

    grant from the U.S. Department of Defense to study the role heredity plays in prostate cancer among African Americans. "Prostate cancer is the...visit our website at: www.creighton.edu. Creighton gets grant to study heredity -cancer link - Houston Chronicle Coogle offers Google Offers Deals on...traffic Nahan & world Politics Health News bizarre Deaths Hurncanes Creighton gets grant to study heredity -cancer link Published 04 :40a.m., Monday

  20. Sanguinarine: A Novel Agent Against Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    The traditional therapeutic and surgical approaches have not been successful in the management of prostate cancer (CaP). Natural plant - based...Natural plant -based products have shown promise as anticancer agents. Ideally, the anti- cancer drugs should specifically target the neoplastic cells... plant alkaloid sanguinarine against prostate cancer development in a nude mice xenograft model. Proc Amer Assoc Cancer Res 46: 1012-1013, 2005. 3

  1. Bone-targeting agents in prostate cancer

    PubMed Central

    Suzman, Daniel L.; Boikos, Sosipatros A.; Carducci, Michael A.

    2014-01-01

    Bone metastases are present in the vast majority of men with advanced prostate cancer, representing the main cause for morbidity and mortality. Recurrent or metastatic disease is managed initially with androgen deprivation but the majority of the patients eventually will progress to castration-resistant prostate cancer, with patients developing bone metastases in most of the cases. Survival and growth of the metastatic prostate cancer cells is dependent on a complex microenvironment (onco-niche) that includes the osteoblasts, the osteoclasts, the endothelium, and the stroma. This review summarizes agents that target the pathways involved in this complex interaction between prostate cancer and bone micro-environment and aim to transform lethal metastatic prostate cancer into a chronic disease. PMID:24398856

  2. Prostate Cancer-Specific and Potent Antitumor Effect of a DD3-Controlled Oncolytic Virus Harboring the PTEN Gene

    PubMed Central

    Ding, Miao; Cao, Xin; Xu, Hai-neng; Fan, Jun-kai; Huang, Hong-ling; Yang, Dong-qin; Li, Yu-hua; Wang, Jian; Li, Runsheng; Liu, Xin-Yuan

    2012-01-01

    Prostate cancer is a major health problem for men in Western societies. Here we report a Prostate Cancer-Specific Targeting Gene-Viro-Therapy (CTGVT-PCa), in which PTEN was inserted into a DD3-controlled oncolytic viral vector (OV) to form Ad.DD3.E1A.E1B(Δ55)-(PTEN) or, briefly, Ad.DD3.D55-PTEN. The woodchuck post-transcriptional element (WPRE) was also introduced at the downstream of the E1A coding sequence, resulting in much higher expression of the E1A gene. DD3 is one of the most prostate cancer-specific genes and has been used as a clinical bio-diagnostic marker. PTEN is frequently inactivated in primary prostate cancers, which is crucial for prostate cancer progression. Therefore, the Ad.DD3.D55-PTEN has prostate cancer specific and potent antitumor effect. The tumor growth rate was almost completely inhibited with the final tumor volume after Ad.DD3.D55-PTEN treatment less than the initial volume at the beginning of Ad.DD3.D55-PTEN treatment, which shows the powerful antitumor effect of Ad.DD3.D55-PTEN on prostate cancer tumor growth. The CTGVT-PCa construct reported here killed all of the prostate cancer cell lines tested, such as DU145, 22RV1 and CL1, but had a reduced or no killing effect on all the non-prostate cancer cell lines tested. The mechanism of action of Ad.DD3.D55-PTEN was due to the induction of apoptosis, as detected by TUNEL assays and flow cytometry. The apoptosis was mediated by mitochondria-dependent and -independent pathways, as determined by caspase assays and mitochondrial membrane potential. PMID:22509396

  3. PSA and beyond: alternative prostate cancer biomarkers

    PubMed Central

    2016-01-01

    Background The use of biomarkers for prostate cancer screening, diagnosis and prognosis has the potential to improve the clinical management of the patients. Owing to inherent limitations of the biomarker prostate-specific antigen (PSA), intensive efforts are currently directed towards a search for alternative prostate cancer biomarkers, particularly those that can predict disease aggressiveness and drive better treatment decisions. Methods A literature search of Medline articles focused on recent and emerging advances in prostate cancer biomarkers was performed. The most promising biomarkers that have the potential to meet the unmet clinical needs in prostate cancer patient management and/or that are clinically implemented were selected. Conclusions With the advent of advanced genomic and proteomic technologies, we have in recent years seen an enormous spurt in prostate cancer biomarker research with several promising alternative biomarkers being discovered that show an improved sensitivity and specificity over PSA. The new generation of biomarkers can be tested via serum, urine, or tissue-based assays that have either received regulatory approval by the US Food and Drug Administration or are available as Clinical Laboratory Improvement Amendments-based laboratory developed tests. Additional emerging novel biomarkers for prostate cancer, including circulating tumor cells, microRNAs and exosomes, are still in their infancy. Together, these biomarkers provide actionable guidance for prostate cancer risk assessment, and are expected to lead to an era of personalized medicine. PMID:26790878

  4. Endometase in Androgen-Repressed Human Prostate Cancer

    DTIC Science & Technology

    2005-03-01

    intraepithelial neoplasia from multiple patients were significantly higher than those in prostatitis, benign prostate hyperplasia, and normal prostate glandular...prostate cancer cell invasion. 3. We showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were significantly...inhibitors of MMP-26 block prostate cancer invasion. We have showed that the levels of MMP-26 protein in human prostate carcinomas from multiple patients were

  5. Identification of Androgen Receptor and Beta-Catenin Target Genes in Prostate and Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    Transdisciplinary Research in Epigenetics and Cancer Journal Clubs and Transdisciplinary Science Meetings, biweekly and monthly 3. To gain expertise...Target Genes in Prostate and Prostate Cancer PRINCIPAL INVESTIGATOR: Laura Lamb CONTRACTING ORGANIZATION: Washington University...TITLE AND SUBTITLE Identification of Androgen Receptor and Beta-Catenin Target Genes in Prostate and Prostate Cancer 5a. CONTRACT NUMBER Genes in

  6. Defining the radiobiology of prostate cancer progression: An important question in translational prostate cancer research

    PubMed Central

    Vourganti, Srinivas; Donaldson, Jeffrey; Johnson, Linda; Turkbey, Baris; Bratslavsky, Gennady; Kotula, Leszek

    2015-01-01

    Prostate cancer is one of the most common malignancies affecting men worldwide. High mortality rates from advanced and metastatic prostate cancer in the United States are contrasted by a relatively indolent course in the majority of cases. This gives hope for finding methods that could direct personalized diagnostic, preventative, and treatment approaches to patients with prostate cancer. Recent advances in multiparametric magnetic resonance imaging (MP-MRI) offer a noninvasive diagnostic intervention which allows correlation of prostate tumor image characteristics with underlying biologic evidence of tumor progression. The power of MP-MRI includes examination of both local invasion and nodal disease and might overcome the challenges of analyzing the multifocal nature of prostate cancer. Future directions include a careful analysis of the genomic signature of individual prostatic lesions utilizing image-guided biopsies. This review examines the diagnostic potential of MRI in prostate cancer. PMID:24879423

  7. Diagnosis of prostate cancer via nanotechnological approach.

    PubMed

    Kang, Benedict J; Jeun, Minhong; Jang, Gun Hyuk; Song, Sang Hoon; Jeong, In Gab; Kim, Choung-Soo; Searson, Peter C; Lee, Kwan Hyi

    2015-01-01

    Prostate cancer is one of the leading causes of cancer-related deaths among the Caucasian adult males in Europe and the USA. Currently available diagnostic strategies for patients with prostate cancer are invasive and unpleasant and have poor accuracy. Many patients have been overly or underly treated resulting in a controversy regarding the reliability of current conventional diagnostic approaches. This review discusses the state-of-the-art research in the development of novel noninvasive prostate cancer diagnostics using nanotechnology coupled with suggested diagnostic strategies for their clinical implication.

  8. Screening for Stromal and Matrix Effects in 3D Microenvironments of Breast Cancer Cells

    NASA Astrophysics Data System (ADS)

    Montanez-Sauri, Sara I.

    Breast cancer progression ensures through the acquisition of genetic mutations, the uncontrollable growth of cells, and their progression to invasion. Studies have shown that the surrounding three-dimensional (3D) microenvironment can also influence breast cancer cell progression by controlling the morphology, differentiation, proliferation, and migration of cells. However, most of the currently available in vitro screening platforms are based on the two-dimensional (2D) culture of cells, and do not provide cells with the complex 3D microenvironment that exists in vivo. Therefore, there is a need for more biologically relevant in vitro platforms to help decipher the complexity of the microenvironment and its influence in breast cancer. In this dissertation we present an automated microfluidic platform that allows to efficiently screen for the effect of multiple matrix and stromal microenvironment in 3D cultures of breast cancer cells. Several extracellular matrix (ECM) compositions and stromal cells are included in the 3D microenvironments to examine their influence on breast cancer cell behavior. The screening results suggest that collagen gels with fibronectin might be influencing paracrine signals between breast cancer cells and stromal cells. The ability of the platform to culture and treat cells in 3D microenvironments offers a powerful screening tool for the identification of compounds and interactions using more in vivo-like 3D microenvironments. The identification of these mechanisms will increase our current understanding of breast cancer, and will aid in the identification of potential therapeutics.

  9. Prostate cancer vaccines in clinical trials.

    PubMed

    Lubaroff, David M

    2012-07-01

    This review presents important information about the current state of the art for vaccine immunotherapy of prostate cancer. It includes important preclinical research for each of the important prostate cancer vaccines to have reached clinical trials. To date, the only prostate cancer vaccine that has completed Phase III trials and has been approved and licensed by the US FDA is Sipuleucel-T, which immunizes patients against the prostate-associated antigen prostatic acid phosphatase. The benefits and concerns associated with the vaccine are presented. A current Phase III trial is currently underway using the vaccinia-based prostate-specific antigen vaccine Prostvac-TRICOM. Other immunotherapeutic vaccines in trials include the Ad/prostate-specific antigen vaccine Ad5-prostate-specific antigen and the DNA/prostatic acid phosphatase vaccine. A cellular vaccine, GVAX, has been in clinical trials but has not seen continuous study. This review also delves into the multiple immune regulatory elements that must be overcome in order to obtain strong antitumor-associated antigen immune responses capable of effectively destroying prostate tumor cells.

  10. ETS fusion genes in prostate cancer.

    PubMed

    Gasi Tandefelt, Delila; Boormans, Joost; Hermans, Karin; Trapman, Jan

    2014-06-01

    Prostate cancer is very common in elderly men in developed countries. Unravelling the molecular and biological processes that contribute to tumor development and progressive growth, including its heterogeneity, is a challenging task. The fusion of the genes ERG and TMPRSS2 is the most frequent genomic alteration in prostate cancer. ERG is an oncogene that encodes a member of the family of ETS transcription factors. At lower frequency, other members of this gene family are also rearranged and overexpressed in prostate cancer. TMPRSS2 is an androgen-regulated gene that is preferentially expressed in the prostate. Most of the less frequent ETS fusion partners are also androgen-regulated and prostate-specific. During the last few years, novel concepts of the process of gene fusion have emerged, and initial experimental results explaining the function of the ETS genes ERG and ETV1 in prostate cancer have been published. In this review, we focus on the most relevant ETS gene fusions and summarize the current knowledge of the role of ETS transcription factors in prostate cancer. Finally, we discuss the clinical relevance of TMRPSS2-ERG and other ETS gene fusions in prostate cancer.

  11. Prostate Cancer and Bone: The Elective Affinities

    PubMed Central

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing challenge for researchers also because the preference of prostate cancer cells for the bone is the result of a sequential series of targetable molecular events. Many factors have been associated with the peculiar ability of prostate cancer cells to migrate in bone marrow and to determine mixed osteoblastic/osteolytic lesions. As anticipated by the success of current targeted therapy aimed to block bone resorption, a better understanding of molecular affinity between prostate cancer and bone microenvironment will permit us to cure bone metastasis and to improve prognosis of prostate cancer patients. PMID:24971315

  12. Augmented Reality Imaging System: 3D Viewing of a Breast Cancer

    PubMed Central

    Douglas, David B.; Boone, John M.; Petricoin, Emanuel; Liotta, Lance; Wilson, Eugene

    2016-01-01

    Objective To display images of breast cancer from a dedicated breast CT using Depth 3-Dimensional (D3D) augmented reality. Methods A case of breast cancer imaged using contrast-enhanced breast CT (Computed Tomography) was viewed with the augmented reality imaging, which uses a head display unit (HDU) and joystick control interface. Results The augmented reality system demonstrated 3D viewing of the breast mass with head position tracking, stereoscopic depth perception, focal point convergence and the use of a 3D cursor and joy-stick enabled fly through with visualization of the spiculations extending from the breast cancer. Conclusion The augmented reality system provided 3D visualization of the breast cancer with depth perception and visualization of the mass's spiculations. The augmented reality system should be further researched to determine the utility in clinical practice. PMID:27774517

  13. Risks of Prostate Cancer Screening

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system located just below the bladder (the organ that ... up part of semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  14. Treatment Option Overview (Prostate Cancer)

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  15. General Information about Prostate Cancer

    MedlinePlus

    ... prostate. The prostate is a gland in the male reproductive system . It lies just below the bladder (the organ ... part of the semen . Enlarge Anatomy of the male reproductive and urinary systems, showing the prostate, testicles, bladder, and other organs. ...

  16. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    saturation bands (six for fat and two for water) were used to minimize lipid/water contamination to the VOI. The 2D MRSI sequence details are: TR/TE... fat as measured by in-vivo imaging using proton magnetic resonance spectroscopy imaging in the prediction of prostate disease aggressiveness...histology, in-vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism, and prostate cancer

  17. Incidence of prostate cancer in Lithuania after introduction of the Early Prostate Cancer Detection Programme.

    PubMed

    Smailyte, G; Aleknaviciene, B

    2012-12-01

    In Lithuania, prostate-specific antigen (PSA) testing is offered to healthy asymptomatic men as a screening test in the population-based Early Prostate Cancer Detection Programme (EPCDP). The aim of this study was to analyse the incidence of prostate cancer before and after introduction of the EPCDP in Lithuania. Prostate cancer incidence and mortality data from the Lithuanian Cancer Registry were analysed for the period 1990-2008. Age-specific incidence and mortality data were adjusted to the European Standard Population. There have been extraordinary changes in the incidence of prostate cancer in Lithuania following introduction of the EPCDP, and there is strong evidence that these changes are the result of increased detection rates, especially in men of screening age. Further observation of changes in prostate cancer incidence and mortality in Lithuania may help to determine the extent to which PSA testing at the population level influences incidence and mortality in the general population.

  18. Presence of PSA auto-antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis).

    PubMed

    Lokant, M T; Naz, R K

    2015-04-01

    Prostate-specific antigen (PSA), produced by the prostate, liquefies post-ejaculate semen. PSA is detected in semen and blood. Increased circulating PSA levels indicate prostate abnormality [prostate cancer (PC), benign prostatic hyperplasia (BPH), prostatitis (PTIS)], with variance among individuals. As the prostate has been proposed as an immune organ, we hypothesise that variation in PSA levels among men may be due to presence of auto-antibodies against PSA. Sera from healthy men (n = 28) and men having prostatitis (n = 25), BPH (n = 30) or PC (n = 29) were tested for PSA antibody presence using enzyme-linked immunosorbent assay (ELISA) values converted to standard deviation (SD) units, and Western blotting. Taking ≥2 SD units as cut-off for positive immunoreactivity, 0% of normal men, 0% with prostatitis, 33% with BPH and 3.45% with PC demonstrated PSA antibodies. One-way analysis of variance (anova) performed on the mean absorbance values and SD units of each group showed BPH as significantly different (P < 0.01) compared with PC and prostatitis. All others were nonsignificant (P < 0.05). Men (33%) with BPH had PSA antibodies by ELISA and Western blot. These discoveries may find clinical application in differential diagnosis among prostate abnormalities, especially differentiating BPH from prostate cancer and prostatitis.

  19. Humanin: A Novel Therapeutic Target in Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    benign prostatic hyperplasia (BPH; n=107), prostatic intraepithelial neoplasia (PIN; n=41) and invasive prostate cancer (Cancer; n=574). Both cytoplasmic...expression was significantly higher in cancer (ProsCa) compared to normal (NL; p=0028), and benign prostatic hyperplasia (BPH; p=0.0017). Humanin expression

  20. Inorganic Arsenic and Human Prostate Cancer

    PubMed Central

    Benbrahim-Tallaa, Lamia; Waalkes, Michael P.

    2008-01-01

    Objective We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. Data sources We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. Data synthesis Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose–response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. Conclusion Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important. PMID:18288312

  1. Intrafraction motion of the prostate during an IMRT session: a fiducial-based 3D measurement with Cone-beam CT

    PubMed Central

    Boda-Heggemann, Judit; Köhler, Frederick Marc; Wertz, Hansjörg; Ehmann, Michael; Hermann, Brigitte; Riesenacker, Nadja; Küpper, Beate; Lohr, Frank; Wenz, Frederik

    2008-01-01

    Background Image-guidance systems allow accurate interfractional repositioning of IMRT treatments, however, these may require up to 15 minutes. Therefore intrafraction motion might have an impact on treatment precision. 3D geometric data regarding intrafraction prostate motion are rare; we therefore assessed its magnitude with pre- and post-treatment fiducial-based imaging with cone-beam-CT (CBCT). Methods 39 IMRT fractions in 5 prostate cancer patients after 125I-seed implantation were evaluated. Patient position was corrected based on the 125I-seeds after pre-treatment CBCT. Immediately after treatment delivery, a second CBCT was performed. Differences in bone- and fiducial position were measured by seed-based grey-value matching. Results Fraction time was 13.6 ± 1.6 minutes. Median overall displacement vector length of 125I-seeds was 3 mm (M = 3 mm, Σ = 0.9 mm, σ = 1.7 mm; M: group systematic error, Σ: SD of systematic error, σ: SD of random error). Median displacement vector of bony structures was 1.84 mm (M = 2.9 mm, Σ = 1 mm, σ = 3.2 mm). Median displacement vector length of the prostate relative to bony structures was 1.9 mm (M = 3 mm, Σ = 1.3 mm, σ = 2.6 mm). Conclusion a) Overall displacement vector length during an IMRT session is < 3 mm. b) Positioning devices reducing intrafraction bony displacements can further reduce overall intrafraction motion. c) Intrafraction prostate motion relative to bony structures is < 2 mm and may be further reduced by institutional protocols and reduction of IMRT duration. PMID:18986517

  2. Targeting the Neural Microenvironment in Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer (PCa) remains the most common malignancy and the second leading cause of cancer-related death for men in the...cancer (PCa) remains the most common malignancy and the second leading cause of cancer-related death for men in the United States. The tumor

  3. Primary and salvage cryotherapy for prostate cancer.

    PubMed

    Finley, David S; Pouliot, Frederic; Miller, David C; Belldegrun, Arie S

    2010-02-01

    Cryotherapy is a technique to ablate tissue by local induction of extremely cold temperatures. Recently, the American Urological Association Best Practice Statement recognized cryoablation of the prostate as an established treatment option for men with newly diagnosed or radiorecurrent organ-confined prostate cancer. Emerging data suggest that, in select cases, cryoablation may have a role in focal ablation of prostate. The current state of the art of cryoablation in these applications is reviewed.

  4. Evolving Recommendations on Prostate Cancer Screening.

    PubMed

    Brawley, Otis W; Thompson, Ian M; Grönberg, Henrik

    2016-01-01

    Results of a number of studies demonstrate that the serum prostate-specific antigen (PSA) in and of itself is an inadequate screening test. Today, one of the most pressing questions in prostate cancer medicine is how can screening be honed to identify those who have life-threatening disease and need aggressive treatment. A number of efforts are underway. One such effort is the assessment of men in the landmark Prostate Cancer Prevention Trial that has led to a prostate cancer risk calculator (PCPTRC), which is available online. PCPTRC version 2.0 predicts the probability of the diagnosis of no cancer, low-grade cancer, or high-grade cancer when variables such as PSA, age, race, family history, and physical findings are input. Modern biomarker development promises to provide tests with fewer false positives and improved ability to find high-grade cancers. Stockholm III (STHLM3) is a prospective, population-based, paired, screen-positive, prostate cancer diagnostic study assessing a combination of plasma protein biomarkers along with age, family history, previous biopsy, and prostate examination for prediction of prostate cancer. Multiparametric MRI incorporates anatomic and functional imaging to better characterize and predict future behavior of tumors within the prostate. After diagnosis of cancer, several genomic tests promise to better distinguish the cancers that need treatment versus those that need observation. Although the new technologies are promising, there is an urgent need for evaluation of these new tests in high-quality, large population-based studies. Until these technologies are proven, most professional organizations have evolved to a recommendation of informed or shared decision making in which there is a discussion between the doctor and patient.

  5. Hormones and prostate cancer: what's next?

    PubMed

    Hsing, A W

    2001-01-01

    In summary, the hormonal hypothesis remains one of the most important hypotheses in prostate cancer etiology. Although epidemiologic data regarding the role of hormones are still inconclusive, there are many intriguing leads. Armed with more complete methodological data, state-of-the-art hormone assays, sound epidemiologic design, and a more thorough analytical approach, a new generation of studies should yield critical data and insights to help clarify further the role of hormones in prostate cancer. These new studies may determine ultimately whether racial/ethnic differences in hormonal levels and in genetic susceptibility to hormone-metabolizing genes can help explain the very large racial/ethnic differences in prostate cancer risk.

  6. Novel diagnostic biomarkers for prostate cancer

    PubMed Central

    Madu, Chikezie O.; Lu, Yi

    2010-01-01

    Prostate cancer is the most frequently diagnosed malignancy in American men, and a more aggressive form of the disease is particularly prevalent among African Americans. The therapeutic success rate for prostate cancer can be tremendously improved if the disease is diagnosed early. Thus, a successful therapy for this disease depends heavily on the clinical indicators (biomarkers) for early detection of the presence and progression of the disease, as well as the prediction after the clinical intervention. However, the current clinical biomarkers for prostate cancer are not ideal as there remains a lack of reliable biomarkers that can specifically distinguish between those patients who should be treated adequately to stop the aggressive form of the disease and those who should avoid overtreatment of the indolent form. A biomarker is a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention. A biomarker reveals further information to presently existing clinical and pathological analysis. It facilitates screening and detecting the cancer, monitoring the progression of the disease, and predicting the prognosis and survival after clinical intervention. A biomarker can also be used to evaluate the process of drug development, and, optimally, to improve the efficacy and safety of cancer treatment by enabling physicians to tailor treatment for individual patients. The form of the prostate cancer biomarkers can vary from metabolites and chemical products present in body fluid to genes and proteins in the prostate tissues. Current advances in molecular techniques have provided new tools facilitating the discovery of new biomarkers for prostate cancer. These emerging biomarkers will be beneficial and critical in developing new and clinically reliable indicators that will have a high specificity for the diagnosis and prognosis of prostate cancer. The

  7. Nanotherapies for treating prostate cancer

    NASA Astrophysics Data System (ADS)

    Danquah, Michael

    Current prostate cancer treatment remains ineffective primarily due to ineffectual therapeutic strategies and numerous tumor-associated physiological barriers which hinder efficacy of anticancer agents. Therefore, the focus of this study was to investigate a new combination therapy approach for treating prostate cancer and develop polymeric nanocarriers to facilitate anticancer drug and nucleic acid delivery. It was hypothesized that simultaneously targeting androgen-androgen receptor (AR) and X-linked inhibitor of apoptosis protein (XIAP) signaling pathways would be effective in treating prostate cancer. The effect of bicalutamide (antiandrogen) and embelin (XIAP inhibitor) on the growth of prostate cancer cells in vitro and in vivo was first examined. Embelin induced caspase 3 and 9 activation in LNCaP and C4-2 cells by decreasing XIAP expression and was more potent than bicalutamide in killing prostate tumor cells irrespective of their androgen status. Using a combination of MTT assay and isobologram analyses, combination of bicalutamide and embelin was observed to be cell line and schedule dependent. Since bicalutamide and embelin are extremely hydrophobic, polymeric micelles were fabricated using polyethylene glycol-b-polylactic acid (PEG-b-PLA) copolymer to improve drug solubility. Micellar formulations were found to result in at least 60-fold increase in the aqueous solubility of bicalutamide and embelin. Tumor growth was also effectively regressed upon treatment with bicalutamide, but the extent of tumor regression was significantly higher when bicalutamide was formulated in micelles. To further improve bicalutamide aqueous solubility, a series of novel biodegradable copolymers for the systematic micellar delivery of bicalutamide was designed and synthesized. Flory-Huggins interaction parameter (χFH) was used to assess compatibility between bicalutamide and poly (L-lactide) or poly (carbonate-co-lactide) polymer pairs. Polyethylene glycol-b-poly (carbonate

  8. Statin Use in Prostate Cancer: An Update

    PubMed Central

    Babcook, Melissa A.; Joshi, Aditya; Montellano, Jeniece A.; Shankar, Eswar; Gupta, Sanjay

    2016-01-01

    3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, known as statins, are commonly prescribed for the treatment of hypercholesterolemia and cardiovascular disease. A systematic review was conducted using the keywords “statin and prostate cancer” within the title search engines including PubMed, Web of Science, and the Cochrane Library for relevant research work published between 2004 and December 2015. Although still premature, accumulating clinical evidence suggests that statin use may be beneficial in the prevention and/or treatment of prostate cancer. These human studies consist of meta-analyses of secondary endpoints obtained from randomized, controlled cardiovascular disease clinical trials of statins, patient database, observational studies, and a few, small case–control studies, directly addressing statin use on prostate cancer pathology and recurrence. This review summarizes and discusses the recent clinical literature on statins and prostate cancer with a recommendation to move forward with randomized, placebo-controlled clinical trials, investigating the use of statins. Additional preclinical testing of statins on prostate cancer cell lines and in vivo models is needed to elucidate pathways and determine its efficacy for prevention and/or treatment of prostate cancer, more specifically, the difference in the effectiveness of lipophilic versus hydrophilic statins in prostate cancer. PMID:27441003

  9. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    ClinicalTrials.gov

    2016-11-23

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  10. 3D-segmentation of the 18F-choline PET signal for target volume definition in radiation therapy of the prostate.

    PubMed

    Ciernik, I Frank; Brown, Derek W; Schmid, Daniel; Hany, Thomas; Egli, Peter; Davis, J Bernard

    2007-02-01

    Volumetric assessment of PET signals becomes increasingly relevant for radiotherapy (RT) planning. Here, we investigate the utility of 18F-choline PET signals to serve as a structure for semi-automatic segmentation for forward treatment planning of prostate cancer. 18F-choline PET and CT scans of ten patients with histologically proven prostate cancer without extracapsular growth were acquired using a combined PET/CT scanner. Target volumes were manually delineated on CT images using standard software. Volumes were also obtained from 18F-choline PET images using an asymmetrical segmentation algorithm. PTVs were derived from CT 18F-choline PET based clinical target volumes (CTVs) by automatic expansion and comparative planning was performed. As a read-out for dose given to non-target structures, dose to the rectal wall was assessed. Planning target volumes (PTVs) derived from CT and 18F-choline PET yielded comparable results. Optimal matching of CT and 18F-choline PET derived volumes in the lateral and cranial-caudal directions was obtained using a background-subtracted signal thresholds of 23.0+/-2.6%. In antero-posterior direction, where adaptation compensating for rectal signal overflow was required, optimal matching was achieved with a threshold of 49.5+/-4.6%. 3D-conformal planning with CT or 18F-choline PET resulted in comparable doses to the rectal wall. Choline PET signals of the prostate provide adequate spatial information amendable to standardized asymmetrical region growing algorithms for PET-based target volume definition for external beam RT.

  11. Functional imaging for prostate cancer: therapeutic implications.

    PubMed

    Mari Aparici, Carina; Seo, Youngho

    2012-09-01

    Functional radionuclide imaging modalities, now commonly combined with anatomical imaging modalities computed tomography (CT) or magnetic resonance imaging (single photon emission computed tomography [SPECT]/CT, positron emission tomography [PET]/CT, and PET/magnetic resonance imaging), are promising tools for the management of prostate cancer, particularly for therapeutic implications. Sensitive detection capability of prostate cancer using these imaging modalities is one issue; however, the treatment of prostate cancer using the information that can be obtained from functional radionuclide imaging techniques is another challenging area. There are not many SPECT or PET radiotracers that can cover the full spectrum of the management of prostate cancer from initial detection to staging, prognosis predictor, and all the way to treatment response assessment. However, when used appropriately, the information from functional radionuclide imaging improves, and sometimes significantly changes, the whole course of the cancer management. The limitations of using SPECT and PET radiotracers with regard to therapeutic implications are not so much different from their limitations solely for the task of detecting prostate cancer; however, the specific imaging target and how this target is reliably imaged by SPECT and PET can potentially make significant impact in the treatment of prostate cancer. Finally, although the localized prostate cancer is considered manageable, there is still significant need for improvement in noninvasive imaging of metastatic prostate cancer, in treatment guidance, and in response assessment from functional imaging, including radionuclide-based techniques. In this review article, we present the rationale of using functional radionuclide imaging and the therapeutic implications for each of radionuclide imaging agent that have been studied in human subjects.

  12. Farming, reported pesticide use, and prostate cancer.

    PubMed

    Ragin, Camille; Davis-Reyes, Brionna; Tadesse, Helina; Daniels, Dennis; Bunker, Clareann H; Jackson, Maria; Ferguson, Trevor S; Patrick, Alan L; Tulloch-Reid, Marshall K; Taioli, Emanuela

    2013-03-01

    Prostate cancer is the leading cancer type diagnosed in American men and is the second leading cancer diagnosed in men worldwide. Although studies have been conducted to investigate the association between prostate cancer and exposure to pesticides and/or farming, the results have been inconsistent. We performed a meta-analysis to summarize the association of farming and prostate cancer. The PubMed database was searched to identify all published case-control studies that evaluated farming as an occupational exposure by questionnaire or interview and prostate cancer. Ten published and two unpublished studies were included in this analysis, yielding 3,978 cases and 7,393 controls. Prostate cancer cases were almost four times more likely to be farmers compared with controls with benign prostate hyperplasia (BPH; meta odds ratio [OR], crude = 3.83, 95% confidence interval [CI] = 1.96-7.48, Q-test p value = .352; two studies); similar results were obtained when non-BPH controls were considered, but with moderate heterogeneity between studies (meta OR crude = 1.38, 95% CI = 1.16-1.64, Q-test p value = .216, I (2) = 31% [95% CI = 0-73]; five studies). Reported pesticide exposure was inversely associated with prostate cancer (meta OR crude = 0.68, 95% CI = 0.49-0.96, Q-test p value = .331; four studies), whereas no association with exposure to fertilizers was observed. Our findings confirm that farming is a risk factor for prostate cancer, but this increased risk may not be due to exposure to pesticides.

  13. Individualised 3D printed vaginal template for MRI guided brachytherapy in locally advanced cervical cancer.

    PubMed

    Lindegaard, Jacob Christian; Madsen, Mikkel Lænsø; Traberg, Anders; Meisner, Bjarne; Nielsen, Søren Kynde; Tanderup, Kari; Spejlborg, Harald; Fokdal, Lars Ulrik; Nørrevang, Ole

    2016-01-01

    Intracavitary-interstitial applicators for MRI guided brachytherapy are becoming increasingly important in locally advanced cervical cancer. The 3D printing technology enables a versatile method for obtaining a high degree of individualisation of the implant. Our clinical workflow is presented and exemplified by a stage IVA cervical cancer with superior dose distribution.

  14. Molecular pathways and targets in prostate cancer

    PubMed Central

    Shtivelman, Emma; Beer, Tomasz M.; Evans, Christopher P.

    2014-01-01

    Prostate cancer co-opts a unique set of cellular pathways in its initiation and progression. The heterogeneity of prostate cancers is evident at earlier stages, and has led to rigorous efforts to stratify the localized prostate cancers, so that progression to advanced stages could be predicted based upon salient features of the early disease. The deregulated androgen receptor signaling is undeniably most important in the progression of the majority of prostate tumors. It is perhaps because of the primacy of the androgen receptor governed transcriptional program in prostate epithelium cells that once this program is corrupted, the consequences of the ensuing changes in activity are pleotropic and could contribute to malignancy in multiple ways. Following localized surgical and radiation therapies, 20-40% of patients will relapse and progress, and will be treated with androgen deprivation therapies. The successful development of the new agents that inhibit androgen signaling has changed the progression free survival in hormone resistant disease, but this has not changed the almost ubiquitous development of truly resistant phenotypes in advanced prostate cancer. This review summarizes the current understanding of the molecular pathways involved in localized and metastatic prostate cancer, with an emphasis on the clinical implications of the new knowledge. PMID:25277175

  15. Management of Complications of Prostate Cancer Treatment

    PubMed Central

    Michaelson, M. Dror; Cotter, Shane E.; Gargollo, Patricio C.; Zietman, Anthony L.; Dahl, Douglas M.; Smith, Matthew R.

    2010-01-01

    Prostate cancer is the most commonly diagnosed noncutaneous cancer in men in the United States. Treatment of men with prostate cancer commonly involves surgical, radiation, or hormone therapy. Most men with prostate cancer live for many years after diagnosis and may never suffer morbidity or mortality attributable to prostate cancer. The short-term and long-term adverse consequences of therapy are, therefore, of great importance. Adverse effects of radical prostatectomy include immediate postoperative complications and long-term urinary and sexual complications. External beam or interstitial radiation therapy in men with localized prostate cancer may lead to urinary, gastrointestinal, and sexual complications. Improvements in surgical and radiation techniques have reduced the incidence of many of these complications. Hormone treatment typically consists of androgen deprivation therapy, and consequences of such therapy may include vasomotor flushing, anemia, and bone density loss. Numerous clinical trials have studied the role of bone antiresorptive therapy for prevention of bone density loss and fractures. Other long-term consequences of androgen deprivation therapy may include adverse body composition changes and increased risk of insulin resistance, diabetes, and cardiovascular disease. Ongoing and planned clinical trials will continue to address strategies to prevent treatment-related side effects and improve quality of life for men with prostate cancer. PMID:18502900

  16. Serum Autoantibodies in Chronic Prostate Inflammation in Prostate Cancer Patients

    PubMed Central

    Schlick, Bettina; Massoner, Petra; Lueking, Angelika; Charoentong, Pornpimol; Blattner, Mirjam; Schaefer, Georg; Marquart, Klaus; Theek, Carmen; Amersdorfer, Peter; Zielinski, Dirk; Kirchner, Matthias; Trajanoski, Zlatko; Rubin, Mark A.; Müllner, Stefan; Schulz-Knappe, Peter; Klocker, Helmut

    2016-01-01

    Background Chronic inflammation is frequently observed on histological analysis of malignant and non-malignant prostate specimens. It is a suspected supporting factor for prostate diseases and their progression and a main cause of false positive PSA tests in cancer screening. We hypothesized that inflammation induces autoantibodies, which may be useful biomarkers. We aimed to identify and validate prostate inflammation associated serum autoantibodies in prostate cancer patients and evaluate the expression of corresponding autoantigens. Methods Radical prostatectomy specimens of prostate cancer patients (N = 70) were classified into high and low inflammation groups according to the amount of tissue infiltrating lymphocytes. The corresponding pre-surgery blood serum samples were scrutinized for autoantibodies using a low-density protein array. Selected autoantigens were identified in prostate tissue and their expression pattern analyzed by immunohistochemistry and qPCR. The identified autoantibody profile was cross-checked in an independent sample set (N = 63) using the Luminex-bead protein array technology. Results Protein array screening identified 165 autoantibodies differentially abundant in the serum of high compared to low inflammation patients. The expression pattern of three corresponding antigens were established in benign and cancer tissue by immunohistochemistry and qPCR: SPAST (Spastin), STX18 (Syntaxin 18) and SPOP (speckle-type POZ protein). Of these, SPAST was significantly increased in prostate tissue with high inflammation. All three autoantigens were differentially expressed in primary and/or castration resistant prostate tumors when analyzed in an inflammation-independent tissue microarray. Cross-validation of the inflammation autoantibody profile on an independent sample set using a Luminex-bead protein array, retrieved 51 of the significantly discriminating autoantibodies. Three autoantibodies were significantly upregulated in both screens, MUT

  17. Prostate Cancer Stem Cells: Research Advances

    PubMed Central

    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease. PMID:26593898

  18. sEphB4-HSA Before Surgery in Treating Patients With Bladder Cancer, Prostate Cancer, or Kidney Cancer

    ClinicalTrials.gov

    2016-05-06

    Infiltrating Bladder Urothelial Carcinoma; Recurrent Bladder Carcinoma; Stage I Prostate Cancer; Stage I Renal Cell Cancer; Stage II Bladder Urothelial Carcinoma; Stage II Renal Cell Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer; Stage III Renal Cell Cancer

  19. Radium-223 for Advanced Prostate Cancer

    Cancer.gov

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  20. Clinical controversies: proton therapy for prostate cancer.

    PubMed

    Mouw, Kent W; Trofimov, Alexei; Zietman, Anthony L; Efstathiou, Jason A

    2013-04-01

    Proton therapy has been used in the treatment of prostate cancer for several decades, and interest surrounding its use continues to grow. Proton-based treatment techniques have evolved significantly over this period, and several centers now routinely use technologies such as pencil-beam scanning. However, whether the theoretical dosimetric advantages of the proton beam translate into clinically meaningful improvements for prostate cancer patients is unknown, and outcomes from single-arm experiences using whole courses of proton beam therapy in the treatment of early-stage prostate cancer have shown mixed results when compared with contemporary intensity-modulated radiotherapy. A randomized trial comparing proton beam therapy with intensity-modulated radiotherapy in early-stage disease has been launched and will be important in defining the role for proton therapy in this setting. We review the available evidence and present the current state of proton beam therapy for prostate cancer.

  1. Abiraterone Improves Survival in Metastatic Prostate Cancer

    Cancer.gov

    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  2. Do We Know What Causes Prostate Cancer?

    MedlinePlus

    ... account for a small number of prostate cancers. DNA mismatch repair genes (such as MSH2 and MLH1 ): These genes normally help fix mistakes (mismatches) in DNA that are made when a cell is preparing ...

  3. Effects of Presurgical Treatment for Prostate Cancer

    Cancer.gov

    In this study, men diagnosed with androgen-sensitive prostate cancer with intermediate- or high-risk features will be examined with mpMRI, undergo targeted biopsies, and be treated with neoadjuvant androgen deprivation therapy.

  4. Validation of Biomarkers for Prostate Cancer Prognosis

    DTIC Science & Technology

    2013-10-01

    incontinence and urinary urgency as well as sexual dysfunction. Furthermore, evidence from many sources suggests that most prostate cancers are...mainly surgery and radiation therapy, result in well documented significant morbidities, including significant lower urinary tract symptoms such as

  5. Testosterone therapy and prostate cancer

    PubMed Central

    Pastuszak, Alexander W.; Rodriguez, Katherine M.; Nguyen, Taylor M.

    2016-01-01

    The use of exogenous testosterone to treat hypogonadism in the men with a history of prostate cancer (CaP) remains controversial due to fears of cancer recurrence or progression. Due to the detrimental impact of hypogonadism on patient quality of life, recent work has examined the safety of testosterone therapy (TTh) in men with a history of CaP. In this review, we evaluate the literature with regards to the safety of TTh in men with a history of CaP. TTh results in improvements in quality of life with little evidence of biochemical recurrence or progression in men with a history of CaP, or de novo cancer in unaffected men. An insufficient amount of evidence is currently available to truly demonstrate the safe use of TTh in men with low risk CaP. In men with high-risk cancer, more limited data suggest that TTh may be safe, but these findings remain inconclusive. Despite the historic avoidance of TTh in men with a history of CaP, the existing body of evidence largely supports the safe and effective use of testosterone in these men, although additional study is needed before unequivocal safety can be demonstrated. PMID:28078223

  6. Serum selenium levels and prostate cancer risk

    PubMed Central

    Cui, Zhigang; Liu, Dezhong; Liu, Chun; Liu, Gang

    2017-01-01

    Abstract Some observational studies have shown that elevated serum selenium levels are associated with reduced prostate cancer risk; however, not all published studies support these results. A literature search of PubMed, Embase, Medline, and the Cochrane Library up until September 2016 identified 17 studies suitable for further investigation. A meta-analysis was conducted on these studies to investigate the association between serum selenium levels and subsequent prostate cancer risk. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the overall OR of prostate cancer for the highest versus the lowest levels of serum selenium. We found a pooled OR (95% CI) of 0.76 (0.64, 0.91; P < 0.05). In subgroup analysis, an inverse association between serum selenium levels and prostate cancer risk was found in each of case–control studies, current and former smokers, high-grade cancer cases, advanced cancer cases, and different populations. Such correlations were not found for subgroups containing each of cohort studies, nonsmokers, low-grade cancer cases, and early stage cancer cases. In conclusion, our study suggests an inverse relationship between serum selenium levels and prostate cancer risk. However, further cohort studies and randomized control trials based on non-Western populations are required. PMID:28151881

  7. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2012-11-01

    randomized placebo-controlled clinical trial to determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer...and that this risk differed between men who took finasteride versus those who took the placebo. The strongest association was seen for a cluster of 9...SNPs in NPAS2, which was associated with total prostate cancer risk in the finasteride group but not in the placebo group. The most significant NPAS2

  8. Imaging Prostate Cancer (Pca) Phenotype and Evolution

    DTIC Science & Technology

    2014-10-01

    prostate cancer cells. To further investigate the effects of DFP on prostate cancer cells we carried out extracellular flux analysis experiments. Our...Extracellular flux analysis experiments with the Seahorse system showed a marked decrease in OCR after inhibition of ATP synthase by oligomycin...the means. Figure 5 – Extracellular flux analysis in TRAMP C2 cells incubated with different concentrations of DFP. Left: OCR measurements. Right

  9. Characterization of SPINK1 in Prostate Cancer

    DTIC Science & Technology

    2009-07-01

    rearrangement by FISH. A TMPRSS2:ERG rearrangement through intrachromosomal deletion is indicated by loss of one 50 ( green ) ERG signal. (B) Contingency tables...pancreatic juice, its normal function is thought to be the inhibition of serine proteases such as trypsin ( Greene et al., 1976; Haverback et al., 1960; Kazal...lesions to function in prostate cancer, we assayed prostate cancer cell lines by quan- titative PCR for SPINK1 (yellow), ERG (blue), and ETV1 ( green

  10. Targeting TMPRSS2-ERG in Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    ABSTRACT About half of all prostate cancers are known to harbor a genetic mutation that fuses a gene known as ERG to the regulatory region of the gene...activity. We applied this technique to screen genetic and chemical libraries to study ERG mediated tumorigenesis and identify novel therapeutic...agents targeting ERG activity. 15. SUBJECT TERMS Prostate cancer, ERG, gene expression, high throughput screening, small molecule microarray, genetic

  11. Enhancing Therapeutic Cellular Prostate Cancer Vaccines

    DTIC Science & Technology

    2013-06-01

    10-1-0225 TITLE: “Enhancing Therapeutic Cellular Prostate Cancer Vaccines ” PRINCIPAL INVESTIGATOR: Christian R. Gomez, Ph.D...SUBTITLE “Enhancing Therapeutic Cellular Prostate Cancer Vaccines ” 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-10-1-0225 5c. PROGRAM ELEMENT...cell CaP vaccines by taking into consideration tumor-associated hypoxia as a relevant determinant of tumor antigenicity. Major Findings: Gene

  12. Metallated DNA Aptamers For Prostate Cancer Treatment

    DTIC Science & Technology

    2012-03-01

    including a polydA tail in one aptamer complex and a polydT tail in a second aptamer complex, with dimerization occurring by Watson - Crick base pair...by ANSI Std. Z39.18 W81XWH-10-1-0132 Metallated DNA Aptamers for Prostate Cancer Treatment Dr. William Gmeiner Wake Forest University Winston...efficacious for prostate cancer treatment. Significant progress has been made on refining novel Zn2+-binding DNA motifs that utilize FdU

  13. Proteomics in prostate cancer research.

    PubMed

    Hellström, Magnus; Lexander, Helena; Franzén, Bo; Egevad, Lars

    2007-02-01

    The incidence of early prostate cancer (PCa) among middle-aged men has increased rapidly. For many of these men, curatively intended treatment does more harm than good. Established prognostic factors are tumor stage and grade. As a result of earlier detection a majority of patients now have nonpalpable tumors (T1c) of intermediate grade (Gleason score 6). Prostate specific antigen in serum in such cases is generally at a low level and not a reliable predictor of prognosis. Altogether there is an urgent need for adjunctive prognostic indicators. In the search for relevant tumor markers for improved patient selection an exploration of the proteome (the human proteins) could be fruitful. This paper critically reviews the use of 2-dimensional gel electrophoresis (2-DE) for proteome research. Additional steps such as image analysis and mass spectrometry are described. Techniques based on non-2-DE platforms: surface-enhanced laser desorption/ionization (SELDI), isotope coded affinity tags (ICAT) and array-based technologies are also summarized. Although labor-intensive and time-consuming, 2-DE is presently the most powerful method for analysis of cellular protein phenotype and may potentially reveal gene regulations that cannot be detected on a genetic level.

  14. Role of Foxm1 in the Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2011-07-01

    LADY transgenic (TG) mouse models of prostate cancer . Ubiquitous over-expression of Foxm1 accelerates development of PCa, as well as significantly...types in Rosa26-Foxm1 mice, the direct role of Foxm1 in prostate epithelial cells, the cells from which prostate cancer arises, remains unknown...prostate cancer by regulating genes critical for proliferation of prostate epithelial cells and (2) that Foxm1 is negatively regulated by p19ARF tumor

  15. TRICHOMONOSIS AND SUBSEQUENT RISK OF PROSTATE CANCER IN THE PROSTATE CANCER PREVENTION TRIAL

    PubMed Central

    Sutcliffe, Siobhan; Alderete, John F.; Till, Cathee; Goodman, Phyllis J.; Hsing, Ann W.; Zenilman, Jonathan M.; De Marzo, Angelo M.; Platz, Elizabeth A.

    2009-01-01

    We previously observed a positive association between a history of trichomonosis, a sexually transmitted infection caused by the protozoan, Trichomonas vaginalis, and prostate cancer risk in the Health Professionals Follow-up Study. To determine the reproducibility of this finding, we conducted a second, prospective investigation of trichomonosis and prostate cancer in the Prostate Cancer Prevention Trial. Participants were men ≥55 years of age with no evidence of prostate cancer at enrollment (n=18,882). Men were screened annually for prostate cancer, and if not diagnosed during the trial, were offered an end-of-study prostate biopsy. Cases were a sample of men diagnosed with prostate cancer on any biopsy after visit 2 or on their end-of-study biopsy (n=616). Controls were men not diagnosed with prostate cancer during the trial or on their end-of-study biopsy (n=616). Controls were frequency-matched to cases by age, treatment arm, and family history of prostate cancer. Serum from visit 2 was tested for anti-T. vaginalis IgG antibodies. No association was observed between T. vaginalis serostatus and prostate cancer. 21.5% of cases and 24.8% of controls had low seropositivity, and 15.2% and 15.0% had high seropositivity. Compared to seronegative men, the odds ratio of prostate cancer for men with low seropositivity was 0.83 (95% confidence interval (CI): 0.63–1.09), and that for men with high seropositivity was 0.97 (95% CI: 0.70–1.34). Given the original strong biologic rationale and potential for prevention, additional studies are warranted to help resolve discrepancies between study findings, and further investigate this hypothesis from a variety of different approaches. PMID:19117055

  16. Updates of prostate cancer staging: Prostate-specific membrane antigen

    PubMed Central

    Lamb, Alastair; Nair, Rajesh; Geurts, Nicolas; Mitchell, Catherine; Lawrentschuk, Nathan L; Moon, Daniel A; Murphy, Declan G

    2016-01-01

    The ability to accurately stage prostate cancer in both the primary and secondary staging setting can have a major impact on management. Until recently radiological staging has relied on computer tomography, magnetic resonance imaging, and nuclear bone scans to evaluate the extent of disease. However, the utility of these imaging technologies has been limited by their sensitivity and specificity especially in detecting early recurrence. Functional imaging using positron-emission tomography with a radiolabeled ligand targeted to prostate-specific membrane antigen has transformed the prostate cancer imaging landscape. Initial results suggest that it is a substantial improvement over conventional imaging in the setting of recurrence following primary therapy by having a superior ability to detect disease and to do so at an earlier stage. Additionally, it appears that the benefits seen in the secondary staging setting may also exist in the primary staging setting. PMID:27995218

  17. 75 FR 54453 - National Prostate Cancer Awareness Month, 2010

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ... Documents#0;#0; ] Proclamation 8552 of August 31, 2010 National Prostate Cancer Awareness Month, 2010 By the... the last decade, prostate cancer is still the second leading cause of cancer deaths among men in the United States. This year alone, nearly 218,000 men will be diagnosed with prostate cancer, and more...

  18. Genetics of Prostate Cancer (PDQ®)—Health Professional Version

    Cancer.gov

    Expert-reviewed information summary about the genetics of prostate cancer, including information about specific genes and family cancer syndromes. The summary also contains information about screening for prostate cancer and research aimed at prevention of this disease. Psychosocial issues associated with genetic testing and counseling of individuals who may have hereditary prostate cancer syndrome are also discussed.

  19. Management of Clinically Localized Prostate Cancer

    PubMed Central

    Lepor, Herbert

    2004-01-01

    Critics of screening have stated that early detection of prostate cancer does not necessarily reflect a diminishing death rate from the disease. However, several recent reports have demonstrated that the death rate from prostate cancer is decreasing, representing the most compelling validation for aggressive screening. Prostate cancer can be halted only if there is no evidence of systemic or regional metastases and the disease is confined to the surgical field or the radiation template. Surgeons and radiation oncologists must make a concerted effort to exclude men with regional and systemic metastases who are unlikely to benefit from treatment. With the widespread acceptance of prostate-specific antigen screening, a greater proportion of men are being diagnosed with clinically localized prostate cancer. Both radical prostatectomy and radiation therapy are able to halt disease spread in this significant subset of men, but survival outcomes indicate that radical prostatectomy is a more reliable treatment than radiation therapy for clinically localized prostate cancer. Overall, the immediate treatment-related morbidity of radical prostatectomy and radiation therapy in the modern era is quite low. Radical prostatectomy and radiation therapy appear to have a similar impact on continence and erectile function. There is a need for neoadjuvant and adjuvant therapies that can be utilized in those cases where radical prostatectomy and radiation are less likely to completely eradicate or destroy the cancer. PMID:16985859

  20. Radioisotopes in management of metastatic prostate cancer

    PubMed Central

    Raval, Amar; Dan, Tu D.; Williams, Noelle L.; Pridjian, Andrew; Den, Robert B.

    2016-01-01

    Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life. PMID:27843209

  1. Prostate cancer and diet: food for thought?

    PubMed

    Hori, Satoshi; Butler, Elizabeth; McLoughlin, John

    2011-05-01

    • There is now increasing evidence that diet plays a major role in prostate cancer biology and tumorigenesis. • In a health conscious society, it is becoming increasingly common for Urologists to be asked about the impact of diet on prostate cancer. • In the present review, we explore the current evidence for the role of different dietary components and its' effect on prostate cancer prevention and progression. • A literature search was conducted using PubMed® to identify key studies. • There was some evidence to suggest that green tea, isoflavones, lycopenes, cruciferous vegetables and omega 3 polyunsaturated fatty acid intake to be beneficial in the prevention and/or progression of prostate cancer. • There was also evidence to suggest that a high total fat, meat (especially well cooked) and multivitamin intake may be associated with an increased risk of developing prostate cancer. • To date publications have been highly heterogeneous and variable in quality and design. More robust, high quality research trials are needed to help us understand the complex relationship between diet and prostate cancer.

  2. Molecular targets of selenium in prostate cancer prevention (Review).

    PubMed

    Abdulah, Rizky; Kobayashi, Kenji; Yamazaki, Chiho; Koyama, Hiroshi

    2011-08-01

    Prostate cancer is one of the leading causes of cancer-related deaths among males. Although use of the micro-nutrient selenium in prostate cancer clinical trials is limited, the outcomes indicate that selenium is a promising treatment. Furthermore, selenium inhibits prostate cancer through multiple mechanisms, and it is beneficial in controlling the development of this disease. This review highlights the latest epidemiological and biomolecular research on selenium in prostate cancer, as well as its prospects for future clinical use.

  3. Hypoxia, notch signalling, and prostate cancer.

    PubMed

    Marignol, Laure; Rivera-Figueroa, Karla; Lynch, Thomas; Hollywood, Donal

    2013-07-01

    The notch signalling pathway is involved in differentiation, proliferation, angiogenesis, vascular remodelling, and apoptosis. Deregulated expression of notch receptors, ligands, and targets is observed in many solid tumours, including prostate cancer. Hypoxia is a common feature of prostate tumours, leading to increased gene instability, reduced treatment response, and increased tumour aggressiveness. The notch signalling pathway is known to regulate vascular cell fate and is responsive to hypoxia-inducible factors. Evidence to date suggests similar, therapeutically exploitable, behaviour of notch-activated and hypoxic prostate cancer cells.

  4. [An unusual presentation of prostate cancer].

    PubMed

    Joual, A; Rabii, R; Aboutaeib, R; el Moussaoui, A; Benjelloun, S

    1996-01-01

    The authors report an uncommon case of a 74-year old man with prostatic cancer revealed by pelvic mass. Ultrasound exam and CT-scan showed a bilateral laterorectal mass with high density. Presence of such a mass in an old patient is very suggestive of lymph nodes than retroperitoneal tumor. Serum prostate specific antigen (PSA) is rather helpful in such conditions. Biopsy of the mass allows confirmation of the prostatic cancer diagnosis. Bilateral Surgical pulpectomy is performed in combination with oral hormonal therapy. Follow-up after 6 months showed a good course or ultrasound exam and PSA level.

  5. The politics of prostate cancer screening.

    PubMed

    Kaffenberger, Samuel D; Penson, David F

    2014-05-01

    The controversial recent recommendation by the United States Preventive Services Task Force (USPSTF) against prostate-specific antigen (PSA) screening for early-stage prostate cancer has caused much debate. Whereas USPSTF recommendations against routine screening mammography in younger women resulted in fierce public outcry and eventual alteration in the language of the recommendation, the same public and political response has not been seen with PSA screening for prostate cancer. It is of paramount importance to ensure improved efficiency and transparency of the USPSTF recommendation process, and resolution of concerns with the current USPSTF recommendation against PSA screening for all ages.

  6. Family history and prostate cancer risk.

    PubMed

    Lesko, S M; Rosenberg, L; Shapiro, S

    1996-12-01

    The authors examined the relation between family history of prostate cancer and the risk of this cancer in a population-based case-control study conducted in Massachusetts between December 1992 and October 1994. Cases were all incident cases of prostate cancer in men younger than 70 years (n = 563); controls were men with no history of the disease matched to the cases on age and town of residence (n = 703). Prostate cancer risk was increased among men who reported a history of this cancer in either their fathers or brothers (odds ratio (OR) = 2.3, 95% confidence interval (CI) 1.7-3.3). Risk varied with the number of relatives affected and their relationship to the case. For a history of prostate cancer in one relative, the OR was 2.2 (95% CI 1.5-3.2); if two or more relatives were affected, it was 3.9 (95% CI 1.7-5.2). For prostate cancer in the father, the OR was 1.9 (95% CI 1.2-3.0); for prostate cancer in a brother, it was 3.0 (95% CI 1.8-4.9). Risk was inversely related to the subject's age and to age at diagnosis of prostate cancer in his affected relative. Among probands younger than 60 years, the OR was 5.3 (95% CI 2.5-12); for those 60-64 years of age, the OR was 2.7 (95% CI 1.3-5.5); and for those 65 years of age and older, the OR was 1.6 (95% CI 1.0-2.5). For prostate cancer diagnosed in a relative before age 65, the OR was 4.1 (95% CI 2.3-7.3); for detection of the disease after age 74, the OR was 0.76 (95% CI 0.38-1.5). The association was present both among men with local and advanced stage disease and among men whose prostate cancer was detected either by screening or because of symptoms. These data provide evidence that after controlling for diet and other potential confounders, familial factors are significantly associated with the risk of prostate cancer.

  7. Stereotactic Body Radiation Therapy in Treating Patients With Metastatic Breast Cancer, Non-small Cell Lung Cancer, or Prostate Cancer

    ClinicalTrials.gov

    2016-06-17

    Male Breast Carcinoma; Prostate Adenocarcinoma; Recurrent Breast Carcinoma; Recurrent Non-Small Cell Lung Carcinoma; Recurrent Prostate Carcinoma; Stage IV Breast Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Prostate Cancer

  8. Automated localization of implanted seeds in 3D TRUS images used for prostate brachytherapy

    SciTech Connect

    Wei Zhouping; Gardi, Lori; Downey, Donal B.; Fenster, Aaron

    2006-07-15

    An algorithm has been developed in this paper to localize implanted radioactive seeds in 3D ultrasound images for a dynamic intraoperative brachytherapy procedure. Segmentation of the seeds is difficult, due to their small size in relatively low quality of transrectal ultrasound (TRUS) images. In this paper, intraoperative seed segmentation in 3D TRUS images is achieved by performing a subtraction of the image before the needle has been inserted, and the image after the seeds have been implanted. The seeds are searched in a 'local' space determined by the needle position and orientation information, which are obtained from a needle segmentation algorithm. To test this approach, 3D TRUS images of the agar and chicken tissue phantoms were obtained. Within these phantoms, dummy seeds were implanted. The seed locations determined by the seed segmentation algorithm were compared with those obtained from a volumetric cone-beam flat-panel micro-CT scanner and human observers. Evaluation of the algorithm showed that the rms error in determining the seed locations using the seed segmentation algorithm was 0.98 mm in agar phantoms and 1.02 mm in chicken phantoms.

  9. Prostatic Fatty Acids and Cancer Recurrence Following Radical Prostatectomy for Early-Stage Prostate Cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Results from some observational studies suggest that diet and energy balance influence the clinical course of early-stage prostate cancer. To evaluate possible mechanisms, we prospectively examined the relation between prostatic concentrations of fatty acids at diagnosis and cancer recurr...

  10. Update: Immunological Strategies for Prostate Cancer

    PubMed Central

    Antonarakis, Emmanuel S.

    2014-01-01

    Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena. PMID:20425628

  11. Update: immunological strategies for prostate cancer.

    PubMed

    Drake, Charles G; Antonarakis, Emmanuel S

    2010-05-01

    Prostate cancer is the second most common cause of cancer-related death in US men. Along with initial therapy using surgery, radiotherapy, or cryotherapy, hormonal therapy is the mainstay of treatment. For men with advanced (metastatic) disease, docetaxel-based chemotherapy is US Food and Drug Administration (FDA)-approved, and provides a significant survival advantage. This relative paucity of treatment options drives an ongoing quest for additional treatment modalities; among these is immunotherapy. The concept that prostate cancer is a malignancy that can be targeted by the immune system may seem counterintuitive; certainly kidney cancer and melanoma are more traditionally thought of as immune responsive cancers. However, prostate cancer arises in a relatively unique organ and may express a number of proteins (antigens) against which an immune response can be generated. More importantly, several of these agents have now demonstrated a significant survival benefit in randomized controlled clinical trials, and one agent in particular (Sipuleucel-T, Dendreon Corporation, Seattle, WA) could be FDA-approved in 2010. This update summarizes recent clinical developments in the field of prostate cancer immunotherapy, with a focus on dendritic cell vaccines, virus-based vaccines, DNA-based vaccines, and cell-based vaccines. In addition, the notion of agents that target immune checkpoints is introduced. Enthusiasm for prostate cancer immunotherapy is founded upon its potential to mediate targeted, specific, tumor cell destruction without significant systemic toxicity; however, this has yet to be fully realized in the clinical arena.

  12. [Immunotherapy: a therapeutic revolution against prostate cancer?].

    PubMed

    Pracht, Marc; Herrera, Fernanda; Tawadros, Thomas; Berthold, Dominik

    2013-05-22

    The interaction between the immune system and cancer was an area of research interest for several decades. The recent U.S. Food and Drug Administration approval of sipuleucel-T and ipilimumab stimulated broader interest in manipulating immunity to fight cancer. In the context of prostate cancer, the immunotherapy strategies under development are therapeutic vaccination strategies, such as sipuleucel-T and PROSTVAC-VF, or immune checkpoint blockade of CTLA-4. Improved understanding of the immune responses generated by the development of predictive biomarkers for patient selection will guide rational combinations of these treatments and provide new treatment options in prostate cancer.

  13. Genetic counseling for prostate cancer risk.

    PubMed

    Nieder, A M; Taneja, S S; Zeegers, M P A; Ostrer, H

    2003-03-01

    Major risk factors for developing prostate cancer, including positive family history and African-American ethnicity, can be quantified for genetic counseling. Factors increasing familial risk for prostate cancer are closer degree of kinship, number of affected relatives, and early age of onset (< 50 years) among the affected relatives. Genetic testing may be useful for modification of risk, but currently should be performed only within the context of a well-designed research study that will determine penetrance and genotype-phenotype correlation of specific mutations. Even in the absence of genetic testing, African-American men and men with a strong family history of prostate cancer may opt to initiate screening by prostate specific antigen (PSA) and digital rectal exam (DRE) screening at age 40.

  14. Chemotherapy of prostate cancer: present and future.

    PubMed

    Trump, Donald; Lau, Yiu-Keung

    2003-06-01

    The role of chemotherapy in prostate cancer continues to evolve. In men with symptomatic androgen-independent prostate cancer, significant reduction in pain and analgesic requirements are achievable with mitoxantrone and glucocorticoid combinations compared with glucocorticoids alone. However, survival rates are not improved. Taxane-based combinations with estramustine phosphate or other new agents show promise. Prostate-specific antigen response rates with these combinations appear to be 1.5 to 2 times more frequent than with mitoxantrone-based combinations. Randomized trials of taxane versus mitoxantrone-based therapies are underway. New agents and applications of current agents in adjuvant settings should be explored if survival in men with prostate cancer is to be improved.

  15. Prostate cancer immunology: biology, therapeutics, and challenges.

    PubMed

    Webster, W Scott; Small, Eric J; Rini, Brian I; Kwon, Eugene D

    2005-11-10

    A number of recently developed and promising approaches to antitumoral immunotherapy are being investigated as potential treatments for advanced prostate cancer. These approaches largely revolve around strategies to increase antigen-specific T-cell activation against prostate tumors as well as precise manipulations of critical co-regulatory receptors that help to maintain and prolong the activity of antigen-presenting cells and T cells that are capable of mediating tumor regression. Herein, we describe the experience with the most recent and promising approaches pertaining to prostate cancer immunotherapy. Additionally, we discuss the mechanistic basis for these approaches as well as current limitations that must still be addressed in order to propel immunotherapy into the forefront of prostate cancer treatment.

  16. Disruption of Prostate Epithelial Differentiation Pathways and Prostate Cancer Development

    PubMed Central

    Frank, Sander B.; Miranti, Cindy K.

    2013-01-01

    One of the foremost problems in the prostate cancer (PCa) field is the inability to distinguish aggressive from indolent disease, which leads to difficult prognoses and thousands of unnecessary surgeries. This limitation stems from the fact that the mechanisms of tumorigenesis in the prostate are poorly understood. Some genetic alterations are commonly reported in prostate tumors, including upregulation of Myc, fusion of Ets genes to androgen-regulated promoters, and loss of Pten. However, the specific roles of these aberrations in tumor initiation and progression are poorly understood. Likewise, the cell of origin for PCa remains controversial and may be linked to the aggressive potential of the tumor. One important clue is that prostate tumors co-express basal and luminal protein markers that are restricted to their distinct cell types in normal tissue. Prostate epithelium contains layer-specific stem cells as well as rare bipotent cells, which can differentiate into basal or luminal cells. We hypothesize that the primary oncogenic cell of origin is a transient-differentiating bipotent cell. Such a cell must maintain tight temporal and spatial control of differentiation pathways, thus increasing its susceptibility for oncogenic disruption. In support of this hypothesis, many of the pathways known to be involved in prostate differentiation can be linked to genes commonly altered in PCa. In this article, we review what is known about important differentiation pathways (Myc, p38MAPK, Notch, PI3K/Pten) in the prostate and how their misregulation could lead to oncogenesis. Better understanding of normal differentiation will offer new insights into tumor initiation and may help explain the functional significance of common genetic alterations seen in PCa. Additionally, this understanding could lead to new methods for classifying prostate tumors based on their differentiation status and may aid in identifying more aggressive tumors. PMID:24199173

  17. 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

  18. 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.

  19. Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

    DTIC Science & Technology

    2007-04-01

    in part - to it’s strong positive association with age.6,7 Benign prostatic hyperplasia , which is also highly associated with age, contributes to...prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated with age, can raise PSA levels and further muddy...contemporary referral series of men with prostate cancer. 60(4 Suppl 1):47-52, 2002 8. Fitzpatrick JM. The natural history of benign prostatic hyperplasia . BJU

  20. Magnetic Resonance Spectroscopy (MRS) of Prostatic Fluids for Early Detection of Prostate Cancer

    DTIC Science & Technology

    2006-10-01

    strong positive association with age.6,7 Benign prostatic hyperplasia , which is also highly associated with age, contributes to increased PSA levels and...prostate cancer risk. Moreover, benign prostatic hyperplasia (BPH), which is also strongly associated with age, can raise PSA levels and further muddy...contemporary referral series of men with prostate cancer. 60(4 Suppl 1):47-52, 2002 8. Fitzpatrick JM. The natural history of benign prostatic hyperplasia . BJU

  1. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

    NASA Astrophysics Data System (ADS)

    Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

    2016-08-01

    Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

  2. Radiosensitization in prostate cancer: mechanisms and targets

    PubMed Central

    2013-01-01

    Prostate cancer is the second most commonly diagnosed cancer in American men over the age of 45 years and is the third most common cause of cancer related deaths in American men. In 2012 it is estimated that 241,740 men will be diagnosed with prostate cancer and 28,170 men will succumb to prostate cancer. Currently, radiation therapy is one of the most common definitive treatment options for localized prostate cancer. However, significant number of patients undergoing radiation therapy will develop locally persistent/recurrent tumours. The varying response rates to radiation may be due to 1) tumor microenvironment, 2) tumor stage/grade, 3) modality used to deliver radiation, and 4) dose of radiation. Higher doses of radiation has not always proved to be effective and have been associated with increased morbidity. Compounds designed to enhance the killing effects of radiation, radiosensitizers, have been extensively investigated over the past decade. The development of radiosensitizing agents could improve survival, improve quality of life and reduce costs, thus benefiting both patients and healthcare systems. Herin, we shall review the role and mechanisms of various agents that can sensitize tumours, specifically prostate cancer. PMID:23351141

  3. Prostate cancer in men of African origin.

    PubMed

    McGinley, Kathleen F; Tay, Kae Jack; Moul, Judd W

    2016-02-01

    Men of African origin are disproportionately affected by prostate cancer: prostate cancer incidence is highest among men of African origin in the USA, prostate cancer mortality is highest among men of African origin in the Caribbean, and tumour stage and grade at diagnosis are highest among men in sub-Saharan Africa. Socioeconomic, educational, cultural, and genetic factors, as well as variations in care delivery and treatment selection, contribute to this cancer disparity. Emerging data on single-nucleotide-polymorphism patterns, epigenetic changes, and variations in fusion-gene products among men of African origin add to the understanding of genetic differences underlying this disease. On the diagnosis of prostate cancer, when all treatment options are available, men of African origin are more likely to choose radiation therapy or to receive no definitive treatment than white men. Among men of African origin undergoing surgery, increased rates of biochemical recurrence have been identified. Understanding differences in the cancer-survivorship experience and quality-of-life outcomes among men of African origin are critical to appropriately counsel patients and improve cultural sensitivity. Efforts to curtail prostate cancer screening will likely affect men of African origin disproportionately and widen the racial disparity of disease.

  4. Dosimetric Study of Pelvic Proton Radiotherapy for High-Risk Prostate Cancer

    SciTech Connect

    Chera, Bhishamjit S.; Vargas, Carlos; Morris, Christopher G.; Louis, Debbie; Flampouri, Stella; Yeung, Daniel; Duvvuri, Srividya; Li Zuofeng; Mendenhall, Nancy Price

    2009-11-15

    Purpose: To compare dose distributions in targeted tissues (prostate, seminal vesicles, pelvic regional nodes) and nontargeted tissues in the pelvis with intensity-modulated radiotherapy (IMRT) and forward-planned, double-scattered, three-dimensional proton radiotherapy (3D-PRT). Methods and Materials: IMRT, IMRT followed by a prostate 3D-PRT boost (IMRT/3D-PRT), and 3D-PRT plans were created for 5 high-risk prostate cancer patients (n = 15 plans). A 78-CGE/Gy dose was prescribed to the prostate and proximal seminal vesicles and a 46-CGE/Gy was prescribed to the pelvic nodes. Various dosimetric endpoints were compared. Results: Target coverage of the prostate and nodal planning target volumes was adequate for all three plans. Compared with the IMRT and IMRT/3D-PRT plans, the 3D-PRT plans reduced the mean dose to the rectum, rectal wall, bladder, bladder wall, small bowel, and pelvis. The relative benefit of 3D-PRT (vs IMRT) at reducing the rectum and rectal wall V5-V40 was 53% to 71% (p < 0.05). For the bladder and bladder wall, the relative benefit for V5 to V40 CGE/Gy was 40% to 63% (p < 0.05). The relative benefit for reducing the volume of small bowel irradiated from 5 to 30 CGE/Gy in the 3D-PRT ranged from 62% to 69% (p < 0.05). Use of 3D-PRT did not produce the typical low-dose 'bath' of radiation to the pelvis seen with IMRT. Femoral head doses were higher for the 3D-PRT. Conclusions: Use of 3D-PRT significantly reduced the dose to normal tissues in the pelvis while maintaining adequate target coverage compared with IMRT or IMRT/3D-PRT. When treating the prostate, seminal vesicles, and pelvic lymph nodes in prostate cancer, proton therapy may improve the therapeutic ratio beyond what is possible with IMRT.

  5. Postoperative Intensity Modulated Radiation Therapy in High Risk Prostate Cancer: A Dosimetric Comparison

    SciTech Connect

    Digesu, Cinzia; Cilla, Savino; De Gaetano, Andrea; Massaccesi, Mariangela; Macchia, Gabriella; Ippolito, Edy; Deodato, Francesco; Panunzi, Simona; Iapalucci, Chiara; Mattiucci, Gian Carlo; D'Angelo, Elisa; Padula, Gilbert D.A.; Valentini, Vincenzo; Cellini, Numa

    2011-10-01

    The aim of this study was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal technique (3D-CRT), with respect to target coverage and irradiation of organs at risk for high dose postoperative radiotherapy (PORT) of the prostate fossa. 3D-CRT and IMRT treatment plans were compared with respect to dose to the rectum and bladder. The dosimetric comparison was carried out in 15 patients considering 2 different scenarios: (1) exclusive prostate fossa irradiation, and (2) pelvic node irradiation followed by a boost on the prostate fossa. In scenario (1), a 3D-CRT plan (box technique) and an IMRT plan were calculated and compared for each patient. In scenario (2), 3 treatment plans were calculated and compared for each patient: (a) 3D-CRT box technique for both pelvic (prophylactic nodal irradiation) and prostate fossa irradiation (3D-CRT only); (b) 3D-CRT box technique for pelvic irradiation followed by an IMRT boost to the prostatic fossa (hybrid 3D-CRT and IMRT); and (c) IMRT for both pelvic and prostate fossa irradiation (IMRT only). For exclusive prostate fossa irradiation, IMRT significantly reduced the dose to the rectum (lower Dmean, V50%, V75%, V90%, V100%, EUD, and NTCP) and the bladder (lower Dmean, V50%, V90%, EUD and NTCP). When prophylactic irradiation of the pelvis was also considered, plan C (IMRT only) performed better than plan B (hybrid 3D-CRT and IMRT) as respect to both rectum and bladder irradiation (reduction of Dmean, V50%, V75%, V90%, equivalent uniform dose [EUD], and normal tissue complication probability [NTCP]). Plan (b) (hybrid 3D-CRT and IMRT) performed better than plan (a) (3D-CRT only) with respect to dose to the rectum (lower Dmean, V75%, V90%, V100%, EUD, and NTCP) and the bladder (Dmean, EUD, and NTCP). Postoperative IMRT in prostate cancer significantly reduces rectum and bladder irradiation compared with 3D-CRT.

  6. Prostate Cancer Treatments Have Varying Side Effects, Study Shows

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164200.html Prostate Cancer Treatments Have Varying Side Effects, Study Shows Even ' ... News) -- The long-term side effects of different prostate cancer treatments vary -- and knowing that may help men ...

  7. Anxiety May Lead to Unneeded Prostate Cancer Treatments

    MedlinePlus

    ... fullstory_163295.html Anxiety May Lead to Unneeded Prostate Cancer Treatments Researchers suggest that dealing with a patient's ... Jan. 27, 2017 (HealthDay News) -- Anxiety may prompt prostate cancer patients to opt for potentially unnecessary treatments, a ...

  8. Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program

    DTIC Science & Technology

    2014-10-01

    TITLE: Georgetown University and Hampton University Prostate Cancer Undergraduate Fellowship Program PRINCIPAL INVESTIGATOR: Anatoly...University Prostate Cancer Undergraduate Fellowship Program 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  9. Breast and Prostate Cancer Cohort Consortium (BPC3)

    Cancer.gov

    Breast and Prostate Cancer Cohort Consortium collaborates with three genomic facilities, epidemiologists, population geneticists, and biostatisticians from multiple institutions to study hormone-related gene variants and environmental factors in breast and prostate cancers.

  10. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up

    PubMed Central

    Vaarala, Markku H.; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A.

    2016-01-01

    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996–1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62–1.99] and 0.44 (95% CI, 0.29–0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation. PMID:27446410

  11. Prostate cancer incidence in men with self-reported prostatitis after 15 years of follow-up.

    PubMed

    Vaarala, Markku H; Mehik, Aare; Ohtonen, Pasi; Hellström, Pekka A

    2016-08-01

    Controversy exists regarding a possible association between prostatitis and prostate cancer. To further evaluate the incidence of prostate cancer following prostatitis, a study of prostate cancer incidence in a cohort of Finnish men was performed. The original survey evaluating self-reported prostatitis was conducted in 1996-1997. A database review was conducted focusing on prostate cancer diagnoses in the cohort. In 2012, there were 13 (5.2%) and 27 (1.8%) prostate cancer cases among men with (n=251) and without (n=1,521) prostatitis symptoms, respectively. There were no significant differences in age, primary therapy distribution, prostate-specific antigen levels, Gleason score, clinical T-class at the time of prostate cancer diagnosis, or time lag between the original survey and prostate cancer diagnosis. The standardized incidence ratio (SIR) of prostate cancer was 1.16 [95% confidence interval (CI), 0.62-1.99] and 0.44 (95% CI, 0.29-0.64) among men with and without prostatitis symptoms, respectively. After 15 years of follow-up subsequent to self-reported prostatitis, no evident increase in incidence of prostate cancer was detected among Finnish men with prostatitis symptoms. The higher percentage of prostate cancer among men with prostatitis symptoms appears to be due to coincidentally low SIR of prostate cancer among men without prostatitis symptoms, and may additionally be due to increased diagnostic examinations. Further research is required to confirm this speculation.

  12. Deciding on radiation therapy for prostate cancer: the physician's perspective.

    PubMed

    Krisch, E B; Koprowski, C D

    2000-08-01

    Multiple treatment options are available for the radiation therapy of prostate cancer including whole pelvic radiotherapy (WPRT), prostate-only radiotherapy (PORT), three-dimensional conformal radiotherapy (3DCRT), intensity modulated radiotherapy (IMRT), as well as proton or neutron beam based therapies and brachytherapy. Numerous technical variations hamper objective assessment of these different treatment modalities. These variations are extensive and often subtle (dose to the prostate, the dose per fraction, number and size of fields, the photon energy, patient positioning, prostatic motion, the use of immobilization devices, 2D or 3D planning for treatment, and others) may cause interpretive uncertainty. Despite this confusion, there is some consensus. Prostate-specific antigen (PSA) nadirs, as well as pretreatment PSA levels, significantly alter outcome. Low-risk patients do well no matter which treatment they receive, although the question of dose-escalation therapy to improve results remains unanswered. High-risk patients do poorly regardless of treatment, although the addition of androgen ablation and dose-escalation therapy may improve results. Quality of life (QOL) studies continue to show a problem for radical prostatectomy (RP) patients secondary to impotence and incontinence and a problem for radiotherapy patients due to gastrointestinal (GI) disturbances. Patients can have access to any specific study through technologies such as the Internet. Although this information can be useful, the subtleties of each different article are usually beyond the understanding of most patients. This report examines some of the new radiotherapy modalities as well as corrects some misconceptions regarding radiotherapy results and morbidity. In addition, we discuss some studies comparing surgery and radiotherapy and attempt to objectively compare different radiation therapy strategies for localized prostate cancer.

  13. Sci—Fri PM: Dosimetry—06: Commissioning of a 3D patient specific QA system for hypofractionated prostate treatments

    SciTech Connect

    Rivest, R; Venkataraman, S; McCurdy, B

    2014-08-15

    The objective of this work is to commission the 6MV-SRS beam model in COMPASS (v2.1, IBA-Dosimetry) and validate its use for patient specific QA of hypofractionated prostate treatments. The COMPASS system consists of a 2D ion chamber array (MatriXX{sup Evolution}), an independent gantry angle sensor and associated software. The system can either directly calculate or reconstruct (using measured detector responses) a 3D dose distribution on the patient CT dataset for plan verification. Beam models are developed and commissioned in the same manner as a beam model is commissioned in a standard treatment planning system. Model validation was initially performed by comparing both COMPASS calculations and reconstructions to measured open field beam data. Next, 10 hypofractionated prostate RapidArc plans were delivered to both the COMPASS system and a phantom with ion chamber and film inserted. COMPASS dose distributions calculated and reconstructed on the phantom CT dataset were compared to the chamber and film measurements. The mean (± standard deviation) difference between COMPASS reconstructed dose and ion chamber measurement was 1.4 ± 1.0%. The maximum discrepancy was 2.6%. Corresponding values for COMPASS calculation were 0.9 ± 0.9% and 2.6%, respectively. The average gamma agreement index (3%/3mm) for COMPAS reconstruction and film was 96.7% and 95.3% when using 70% and 20% dose thresholds, respectively. The corresponding values for COMPASS calculation were 97.1% and 97.1%, respectively. Based on our results, COMPASS can be used for the patient specific QA of hypofractionated prostate treatments delivered with the 6MV-SRS beam.

  14. A 3D-printed local drug delivery patch for pancreatic cancer growth suppression.

    PubMed

    Yi, Hee-Gyeong; Choi, Yeong-Jin; Kang, Kyung Shin; Hong, Jung Min; Pati, Ruby Gupta; Park, Moon Nyeo; Shim, In Kyong; Lee, Chan Mi; Kim, Song Cheol; Cho, Dong-Woo

    2016-09-28

    Since recurrence and metastasis of pancreatic cancer has a worse prognosis, chemotherapy has been typically performed to attack the remained malignant cells after resection. However, it is difficult to achieve the therapeutic concentration at the tumor site with systemic chemotherapy. Numerous local drug delivery systems have been studied to overcome the shortcomings of systemic delivery. However, because most systems involve dissolution of the drug within the carrier, the concentration of the drug is limited to the saturation solubility, and consequently cannot reach the sufficient drug dose. Therefore, we hypothesized that 3D printing of a biodegradable patch incorporated with a high drug concentration would provide a versatile shape to be administered at the exact tumor site as well as an appropriate therapeutic drug concentration with a controlled release. Here, we introduce the 3D-printed patches composed of a blend of poly(lactide-co-glycolide), polycaprolactone, and 5-fluorouracil for delivering the anti-cancer drug in a prolonged controlled manner and therapeutic dose. 3D printing technology can manipulate the geometry of the patch and the drug release kinetics. The patches were flexible, and released the drug over four weeks, and thereby suppressed growth of the subcutaneous pancreatic cancer xenografts in mice with minimized side effects. Our approach reveals that 3D printing of bioabsorbable implants containing anti-cancer drugs could be a powerful method for an effective local delivery of chemotherapeutic agents to treatment of cancers.

  15. Role of GGAP/PIKE-A in prostate cancer progression

    DTIC Science & Technology

    2009-05-01

    isoform which also contains a COOH-terminal Arf-GAP domain and two ankyrin repeats . Both of these proteins can bind PI3-K via their proline-rich...may contribute to increased activity of GGAP2 in prostate cancer. In summary, GGAP2 may promote prostate cancer growth and progression via...that they may contribute to the functions of GGAP2 in prostate cancer. In summary, GGAP2 may promote prostate cancer growth and progression via

  16. Oxidative Stress, DNA Repair, and Prostate Cancer Risk

    DTIC Science & Technology

    2011-08-01

    have concluded that DRC is not a risk factor for prostate cancer microRNA prostate cancer Hua.Zhao@RoswellPark.org Table of Contents...known and suspected risk factors for prostate cancer are associated with elevated levels of reactive oxygen species (ROS) (advancing age, inflammation...association between DNA repair capacity and prostate cancer risk might be due to the fact of using surrogate tissues , not the target tissues . In this study

  17. Prostate cancer epigenetics and its clinical implications.

    PubMed

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy.

  18. Prostate cancer epigenetics and its clinical implications

    PubMed Central

    Yegnasubramanian, Srinivasan

    2016-01-01

    Normal cells have a level of epigenetic programming that is superimposed on the genetic code to establish and maintain their cell identity and phenotypes. This epigenetic programming can be thought as the architecture, a sort of cityscape, that is built upon the underlying genetic landscape. The epigenetic programming is encoded by a complex set of chemical marks on DNA, on histone proteins in nucleosomes, and by numerous context-specific DNA, RNA, protein interactions that all regulate the structure, organization, and function of the genome in a given cell. It is becoming increasingly evident that abnormalities in both the genetic landscape and epigenetic cityscape can cooperate to drive carcinogenesis and disease progression. Large-scale cancer genome sequencing studies have revealed that mutations in genes encoding the enzymatic machinery for shaping the epigenetic cityscape are among the most common mutations observed in human cancers, including prostate cancer. Interestingly, although the constellation of genetic mutations in a given cancer can be quite heterogeneous from person to person, there are numerous epigenetic alterations that appear to be highly recurrent, and nearly universal in a given cancer type, including in prostate cancer. The highly recurrent nature of these alterations can be exploited for development of biomarkers for cancer detection and risk stratification and as targets for therapeutic intervention. Here, we explore the basic principles of epigenetic processes in normal cells and prostate cancer cells and discuss the potential clinical implications with regards to prostate cancer biomarker development and therapy. PMID:27212125

  19. Functional CT imaging of prostate cancer

    NASA Astrophysics Data System (ADS)

    Henderson, Elizabeth; Milosevic, Michael F.; Haider, Masoom A.; Yeung, Ivan W. T.

    2003-09-01

    The purpose of this paper is to investigate the distribution of blood flow (F), mean capillary transit time (Tc), capillary permeability (PS) and blood volume (vb) in prostate cancer using contrast-enhanced CT. Nine stage T2-T3 prostate cancer patients were enrolled in the study. Following bolus injection of a contrast agent, a time series of CT images of the prostate was acquired. Functional maps showing the distribution of F, Tc, PS and vb within the prostate were generated using a distributed parameter tracer kinetic model, the adiabatic approximation to the tissue homogeneity model. The precision of the maps was assessed using covariance matrix analysis. Finally, maps were compared to the findings of standard clinical investigations. Eight of the functional maps demonstrated regions of increased F, PS and vb, the locations of which were consistent with the results of standard clinical investigations. However, model parameters other than F could only be measured precisely within regions of high F. In conclusion functional CT images of cancer-containing prostate glands demonstrate regions of elevated F, PS and vb. However, caution should be used when applying a complex tracer kinetic model to the study of prostate cancer since not all parameters can be measured precisely in all areas.

  20. [The treatment options for localized prostate cancer].

    PubMed

    Livne, Pinhas M

    2006-01-01

    Prostate cancer is a very common tumor in men. Today the disease is very often diagnosed early because of an elevated PSA without symptoms and the disease is localized to the prostate. Patients with prostate cancer can be divided into 3 subgroups for the carcinoma: favorable, moderate, and poorly. The grouping depends mainly on the Gleason score of the prostate biopsy. According to the Gleason score, favorable cancer is up to score 6 (3 + 3), moderate score 7, and poor--Gleason score 8-10. The other favorable clinical factors are PSA < 10 ng/ml, and clinical stage by DRE of T1C or T2 (no nodule or palpable nodule not extending beyond the prostatic capsule). The treatment options for cure when the prostate cancer is localized are either radical prostatectomy or radiotherapy (external or brachytherapy or combination). Each of these therapies has side effects and each has advantages and disadvantages. Sometimes the treatment choice is not for cure and the options are hormonal treatment or watchful waiting. Twenty to 30% of the patients treated for cure may fail the treatment and have elevation of PSA without any clinical symptoms, or signs of local recurrence or distant spread. Some of these patients with biochemical failure may be cured by salvage treatment: radiotherapy after radical prostatectomy and salvage radical prostatectomy or cryotherapy following failure of radiotherapy.

  1. How Precisely Can Prostate Cancer Be Managed?

    PubMed Central

    2016-01-01

    Progress has been made in applying genetic information to disease management in the postgenomic era, and precision medicine is emerging in prostate cancer management. The prostate health index, the 4-kallikrein (4K) score, and the PCA3, TMPRSS2-ERG, and Prostarix tests have potential for refining prostate cancer screening in conjunction with traditional prostate-specific antigen testing. The Confirm MDx and PCA3 tests have shown promise in identifying men who need be rebiopsied after a primary negative biopsy. Oncotype DX, Prolaris, the biopsy-based Decipher prostate cancer test, and ProMark may improve predictive risk stratification in addition to the traditional Gleason score and tumor stage. Decipher and Prolaris may predict biochemical recurrence and metastasis after radical prostatectomy and possibly help identify patients who need adjuvant therapy. Androgen receptor splice variant 7 appears effective in guiding the selection of second hormonal manipulation with abiraterone or enzalutamide versus chemotherapy when treating metastatic castration-resistant prostate cancer. PMID:27915475

  2. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    SciTech Connect

    Chen, Chih-Hao; Kuo, Shyh Ming; Liu, Guei-Sheung; Chen, Wan-Nan U.; Chuang, Chin-Wen; Liu, Li-Feng

    2012-11-09

    Highlights: Black-Right-Pointing-Pointer Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. Black-Right-Pointing-Pointer Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. Black-Right-Pointing-Pointer 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 {mu}m porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  3. Extremely Early Diagnostic Test for Prostate Cancer

    SciTech Connect

    James, Veronica Jean

    2011-11-17

    This article reports the results of a blinded fiber diffraction study of skin samples taken from TRAMP mice and age-matched controls to determine whether changes noted in fiber diffraction studies of human skin were present in these TRAMP mice studies. These mice are bred to progress to Gleeson Type 3 to Type 5 prostate cancer. Small strips, 1 mm x 5 mm, cut from the mouse skin samples were loaded into cells in the same way as human samples and slightly stretched to remove the crimp. They remained fully hydrated throughout exposure to the synchrotron beam. The added change that was reported for prostate cancer in 2009 was obtained for all TRAMP mice samples, indicating that this change can be read as High Grade Cancer in human diagnostic tests. These changes were evident for all 3 and 7 week old TRAMP mice samples but not for any of the control samples. This indicates that the changes in the fibre diffraction patterns appear much earlier than in any other available prostate cancer diagnostic test, as none of these can verify the presence of prostate cancer in the TRAMP mice before 10 weeks of age. The fiber diffraction test is therefore the most accurate and earliest test for high grade prostate cancer.

  4. Risk stratification in prostate cancer screening.

    PubMed

    Roobol, Monique J; Carlsson, Sigrid V

    2013-01-01

    Screening for prostate cancer is a controversial topic within the field of urology. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial did not demonstrate any difference in prostate-cancer-related mortality rates between men screened annually rather than on an 'opportunistic' basis. However, in the world's largest trial to date--the European Randomised Study of Screening for Prostate Cancer--screening every 2-4 years was associated with a 21% reduction in prostate-cancer-related mortality rate after 11 years. Citing the uncertain ratio between potential harm and potential benefit, the US Preventive Services Task Force recently recommended against serum PSA screening. Although this ratio has yet to be elucidated, PSA testing--and early tumour detection--is undoubtedly beneficial for some individuals. Instead of adopting a 'one size fits all' approach, physicians are likely to perform personalized risk assessment to minimize the risk of negative consequences, such as anxiety, unnecessary testing and biopsies, overdiagnosis, and overtreatment. The PSA test needs to be combined with other predictive factors or be used in a more thoughtful way to identify men at risk of symptomatic or life-threatening cancer, without overdiagnosing indolent disease. A risk-adapted approach is needed, whereby PSA testing is tailored to individual risk.

  5. Peptide hydrogelation and cell encapsulation for 3D culture of MCF-7 breast cancer cells.

    PubMed

    Huang, Hongzhou; Ding, Ying; Sun, Xiuzhi S; Nguyen, Thu A

    2013-01-01

    Three-dimensional (3D) cell culture plays an invaluable role in tumor biology by providing in vivo like microenviroment and responses to therapeutic agents. Among many established 3D scaffolds, hydrogels demonstrate a distinct property as matrics for 3D cell culture. Most of the existing pre-gel solutions are limited under physiological conditions such as undesirable pH or temperature. Here, we report a peptide hydrogel that shows superior physiological properties as an in vitro matrix for 3D cell culture. The 3D matrix can be accomplished by mixing a self-assembling peptide directly with a cell culture medium without any pH or temperature adjustment. Results of dynamic rheological studies showed that this hydrogel can be delivered multiple times via pipetting without permanently destroying the hydrogel architecture, indicating the deformability and remodeling ability of the hydrogel. Human epithelial cancer cells, MCF-7, are encapsulated homogeneously in the hydrogel matrix during hydrogelation. Compared with two-dimensional (2D) monolayer culture, cells residing in the hydrogel matrix grow as tumor-like clusters in 3D formation. Relevant parameters related to cell morphology, survival, proliferation, and apoptosis were analyzed using MCF-7 cells in 3D hydrogels. Interestingly, treatment of cisplatin, an anti-cancer drug, can cause a significant decrease of cell viability of MCF-7 clusters in hydrogels. The responses to cisplatin were dose- and time-dependent, indicating the potential usage of hydrogels for drug testing. Results of confocal microscopy and Western blotting showed that cells isolated from hydrogels are suitable for downstream proteomic analysis. The results provided evidence that this peptide hydrogel is a promising 3D cell culture material for drug testing.

  6. Solitary Fibrous Tumor of the Prostate Which Was Initially Misdiagnosed as Prostate Cancer

    PubMed Central

    Osamu, Soma; Murasawa, Hiromi; Yoneyama, Takahiro; Koie, Takuya; Ohyama, Chikara

    2017-01-01

    Solitary fibrous tumor (SFT) of the prostate is a very rare tumor. We report a case of 65-year-old man with SFT of the prostate which was initially misdiagnosed as prostate cancer. Finally, we performed total prostatectomy and the tumor was histologically diagnosed as SFT of the prostate. The patient's clinical course has progressed favorably with no obvious recurrence 18 months postoperatively.

  7. Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy

    DTIC Science & Technology

    2010-03-01

    Exploiting a Molecular Gleason Grade for Prostate Cancer Therapy PRINCIPAL INVESTIGATOR: Peter S. Nelson, MD...Molecular Gleason Grade for Prostate Cancer Therapy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-07-1-0149 5c. PROGRAM ELEMENT... levels of cognate serum proteins. #3 Write final report. (Note the original Aim 3 involving animal studies of altering prostate cancer grade

  8. Racial Disparities in Palliative Care for Prostate Cancer

    DTIC Science & Technology

    2013-10-01

    0802 TITLE: Racial Disparities in Palliative Care for Prostate Cancer PRINCIPAL INVESTIGATOR: Alfred I. Neugut, MD, PhD...Disparities in Palliative Care for Prostate Cancer 5b. GRANT NUMBER W81XWH-10-1-0802 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S... palliative treatments. 15. SUBJECT TERMS Prostate cancer, palliative care , ureteral obstruction, cord compression 16. SECURITY CLASSIFICATION OF

  9. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    therapy -­‐resistant   prostate   cancer  cells  and  in  combination   therapy  (SOW...treatment resistance in advanced prostate cancer PRINCIPAL INVESTIGATOR: Dr. Karin Scarpinato CONTRACTING ORGANIZATION: Georgia Southern...SUPPLEMENTARY NOTES 14. ABSTRACT The purpose of this project is to determine if rescinnamine is effective against prostate cancer and

  10. 76 FR 55551 - National Prostate Cancer Awareness Month, 2011

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... Documents#0;#0; ] Proclamation 8706 of September 1, 2011 National Prostate Cancer Awareness Month, 2011 By the President of the United States of America A Proclamation Prostate cancer is the second leading... only by the men living with and fighting prostate cancer, but also by their families, friends,...

  11. NCCU/BBRI-Duke/Urology Partnership In Prostate Cancer Research

    DTIC Science & Technology

    2011-06-01

    endocannabinoid methanandamide- mediated cell proliferation and androgen receptor expression in EA006AA African American prostate cancer cells. 2...therapeutic intervention against prostate cancer Pilot Project #5: Feasibility of Endurance Exercise Training on Cardiovascular Risk Factors...endurance exercise training on exercise capacity following radical prostatectomy among with men with localized prostate cancer . 2. To assess the

  12. Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer

    DTIC Science & Technology

    2009-03-01

    Exploiting the Immunological Effects of Standard Treatments in Prostate Cancer PRINCIPAL INVESTIGATOR: Brad H. Nelson, Ph.D...From - To) 1 MAR 2008 - 28 FEB 2009 4. TITLE AND SUBTITLE Exploiting the immunological effects of standard treatments in 5a. CONTRACT NUMBER...treatment of prostate cancer. 15. SUBJECT TERMS Tumor immunology , immunotherapy, prostate cancer, antibody, T cell, tumor antigen, hormone therapy

  13. Disparities in Prostate Cancer Treatment Modality and Quality of Life

    DTIC Science & Technology

    2010-11-01

    producing hormones) 1 0 10 11 B8f. Watchful waiting (no treatment, wait and see if your prostate cancer grows) 1 0 10 11 B8g. Cryotherapy (process...your prostate cancer grows) 7 Cryotherapy (process to freeze and destroy prostate tissue) 8 Chemotherapy (use of anti-cancer drugs) 9 Any other

  14. The evolving biology and treatment of prostate cancer

    PubMed Central

    Taichman, Russel S.; Loberg, Robert D.; Mehra, Rohit; Pienta, Kenneth J.

    2007-01-01

    Since the effectiveness of androgen deprivation for treatment of advanced prostate cancer was first demonstrated, prevention strategies and medical therapies for prostate cancer have been based on understanding the biologic underpinnings of the disease. Prostate cancer treatment is one of the best examples of a systematic therapeutic approach to target not only the cancer cells themselves, but the microenvironment in which they are proliferating. As the population ages and prostate cancer prevalence increases, challenges remain in the diagnosis of clinically relevant prostate cancer as well as the management of the metastatic and androgen-independent metastatic disease states. PMID:17786228

  15. Using 3D Super-Resolution Microscopy to Probe Breast Cancer Stem Cells and Their Microenvironment

    DTIC Science & Technology

    2014-05-01

    microenvironments on breast cancer by creating arrays of polydimethlysiloxane (PDMS) microposts of different stiffness and sizes and seeded them with MCF-7 cells...of MCF-7s. Finally, with QPI, we investigated the real-time response of breast- cancer cells to different microenvironmental cues . We thus have...controls this cellular phenotype. To realize this goal, we had proposed to use 3D super-resolution microscopy to visualize how individual breast CaSCs

  16. Mechanisms of VEGF Availability in Prostate Cancer

    DTIC Science & Technology

    2005-01-01

    the information obtained from this proposal has now been used to further understand resistance to VEGF 7 therapy in cancer progression. We...prostate cancer biology. Thanks to this training, Dr. Monvoisin is currently faculty at the Institut de Physiologie et Biologie Cellulaires , Université de

  17. Regulation of the Prostate Cancer Tumor Microenvironment

    DTIC Science & Technology

    2015-04-01

    are interested in understanding the mechanisms for development of TILs and how they modulate prostate cancer. Our hypothesis is that the innate ...growth can be altered through modulating the composition of TILs through innate immunity. Body Pathogens or cancerous cells alike can produce danger... innate immunity, including Toll-like receptors (TLRs). Thirteen mammalian TLRs have been identified to date with ligands ranging from

  18. Role of Mitochondria in Prostate Cancer

    DTIC Science & Technology

    2006-12-01

    prostate epithelial cell line, PNT1A. This is consistent with the enzymatic activity and protein level of mGPDH. However, cytochrome c oxidase (COX...dehydrogenase; Reactive oxygen species; Cytochrome c oxidase ; Antioxidant enzymes; Liver tissues; Glycerophosphate shuttle; Prostate cancer...Although cytochrome c oxidase (COX) itself is not a source of ROS, inhibition of COX may facilitate ROS production from other complexes [11

  19. Beta Catenin in Prostate Cancer Apoptosis

    DTIC Science & Technology

    2014-04-01

    insensitive cell types to determine whether this apoptosis pathway is only specific to androgen sensitive cell types. In order to determine the role of β...obtained: Effect of TRAIL-TZD combination on the apoptosis potential and β-catenin expression of androgen sensitive and androgen insensitive prostate...and 22RV1) and androgen insensitive (DU145 and PC3) prostate cancer cells were treated with either DMSO or a combination of 100ng/ml TRAIL and

  20. Tyrosine Kinase Display of Prostate Cancer Cells

    DTIC Science & Technology

    2001-10-01

    transdifferentiation . The fact that some prostate cancer cell lines, such as LNCaP, can undergo NE differentiation suggests that at least a subset of NE cells is...Katz, C. A. Olsson, and R. Buttyan. 1997. Transdifferentiation of cultured human prostate cells to a neuroendocrine cell phenotype in a hormone...in the above-mentioned cases 3), and some of these cells can be induced to transdifferentiate are tyrosine kinases, which are known initiators of

  1. The Prostate Cancer Biorepository Network (PCBN)

    DTIC Science & Technology

    2015-10-01

    and RNA ) from prostate cancer patients. These specimens are linked to clinical and outcome data and supported by an informatics infrastructure. In...models, manufactured and provided TMAs, and derived RNA and DNA where required. In addition, we have provided material to conduct biospecimen science...extensive collection of blood (serum, plasma, and buffy coat), prostatectomy tissues (frozen), and derived specimens (DNA and RNA ) from prostate

  2. The Infectious Pathogenesis of Prostate Cancer

    DTIC Science & Technology

    2008-03-01

    Press, 2002:385. 11. Sutcliffe S, Giovannucci E, Alderete JF, et al. Plasma antibodies against Trichomonas vaginalis and subsequent risk of...consistently been identified. In this project, we are examining two specific infectious agents with respect to prostate cancer: T vaginalis , the...of the newly identified XMRV virus in prostate carcinogenesis and progression; 2-) To characterize the role of the infectious protozoa T. vaginalis

  3. Androgen receptor profiling predicts prostate cancer outcome

    PubMed Central

    Stelloo, Suzan; Nevedomskaya, Ekaterina; van der Poel, Henk G; de Jong, Jeroen; van Leenders, Geert JLH; Jenster, Guido; Wessels, Lodewyk FA; Bergman, Andries M; Zwart, Wilbert

    2015-01-01

    Prostate cancer is the second most prevalent malignancy in men. Biomarkers for outcome prediction are urgently needed, so that high-risk patients could be monitored more closely postoperatively. To identify prognostic markers and to determine causal players in prostate cancer progression, we assessed changes in chromatin state during tumor development and progression. Based on this, we assessed genomewide androgen receptor/chromatin binding and identified a distinct androgen receptor/chromatin binding profile between primary prostate cancers and tumors with an acquired resistance to therapy. These differential androgen receptor/chromatin interactions dictated expression of a distinct gene signature with strong prognostic potential. Further refinement of the signature provided us with a concise list of nine genes that hallmark prostate cancer outcome in multiple independent validation series. In this report, we identified a novel gene expression signature for prostate cancer outcome through generation of multilevel genomic data on chromatin accessibility and transcriptional regulation and integration with publically available transcriptomic and clinical datastreams. By combining existing technologies, we propose a novel pipeline for biomarker discovery that is easily implementable in other fields of oncology. PMID:26412853

  4. Image guidance of breast cancer surgery using 3-D ultrasound images and augmented reality visualization.

    PubMed

    Sato, Y; Nakamoto, M; Tamaki, Y; Sasama, T; Sakita, I; Nakajima, Y; Monden, M; Tamura, S

    1998-10-01

    This paper describes augmented reality visualization for the guidance of breast-conservative cancer surgery using ultrasonic images acquired in the operating room just before surgical resection. By combining an optical three-dimensional (3-D) position sensor, the position and orientation of each ultrasonic cross section are precisely measured to reconstruct geometrically accurate 3-D tumor models from the acquired ultrasonic images. Similarly, the 3-D position and orientation of a video camera are obtained to integrate video and ultrasonic images in a geometrically accurate manner. Superimposing the 3-D tumor models onto live video images of the patient's breast enables the surgeon to perceive the exact 3-D position of the tumor, including irregular cancer invasions which cannot be perceived by touch, as if it were visible through the breast skin. Using the resultant visualization, the surgeon can determine the region for surgical resection in a more objective and accurate manner, thereby minimizing the risk of a relapse and maximizing breast conservation. The system was shown to be effective in experiments using phantom and clinical data.

  5. State-of-the-art imaging of prostate cancer.

    PubMed

    Marko, Jamie; Gould, C Frank; Bonavia, Grant H; Wolfman, Darcy J

    2016-03-01

    Prostate cancer is the most common cancer in men. Modern medical imaging is intimately involved in the diagnosis and management of prostate cancer. Ultrasound is primarily used to guide prostate biopsy to establish the diagnosis of prostate carcinoma. Prostate magnetic resonance imaging uses a multiparametric approach, including anatomic and functional imaging sequences. Multiparametric magnetic resonance imaging can be used for detection and localization of prostate cancer and to evaluate for disease recurrence. Computed tomography and scintigraphic imaging are primarily used to detect regional lymph node spread and distant metastases. Recent advancements in ultrasound, multiparametric magnetic resonance imaging, and scintigraphic imaging have the potential to change the way prostate cancer is diagnosed and managed. This article addresses the major imaging modalities involved in the evaluation of prostate cancer and updates the reader on the state of the art for each modality.

  6. Acne and risk of prostate cancer.

    PubMed

    Sutcliffe, Siobhan; Giovannucci, Edward; Isaacs, William B; Willett, Walter C; Platz, Elizabeth A

    2007-12-15

    In a recent study, prostatectomy specimens from which Propionibacterium acnes was cultured were more likely to have inflammation than culture-negative specimens or specimens positive for other bacteria, leading the authors to hypothesize that P. acnes-mediated inflammation may contribute to prostate carcinogenesis. To indirectly explore associations between P. acnes and prostate cancer, we investigated severe acne, as measured by tetracycline use for 4 or more years, in relation to incident prostate cancer in the Health Professionals Follow-up Study. On the 1992 follow-up questionnaire, participants were asked whether they had ever used "tetracycline for at least 2 months at a time (e.g., for acne or other reason)" and their duration of use. Prostate cancer diagnoses were ascertained on each subsequent biennial questionnaire and confirmed by medical record review. Between 1992 and 2002, 2,147 cases of prostate cancer were reported among 34,629 eligible participants. Men who used tetracycline for 4 or more years had a significantly higher risk of prostate cancer (16 cases, 1,569 person-years) than men who did not use tetracycline (2,071 cases, 304,822 person-years, multivariable-adjusted RR = 1.70, 95% CI: 1.03-2.80). Although intriguing, this finding should be viewed cautiously because of the small number of exposed cases, indirect assessment of severe acne, and complex etiology of acne, which is not limited to P. acnes infection. Therefore, additional biologic and epidemiologic studies are necessary to determine and elucidate the possible role of P. acnes infection in prostate carcinogenesis.

  7. Current clinical challenges in prostate cancer

    PubMed Central

    Silberstein, Jonathan L.; Pal, Sumanta Kumar; Lewis, Brian

    2013-01-01

    Prostate cancer is the most common malignancy and the second leading cause of cancer death in men in the United States. Close to $12 billion are spent annually on the treatment of prostate cancer in the US alone. Yet still there remain tremendous controversies and challenges that exist in all facets of the disease. This review and discussion will focus on issues and challenges for clinicians and patients diagnosed with the disease. Appropriate risk stratification for men with newly diagnosed prostate cancer is an appropriate first step for all patients. Once risk-stratified, for those with low-risk of death, it is increasingly recognized that overtreatment creates an unnecessary burden for many patients. This is particularly evident when put in the context of competing comorbidities in an elderly population. For those with advanced or high-risk localized disease, under-treatment remains too common. For those with a high-risk of recurrence or failure following primary treatment, adjuvant or salvage therapies are an option, but how and when to best deploy these treatments are controversial. Recently, tremendous progress has been made for those with advanced disease, in particular those with metastatic castrate-resistant prostate cancer (mCRPC). Within the last 4 years, five novel FDA approved agents, acting through distinct mechanisms have been FDA approved for mCRPC. With the introduction of these new agents a host of new challenges have arisen. Timing, sequencing and combinations of these novel agents are welcomed challenges when compared with the lack of available therapies just a few years ago. In this summary of current clinical challenges in prostate cancer we review critical recent studies that have created or shifted the current paradigms of treatment for prostate cancer. We will also highlight ongoing issues that continue to challenge our field. PMID:26816735

  8. [Pharmaco and diet based prostate cancer prevention].

    PubMed

    Eisinger, François; Cancel-Tassin, Géraldine; Azzouzi, Abdel Rahmene; Gravis, Gwenaelle; Rossi, Dominique; Cussenot, Olivier

    2013-05-01

    In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

  9. Real-time 3D surface-image-guided beam setup in radiotherapy of breast cancer

    SciTech Connect

    Djajaputra, David; Li Shidong

    2005-01-01

    We describe an approach for external beam radiotherapy of breast cancer that utilizes the three-dimensional (3D) surface information of the breast. The surface data of the breast are obtained from a 3D optical camera that is rigidly mounted on the ceiling of the treatment vault. This 3D camera utilizes light in the visible range therefore it introduces no ionization radiation to the patient. In addition to the surface topographical information of the treated area, the camera also captures gray-scale information that is overlaid on the 3D surface image. This allows us to visualize the skin markers and automatically determine the isocenter position and the beam angles in the breast tangential fields. The field sizes and shapes of the tangential, supraclavicular, and internal mammary gland fields can all be determined according to the 3D surface image of the target. A least-squares method is first introduced for the tangential-field setup that is useful for compensation of the target shape changes. The entire process of capturing the 3D surface data and subsequent calculation of beam parameters typically requires less than 1 min. Our tests on phantom experiments and patient images have achieved the accuracy of 1 mm in shift and 0.5 deg. in rotation. Importantly, the target shape and position changes in each treatment session can both be corrected through this real-time image-guided system.

  10. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer.

    PubMed

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease.

  11. Unfoldomics of prostate cancer: on the abundance and roles of intrinsically disordered proteins in prostate cancer

    PubMed Central

    Landau, Kevin S; Na, Insung; Schenck, Ryan O; Uversky, Vladimir N

    2016-01-01

    Prostatic diseases such as prostate cancer and benign prostatic hyperplasia are highly prevalent among men. The number of studies focused on the abundance and roles of intrinsically disordered proteins in prostate cancer is rather limited. The goal of this study is to analyze the prevalence and degree of disorder in proteins that were previously associated with the prostate cancer pathogenesis and to compare these proteins to the entire human proteome. The analysis of these datasets provides means for drawing conclusions on the roles of disordered proteins in this common male disease. We also hope that the results of our analysis can potentially lead to future experimental studies of these proteins to find novel pathways associated with this disease. PMID:27453073

  12. Quantification of tumor morphology via 3D histology: application to oral cavity cancers

    NASA Astrophysics Data System (ADS)

    Doyle, Scott; Brandwein-Gensler, Margaret; Tomaszewski, John

    2016-03-01

    Traditional histopathology quantifies disease through the study of glass slides, i.e. two-dimensional samples that are representative of the overall process. We hypothesize that 3D reconstruction can enhance our understanding of histopathologic interpretations. To test this hypothesis, we perform a pilot study of the risk model for oral cavity cancer (OCC), which stratifies patients into low-, intermediate-, and high-risk for locoregional disease-free survival. Classification is based on study of hematoxylin and eosin (H and E) stained tissues sampled from the resection specimens. In this model, the Worst Pattern of Invasion (WPOI) is assessed, representing specific architectural features at the interface between cancer and non-cancer tissue. Currently, assessment of WPOI is based on 2D sections of tissue, representing complex 3D structures of tumor growth. We believe that by reconstructing a 3D model of tumor growth and quantifying the tumor-host interface, we can obtain important diagnostic information that is difficult to assess in 2D. Therefore, we introduce a pilot study framework for visualizing tissue architecture and morphology in 3D from serial sections of histopathology. This framework can be used to enhance predictive models for diseases where severity is determined by 3D biological structure. In this work we utilize serial H and E-stained OCC resections obtained from 7 patients exhibiting WPOI-3 (low risk of recurrence) through WPOI-5 (high risk of recurrence). A supervised classifier automatically generates a map of tumor regions on each slide, which are then co-registered using an elastic deformation algorithm. A smooth 3D model of the tumor region is generated from the registered maps, which is suitable for quantitative tumor interface morphology feature extraction. We report our preliminary models created with this system and suggest further enhancements to traditional histology scoring mechanisms that take spatial architecture into consideration.

  13. Early detection of prostate cancer. Role of prostate-specific antigen.

    PubMed Central

    Prabhakaran, V. M.

    1996-01-01

    Pressure to request prostate-specific antigen (PSA) tests for early detection of prostate cancer in middle-aged and older men is increasing. However, current scientific data suggest that such testing does more harm than good. Most professional groups do not advise routine screening for prostate cancer. This paper reviews the current status of PSA testing. PMID:8653039

  14. Risk of Second Cancers According to Radiation Therapy Technique and Modality in Prostate Cancer Survivors

    SciTech Connect

    Berrington de Gonzalez, Amy; Wong, Jeannette; Kleinerman, Ruth; Kim, Clara; Morton, Lindsay; Bekelman, Justin E.

    2015-02-01

    Purpose: Radiation therapy (RT) techniques for prostate cancer are evolving rapidly, but the impact of these changes on risk of second cancers, which are an uncommon but serious consequence of RT, are uncertain. We conducted a comprehensive assessment of risks of second cancer according to RT technique (>10 MV vs ≤10 MV and 3-dimensional [3D] vs 2D RT) and modality (external beam RT, brachytherapy, and combined modes) in a large cohort of prostate cancer patients. Methods and Materials: The cohort was constructed using the Surveillance Epidemiology and End Results-Medicare database. We included cases of prostate cancer diagnosed in patients 66 to 84 years of age from 1992 to 2004 and followed through 2009. We used Poisson regression analysis to compare rates of second cancer across RT groups with adjustment for age, follow-up, chemotherapy, hormone therapy, and comorbidities. Analyses of second solid cancers were based on the number of 5-year survivors (n=38,733), and analyses of leukemia were based on number of 2-year survivors (n=52,515) to account for the minimum latency period for radiation-related cancer. Results: During an average of 4.4 years' follow-up among 5-year prostate cancer survivors (2DRT = 5.5 years; 3DRT = 3.9 years; and brachytherapy = 2.7 years), 2933 second solid cancers were diagnosed. There were no significant differences in second solid cancer rates overall between 3DRT and 2DRT patients (relative risk [RR] = 1.00, 95% confidence interval [CI]: 0.91-1.09), but second rectal cancer rates were significantly lower after 3DRT (RR = 0.59, 95% CI: 0.40-0.88). Rates of second solid cancers for higher- and lower-energy RT were similar overall (RR = 0.97, 95% CI: 0.89-1.06), as were rates for site-specific cancers. There were significant reductions in colon cancer and leukemia rates in the first decade after brachytherapy compared to those after external beam RT. Conclusions: Advanced treatment planning may have reduced rectal

  15. RB Loss Promotes Prostate Cancer Metastasis.

    PubMed

    Thangavel, Chellappagounder; Boopathi, Ettickan; Liu, Yi; Haber, Alex; Ertel, Adam; Bhardwaj, Anshul; Addya, Sankar; Williams, Noelle; Ciment, Stephen J; Cotzia, Paolo; Dean, Jeffry L; Snook, Adam; McNair, Chris; Price, Matt; Hernandez, James R; Zhao, Shuang G; Birbe, Ruth; McCarthy, James B; Turley, Eva A; Pienta, Kenneth J; Feng, Felix Y; Dicker, Adam P; Knudsen, Karen E; Den, Robert B

    2017-02-15

    RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a prometastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelial-mesenchymal transition, motility, and invasion by cancer cells. Genetic modulation or pharmacologic inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer. Mechanistic studies in this setting established that RHAMM stabilized F-actin polymerization by controlling ROCK signaling. Collectively, our findings show how RB loss drives metastatic capacity and highlight RHAMM as a candidate therapeutic target for treating advanced prostate cancer. Cancer Res; 77(4); 982-95. ©2016 AACR.

  16. Photoacoustic imaging of prostate cancer using cylinder diffuse radiation

    NASA Astrophysics Data System (ADS)

    Xie, Wenming; Li, Li; Li, Zhifang; Li, Hui

    2012-12-01

    Prostate cancer is one of diseases with high mortality in man. Many clinical imaging modalities are utilized for the detection, grading and staging of prostate cancer, such as ultrasound, CT, MRI, etc. But they lacked adequate sensitivity and specificity for finding cancer in transition or central zone of prostate. To overcome these problems, we propose a photoacoustic imaging modality based on cylinder diffuse radiation through urethra for prostate cancer detection. We measure the related parameters about this system like lateral resolution (~2mm) and axial resolution(~333μm). Finally, simulated sample was imaged by our system. The results demonstrate the feasibility for detecting prostate cancer by our system.

  17. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    effects due to the loss of testosterone (including fatigue, decreased sexual desire, weight gain, loss of muscle mass and osteoporosis ) and the well...beyond the prostate, immunotherapy may be the only way to treat it [6, 7]. A majority of clinical trials for the immunotherapy of prostate cancer...Localized Prostate Cancer. J Sex Med, 2012. 5. Fitzpatrick, J.M., Management of localized prostate cancer in senior adults : the crucial role of comorbidity

  18. Invariant NKT Cell Ligands for Prostate Cancer Vaccines

    DTIC Science & Technology

    2011-06-01

    NUMBER Invariant NKT Cell Ligands for Prostate Cancer Vaccines 5b. GRANT NUMBER W81XWH-09-1-0156 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...efficacy in tumor bearing mice. 15. SUBJECT TERMS prostate cancer , immunotherapy, NKT cells 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...proposal have shown that mice bearing prostate cancers in the TRAMP model ( prostate specific expression on SV40 T antigen, Tag, oncogene) do not respond

  19. Tracking Origins of Prostate Cancer: An Innovative in Vivo Modeling

    DTIC Science & Technology

    2014-11-01

    could express specifically in prostate under PB- Cre4 control, and could label normal, hyperplasic, neoplastic and malignant carcinoma cells . More...propose to develop an innovative and hitherto not attempted in vivo prostate cancer model that will delineate the exact cell of origin through...different stages of prostate cancer development and progression. We propose to study possible cell (s) of origin for prostate cancer by combinatorial

  20. Role of Human Polyomavirus Bkv in Prostate Cancer

    DTIC Science & Technology

    2007-12-01

    been surgically removed due to prostate cancer diagnosis . A normal prostate is defined as prostate that has been removed either during autopsy or by...immunosuppressed transplant patients, in whom it is associated with haemorrhagic cystitis and polyomavirus nephropathy (5, 35, 58, 70). BKV transforms rodent cells...cystoprostatectomy specimens from bladder cancer patients with the diagnosis of muscle invasive high grade urothelial carcinoma, with no prostate cancer histology

  1. Increasing Sustained Participation in Free Mass Prostate Cancer Screening Clinics

    DTIC Science & Technology

    2005-05-01

    Prostate - Screening Clinic? If I had signs of prostate cancer I wanted to find out so - Newspaper that treatment decisions can be made early ...three study years. 15. SUBJECT TERMS Prostate Cancer, Screening, Early Detection, African Americans 16. SECURITY CLASSIFICATION OF: 17. LIMITATION 18...prostate cancer screening and early detection. Pastors who participated in a focus group in Year I continue to be contacted, and we continue to follow-up

  2. Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

    PubMed Central

    Jeon, Jessie S.; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L.; Moretti, Matteo; Kamm, Roger D.

    2015-01-01

    A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. PMID:25524628

  3. SOST Inhibits Prostate Cancer Invasion

    SciTech Connect

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; Kohlgruber, Ayano; Sebastian, Aimy; Collette, Nicole M.; Coleman, Matthew A.; Christiansen, Blaine A.; Loots, Gabriela G.

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varying amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.

  4. SOST Inhibits Prostate Cancer Invasion

    DOE PAGES

    Hudson, Bryan D.; Hum, Nicholas R.; Thomas, Cynthia B.; ...

    2015-11-06

    Inhibitors of Wnt signaling have been shown to be involved in prostate cancer (PC) metastasis; however the role of Sclerostin (Sost) has not yet been explored. Here we show that elevated Wnt signaling derived from Sost deficient osteoblasts promotes PC invasion, while rhSOST has an inhibitory effect. In contrast, rhDKK1 promotes PC elongation and filopodia formation, morphological changes characteristic of an invasive phenotype. Furthermore, rhDKK1 was found to activate canonical Wnt signaling in PC3 cells, suggesting that SOST and DKK1 have opposing roles on Wnt signaling in this context. Gene expression analysis of PC3 cells co-cultured with OBs exhibiting varyingmore » amounts of Wnt signaling identified CRIM1 as one of the transcripts upregulated under highly invasive conditions. We found CRIM1 overexpression to also promote cell-invasion. These findings suggest that bone-derived Wnt signaling may enhance PC tropism by promoting CRIM1 expression and facilitating cancer cell invasion and adhesion to bone. We concluded that SOST and DKK1 have opposing effects on PC3 cell invasion and that bone-derived Wnt signaling positively contributes to the invasive phenotypes of PC3 cells by activating CRIM1 expression and facilitating PC-OB physical interaction. As such, we investigated the effects of high concentrations of SOST in vivo. In conclusion, we found that PC3-cells overexpressing SOST injected via the tail vein in NSG mice did not readily metastasize, and those injected intrafemorally had significantly reduced osteolysis, suggesting that targeting the molecular bone environment may influence bone metastatic prognosis in clinical settings.« less

  5. Filopodia in cell adhesion, 3D migration and cancer cell invasion.

    PubMed

    Jacquemet, Guillaume; Hamidi, Hellyeh; Ivaska, Johanna

    2015-10-01

    This review discusses recent advances in our understanding of the role filopodia and filopodia-like structures in cell adhesion and three dimensional (3D) cell migration both in vitro and in vivo. In particular, we focus on recent advances demonstrating that filopodia are involved in substrate tethering and environment sensing in vivo. We further discuss the emerging role of filopodia and filopodial proteins in tumor dissemination as mounting in vitro, in vivo and clinical evidence suggest that filopodia drive cancer cell invasion and highlight filopodia proteins as attractive therapeutic targets. Finally, we outline outstanding questions that remain to be addressed to elucidate the role of filopodia during 3D cell migration.

  6. A 3D biomimetic model of tissue stiffness interface for cancer drug testing.

    PubMed

    Lam, Chee Ren Ivan; Wong, Hui Kian; Nai, Spencer; Chua, Chee Kai; Tan, Nguan Soon; Tan, Lay Poh

    2014-07-07

    Contrary to oversimplified preclinical drug screens that derive treatment responses of cancer cells grown on plastic cell culturing surfaces, the actual in vivo scenario for cancer cell invasion is confronted with a diversity of tissue stiffness. After all, the packing of organs and tissues in the body translates to the abundant presence of tissue stiffness interfaces. The invasive dissemination of cancer cells in vivo might be encouraged by favorable tissue stiffness gradients, likely explaining the preferential spread of cancer cells which is subjective to the cancer type and origin of the primary site. Yet these critical tumor microenvironmental influences cannot be recapitulated in 2D preclinical drug screens, hence omitting potentially invaluable in vivo patterns of drug responses that may support safer clinical dosage implementation of cancer drugs. Current attempts to study stiffness implications on cancer cells are largely confined to 2D surfaces of tunable stiffness. While these studies collectively show that cancer cells migrate better on a stiffer matrix, the generation of a biomimetic 3D tissue stiffness interface for cancer cell migration would clearly give a more definitive understanding on the probable push and pull influences of the 3D ECM. Herein, we developed a biomimetic platform which enables the precise placement of spheroids at tissue stiffness interfaces constructed with natural ECM collagen type I. This enables a standardized comparison of spheroid invasion under a 3D stiffness gradient influence. We found that cancer cells in 3D infiltrated more extensively into a softer matrix of 300 Pa while showing significantly reduced invasion into stiffer matrix of 1200 and 6000 Pa. These biomimetic spheroid cultures postinvasion were suitably subjected to paclitaxel treatment and subsequent daily live quantification of apoptotic cells to evaluate the implications of tissue stiffness on chemotherapeutic treatment. We importantly found that cancer

  7. Management of progressive metastatic prostate cancer.

    PubMed

    Waselenko, J K; Dawson, N A

    1997-10-01

    Metastatic prostate cancer is a growing health problem and is the second leading cause of cancer death in men. While the response of patients with metastatic prostate cancer to initial hormonal manipulation is excellent, the majority of patients eventually progress. As a result, a growing number of patients and their physicians need-to-find acceptable therapeutic alternatives. Fortunately, the number of therapies in the management armamentarium is growing and includes: alternative hormonal therapies, chemotherapy, radioisotopes, and investigational agents. The major focus of treatment has shifted to palliation and quality of life. The decline of prostate-specific antigen (PSA) has become another important end point as evidence supporting a correlation with prolonged survival mounts. Enrolling eligible patients in clinical trials is critical to the development of new treatment strategies for this difficult disease.

  8. A Promising Future for Prostate Cancer Diagnostics

    PubMed Central

    Assinder, Stephen J.; Bhoopalan, Vanitha

    2017-01-01

    It has been estimated that globally there is a death attributable to prostate cancer every four minutes. As life expectancy in all world regions increases, so too incidence of this disease of the ageing male will increase. For many men diagnosis occurs after presentation with symptoms of altered urinary dynamics. Unfortunately, these changes, whilst also associated with benign disease, are evident quite late in the aetiology of prostate cancer. Early detection provides for better management and prognosis. This Special Issue provides an up to date view of the advances made towards early diagnosis and prognosis. It provides reviews of advanced imaging techniques (e.g., multiparametric MRI and protocols), and of biomaterials and molecular biomarkers currently being explored (e.g., microRNAs, proteomics) and the technologies that are revolutionizing this field. It describes the multi-disciplinary approaches that are essential to inexpensive, deliverable and accurate platforms for prostate cancer diagnostics. PMID:28106714

  9. Prostate cancer: appraisal, coping, and health status.

    PubMed

    Ahmad, Muayyad M; Musil, Carol M; Zauszniewski, Jaclene A; Resnick, Martin I

    2005-10-01

    The purpose of this study was to identify how cognitive appraisal and types of coping affect the health status of men with prostate cancer. Lazarus and Folkman's model of stress and coping guided this correlational, cross-sectional study. The convenience sample was composed of 131 men with prostate cancer who completed the Cognitive Appraisal of Health Scale, the Ways of Coping Checklist, and the Short-Form Health Survey using mailed questionnaires. Participants who appraised more harm or loss experienced worse physical and mental health. When participants perceived their diagnosis as posing more harm or loss or a greater threat, they were more likely to use emotion-focused coping. When the diagnosis was perceived as a challenge, men were more likely to use more problem-focused coping. The findings of this study enable health care providers to be more attentive to the psychosocial needs of prostate cancer patients.

  10. The Impact of Dose Escalation on Secondary Cancer Risk After Radiotherapy of Prostate Cancer

    SciTech Connect

    Schneider, Uwe . E-mail: uwe.schneider@psi.ch; Lomax, Antony; Besserer, Juergen; Pemler, Peter; Lombriser, Norbert; Kaser-Hotz, Barbara D.V.M.

    2007-07-01

    Purpose: To estimate secondary cancer risk due to dose escalation in patients treated for prostatic carcinoma with three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated RT (IMRT), and spot-scanned proton RT. Methods and Materials: The organ equivalent dose (OED) concept with a linear-exponential, a plateau, and a linear dose-response curve was applied to dose distributions of 23 patients who received RT of prostate cancer. Conformal RT was used in 7 patients, 8 patients received IMRT with 6- and 15-MV photons, and 8 patients were treated with spot-scanned protons. We applied target doses ranging from 70 Gy to 100 Gy. Cancer risk was estimated as a function of target dose and tumor control probability. Results: At a 100-Gy target dose the secondary cancer risk relative to the 3D treatment plan at 70 Gy was +18.4% (15.0% for a plateau model, 22.3% for a linear model) for the 6-MV IMRT plan, +25.3% (17.0%, 14.1%) for the 15-MV IMRT plan, and -40.7% (-41.3%, -40.0%) for the spot-scanned protons. The increasing risk of developing a radiation-associated malignancy after RT with increasing dose was balanced by the enhanced cure rates at a larger dose. Conclusions: Cancer risk after dose escalation for prostate RT is expected to be equal to or lower than for conventional 3D treatment at 70 Gy, independent of treatment modality or dose-response model. Spot-scanned protons are the treatment of choice for dose escalation because this therapy can halve the risk of secondary cancers.

  11. Clinical adenoviral gene therapy for prostate cancer.

    PubMed

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  12. Large-scale pharmacological profiling of 3D tumor models of cancer cells

    PubMed Central

    Mathews Griner, Lesley A; Zhang, Xiaohu; Guha, Rajarshi; McKnight, Crystal; Goldlust, Ian S; Lal-Nag, Madhu; Wilson, Kelli; Michael, Sam; Titus, Steve; Shinn, Paul; Thomas, Craig J; Ferrer, Marc

    2016-01-01

    The discovery of chemotherapeutic agents for the treatment of cancer commonly uses cell proliferation assays in which cells grow as two-dimensional (2D) monolayers. Compounds identified using 2D monolayer assays often fail to advance during clinical development, most likely because these assays do not reproduce the cellular complexity of tumors and their microenvironment in vivo. The use of three-dimensional (3D) cellular systems have been explored as enabling more predictive in vitro tumor models for drug discovery. To date, small-scale screens have demonstrated that pharmacological responses tend to differ between 2D and 3D cancer cell growth models. However, the limited scope of screens using 3D models has not provided a clear delineation of the cellular pathways and processes that differentially regulate cell survival and death in the different in vitro tumor models. Here we sought to further understand the differences in pharmacological responses between cancer tumor cells grown in different conditions by profiling a large collection of 1912 chemotherapeutic agents. We compared pharmacological responses obtained from cells cultured in traditional 2D monolayer conditions with those responses obtained from cells forming spheres versus cells already in 3D spheres. The target annotation of the compound library screened enabled the identification of those key cellular pathways and processes that when modulated by drugs induced cell death in all growth conditions or selectively in the different cell growth models. In addition, we also show that many of the compounds targeting these key cellular functions can be combined to produce synergistic cytotoxic effects, which in many cases differ in the magnitude of their synergism depending on the cellular model and cell type. The results from this work provide a high-throughput screening framework to profile the responses of drugs both as single agents and in pairwise combinations in 3D sphere models of cancer cells. PMID

  13. The Genomic Evolution of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    addition, multiple genetic alterations are associated with disease evolution in response to therapy. This project aims to characterize evolution of...of castrate resistant metastatic cancer from primary foci. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer... genetic alterations are found more often in advanced disease. It is not known if these arise after metastases occur or are found in a subclone of the

  14. [Prostate cancer external beam radiotherapy].

    PubMed

    de Crevoisier, R; Pommier, P; Latorzeff, I; Chapet, O; Chauvet, B; Hennequin, C

    2016-09-01

    The prostate external beam radiotherapy techniques are described, when irradiating the prostate or after prostatectomy, with and without pelvic lymph nodes. The following parts are presented: indications of radiotherapy, total dose and fractionation, planning CT image acquisition, volume of interest delineation (target volumes and organs at risk) and margins, Intensity modulated radiotherapy planning and corresponding dose-volume constraints, and finally Image guided radiotherapy.

  15. High Prevalence of Screen Detected Prostate Cancer in West Africans: Implications for Racial Disparity of Prostate Cancer

    PubMed Central

    Hsing, Ann W.; Yeboah, Edward; Biritwum, Richard; Tettey, Yao; De Marzo, Angelo M.; Adjei, Andrew; Netto, George J.; Yu, Kai; Li, Yan; Chokkalingam, Anand P.; Chu, Lisa W.; Chia, David; Partin, Alan; Thompson, Ian M.; Quraishi, Sabah M.; Niwa, Shelley; Tarone, Robert; Hoover, Robert N.

    2015-01-01

    Purpose To our knowledge the reasons for the high rates of prostate cancer in black American men are unknown. Genetic and lifestyle factors have been implicated. Better understanding of prostate cancer rates in West African men would help clarify why black American men have such high rates since the groups share genetic ancestry and yet have different lifestyles and screening practices. To estimate the prostate cancer burden in West African men we performed a population based screening study with biopsy confirmation in Ghana. Materials and Methods We randomly selected 1,037 healthy men 50 to 74 years old from Accra, Ghana for prostate cancer screening with prostate specific antigen testing and digital rectal examination. Men with a positive screen result (positive digital rectal examination or prostate specific antigen greater than 2.5 ng/ml) underwent transrectal ultrasound guided biopsies. Results Of the 1,037 men 154 (14.9%) had a positive digital rectal examination and 272 (26.2%) had prostate specific antigen greater than 2.5 ng/ml, including 166 with prostate specific antigen greater than 4.0 ng/ml. A total of 352 men (33.9%) had a positive screen by prostate specific antigen or digital rectal examination and 307 (87%) underwent biopsy. Of these men 73 were confirmed to have prostate cancer, yielding a 7.0% screen detected prostate cancer prevalence (65 patients), including 5.8% with prostate specific antigen greater than 4.0 ng/ml. Conclusions In this relatively unscreened population in Africa the screen detected prostate cancer prevalence is high, suggesting a possible role of genetics in prostate cancer etiology and the disparity in prostate cancer risk between black and white American men. Further studies are needed to confirm the high prostate cancer burden in African men and the role of genetics in prostate cancer etiology. PMID:24747091

  16. Hormone Therapy for Prostate Cancer

    MedlinePlus

    ... Partners & Collaborators Spotlight on Scientists Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ... Collaborators Spotlight on Scientists NCI Research Areas Cancer Biology Cancer Genomics Causes of Cancer Diagnosis Prevention Screening & ...

  17. Concepts of epigenetics in prostate cancer development

    PubMed Central

    Cooper, C S; Foster, C S

    2008-01-01

    Substantial evidence now supports the view that epigenetic changes have a role in the development of human prostate cancer. Analyses of the patterns of epigenetic alteration are providing important insights into the origin of this disease and have identified specific alterations that may serve as useful diagnostic and prognostic biomarkers. Examination of cancer methylation patterns supports a stem cell origin of prostate cancer. It is well established that methylation of GSTpi is a marker of prostate cancer, and global patterns of histone marking appear to be linked to cancer prognosis with levels of acetylated histones H3K9, H3K18, and H4K12, and of dimethylated H4R3 and H3K4, dividing low-grade prostate cancer (Gleason 6 or less) into two prognostically separate groups. Elevated levels of several components of the polycomb group protein complex, EZH2, BMI1, and RING1, can also act as biomarkers of poor clinical outcome. Many components of the epigenetic machinery, including histone deacetylase (whose expression level is linked to the TMPRSS2:ERG translocation) and the histone methylase EZH2, are potential therapeutic targets. The recent discovery of the role of small RNAs in governing the epigenetic status of individual genes offers exciting new possibilities in therapeutics and chemoprevention. PMID:19002169

  18. Nanoparticle therapeutics for prostate cancer treatment.

    PubMed

    Sanna, Vanna; Sechi, Mario

    2012-09-01

    The application of nanotechnology in medicine is offering many exciting possibilities in healthcare. Engineered nanoparticles have the potential to revolutionize the diagnosis and the therapy of several diseases, particularly by targeted delivery of anticancer drugs and imaging contrast agents. Prostate cancer, the second most common cancer in men, represents one of the major epidemiological problems, especially for patients in the advanced age. There is a substantial interest in developing therapeutic options for treatment of prostate cancer based on use of nanodevices, to overcome the lack of specificity of conventional chemotherapeutic agents as well as for the early detection of precancerous and malignant lesions. Herein, we highlight on the recent development of nanotechnology strategies adopted for the management of prostate cancer. In particular, the combination of targeted and controlled-release polymer nanotechnologies has recently resulted in the clinical development of BIND-014, a promising targeted Docetaxel-loaded nanoprototype, which can be validated for use in the prostate cancer therapy. However, several limitations facing nanoparticle delivery to solid tumours, such as heterogeneity of intratumoural barriers and vasculature, cytotoxicity and/or hypersensitivity reactions to currently available cancer nanomedicines, and the difficult in developing targeted nanoparticles with optimal biophysicochemical properties, should be still addressed for a successful tumour eradication.

  19. Chimeric Amino Acid Rearrangements as Immune Targets in Prostate Cancer

    DTIC Science & Technology

    2016-05-01

    cancer using a variety of approaches, including dendritic cell-based vaccines (e.g. Provegene), pox-based vaccines (e.g. PROSTVAC) as well as...Background: Cancer vaccines aim to elicit antigen-specific T cell responses against tumor antigens. Most prostate cancer vaccines to date target mis...therapeutic vaccination against fusion oncogenes in prostate cancer. IMMUNOGENICITY OF CHIMERIC AMINO ACID SEQUENCES IN PROSTATE CANCER Jennifer L

  20. The 21st Annual Prostate Cancer Foundation Scientific Retreat report.

    PubMed

    Miyahira, Andrea K; Simons, Jonathan W; Soule, Howard R

    2015-08-01

    The 21st Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held from October 23-25, 2014, in Carlsbad, CA. This event is the world's foremost scientific meeting focusing on prostate cancer and brings together leading basic, translational and clinical researchers in prostate cancer and other diverse disciplines to discuss the newest findings most likely to advance the understanding of prostate cancer and the clinical care of prostate cancer patients. This year's meeting highlighted themes including: (i) research integrity and standards for scientific reproducibility; (ii) prostate cancer disparities; (iii) mechanisms and models of prostate cancer progression and dormancy; (iv) mechanisms of therapeutic resistance; and (v) advancements in precision medicine treatments, treatment models, and predictive and prognostic biomarkers.

  1. Role of Obesity in Prostate Cancer Development

    DTIC Science & Technology

    2011-04-01

    prostate cancer development in this model. A second experiment was conducted using a prostate cancer cell line developed from a TRAMP mouse tumor, TRAMP...antibodies used are shown along the left hand side. 11 Study using TRAMP-C2 Cells Because of the difficulties with GTG injections described above we...Lynch,C.F., Rubenstein,L.M., Lemke,J.H., Cohen,M.B., Lubaroff,D.M., and Wallace,R.B. (1997) Association of smoking , body mass, and physical activity

  2. Prostate Specific or Enriched Genes as Composite Biomarkers for Prostate Cancer

    DTIC Science & Technology

    2010-02-01

    research: To evaluate prostate specific genes such as WDR19, NDRG1 , TAGLN2 as diagnosis and prognosis markers for prostate cancers. Major findings: (1) We...have determined that WDR19, NDRG1 are not as good a marker as PSA for prostate cancer stratification. (2) We developed a mouse antibody for a...optimize sandwich ELISA assays for WDR19, NDRG1 , or other novel prostate-specific biomarker candidates. During the past two years, we have evaluated the

  3. Angiostatic Therapy: A New Treatment Modality for Prostate Cancer

    DTIC Science & Technology

    2001-07-01

    could be a new innovative treatment regimen for hormone-refractory prostate cancer. This was to be achieved with human prostate cancer tissue and...indices, low cell death and a highly invasive phenotype. Using this model we identified surgical castration, COX-2 inhibition and dendritic cell based immunotherapy as effective mono and combined therapies for prostate carcinoma.

  4. Accurate positioning for head and neck cancer patients using 2D and 3D image guidance

    PubMed Central

    Kang, Hyejoo; Lovelock, Dale M.; Yorke, Ellen D.; Kriminiski, Sergey; Lee, Nancy; Amols, Howard I.

    2011-01-01

    Our goal is to determine an optimized image-guided setup by comparing setup errors determined by two-dimensional (2D) and three-dimensional (3D) image guidance for head and neck cancer (HNC) patients immobilized by customized thermoplastic masks. Nine patients received weekly imaging sessions, for a total of 54, throughout treatment. Patients were first set up by matching lasers to surface marks (initial) and then translationally corrected using manual registration of orthogonal kilovoltage (kV) radiographs with DRRs (2D-2D) on bony anatomy. A kV cone beam CT (kVCBCT) was acquired and manually registered to the simulation CT using only translations (3D-3D) on the same bony anatomy to determine further translational corrections. After treatment, a second set of kVCBCT was acquired to assess intrafractional motion. Averaged over all sessions, 2D-2D registration led to translational corrections from initial setup of 3.5 ± 2.2 (range 0–8) mm. The addition of 3D-3D registration resulted in only small incremental adjustment (0.8 ± 1.5 mm). We retrospectively calculated patient setup rotation errors using an automatic rigid-body algorithm with 6 degrees of freedom (DoF) on regions of interest (ROI) of in-field bony anatomy (mainly the C2 vertebral body). Small rotations were determined for most of the imaging sessions; however, occasionally rotations > 3° were observed. The calculated intrafractional motion with automatic registration was < 3.5 mm for eight patients, and < 2° for all patients. We conclude that daily manual 2D-2D registration on radiographs reduces positioning errors for mask-immobilized HNC patients in most cases, and is easily implemented. 3D-3D registration adds little improvement over 2D-2D registration without correcting rotational errors. We also conclude that thermoplastic masks are effective for patient immobilization. PMID:21330971

  5. Proton radiation for localized prostate cancer.

    PubMed

    Coen, John J; Zietman, Anthony L

    2009-06-01

    Proton radiation is an emerging therapy for localized prostate cancer that is being sought with increasing frequency by patients. The physical properties of a proton beam make it ideal for clinical applications; the Bragg peak allows for deposition of dose at a well-defined depth with essentially no exit dose. Thus, high doses can be delivered to a target while largely sparing adjacent normal tissue. Proton radiation has proven effective in dose escalation for prostate cancer. This is important, as high-dose conformal radiation is now the standard form of external radiation for this disease. Intensity-modulated radiation therapy, which uses X-rays, is another means of delivering high radiation doses to the prostate and is currently the most widely used form of external radiation in the US. At present prices, it is probably more cost-effective than proton radiation; this could change. Clear dosimetric superiority of protons in the high-dose region has not yet been demonstrated. A dosimetric advantage may emerge as pencil-beam scanning replaces passive scanning, and intensity-modulated proton therapy becomes possible. This technique would be particularly well suited to partial prostate 'boosts', hypofractionation regimens and stereotactic delivery of radiation, all new approaches to prostate cancer that are being investigated.

  6. Tissue-engineered 3D cancer-in-bone modeling: silk and PUR protocols.

    PubMed

    Dadwal, Ushashi; Falank, Carolyne; Fairfield, Heather; Linehan, Sarah; Rosen, Clifford J; Kaplan, David L; Sterling, Julie; Reagan, Michaela R

    2016-01-01

    Cancers that metastasize or grow in the bone marrow are typically considered incurable and cause extensive damage to the bone and bone marrow. The bone is a complex, dynamic, three-dimensional (3D) environment composed of a plethora of cells that may contribute to, or constrain, the growth of tumor cells and development of bone disease. The development of safe and effective drugs is currently hampered by pre-clinical two-dimensional (2D) models whose poor predictive power does not accurately predict the success or failure of therapeutics. These inadequate models often result in drugs proceeding through extensive pre-clinical studies only to fail clinically. Consistently, 3D co-culture systems prove superior to 2D mono-cultures in modeling in vivo cell phenotypes, disease progression and response to therapeutics. As a complex, multicellular, multidimensional bone microenvironment, 3D models allow for more accurate predictions of tumor growth, cell-cell and cell-matrix interactions, and resulting therapeutic responses. In this review we will discuss various 3D models available and describe step-by-step protocols for two of the most well-established 3D culture models for studying tumor-induced bone disease.

  7. 3D texture analysis for classification of second harmonic generation images of human ovarian cancer

    PubMed Central

    Wen, Bruce; Campbell, Kirby R.; Tilbury, Karissa; Nadiarnykh, Oleg; Brewer, Molly A.; Patankar, Manish; Singh, Vikas; Eliceiri, Kevin. W.; Campagnola, Paul J.

    2016-01-01

    Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class. By applying k-nearest neighbor classification using these learned models, we achieved 83–91% accuracies for the six classes. The 3D method outperformed the analogous 2D classification on the same tissues, where we suggest this is due the increased information content. This classification based on ECM structural changes will complement conventional classification based on genetic profiles and can serve as an additional biomarker. Moreover, the texture analysis algorithm is quite general, as it does not rely on single morphological metrics such as fiber alignment, length, and width but their combined convolution with a customizable basis set. PMID:27767180

  8. 3D texture analysis for classification of second harmonic generation images of human ovarian cancer

    NASA Astrophysics Data System (ADS)

    Wen, Bruce; Campbell, Kirby R.; Tilbury, Karissa; Nadiarnykh, Oleg; Brewer, Molly A.; Patankar, Manish; Singh, Vikas; Eliceiri, Kevin. W.; Campagnola, Paul J.

    2016-10-01

    Remodeling of the collagen architecture in the extracellular matrix (ECM) has been implicated in ovarian cancer. To quantify these alterations we implemented a form of 3D texture analysis to delineate the fibrillar morphology observed in 3D Second Harmonic Generation (SHG) microscopy image data of normal (1) and high risk (2) ovarian stroma, benign ovarian tumors (3), low grade (4) and high grade (5) serous tumors, and endometrioid tumors (6). We developed a tailored set of 3D filters which extract textural features in the 3D image sets to build (or learn) statistical models of each tissue class. By applying k-nearest neighbor classification using these learned models, we achieved 83–91% accuracies for the six classes. The 3D method outperformed the analogous 2D classification on the same tissues, where we suggest this is due the increased information content. This classification based on ECM structural changes will complement conventional classification based on genetic profiles and can serve as an additional biomarker. Moreover, the texture analysis algorithm is quite general, as it does not rely on single morphological metrics such as fiber alignment, length, and width but their combined convolution with a customizable basis set.

  9. Harmonic filters for 3D multichannel data: rotation invariant detection of mitoses in colorectal cancer.

    PubMed

    Schlachter, Matthias; Reisert, Marco; Herz, Corinna; Schlürmann, Fabienne; Lassmann, Silke; Werner, Martin; Burkhardt, Hans; Ronneberger, Olaf

    2010-08-01

    In this paper, we present a novel approach for a trainable rotation invariant detection of complex structures in 3D microscopic multichannel data using a nonlinear filter approach. The basic idea of our approach is to compute local features in a window around each 3D position and map these features by means of a nonlinear mapping onto new local harmonic descriptors of the local window. These local harmonic descriptors are then combined in a linear way to form the output of the filter. The optimal combination of the computed local harmonic descriptors is determined in previous training step, and allows the filter to be adapted to an arbitrary structure depending on the problem at hand. Our approach is not limited to scalar-valued images and can also be used for vector-valued (multichannel) images such as gradient vector flow fields. We present realizations of a scalar-valued and a vector-valued multichannel filter. Our proposed algorithm was quantitatively evaluated on colorectal cancer cell lines (cells grown under controlled conditions), on which we successfully detected complex 3D mitotic structures. For a qualitative evaluation we tested our algorithms on human 3D tissue samples of colorectal cancer. We compare our results with a steerable filter approach as well as a morphology-based approach.

  10. PROSTVAC® targeted immunotherapy candidate for prostate cancer.

    PubMed

    Shore, Neal D

    2014-01-01

    Targeted immunotherapies represent a valid strategy for the treatment of metastatic castrate-resistant prostate cancer. A randomized, double-blind, Phase II clinical trial of PROSTVAC® demonstrated a statistically significant improvement in overall survival and a large, global, Phase III trial with overall survival as the primary end point is ongoing. PROSTVAC immunotherapy contains the transgenes for prostate-specific antigen and three costimulatory molecules (designated TRICOM). Research suggests that PROSTVAC not only targets prostate-specific antigen, but also other tumor antigens via antigen cascade. PROSTVAC is well tolerated and has been safely combined with other cancer therapies, including hormonal therapy, radiotherapy, another immunotherapy and chemotherapy. Even greater benefits of PROSTVAC may be recognized in earlier-stage disease and low-disease burden settings where immunotherapy can trigger a long-lasting immune response.

  11. Androgen regulates ADAMTS15 gene expression in prostate cancer cells.

    PubMed

    Molokwu, Chidi N; Adeniji, Olajumoke O; Chandrasekharan, Shankar; Hamdy, Freddie C; Buttle, David J

    2010-08-01

    Prostate cancer is a major cause of mortality, largely as a consequence of metastases and transformation to androgen-independent growth. Metalloproteinases are implicated in cancer progression. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) are expressed in prostate cancer cells, with ADAMTS-1 and ADAMTS-15 being the most abundant. ADAMTS-15 but not ADAMTS-1 expression was downregulated by androgen in LNCaP prostate cancer cells, possibly through androgen response elements associated with the gene. ADAMTS-15 expression is predictive for survival in breast cancer, and the situation may be similar in prostate cancer, as androgen independence is usually due to aberrant signaling through its receptor.

  12. PSA Velocity Does Not Improve Prostate Cancer Detection

    Cancer.gov

    A rapid increase in prostate-specific antigen (PSA) levels is not grounds for automatically recommending a prostate biopsy, according to a study published online February 24, 2011, in the Journal of the National Cancer Institute.

  13. Postoperative Radiotherapy in Prostate Cancer: The Case of the Missing Target

    SciTech Connect

    Croke, Jennifer; Malone, Shawn; Roustan Delatour, Nicolas; Belanger, Eric; Avruch, Leonard; Morash, Christopher; Kayser, Cathleen; Underhill, Kathryn; Spaans, Johanna

    2012-07-15

    Purpose: Postoperative radiotherapy (XRT) increases survival in high-risk prostate cancer patients. Approximately 50% of patients on long-term follow-up relapse despite adjuvant XRT and the predominant site of failure remains local. Four consensus guidelines define postoperative clinical target volume (CTV) in prostate cancer. We explore the possibility that inadequate CTV coverage is an important cause of local failure. This study evaluates the utility of preoperative magnetic resonance imaging (MRI) in defining prostate bed CTV. Methods and Materials: Twenty prostate cancer patients treated with postoperative XRT who also had preoperative staging MRI were included. The four guidelines were applied and the CTVs were expanded to create planning target volumes (PTVs). Preoperative MRIs were fused with postoperative planning CT scans. MRI-based prostate and gross visible tumors were contoured. Three-dimensional (3D) conformal four- and six-field XRT plans were developed and dose-volume histograms analyzed. Subtraction analysis was conducted to assess the adequacy of prostate/gross tumor coverage. Results: Gross tumor was visible in 18 cases. In all 20 cases, the consensus CTVs did not fully cover the MRI-defined prostate. On average, 35% of the prostate volume and 32% of the gross tumor volume were missed using six-field 3D treatment plans. The entire MRI-defined gross tumor volume was completely covered in only two cases (six-field plans). The expanded PTVs did not cover the entire prostate bed in 50% of cases. Prostate base and mid-zones were the predominant site of inadequate coverage. Conclusions: Current postoperative CTV guidelines do not adequately cover the prostate bed and/or gross tumor based on preoperative MRI imaging. Additionally, expanded PTVs do not fully cover the prostate bed in 50% of cases. Inadequate CTV definition is likely a major contributing factor for the high risk of relapse despite adjuvant XRT. Preoperative imaging may lead to more

  14. 78 FR 54745 - National Prostate Cancer Awareness Month, 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... Documents#0;#0; ] Proclamation 9010 of August 30, 2013 National Prostate Cancer Awareness Month, 2013 By the President of the United States of America A Proclamation Among American men, prostate cancer is both the second most commonly diagnosed cancer and the second-leading cause of cancer deaths. Although...

  15. Impact of Prostate Cancer Diagnosis on Non-Cancer Hospitalizations among Elderly Medicare Beneficiaries with Incident Prostate Cancer

    PubMed Central

    Raval, Amit D.; Madhavan, Suresh; Mattes, Malcolm D.; Salkini, Mohamad; Sambamoorthi, Usha

    2016-01-01

    OBJECTIVES To analyze the impact of cancer diagnosis on non-cancer hospitalizations (NCHs) by comparing these hospitalizations between the pre- and post-cancer period in a cohort of fee-for-service Medicare beneficiaries with incident prostate cancer. METHODS A population-based retrospective cohort study was conducted using the Surveillance, Epidemiology and End-Results (SEER) -Medicare linked database for the years 2000 to 2010. The study cohort consisted of 57,489 elderly men (≥ 67 years) with incident prostate cancer. NCHs were identified in six time periods (t1–t6) before and after the incidence of prostate cancer. Each time period consisted of 120 days. For each time period, NCHs were defined as inpatient admissions with primary diagnosis codes not related to prostate cancer, prostate cancer-related procedures or bowel, sexual and urinary dysfunction. Bivariate and multivariate comparisons on rates of NCHs between the pre- and post-cancer period accounted for the repeated measures design. RESULTS The rate of NCHs during the post-cancer period (5.1%) was higher as compared to the pre-cancer period (3.2%). In both unadjusted and adjusted models, elderly men were 37% (Odds Ratio, OR: 1.37, 95% Confidence Interval, CI: 1.32, 1.41) and 38% (Adjusted OR: 1.38, 95% CI: 1.33, 1.46) more likely to have any NCH during the post-cancer period as compared to the pre-cancer period. CONCLUSIONS Elderly men with prostate cancer had a significant increase in the risk of NCHs after the diagnosis of prostate cancer. The study highlights the need to design interventions for reducing the excess NCHs after diagnosis of prostate cancer among elderly men. PMID:26850489

  16. Circadian Genes and Risk for Prostate Cancer

    DTIC Science & Technology

    2010-09-01

    determine if finasteride (an inhibitor of androgen bioactivation) could prevent prostate cancer. In Year 2 of the award, we were approved by the...Trial (PCPT), a randomized placebo‐ controlled clinical trial to determine if  finasteride  (an inhibitor of androgen bioactivation) could  prevent

  17. Estrogens and Antiestrogens in Prostate Cancer

    DTIC Science & Technology

    2003-01-01

    vitamin E, and lycopene protect against prostate cancer. The project will determine the magnitude of the protective activity of these antioxidants...in particular estrogen- induced animal model, the efficacies of three dietary antioxidants (vitamin E, selenium and lycopene ), singularly or in

  18. Beta Catenin in Prostate Cancer Apoptosis

    DTIC Science & Technology

    2013-04-01

    to be injected with LNCaP prostate cancer cells and following approval from Loyola IACUC and ACURO, the xenograft studies were initiated. As...xenograft studies. 12. Obtained Loyola -IACUC and ACURO approval to utilize the C4-2 and C4-2B cells for in vivo studies. Reportable Outcomes: We had

  19. The molecular taxonomy of primary prostate cancer

    PubMed Central

    2015-01-01

    Summary There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, FLI1) or mutations (SPOP, FOXA1, IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1-mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects. PMID:26544944

  20. The Molecular Taxonomy of Primary Prostate Cancer.

    PubMed

    2015-11-05

    There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.

  1. Targeting TMPRSS2-ERG in Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    in prostate cancer cells. We will complete validation candidate kinases that modulate the ERG signature using shRNA and new CRISPR technology as an...will plan to validate hits using CRISPR -Cas9 technology as an orthogonal system. The CRISPR -Cas9 system was not available at the time of the

  2. New genetic variants associated with prostate cancer

    Cancer.gov

    Researchers have newly identified 23 common genetic variants -- one-letter changes in DNA known as single-nucleotide polymorphisms or SNPs -- that are associated with risk of prostate cancer. These results come from an analysis of more than 10 million SNP

  3. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    of comparing low-risk and high-risk prostate cancer. Figure 1 shows the mapping rates for exon, intron , and inter-genic sequences. The data suggest...Figure 1: Percentage of sequencing reads mapped to exons, introns , and intergenic regions of the human genome by varying amounts of input

  4. A Molecular Epidemiologic Case-Case Study of Prostate Cancer

    DTIC Science & Technology

    2001-03-01

    AD__ _ _ _ Award Number: DAMD17-98-1-8471 TITLE: A Molecular Epidemiologic Case-Case Study of Prostate Cancer PRINCIPAL INVESTIGATOR: Sara S. Strom...Molecular Epidmeiologic Case-Case Study of Prostate DAMD17-98-1-8471 Cancer Susceptibility 6. AUTHOR(S) Sara S. Strom, Ph.D. Sue-Hwa Lin 7. PERFORMING...DISTRIBUTION CODE Approved for Public Release; Distribution Unlimited 13. ABSTRACT (Maximum 200 Words) Although prostate cancer is the most common cancer in

  5. Development of the Meharry Medical College Prostate Cancer Research Program

    DTIC Science & Technology

    2006-03-01

    viable community network ties. One project will investigate health care seeking behavior of AA, another will investigate the role of lycopene in PCa risk...SUBJECT TERMS Prostate cancer, Dietary risk factors, Lycopene , Genetic predisposition, African-Americans, Cancer research training, Prostate cancer...The PI awaits comments from the HSRRB. Project 1: (Dr. Ukoli, PI / Dr. Dittus, Mentor) “ Lycopene in Prostate Cancer Risk among African-Americans

  6. Unique Genomic Alterations in Prostate Cancers in African American Men

    DTIC Science & Technology

    2015-12-01

    analysis of DNAs and RNAs from cancer and benign tissues from African American men with prostate followed by an in depth analysis of the 4p16.3 region...Cancer Tissue Bank. Samples will be from African American (AA) men undergoing radical prostatectomy for treatment of prostate cancer and were...collected with informed consent. Prostate cancer (PCa) samples will have 80% tumor and will have a matched benign tissue available from the same patient

  7. The essential role of methylthioadenosine phosphorylase in prostate cancer

    PubMed Central

    Foster, Barbara A.; Karasik, Ellen; Gillard, Bryan; Morrison, Carl; Mohler, James; Phillips, James G.; Smiraglia, Dominic J.

    2016-01-01

    Prostatic epithelial cells secrete high levels of acetylated polyamines into the prostatic lumen. This distinctive characteristic places added strain on the connected pathways, which are forced to increase metabolite production to maintain pools. The methionine salvage pathway recycles the one-carbon unit lost to polyamine biosynthesis back to the methionine cycle, allowing for replenishment of SAM pools providing a mechanism to help mitigate metabolic stress associated with high flux through these pathways. The rate-limiting enzyme involved in this process is methylthioadenosine phosphorylase (MTAP), which, although commonly deleted in many cancers, is protected in prostate cancer. We report near universal retention of MTAP expression in a panel of human prostate cancer cell lines as well as patient samples. Upon metabolic perturbation, prostate cancer cell lines upregulate MTAP and this correlates with recovery of SAM levels. Furthermore, in a mouse model of prostate cancer we find that both normal prostate and diseased prostate maintain higher SAM levels than other tissues, even under increased metabolic stress. Finally, we show that knockdown of MTAP, both genetically and pharmacologically, blocks androgen sensitive prostate cancer growth in vivo. Our findings strongly suggest that the methionine salvage pathway is a major player in homeostatic regulation of metabolite pools in prostate cancer due to their high level of flux through the polyamine biosynthetic pathway. Therefore, this pathway, and specifically the MTAP enzyme, is an attractive therapeutic target for prostate cancer. PMID:26910893

  8. Imaging Prostate Cancer (PCa) Phenotype and Evolution

    DTIC Science & Technology

    2015-10-01

    1 AWARD NUMBER: W81XWH-13-1-0386 TITLE: Imaging Prostate Cancer (PCa) Phenotype and Evolution PRINCIPAL INVESTIGATOR: Jason A. Koutcher...CONTRACTING ORGANIZATION: Sloan Kettering Institute for Cancer Research New York, NY 10065 REPORT DATE: October 2015 TYPE OF REPORT: Annual Report...time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this

  9. Promoter-Based Theranostics for Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0430 TITLE: Promoter -Based Theranostics for Prostate Cancer PRINCIPAL INVESTIGATOR: Martin Pomper CONTRACTING...ADDRESS. 1. REPORT DATE October 2015 2. REPORT TYPE Annual 3. DATES COVERED 15 Sep 2014 – 14 Sep 2015 4. TITLE AND SUBTITLE Promoter -Based...n/a 1. INTRODUCTION: This project leverages cancer-specific promoters for molecular- genetic endoradiotherapy and in the development of a universal

  10. Molecular Characterization of Indolent Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    active surveillance. During this funding period, we focused on analysis of clinical specimens suitable for RNA sequencing, and identified a finalized...genomic alterations, both genetic and epigenetic, is a defining feature of all human cancers at different stages of disease progression, RNA and DNA...versus higher-risk prostate cancer (Months 1-24). Summary: In our last annual report, we presented data justifying a modified approach to RNA

  11. Exome-Scale Discovery of Hotspot Mutation Regions in Human Cancer Using 3D Protein Structure.

    PubMed

    Tokheim, Collin; Bhattacharya, Rohit; Niknafs, Noushin; Gygax, Derek M; Kim, Rick; Ryan, Michael; Masica, David L; Karchin, Rachel

    2016-07-01

    The impact of somatic missense mutation on cancer etiology and progression is often difficult to interpret. One common approach for assessing the contribution of missense mutations in carcinogenesis is to identify genes mutated with statistically nonrandom frequencies. Even given the large number of sequenced cancer samples currently available, this approach remains underpowered to detect drivers, particularly in less studied cancer types. Alternative statistical and bioinformatic approaches are needed. One approach to increase power is to focus on localized regions of increased missense mutation density or hotspot regions, rather than a whole gene or protein domain. Detecting missense mutation hotspot regions in three-dimensional (3D) protein structure may also be beneficial because linear sequence alone does not fully describe the biologically relevant organization of codons. Here, we present a novel and statistically rigorous algorithm for detecting missense mutation hotspot regions in 3D protein structures. We analyzed approximately 3 × 10(5) mutations from The Cancer Genome Atlas (TCGA) and identified 216 tumor-type-specific hotspot regions. In addition to experimentally determined protein structures, we considered high-quality structural models, which increase genomic coverage from approximately 5,000 to more than 15,000 genes. We provide new evidence that 3D mutation analysis has unique advantages. It enables discovery of hotspot regions in many more genes than previously shown and increases sensitivity to hotspot regions in tumor suppressor genes (TSG). Although hotspot regions have long been known to exist in both TSGs and oncogenes, we provide the first report that they have different characteristic properties in the two types of driver genes. We show how cancer researchers can use our results to link 3D protein structure and the biologic functions of missense mutations in cancer, and to generate testable hypotheses about driver mechanisms. Our results

  12. An in vitro 3D model using collagen coated gelatin nanofibers for studying breast cancer metastasis.

    PubMed

    Janani, G; Pillai, Mamatha M; Selvakumar, R; Bhattacharyya, Amitava; Sabarinath, C

    2017-02-07

    The study of breast cancer metastasis is limited due to poor knowledge of molecular progression of breast tumor and varied heterogeneity. For a better understanding of tumor metastasis, a reliable 3D in vitro model bridging the gap between 2D cultures and in vivo animal model studies is essential. Our study is focused on two key points: (i) designing a 3D microenvironment for studying metastasis and (ii) simulating the metastasis milieu by inducing epithelial to mesenchymal transition (EMT) and mesenchymal to epithelial transition (MET). An electrospun gelatin nanofiber matrix (EGNF) was fabricated using electrospinning and further dip coated with different concentrations of collagen to obtain surface complexity and mechanical properties, similar to connective tissues. Nanofiber matrices were physically characterized by Fourier transform infrared spectroscopy (FTIR), atomic force microscopy (AFM), and field-emission scanning electron microscopy (FESEM). The FTIR, AFM, and FESEM results indicated the crosslinking and confirmed the presence of pores in the nanofiber matrices. Comparative studies on biocompatibility, cell attachment, and the proliferation of MCF-7 cells on EGNF and collagen coated gelatin nanofibrous matrix (CCGM) revealed higher cellular attachment and proliferation in CCGM. CCGM with human metastatic breast cancer cell line (MCF-7) was taken to study breast cancer metastasis using estrogen (induces EMT) and progesterone (induces MET) hormones for 24 h. Quantitative real-time PCR was used for quantifying the expression of metastasis related genes, and fluorescence microscopy for verifying the invasion of cells to the matrices. The expression of E-cadherin and matrix metalloproteinase 2 (MMP 2) confirmed the occurrence of EMT and MET. Live cell imaging and cellular attachment showed significant increase of cellular invasion in crosslinked 0.15% CCGM that serves as a suitable non-toxic, biocompatible, and affordable scaffold for studying breast cancer

  13. Prostate Cancer: Symptoms, Diagnosis and Treatment | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Prostate Cancer Prostate Cancer: Symptoms, Diagnosis and Treatment Past Issues / Winter 2010 Table of Contents Symptoms Prostate cancer has no symptoms in its early stages. They ...

  14. African American Men and Prostate Cancer: Be Your Own Advocate and Understand Screening

    MedlinePlus

    ... the benefits of prostate cancer screening outweigh the harms. Some doctors screen some men for prostate cancer ... find prostate cancers that never would have caused harm in a man’s lifetime. In either case, screening ...

  15. SU-E-T-20: A Correlation Study of 2D and 3D Gamma Passing Rates for Prostate IMRT Plans

    SciTech Connect

    Zhang, D; Wang, B; Ma, C; Deng, X

    2015-06-15

    Purpose: To investigate the correlation between the two-dimensional gamma passing rate (2D %GP) and three-dimensional gamma passing rate (3D %GP) in prostate IMRT quality assurance. Methods: Eleven prostate IMRT plans were randomly selected from the clinical database and were used to obtain dose distributions in the phantom and patient. Three types of delivery errors (MLC bank sag errors, central MLC errors and monitor unit errors) were intentionally introduced to modify the clinical plans through an in-house Matlab program. This resulted in 187 modified plans. The 2D %GP and 3D %GP were analyzed using different dose-difference and distance-toagreement (1%-1mm, 2%-2mm and 3%-3mm) and 20% dose threshold. The 2D %GP and 3D %GP were then compared not only for the whole region, but also for the PTVs and critical structures using the statistical Pearson’s correlation coefficient (γ). Results: For different delivery errors, the average comparison of 2D %GP and 3D %GP showed different conclusions. The statistical correlation coefficients between 2D %GP and 3D %GP for the whole dose distribution showed that except for 3%/3mm criterion, 2D %GP and 3D %GP of 1%/1mm criterion and 2%/2mm criterion had strong correlations (Pearson’s γ value >0.8). Compared with the whole region, the correlations of 2D %GP and 3D %GP for PTV were better (the γ value for 1%/1mm, 2%/2mm and 3%/3mm criterion was 0.959, 0.931 and 0.855, respectively). However for the rectum, there was no correlation between 2D %GP and 3D %GP. Conclusion: For prostate IMRT, the correlation between 2D %GP and 3D %GP for the PTV is better than that for normal structures. The lower dose-difference and DTA criterion shows less difference between 2D %GP and 3D %GP. Other factors such as the dosimeter characteristics and TPS algorithm bias may also influence the correlation between 2D %GP and 3D %GP.

  16. 3D Bioprinting a Cell-Laden Bone Matrix for Breast Cancer Metastasis Study.

    PubMed

    Zhou, Xuan; Zhu, Wei; Nowicki, Margaret; Miao, Shida; Cui, Haitao; Holmes, Benjamin; Glazer, Robert I; Zhang, Lijie Grace

    2016-11-09

    Metastasis is one of the deadliest consequences of breast cancer, with bone being one of the primary sites of occurrence. Insufficient 3D biomimetic models currently exist to replicate this process in vitro. In this study, we developed a biomimetic bone matrix using 3D bioprinting technology to investigate the interaction between breast cancer (BrCa) cells and bone stromal cells (fetal osteoblasts and human bone marrow mesenchymal stem cells (MSCs)). A tabletop stereolithography 3D bioprinter was employed to fabricate a series of bone matrices consisting of osteoblasts or MSCs encapsulated in gelatin methacrylate (GelMA) hydrogel with nanocrystalline hydroxyapatite (nHA). When BrCa cells were introduced into the stromal cell-laden bioprinted matrices, we found that the growth of BrCa cells was enhanced by the presence of osteoblasts or MSCs, whereas the proliferation of the osteoblasts or MSCs was inhibited by the BrCa cells. The BrCa cells co-cultured with MSCs or osteoblasts presented increased vascular endothelial growth factor (VEGF) secretion in comparison to that of monocultured BrCa cells. Additionally, the alkaline phosphatase activity of MSCs or osteoblasts was reduced after BrCa cell co-culture. These results demonstrate that the 3D bioprinted matrix, with BrCa cells and bone stromal cells, provides a suitable model with which to study the interactive effects of cells in the context of an artificial bone microenvironment and thus may serve as a valuable tool for the investigation of postmetastatic breast cancer progression in bone.

  17. Testosterone replacement therapy and the risk of prostate cancer.

    PubMed

    Warburton, Daniel; Hobaugh, Christopher; Wang, Grace; Lin, Haocheng; Wang, Run

    2015-01-01

    Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  18. An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells

    PubMed Central

    Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

    2016-01-01

    One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes. PMID:27765913

  19. Challenges in Clinical Prostate Cancer: Role of Imaging

    PubMed Central

    Kelloff, Gary J.; Choyke, Peter; Coffey, Donald S.

    2010-01-01

    Objective This article reviews a recent 2-day workshop on prostate cancer and imaging technology that was conducted by the Cancer Imaging Program of the National Cancer Institute. The workshop dealt with research trends and avenues for improving imaging and applications across the clinical spectrum of the disease. Conclusion After a summary of prostate cancer incidence and mortality, four main clinical challenges in prostate cancer treatment and management—diagnostic accuracy; risk stratification, initial staging, active surveillance, and focal therapy; prostate-specific antigen relapse after radiation therapy or radical prostatectomy; and assessing response to therapy in advanced disease—were discussed by the 55-member panel. The overarching issue in prostate cancer is distinguishing lethal from nonlethal disease. New technologies and fresh uses for established procedures make imaging effective in both assessing and treating prostate cancer. PMID:19457806

  20. Increased cancer cell proliferation in prostate cancer patients with high levels of serum folate

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A recent clinical trial revealed that folic acid supplementation is associated with an increased incidence of prostate cancer (1). The present study evaluates serum and prostate tissue folate levels in men with prostate cancer, compared to histologically normal prostate glands from can...

  1. Discovery and Classification of Fusion Transcripts in Prostate Cancer and Normal Prostate Tissue.

    PubMed

    Luo, Jian-Hua; Liu, Silvia; Zuo, Ze-Hua; Chen, Rui; Tseng, George C; Yu, Yan P

    2015-07-01

    Fusion transcript formation is one of the fundamental mechanisms that drives the development of prostate cancer. Because of the advance of high-throughput parallel sequencing, many fusion transcripts have been discovered. However, the discovery rate of fusion transcripts specific for prostate cancer is lagging behind the discoveries made on chromosome abnormalities of prostate cancer. Recent analyses suggest that many fusion transcripts are present in both benign and cancerous tissues. Some of these fusion transcripts likely represent important components of normal gene expression in cells. It is necessary to identify the criteria and features of fusion transcripts that are specific for cancer. In this review, we discuss optimization of RNA sequencing depth for fusion transcript discovery and the characteristics of fusion transcripts in normal prostate tissues and prostate cancer. We also propose a new classification of cancer-specific fusion transcripts on the basis of their tail gene fusion protein product and the roles that these fusions may play in cancer development.

  2. N-Cadherin in Prostate Cancer: Downstream Pathways and Their Translational Application for Castrate-Resistant Prostate Cancer

    DTIC Science & Technology

    2012-09-01

    primary prostate cancer, although some patients will experience disease recurrence. Standard treatment for recurrent prostate cancer is androgen... diseases : lessons from a rapid autopsy program. Cancer Res. 2004;64(24):9209-16. PubMed PMID: 15604294. -19- A r t i c l e s 1414 VOLUME 16 | NUMBER 12...DECEMBER 2010 nAture medicine Men with prostate cancer die predominantly from metastatic disease that is resistant to androgen deprivation therapy

  3. Rare Paravertebral and Skull Base Metastases in Prostate Cancer

    PubMed Central

    Samuel, Gbeminiyi; Isbell, Amir; Ogbonna, Onyekachi; Iftikhar, Hasan; Sakruti, Susmita; Atanda, Adebayo; Manchandani, Raj P.

    2016-01-01

    Prostate cancer is the most commonly diagnosed visceral cancer in the United States. A majority of cases exhibit an insidious course and nonaggressive tumor behavior. Prostate cancer can manifest as lesions which remain localized, regionally invading or metastasize to lymph nodes, bones, and lungs. Here, we report a unique case of metastatic prostate cancer to the right upper mediastinum, presenting as a paravertebral mass within 2 years of initial tissue diagnosis. Paravertebral spread has not been described for prostate cancer, and herein, we discuss the clinical presentation, diagnostic workup, and possible therapeutic options available in light of the literature. PMID:27920711

  4. Comparative mechanisms of cancer cell migration through 3D matrix and physiological microtracks.

    PubMed

    Carey, Shawn P; Rahman, Aniqua; Kraning-Rush, Casey M; Romero, Bethsabe; Somasegar, Sahana; Torre, Olivia M; Williams, Rebecca M; Reinhart-King, Cynthia A

    2015-03-15

    Tumor cell invasion through the stromal extracellular matrix (ECM) is a key feature of cancer metastasis, and understanding the cellular mechanisms of invasive migration is critical to the development of effective diagnostic and therapeutic strategies. Since cancer cell migration is highly adaptable to physiochemical properties of the ECM, it is critical to define these migration mechanisms in a context-specific manner. Although extensive work has characterized cancer cell migration in two- and three-dimensional (3D) matrix environments, the migration program employed by cells to move through native and cell-derived microtracks within the stromal ECM remains unclear. We previously reported the development of an in vitro model of patterned type I collagen microtracks that enable matrix metalloproteinase-independent microtrack migration. Here we show that collagen microtracks closely resemble channel-like gaps in native mammary stroma ECM and examine the extracellular and intracellular mechanisms underlying microtrack migration. Cell-matrix mechanocoupling, while critical for migration through 3D matrix, is not necessary for microtrack migration. Instead, cytoskeletal dynamics, including actin polymerization, cortical tension, and microtubule turnover, enable persistent, polarized migration through physiological microtracks. These results indicate that tumor cells employ context-specific mechanisms to migrate and suggest that selective targeting of cytoskeletal dynamics, but not adhesion, proteolysis, or cell traction forces, may effectively inhibit cancer cell migration through preformed matrix microtracks within the tumor stroma.

  5. 3D cell culture systems modeling tumor growth determinants in cancer target discovery.

    PubMed

    Thoma, Claudio R; Zimmermann, Miriam; Agarkova, Irina; Kelm, Jens M; Krek, Wilhelm

    2014-04-01

    Phenotypic heterogeneity of cancer cells, cell biological context, heterotypic crosstalk and the microenvironment are key determinants of the multistep process of tumor development. They sign responsible, to a significant extent, for the limited response and resistance of cancer cells to molecular-targeted therapies. Better functional knowledge of the complex intra- and intercellular signaling circuits underlying communication between the different cell types populating a tumor tissue and of the systemic and local factors that shape the tumor microenvironment is therefore imperative. Sophisticated 3D multicellular tumor spheroid (MCTS) systems provide an emerging tool to model the phenotypic and cellular heterogeneity as well as microenvironmental aspects of in vivo tumor growth. In this review we discuss the cellular, chemical and physical factors contributing to zonation and cellular crosstalk within tumor masses. On this basis, we further describe 3D cell culture technologies for growth of MCTS as advanced tools for exploring molecular tumor growth determinants and facilitating drug discovery efforts. We conclude with a synopsis on technological aspects for on-line analysis and post-processing of 3D MCTS models.

  6. Automated 3D ultrasound image segmentation for assistant diagnosis of breast cancer

    NASA Astrophysics Data System (ADS)

    Wang, Yuxin; Gu, Peng; Lee, Won-Mean; Roubidoux, Marilyn A.; Du, Sidan; Yuan, Jie; Wang, Xueding; Carson, Paul L.

    2016-04-01

    Segmentation of an ultrasound image into functional tissues is of great importance to clinical diagnosis of breast cancer. However, many studies are found to segment only the mass of interest and not all major tissues. Differences and inconsistencies in ultrasound interpretation call for an automated segmentation method to make results operator-independent. Furthermore, manual segmentation of entire three-dimensional (3D) ultrasound volumes is time-consuming, resource-intensive, and clinically impractical. Here, we propose an automated algorithm to segment 3D ultrasound volumes into three major tissue types: cyst/mass, fatty tissue, and fibro-glandular tissue. To test its efficacy and consistency, the proposed automated method was employed on a database of 21 cases of whole breast ultrasound. Experimental results show that our proposed method not only distinguishes fat and non-fat tissues correctly, but performs well in classifying cyst/mass. Comparison of density assessment between the automated method and manual segmentation demonstrates good consistency with an accuracy of 85.7%. Quantitative comparison of corresponding tissue volumes, which uses overlap ratio, gives an average similarity of 74.54%, consistent with values seen in MRI brain segmentations. Thus, our proposed method exhibits great potential as an automated approach to segment 3D whole breast ultrasound volumes into functionally distinct tissues that may help to correct ultrasound speed of sound aberrations and assist in density based prognosis of breast cancer.

  7. Automated 3D ultrasound image segmentation to aid breast cancer image interpretation.

    PubMed

    Gu, Peng; Lee, Won-Mean; Roubidoux, Marilyn A; Yuan, Jie; Wang, Xueding; Carson, Paul L

    2016-02-01

    Segmentation of an ultrasound image into functional tissues is of great importance to clinical diagnosis of breast cancer. However, many studies are found to segment only the mass of interest and not all major tissues. Differences and inconsistencies in ultrasound interpretation call for an automated segmentation method to make results operator-independent. Furthermore, manual segmentation of entire three-dimensional (3D) ultrasound volumes is time-consuming, resource-intensive, and clinically impractical. Here, we propose an automated algorithm to segment 3D ultrasound volumes into three major tissue types: cyst/mass, fatty tissue, and fibro-glandular tissue. To test its efficacy and consistency, the proposed automated method was employed on a database of 21 cases of whole breast ultrasound. Experimental results show that our proposed method not only distinguishes fat and non-fat tissues correctly, but performs well in classifying cyst/mass. Comparison of density assessment between the automated method and manual segmentation demonstrates good consistency with an accuracy of 85.7%. Quantitative comparison of corresponding tissue volumes, which uses overlap ratio, gives an average similarity of 74.54%, consistent with values seen in MRI brain segmentations. Thus, our proposed method exhibits great potential as an automated approach to segment 3D whole breast ultrasound volumes into functionally distinct tissues that may help to correct ultrasound speed of sound aberrations and assist in density based prognosis of breast cancer.

  8. Automated 3D Ultrasound Image Segmentation to Aid Breast Cancer Image Interpretation

    PubMed Central

    Gu, Peng; Lee, Won-Mean; Roubidoux, Marilyn A.; Yuan, Jie; Wang, Xueding; Carson, Paul L.

    2015-01-01

    Segmentation of an ultrasound image into functional tissues is of great importance to clinical diagnosis of breast cancer. However, many studies are found to segment only the mass of interest and not all major tissues. Differences and inconsistencies in ultrasound interpretation call for an automated segmentation method to make results operator-independent. Furthermore, manual segmentation of entire three-dimensional (3D) ultrasound volumes is time-consuming, resource-intensive, and clinically impractical. Here, we propose an automated algorithm to segment 3D ultrasound volumes into three major tissue types: cyst/mass, fatty tissue, and fibro-glandular tissue. To test its efficacy and consistency, the proposed automated method was employed on a database of 21 cases of whole breast ultrasound. Experimental results show that our proposed method not only distinguishes fat and non-fat tissues correctly, but performs well in classifying cyst/mass. Comparison of density assessment between the automated method and manual segmentation demonstrates good consistency with an accuracy of 85.7%. Quantitative comparison of corresponding tissue volumes, which uses overlap ratio, gives an average similarity of 74.54%, consistent with values seen in MRI brain segmentations. Thus, our proposed method exhibits great potential as an automated approach to segment 3D whole breast ultrasound volumes into functionally distinct tissues that may help to correct ultrasound speed of sound aberrations and assist in density based prognosis of breast cancer. PMID:26547117

  9. Elevated Prostate Health Index (phi) and Biopsy Reclassification During Active Surveillance of Prostate Cancer.

    PubMed

    Andreas, Darian; Tosoian, Jeffrey J; Landis, Patricia; Wolf, Sacha; Glavaris, Stephanie; Lotan, Tamara L; Schaeffer, Edward M; Sokoll, Lori J; Ross, Ashley E

    2016-07-01

    The Prostate Health Index (phi) has been FDA approved for decision-making regarding prostate biopsy. Phi has additionally been shown to positively correlate with tumor volume, extraprostatic disease and higher Gleason grade tumors. Here we describe a case in which an elevated phi encouraged biopsy of a gentleman undergoing active surveillance leading to reclassification of his disease as high risk prostate cancer.

  10. African Americans' Perceptions of Prostate-Specific Antigen Prostate Cancer Screening

    ERIC Educational Resources Information Center

    Hunter, Jaimie C.; Vines, Anissa I.; Carlisle, Veronica

    2015-01-01

    Background: In 2012, the U.S. Preventive Services Task Force released a hotly debated recommendation against prostate-specific antigen testing for all men. The present research examines African Americans' beliefs about their susceptibility to prostate cancer (PCa) and the effectiveness of prostate-specific antigen testing in the context of the…

  11. Sonic Hedgehog pathway activity in prostate cancer

    PubMed Central

    BRAGINA, OLGA; NJUNKOVA, NATALJA; SERGEJEVA, SVETLANA; JÄRVEKÜLG, LILIAN; KOGERMAN, PRIIT

    2010-01-01

    Abnormal activation of the Sonic hedgehog (Shh) signaling pathway has been demonstrated in a number of human tumors, including prostate cancer. The study aimed to assess the activity of Shh pathway components (Shh, Gli1, Gli2 and Gli3), as well as the proliferation markers FoxA1 and Notch1 during cancer progression in the transgenic adenocarcinoma of the mouse prostate (TRAMP). We evaluated changes in respective proteins by immunohistochemistry at three time points (12, 17 and 21 weeks of age) in the tissue of TRAMP and C57Bl/6 mice. Moreover, the expression of mRNA of these proteins was assessed. The present study shows a significant age-dependent increase in the number of Shh, Gli1, Gli3 and FoxA1-positive prostate cells and a decrease in Gli2-positive cells in TRAMP. The study also supports the hypothesis that the development of prostate cancer and its metastasis is associated with activation of the Shh signaling pathway. PMID:22966302

  12. Pentraxin 3: a novel biomarker for predicting progression from prostatic inflammation to prostate cancer.

    PubMed

    Stallone, Giovanni; Cormio, Luigi; Netti, Giuseppe Stefano; Infante, Barbara; Selvaggio, Oscar; Fino, Giuseppe Di; Ranieri, Elena; Bruno, Francesca; Prattichizzo, Clelia; Sanguedolce, Francesca; Tortorella, Simona; Bufo, Pantaleo; Grandaliano, Giuseppe; Carrieri, Giuseppe

    2014-08-15

    Pentraxin-3 (PTX3) is a member of the pentraxin family of innate immune regulators, which includes C-reactive protein (CRP). PTX3 has been implicated in angiogenesis, proliferation, and immune escape in cancer. In the present study, we evaluated PTX3 tissue expression and serum concentration as a biomarker to discriminate prostatic inflammation and benign prostatic hyperplasia (BPH) from prostate cancer, and to determine whether PTX3 status may predict progression from BPH to prostate cancer. We analyzed 40 patients with biopsy-proven BPH who underwent a second prostate biopsy 12 to 36 months later when they were diagnosed with prostate cancer or inflammation/BPH (n = 20 patients each group). Furthermore, we evaluated PTX3 serum concentrations in an independent set of patients with biopsy-proven inflammation/BPH (n = 61) and prostate cancer (n = 56). We found reduced PTX3 tissue expression in patients with prostatic inflammation/BPH compared with patients who developed prostate cancer. In the latter group, there was an increase in PTX3 tissue expression between the first and second prostate biopsy. PTX3 serum levels were also higher in patients with prostate cancer than in patients with inflammation/BPH. In contrast, there was no difference in serum PSA or CRP levels in these two groups. ROC curve analysis confirmed the reliability of PTX3 serum levels in predicting prostate cancer development, identifying a cutoff value of 3.25 ng/mL with a sensitivity and a specificity of 89.3% and 88.5%, respectively. In summary, our results encourage further evaluation of PTX3 as a tissue biopsy and blood-borne biomarker to discriminate BPH from prostate cancer.

  13. Current Status of Biomarkers for Prostate Cancer

    PubMed Central

    Velonas, Vicki M.; Woo, Henry H.; dos Remedios, Cristobal G.; Assinder, Stephen J.

    2013-01-01

    Prostate cancer (PCa) is a leading cause of cancer-related death of men globally. Since its introduction, there has been intense debate as to the effectiveness of the prostate specific antigen (PSA) test as a screening tool for PCa. It is now evident that the PSA test produces unacceptably high rates of false positive results and is not prognostic. Here we review the current status of molecular biomarkers that promise to be prognostic and that might inform individual patient management. It highlights current efforts to identify biomarkers obtained by minimally invasive methods and discusses current knowledge with regard to gene fusions, mRNA and microRNAs, immunology, and cancer-associated microparticles. PMID:23708103

  14. EXAFS studies of prostate cancer cell lines

    NASA Astrophysics Data System (ADS)

    Czapla, J.; Kwiatek, W. M.; Lekki, J.; Kisiel, A.; Steininger, R.; Goettlicher, J.

    2013-04-01

    Sulphur plays a vital role in every human organism. It is known, that sulphur-bearing compounds, such as for example cysteine and glutathione, play critical roles in development and progression of many diseases. Any alteration in sulphur's biochemistry could become a precursor of serious pathological conditions. One of such condition is prostate cancer, the most frequently diagnosed malignancy in the western world and the second leading cause of cancer related death in men. The purpose of presented studies was to examine what changes occur in the nearest chemical environment of sulphur in prostate cancer cell lines in comparison to healthy cells. The Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy was used, followed by theoretical calculations. The results of preliminary analysis is presented.

  15. Adenovirus-derived vectors for prostate cancer gene therapy.

    PubMed

    de Vrij, Jeroen; Willemsen, Ralph A; Lindholm, Leif; Hoeben, Rob C; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Dautzenberg, Iris J C; de Ridder, Corrina; Dzojic, Helena; Erbacher, Patrick; Essand, Magnus; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Jennings, Ian; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nugent, Regina; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schenk-Braat, Ellen; Schooten, Erik; Seymour, Len; Slade, Michael; Szyjanowicz, Pio; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; van der Weel, Laura; van Weerden, Wytske; Wagner, Ernst; Zuber, Guy

    2010-07-01

    Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.

  16. Anticancer properties of carotenoids in prostate cancer. A review.

    PubMed

    Soares, Nathalia da Costa Pereira; Teodoro, Anderson Junger; Lotsch, Priscila Falagan; Granjeiro, José Mauro; Borojevic, Radovan

    2015-10-01

    Prostate cancer is the most common noncutaneous cancer of men in the world. Several epidemiological studies have linked increased carotenoids consumption with decreased prostate cancer risk. These findings are supported by in vitro and in vivo experiments showing that carotenoids not only enhance the antioxidant response of prostate cells, but that they are able to inhibit proliferation, induce apoptosis and decrease the metastatic capacity of prostate cancer cells. However, clear clinical evidence supporting the use of carotenoids in prevention or treatment of prostate cancer is not available, due to the limited number of published randomized clinical trials, and the varying protocols used in the existing studies. The scope of the present review is to discuss the potential impact of carotenoids on prostate cancer by giving an overview of the molecular mechanisms and in vitro / in vivo effects.

  17. High-Density Lipoprotein and Prostate Cancer: An Overview

    PubMed Central

    Kotani, Kazuhiko; Sekine, Yoshitaka; Ishikawa, Shizukiyo; Ikpot, Imoh Z.; Suzuki, Kazuhiro; Remaley, Alan T.

    2013-01-01

    Prostate cancer is a common disease in modern, developed societies and has a high incidence and mortality. High-density lipoprotein cholesterol (HDL-C) has recently received much attention as a possible risk marker of prostate cancer development and prognosis. In the present article, we summarized findings from epidemiologic studies of the association between HDL-C and prostate cancer. Low HDL-C level was found to be a risk and prognostic factor of prostate cancer in several epidemiologic studies, although the overall linkage between HDL and prostate cancer has not been definitively established. The mechanisms for this association remain uncertain; however, limited data from experimental studies imply a possible role of HDL in the pathophysiology of prostate cancer. More epidemiologic research, in combination with experimental studies, is needed in this field. PMID:23985823

  18. 3D surface imaging for guidance in breast cancer radiotherapy: organs at risk

    NASA Astrophysics Data System (ADS)

    Alderliesten, Tanja; Betgen, Anja; van Vliet-Vroegindeweij, Corine; Remeijer, Peter

    2013-03-01

    Purpose: To evaluate the variability in heart position in deep-inspiration breath-hold (DIBH) radiotherapy for breast cancer when 3D surface imaging would be used for monitoring the depth of the breath hold during treatment. Materials and Methods: Ten patients who received DIBH radiotherapy after breast-conserving surgery (BCS) were included. Retrospectively, heart-based registrations were performed for cone-beam computed tomography (CBCT) to planning CT and breast surface registrations were performed for a 3D surface (two different regions of interest [ROIs]), captured concurrently with CBCT, to planning CT. The resulting setup errors were compared with linear regression analysis and receiver operating characteristic (ROC) analysis was performed to investigate the prediction quality of 3D surface imaging for 3D heart displacement. Further, the residual setup errors (systematic [Σ] and random [σ]) of the heart were estimated relative to the surface registrations. Results: When surface imaging [ROIleft-side;ROIboth-sides] would be used for monitoring, the residual errors of the heart position are in left-right: Σ=[0.360.12], σ=[0.160.14] cranio-caudal: Σ=[0.540.54], σ=[0.280.31] and in anteriorposterior: Σ=[0.180.14], σ=[0.200.19] cm. Correlations between setup errors were: R2 = [0.23;0.73], [0.67;0.65], [0.65;0.73] in left-right, cranio-caudal, and anterior-posterior direction, respectively. ROC analysis resulted in an area under the ROC curve of [0.82;0.78]. Conclusion: The use of ROIboth-sides provided promising results. However, considerable variability in the heart position, particularly in CC direction, is observed when 3D surface imaging would be used for guidance in DIBH radiotherapy after BCS. Planning organ at risk volume margins should be used to take into account the heart-position variability.

  19. Optimization of Radiation Therapy Techniques for Prostate Cancer With Prostate-Rectum Spacers: A Systematic Review

    SciTech Connect

    Mok, Gary; Benz, Eileen; Vallee, Jean-Paul; Miralbell, Raymond; Zilli, Thomas

    2014-10-01

    Dose-escalated radiation therapy for localized prostate cancer improves disease control but is also associated with worse rectal toxicity. A spacer placed between the prostate and rectum can be used to displace the anterior rectal wall outside of the high-dose radiation regions and potentially minimize radiation-induced rectal toxicity. This systematic review focuses on the published data regarding the different types of commercially available prostate-rectum spacers. Dosimetric results and preliminary clinical data using prostate-rectum spacers in patients with localized prostate cancer treated by curative radiation therapy are compared and discussed.

  20. Ezrin and BCAR1/p130Cas mediate breast cancer growth as 3-D spheroids.

    PubMed

    Konstantinovsky, Sophya; Davidson, Ben; Reich, Reuven

    2012-08-01

    CAS proteins and Ezrin, Radixin, Moesin (ERM) family members act as intracellular scaffolds and are involved in interactions with the cytoskeleton, respectively. Both protein families have previously been associated with metastasis and poor prognosis in cancer. Our group recently reported on the overexpression of EZR/VIL2 and BCAR1 and their protein products in breast carcinoma effusions compared to primary breast carcinoma. In the present study, the role of these two proteins was studied in semi-normal MCF10A cells and metastatic MDA-MB-231 breast carcinoma cells cultured in tri-dimensional (3-D) conditions that were hypothesized to reproduce the in vivo conditions of breast cancer metastasis. MCF10A cells formed spheroid-shaped colonies without any Matrigel invasion, while MDA-MB-231 cells displayed an invasive phenotype and showed satellite projections that bridged multiple cell colonies in 3-D culture. E-cadherin was expressed in MCF10A, but not in MDA-MB-231 cells. The temporal expression of ezrin and BCAR1/p130Cas at the mRNA and protein level differed in the two cell lines upon 3-D culturing on Matrigel. Upregulation of BCAR1/p130cas was observed in the transition of MDA-MB-231 from attached to detached culture. Silencing of Ezrin and p130Cas in MDA-MB-231 cells by short hairpin RNA resulted in decreased invasive potential, and p130Cas silencing further resulted in smaller spheroid/colony formation. Our data show that MCF10A and MDA-MB-231 cells differ in their ability to form spheroids, in expression of E-cadherin and in the expression of Ezrin and BCAR1/p130Cas in 3-D cultures on Matrigel, suggesting a role in tumor progression in breast carcinoma.

  1. Iterative Mesh Transformation for 3D Segmentation of Livers with Cancers in CT Images

    PubMed Central

    Lu, Difei; Wu, Yin; Harris, Gordon; Cai, Wenli

    2015-01-01

    Segmentation of diseased liver remains a challenging task in clinical applications due to the high inter-patient variability in liver shapes, sizes and pathologies caused by cancers or other liver diseases. In this paper, we present a multi-resolution mesh segmentation algorithm for 3D segmentation of livers, called iterative mesh transformation that deforms the mesh of a region-of-interest (ROI) in a progressive manner by iterations between mesh transformation and contour optimization. Mesh transformation deforms the 3D mesh based on the deformation transfer model that searches the optimal mesh based on the affine transformation subjected to a set of constraints of targeting vertices. Besides, contour optimization searches the optimal transversal contours of the ROI by applying the dynamic-programming algorithm to the intersection polylines of the 3D mesh on 2D transversal image planes. The initial constraint set for mesh transformation can be defined by a very small number of targeting vertices, namely landmarks, and progressively updated by adding the targeting vertices selected from the optimal transversal contours calculated in contour optimization. This iterative 3D mesh transformation constrained by 2D optimal transversal contours provides an efficient solution to a progressive approximation of the mesh of the targeting ROI. Based on this iterative mesh transformation algorithm, we developed a semi-automated scheme for segmentation of diseased livers with cancers using as little as five user-identified landmarks. The evaluation study demonstrates that this semiautomated liver segmentation scheme can achieve accurate and reliable segmentation results with significant reduction of interaction time and efforts when dealing with diseased liver cases. PMID:25728595

  2. Iterative mesh transformation for 3D segmentation of livers with cancers in CT images.

    PubMed

    Lu, Difei; Wu, Yin; Harris, Gordon; Cai, Wenli

    2015-07-01

    Segmentation of diseased liver remains a challenging task in clinical applications due to the high inter-patient variability in liver shapes, sizes and pathologies caused by cancers or other liver diseases. In this paper, we present a multi-resolution mesh segmentation algorithm for 3D segmentation of livers, called iterative mesh transformation that deforms the mesh of a region-of-interest (ROI) in a progressive manner by iterations between mesh transformation and contour optimization. Mesh transformation deforms the 3D mesh based on the deformation transfer model that searches the optimal mesh based on the affine transformation subjected to a set of constraints of targeting vertices. Besides, contour optimization searches the optimal transversal contours of the ROI by applying the dynamic-programming algorithm to the intersection polylines of the 3D mesh on 2D transversal image planes. The initial constraint set for mesh transformation can be defined by a very small number of targeting vertices, namely landmarks, and progressively updated by adding the targeting vertices selected from the optimal transversal contours calculated in contour optimization. This iterative 3D mesh transformation constrained by 2D optimal transversal contours provides an efficient solution to a progressive approximation of the mesh of the targeting ROI. Based on this iterative mesh transformation algorithm, we developed a semi-automated scheme for segmentation of diseased livers with cancers using as little as five user-identified landmarks. The evaluation study demonstrates that this semi-automated liver segmentation scheme can achieve accurate and reliable segmentation results with significant reduction of interaction time and efforts when dealing with diseased liver cases.

  3. Prostate cancer: beware of disseminated intravascular coagulation

    PubMed Central

    Desai, Mihir; John, Babbin; Evans, Gillian; Eddy, Ben

    2015-01-01

    Disseminated intravascular coagulation (DIC) is a pathological systemic condition resulting from aberrant activation of the coagulation system. It is characterised by the release and activation of procoagulants into the blood, with an associated consumption coagulopathy. Its association with solid and haematological malignancies is well described in literature. This case describes an elderly man, known to have prostate cancer, who following transurethral resection of the prostate developed DIC with haematuria, spontaneous ecchymoses and mucosal bleeding. Subsequent investigations revealed a prostate-specific antigen (PSA) >1000 µg/L, and staging CT showed multiple sclerotic metastatic lesions affecting the thoracic and lumbar vertebra, as well as infiltration into his left femur. Coagulation normalised with blood products and vitamin K within 1 week, and the patient responded to antiandrogen therapy with a reduction in pain and PSA on discharge. PMID:25819815

  4. Sipuleucel-T (APC8015) for prostate cancer.

    PubMed

    So-Rosillo, Rosendo; Small, Eric J

    2006-09-01

    Sipuleucel-T (Provenge; APC8015; Dendreon Corp, WA, USA) is a novel immunotherapeutic cellular product, which includes autologous dendritic cells pulsed ex vivo with a recombinant fusion protein (PA2024) consisting of granulocyte macrophage colony-stimulating factor and prostatic acid phosphatase. Two Phase II trials in men with androgen-dependent biochemically relapsed prostate cancer have demonstrated a decrease in prostate-specific antigen and prolongation in prostate-specific antigen doubling time. In men with hormone-refractory prostate cancer, clinical trials have demonstrated both biological activity and clinical response to sipuleucel-T. Data from two Phase III trials in men with asymptomatic, metastatic hormone-refractory prostate cancer demonstrated an improved median overall survival in men who received sipuleucel-T compared with placebo. Clinical trials are ongoing or are being developed to evaluate sipuleucel-T in various prostate cancer disease states and in combination with other treatment modalities.

  5. Metastatic Prostate Cancer to the Duodenum: A Rare Case

    PubMed Central

    Kaswala, Dharmesh H.; Patel, Nitin; Jadallah, Sana; Wang, Weizheng

    2014-01-01

    Prostate cancer is the third most common cancer in man. About 1 in 6 males developed prostate cancer and 1 in 35 males die of this disease. Prostate cancer behavior ranges from microscopic tumors to aggressive cancer with metastatic potential. While metastasis to bone is relatively common, prostate cancer rarely metastasizes to the cecum, pituitary gland, small bowel, maxillary sinus and skin. Our case report presents a rare presentation of metastatic prostate cancer to the duodenum. Our search of the literature found only 2 cases of prostate metastases to duodenum published from 1966 to the present. To our knowledge this is the third case of metastatic prostate cancer presenting with duodenal metastasis. Although it is rare but in symptomatic patients small intestine metastasis should not be ignored with advanced prostate cancer. The case demonstrates a novel presentation of a common malignancy, and should raise awareness in clinicians and radiologists that prostate cancer can present with distant metastases in absence of any local lymphadenopathy. PMID:25161979

  6. Can the conventional sextant prostate biopsy accurately predict unilateral prostate cancer in low-risk, localized, prostate cancer?

    PubMed

    Mayes, Janice M; Mouraviev, Vladimir; Sun, Leon; Tsivian, Matvey; Madden, John F; Polascik, Thomas J

    2011-01-01

    We evaluate the reliability of routine sextant prostate biopsy to detect unilateral lesions. A total of 365 men with complete records including all clinical and pathologic variables who underwent a preoperative sextant biopsy and subsequent radical prostatectomy (RP) for clinically localized prostate cancer at our medical center between January 1996 and December 2006 were identified. When the sextant biopsy detects unilateral disease, according to RP results, the NPV is high (91%) with a low false negative rate (9%). However, the sextant biopsy has a PPV of 28% with a high false positive rate (72%). Therefore, a routine sextant prostate biopsy cannot provide reliable, accurate information about the unilaterality of tumor lesion(s).

  7. [Interdisciplinary and individualized therapy of prostate cancer : International prostate cancer symposium Bonn 2013 - challenges and targets].

    PubMed

    Schwardt, M; Debus, J; Feick, G; Hadaschik, B; Hohenfellner, M; Schüle, R; Zacharias, J-P; Combs, S E

    2015-11-01

    Multimodal treatment of prostate cancer is based on specific staging via imaging, clinical parameters, tumor markers and histopathological grading. Risk-adapted therapy encompasses wait and see, active surveillance, surgical intervention, radiotherapy and hormone therapy. Some patients also need a combination of these treatment options. Even though clinical parameters guide the treatment plan, patient wishes and preferences are incorporated. Against this background leading basic research scientists, urologists, radiotherapists, epidemiologists and members of other associated disciplines discussed state of the art treatment concepts, innovative trial designs and translational research projects at the international meeting "Challenges and Chances in Prostate Cancer Research" organized by the German Cancer Aid (Deutsche Krebshilfe).

  8. Superficial urothelial cancer in the prostatic urethra.

    PubMed

    Kirkali, Ziya; Canda, A Erdem

    2006-02-28

    Transitional cell carcinoma (TCC) is a multifocal disease of the urinary tract that can also involve the prostatic urethra (PU). The exact incidence of superficial involvement of the PU in patients with bladder TCC is not well known. Bladder TCC may involve the prostate in 12-40% of the patients and the degree of involvement can include urethral mucosa, ducts, acini, and stroma of the gland, which has been shown to affect the outcome. Risk factors for superficial urothelial cancer in the PU are high-grade, multifocal bladder TCC and presence of carcinoma in situ (CIS) in the bladder. While visible tumors are easy to detect and resect, controversy still exists regarding the optimal technique to identify prostatic involvement by TCC. Prostatic urethral sampling by a transurethral resection biopsy or a cold-cup biopsy, particularly in the high-risk group of bladder cancer patients, has been recommended for detecting prostatic urethral involvement. Management of superficial prostatic involvement by TCC is also unclear. Currently, there is increasing recognition of the value of conservative treatment options with intravesical agents when there is superficial involvement of the PU. Particularly, intravesical bacillus Calmette-Guèrin (BCG) seems to be an effective treatment alternative in the management of superficial involvement of the PU by TCC. Close follow-up by cystoscopy and PU biopsy at 3-month intervals, particularly in intermediate and high-risk patients who respond to intravesical therapy and in whom cystectomy is appropriate, is recommended in order to detect persistent tumor, recurrences, or progression.

  9. New serum biomarkers for prostate cancer diagnosis

    PubMed Central

    Chadha, Kailash C.; Miller, Austin; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Underwood, Willie

    2014-01-01

    Background Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods Concurrent measurements of circulating interleukin-8 (IL-8), Tumor necrosis factor-α (TNF-α) and soluble tumor necrosis factor-α receptors 1 (sTNFR1) were obtained from four groups of men: (1) Controls (2) with elevated prostate-specific antigen with a negative prostate biopsy (elPSA_negBx) (3) with clinically localized CaP and (4) with castration resistant prostate cancer. Results TNF-α Area under the receiver operating characteristic curve (AUC = 0.93) and sTNFR1 (AUC = 0.97) were strong predictors of elPSA_negBx (vs. CaP). The best predictor of elPSA_negBx vs CaP was sTNFR1 and IL-8 combined (AUC = 0.997). The strongest single predictors of localized versus metastatic CaP were TNF-α (AUC = 0.992) and PSA (AUC = 0.963) levels. Conclusions The specificity and sensitivity of a PSA-based CaP diagnosis can be significantly enhanced by concurrent serum measurements of IL-8, TNF-α and sTNFR1. In view of the concerns about the ability of PSA to distinguish clinically relevant CaP from indolent disease, assessment of these biomarkers in the larger cohort is warranted. PMID:25593898

  10. False-positive prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection.

    PubMed

    Smelov, V; Novikov, A; Brown, L J; Eklund, C; Strokova, L; Ouburg, S; Morre, S A; Dillner, J

    2013-06-01

    Symptomatic male urethral Chlamydia trachomatis infection resulted in inflammation of the prostate, with associated increases in both prostate-specific (PSA) and prostate cancer-specific (PCA3) markers with prostate biopsies showing no evidence of malignancy.

  11. Role of Reactive Stroma in Prostate Cancer Progression

    DTIC Science & Technology

    2008-02-01

    AD_________________ Award Number: W81XWH-04-1-0189 TITLE: Role of Reactive Stroma in Prostate Cancer Progression PRINCIPAL INVESTIGATOR: David R...REPORT TYPE Final 3. DATES COVERED 12 JAN 2004 - 11 JAN 2008 4. TITLE AND SUBTITLE Role of Reactive Stroma in Prostate Cancer Progression 5a. CONTRACT...the reactive stroma of experimental prostate cancer . Using a modified approach, we are placing an inducible Cre recombinase behind the FAP gene

  12. The Relationship Between Statins and Prostate Cancer Prevention

    DTIC Science & Technology

    2009-09-01

    The relationship between statins and prostate cancer prevention PRINCIPAL INVESTIGATOR: Wildon R. Farwell, M.D...2008 – 31 Aug 2009 4. TITLE AND SUBTITLE The relationship between statins and prostate cancer prevention 5a. CONTRACT NUMBER W81XWH-08-2-0168...States. Few risk factors and strategies for prostate cancer prevention are known. Some evidence suggests that statins , a class of medications that

  13. Immunological Targeting of Tumor Initiating Prostate Cancer Cells

    DTIC Science & Technology

    2014-10-01

    AD Award Number: W81XWH-13-1-0369 TITLE: Immunological Targeting of Tumor Initiating Prostate Cancer Cells PRINCIPAL...5a. CONTRACT NUMBER Immunological Targeting of Tumor Initiating Prostate Cancer Cells 5b. GRANT NUMBER W81XWH13-1-0369 5c... prostate cancer . In two specific aims, we proposed to first identify novel antigenic targets on these castrate resistant luminal epithelial cells (CRLEC

  14. The Function of Neuroendocrine Cells in Prostate Cancer

    DTIC Science & Technology

    2014-04-01

    still many unanswered questions in prostate cancer. A fundamental and clinically important issue is why prostate cancer responds to hormonal therapy ...adenocarcinoma cells express low levels of CD49f. We then fractionated CD49fhi and CD49flo cells and transplanted both into recipient mice. Both phenotypic...Hsia E, Squires J, Li Z, Zhang Y, Li W, Chen X, Xu H, Huang J. Androgen-deprivation therapy -induced aggressive prostate cancer with neuroendocrine

  15. DNA Damage and Genetic Instability as Harbingers of Prostate Cancer

    DTIC Science & Technology

    2013-01-01

    incidence of prostate cancer as compared to placebo . Primary analysis of this trial indicated no statistically significant effect of selenium...sample of patients that participated in a Phase 2 clinical trial investigating the effect of selenium supplementation on prostate cancer progression...Results of this trial indicated that selenium did not have an effect on prostate cancer aggressiveness as measured by PSA velocity and hence biopsy

  16. Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

    DTIC Science & Technology

    2013-03-01

    target for therapy of prostate cancer , but approaches aimed at Ras itself, or its critical signaling pathways, which are required in normal tissues...Impact: Current therapies for prostate cancer are inadequate, and aberrant activation of Ras or Ras pathways are common. A novel therapeutic modality...to Advanced Prostate Cancer PRINCIPAL INVESTIGATOR: Douglas V. Faller, PhD, MD CONTRACTING ORGANIZATION: Trustees of Boston University

  17. Radiation treatment for patients with intermediate-risk prostate cancer

    PubMed Central

    Mayadev, Jyoti S.; Valicenti, Richard K.

    2012-01-01

    Around 70% of men presenting with prostate cancer will have organ-confined disease, with the majority presenting with low- or intermediate-risk prostate cancer. This article reviews the evidence supporting the current standard of care in radiation oncology for the evaluation and management of men with intermediate-risk prostate cancer. Dose escalation, hormonal therapy, combined modality therapy, and modern techniques for the delivery of radiation therapy are reviewed. PMID:22654963

  18. Hypofractionated External-Beam Radiotherapy for Prostate Cancer

    PubMed Central

    Cho, L. Chinsoo; Timmerman, Robert; Kavanagh, Brian

    2013-01-01

    There are radiobiological rationales supporting hypofractionated radiotherapy for prostate cancer. The recent advancements in treatment planning and delivery allow sophisticated radiation treatments to take advantage of the differences in radiobiology of prostate cancer and the surrounding normal tissues. The preliminary results from clinical studies indicate that abbreviated fractionation programs can result in successful treatment of localized prostate cancer without escalation of late toxicity. PMID:23533777

  19. Regulation of Prostate Cancer Bone Metastasis by DKK1

    DTIC Science & Technology

    2012-09-01

    0030 TITLE: Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, MD, PhD CONTRACTING...of Prostate Cancer Bone Metastasis by DKK1 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-08-1-0030 5c. PROGRAM ELEMENT...Osteoblastic bone metastasis is a common complication of advanced prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 ( DKK1 ) is a

  20. Regulation of Prostate Cancer Bone Metastasis by DKK1

    DTIC Science & Technology

    2012-04-01

    Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, M.D., Ph.D. CONTRACTING ORGANIZATION...Annual 3. DATES COVERED (From - To) 1 April 2011 - 28 Feb 2012 4. TITLE AND SUBTITLE Regulation of Prostate Cancer Bone Metastasis by DKK1 ...prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 ( DKK1 ) is a secreted inhibitor of osteoblast Wnt signaling pathway

  1. Regulation of Prostate Cancer Bone Metastasis by DKK1

    DTIC Science & Technology

    2010-04-01

    0030 TITLE: Regulation of Prostate Cancer Bone Metastasis by DKK1 PRINCIPAL INVESTIGATOR: Gregory A. Clines, MD, PhD CONTRACTING...AND SUBTITLE Regulation of Prostate Cancer Bone Metastasis by DKK1 5a. CONTRACT NUMBER W81XWH-08-1-0030 5b. GRANT NUMBER...metastasis is a common complication of advanced prostate cancer, resulting in pain and pathologic fracture. Dickkopf homolog 1 ( DKK1 ) is a secreted

  2. Sipuleucel-T for the treatment of advanced prostate cancer.

    PubMed

    Frohlich, Mark W

    2012-06-01

    Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response to prostate cancer that prolongs the overall survival of men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). The clinical development program and key efficacy, safety, and immune response findings from the phase III studies are presented. The integration of sipuleucel-T into the treatment paradigm of advanced prostate cancer and future directions for research are discussed.

  3. Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

    DTIC Science & Technology

    2015-10-01

    SUPPLEMENTARY NOTES 14. ABSTRACT In the U.S., African Americans ( AA ) are more likely to be diagnosed with prostate cancer than European American (EA), and...after diagnosis, AA men are more likely to die from prostate cancer than EA men. We hypothesize that differences in DNA methylation patterns across...and adjacent normal tissue derived from both AA and EA individuals. We will determine if DNA methylation patterns in prostate tissue (both cancerous

  4. Solitary brain metastasis from prostate cancer: a case report.

    PubMed

    Barakat, Tasneem; Agarwal, Arnav; McDonald, Rachel; Ganesh, Vithusha; Vuong, Sherlyn; Borean, Michael; Chow, Edward; Soliman, Hany

    2016-07-01

    Brain metastases arising from prostate cancer are exceedingly rare and typically occur late in the course of the disease. Most patients have widespread metastatic disease before developing brain metastases from prostate cancer. We report the case of a 67-year-old male with prostate cancer presenting with an isolated symptomatic brain metastasis. Aggressive treatment of the metastatic site included tumor resection and adjuvant stereotactic radiation treatment (RT) to the surgical bed, resulting in a favorable outcome.

  5. Role of Nonreceptor Protein Kinase Ack1 in Prostate Cancer

    DTIC Science & Technology

    2010-05-01

    initiation and progression of prostate cancer in vivo. 15. SUBJECT TERMS Prostate cancer, transgenic mice , mouse model 16. SECURITY CLASSIFICATION OF...These transgenic mice were generated in the laboratory of our collaborator Dr. Terry Van Dyke and are a mouse model of prostate cancer in which T121...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching

  6. Ethnicity and Prostate Cancer: Vitamin D Genetic and Sociodemographic Factors

    DTIC Science & Technology

    2009-03-01

    proposed that adequate circulating levels of vitamin D are important to protect against prostate cancer . The androgen testosterone and its bioactive form...to act as a regulator of vitamin D activity. When cells from the prostate cancer cell line LNCaP are grown in androgen -depleted medium, vitamin D no...calcitriol (15) and its precursor form (14). Additionally, in two androgen receptor–positive prostate cancer cell lines (DHT binds to androgen receptor

  7. Vitamin D and Related Genes, Race and Prostate Cancer Aggressiveness

    DTIC Science & Technology

    2015-12-29

    vitamin D and genetic polymorphisms act synergistically to affect prostate cancer aggressiveness. We examined these associations among vitamin D...epidemiologic techniques for estimating odds of high aggressive prostate cancer according to vitamin D metabolites, PTH, calcium, phosphorus and genetic ...hypotheses a. Statistical analyses have been performed examining associations between 25(OH)D, 1,25(OH)2D, genetic polymorphisms and prostate cancer

  8. [Prostate cancer dependance upon cholesterol, statins and diet].

    PubMed

    Pilch, Paweł; Radziszewski, Piotr; Maciukiewicz, Piotr

    2012-01-01

    The aim of the work is to analyze the influence of higher cholesterol and LDL level on risk of prostate cancer. The work is based on the available literature in that field. The metabolism of cholesterol is mainly regulated by the statins, which may thus inhibit prostate cancer growth. Keeping the appropriate body mass and level of cholesterol by proper diet and physical exercises may be the prophylaxis of prostate cancer.

  9. Exploration of Prostate Cancer Treatment Induced Neurotoxicity with Neuroimaging

    DTIC Science & Technology

    2008-05-01

    AD_________________ Award Number: W81XWH-06-1-0033 TITLE: Exploration of Prostate Cancer Treatment Induced...Prostate Cancer Treatment Induced Neurotoxicity with Neuroimaging 5b. GRANT NUMBER W81XWH-06-1-0033 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jeri...consequences on brain health of prostate cancer treatments in men despite data suggesting that ADT may cause memory or other cognitive impairments. Our study

  10. Quality of Life and Cost Effectiveness of Prostate Cancer Treatment

    DTIC Science & Technology

    2005-03-01

    AD Award Number: W81XWH-04-1-0257 TITLE: Quality of Life and Cost Effectiveness of Prostate Cancer Treatment PRINCIPAL INVESTIGATOR: Ravishankar...patients across two ethnic groups, (2) analyze and compare short and long term cost-effectiveness of prostate cancer treatment across ethnic groups; and...cost-effectiveness of prostate cancer treatment across ethnic groups; and (3) analyze and compare resource utilization patterns, treatment modalities

  11. Genes Involved in Oxidation and Prostate Cancer Progression

    DTIC Science & Technology

    2008-01-01

    association of genes and prostate cancer progression from these simulated nested case - control studies to what would be observed if the entire...Control Sampling: Methods for Nested Case - Control Studies of Candidate Genes and Prostate Cancer Progression”. This work forms one aim of MS Wang’s...prostate cancer risk: results from two large nested case - control studies . Carcinogenesis. 2007 Nov 13; [Epub ahead of print] PMID: 17999989 Dr

  12. Novel Prostate Cancer Pathway Modeling using Boolean Implication

    DTIC Science & Technology

    2012-09-01

    standard diagnostic marker for prostate cancer despite its serious limitations. Large proportions of men are being diagnosed with prostate cancer but...recent studies imply that many of them don’t need prostate cancer treatment. There is clearly a need for better diagnostic and prognostic marker in...discovery of better diagnostic and prognostic markers . Body Previously, we have published a novel approach to discover Boolean implications

  13. A Genome-wide Pleiotropy Scan for Prostate Cancer Risk

    PubMed Central

    Panagiotou, Orestis A; Travis, Ruth C; Campa, Daniele; Berndt, Sonja I.; Lindstrom, Sara; Kraft, Peter; Schumacher, Fredrick R.; Siddiq, Afshan; Papatheodorou, Stefania I.; Stanford, Janet L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie J.; Diver, W. Ryan; Gapstur, Susan M.; Stevens, Victoria L.; Boeing, Heiner; Bueno-de-Mesquita, H. Bas; Gurrea, Aurelio Barricarte; Kaaks, Rudolf; Khaw, Kay-Tee; Krogh, Vittorio; Overvad, Kim; Riboli, Elio; Trichopoulos, Dimitrios; Giovannucci, Edward; Stampfer, Meir; Haiman, Christopher; Henderson, Brian; Le Marchand, Loic; Gaziano, J. Michael; Hunter, DavidJ.; Koutros, Stella; Yeager, Meredith; Hoover, Robert N.; Chanock, Stephen J.; Wacholder, Sholom; Key, Timothy J.; Tsilidis, Konstantinos K

    2014-01-01

    Background No single-nucleotide polymorphisms (SNPs) specific for aggressive prostate cancer have been identified in genome-wide association studies (GWAS). Objective To test if SNPs associated with other traits may also affect the risk of aggressive prostate cancer. Design, setting, and participants SNPs implicated in any phenotype other than prostate cancer (p ≤ 10−7) were identified through the catalog of published GWAS and tested in 2891 aggressive prostate cancer cases and 4592 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). The 40 most significant SNPs were followed up in 4872 aggressive prostate cancer cases and 24 534 controls from the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Outcome measurements and statistical analysis Odds ratios (ORs) and 95% confidence intervals (CIs) for aggressive prostate cancer were estimated. Results and limitations A total of 4666 SNPs were evaluated by the BPC3. Two signals were seen in regions already reported for prostate cancer risk. rs7014346 at 8q24.21 was marginally associated with aggressive prostate cancer in the BPC3 trial (p = 1.6 × 10-6), whereas after meta-analysis by PRACTICAL the summary OR was 1.21 (95%CI 1.16–1.27; p = 3.22 × 10−18). rs9900242 at 17q24.3 was also marginally associated with aggressive disease in the meta-analysis (OR 0.90, 95% CI 0.86–0.94; p = 2.5 × 10−6). Neither of these SNPs remained statistically significant when conditioning on correlated known prostate cancer SNPs. The meta-analysis by BPC3 and PRACTICAL identified a third promising signal, marked by rs16844874 at 2q34, independent of known prostate cancer loci (OR 1.12,95% CI 1.06–1.19; p = 4.67 × 10−5); it has been shown that SNPs correlated with this signal affect glycine concentrations. The main limitation is the heterogeneity in the definition of aggressive prostate cancer between BPC3 and PRACTICAL. Conclusions We did

  14. (-)-Gossypol reduces invasiveness in metastatic prostate cancer cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acquisition of metastatic ability by prostatic cancer cells is the most lethal aspect of prostatic cancer progression. (-)-Gossypol, a polyphenolic compound present in cottonseeds, possesses anti-proliferation and pro-apoptotic effects in various cancer cells. In this study, the differences betwee...

  15. Partnering Research Involving Mentoring and Education (PRIME) in Prostate Cancer

    DTIC Science & Technology

    2007-02-01

    Duncan, C., Sharifi, ., Gh., Kim, H.S., Christov-Tzelkov, K., van Breemen, R. (2002). Tomato sauce supplementation and prostate cancer: lycopene ...Tomato Products, Lycopene , and Prostate Cancer Risk, Journal National Cancer Institute, 94, 391-398. Giovannucci, E., Rimm, E.B., Liu Y

  16. Oxidative Stress, DNA Repair and Prostate Cancer Risk

    DTIC Science & Technology

    2010-08-01

    progressed smoothly for all three specific aims. 15. SUBJECT TERMS microRNA ovarian cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION... factors for prostate cancer are associated with elevated levels of ROS (advancing age, inflammation, androgen, high-fat diet), or decreased...TITLE: Oxidative Stress, DNA Repair and Prostate Cancer Risk PRINCIPAL INVESTIGATOR: Hua Zhao, Ph.D

  17. Meharry-Johns Hopkins Center for Prostate Cancer Research

    DTIC Science & Technology

    2015-11-01

    questionnaire to assess their prostate cancer health seeking behavior. 15. SUBJECT TERMS Prostate cancer, Dietary risk factors, Lycopene, Genetic ...Institute (NCI) state cancer profiles, the mortality rate is almost three times that of CA men (73.9 per 100,000 AA / 25.6 per 100,000 C). Genetic and

  18. Human Microtumors Generated in 3D: Novel Tools for Integrated In Situ Studies of Cancer Immunotherapies.

    PubMed

    Hambach, Lothar; Buser, Andreas; Vermeij, Marcel; Pouw, Nadine; van der Kwast, Theo; Goulmy, Els

    2016-01-01

    Cellular immunotherapy targeting human tumor antigens is a promising strategy to treat solid tumors. Yet clinical results of cellular immunotherapy are disappointing. Moreover, the currently available in vitro human tumor models are not designed to study the optimization of T-cell therapies of solid tumors. Here, we describe a novel assay for multiparametric in situ analysis of therapeutic effects on individual human three-dimensional (3D) tumors. In this assay, tumors of several millimeter diameter are generated from human cancer cell lines of different tumor entities in a collagen type I microenvironment. A newly developed approach for efficient morphological analysis reveals that these in vitro tumors resemble many characteristics of the corresponding clinical cancers such as histological features, immunohistochemical staining patterns, distinct tumor growth compartments and heterogeneous protein expression. To assess the response to therapy with tumor antigen specific T-cells, standardized protocols are described to determine T-cell infiltration and tumor destruction by monitoring soluble factors and tumor growth. Human tumors engineered in 3D collagen scaffolds are excellent in vitro surrogates for avascular tumor stages allowing integrated analyses of the antitumor efficacy of cancer specific immunotherapy in situ.

  19. Current state of prostate cancer treatment in Jamaica.

    PubMed

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard

    2014-01-01

    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  20. Development of Assays for Detecting Significant Prostate Cancer Based on Molecular Alterations Associated with Cancer in Non-Neoplastic Prostate Tissue

    DTIC Science & Technology

    2012-10-01

    prostate cancer ." Am J Pathol 181(1): 34-42. Li, M. and L. A. Cannizzaro (1999). "Identical clonal origin of synchronous and metachronous low-grade...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue PRINCIPAL INVESTIGATOR...significant prostate cancer based on molecular alterations associated with cancer in non-neoplastic prostate tissue 5a. CONTRACT NUMBER 5b. GRANT