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Sample records for prostatic carcinoma dosimetry

  1. Prostate PDT dosimetry

    PubMed Central

    Zhu, Timothy C.; Finlay, Jarod C.

    2015-01-01

    Summary We provide a review of the current state of dosimetry in prostate photodynamic therapy (PDT). PDT of the human prostate has been performed with a number of different photosensitizers and with a variety of dosimetry schemes. The simplest clinical light dose prescription is to quantify the total light energy emitted per length (J/cm) of cylindrical diffusing fibers (CDF) for patients treated with a defined photosensitizer injection per body weight. However, this approach does not take into account the light scattering by tissue and usually underestimates the local light fluence rate, and consequently the fluence. Techniques have been developed to characterize tissue optical properties and light fluence rates in vivo using interstitial measurements during prostate PDT. Optical methods have been developed to characterize tissue absorption and scattering spectra, which in turn provide information about tissue oxygenation and drug concentration. Fluorescence techniques can be used to quantify drug concentrations and photobleaching rates of photosensitizers. PMID:25046988

  2. Virtual HDR CyberKnife treatment for localized prostatic carcinoma: dosimetry comparison with HDR brachytherapy and preliminary clinical observations.

    PubMed

    Fuller, Donald B; Naitoh, John; Lee, Charles; Hardy, Steven; Jin, Haoran

    2008-04-01

    We tested our ability to approximate the dose (38 Gy), fractionation (four fractions), and distribution of high-dose-rate (HDR) brachytherapy for prostate cancer with CyberKnife (CK) stereotactic body radiotherapy (SBRT) plans. We also report early clinical observations of CK SBRT treatment. Ten patients were treated with CK. For each CK SBRT plan, an HDR plan was designed using common contour sets and simulated HDR catheters. Planning target volume coverage, intraprostatic dose escalation, and urethra, rectum, and bladder exposure were compared. Planning target volume coverage by the prescription dose was similar for CK SBRT and HDR plans, whereas percent of volume of interest receiving 125% of prescribed radiation dose (V125) and V150 values were higher for HDR, reflecting higher doses near HDR source dwell positions. Urethra dose comparisons were lower for CK SBRT in 9 of 10 cases, suggesting that CK SBRT may more effectively limit urethra dose. Bladder maximum point doses were higher with HDR, but bladder dose falloff beyond the maximum dose region was more rapid with HDR. Maximum rectal wall doses were similar, but CK SBRT created sharper rectal dose falloff beyond the maximum dose region. Second CK SBRT plans, constructed by equating urethra radiation dose received by point of maximum exposure of volume of interest to the HDR plan, significantly increased V125 and V150. Clinically, 4-month post-CK SBRT median prostate-specific antigen levels decreased 86% from baseline. Acute toxicity was primarily urologic and returned to baseline by 2 months. Acute rectal morbidity was minimal and transient. It is possible to construct CK SBRT plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively.

  3. [Markers of prostatic carcinoma].

    PubMed

    Safarík, L

    1998-08-31

    Author gives the survey of markers at prostate carcinoma, that has been known so far, their origin and the use in experiment and clinical praxis. He discusses their sensitivity and specificity and shows the perspective of new markers discovered and used in the praxis on basis of molecular genetics.

  4. Carcinoma of the Prostate

    PubMed Central

    Orovan, W. L.; DeMaria, J. E.

    1985-01-01

    Prostatic carcinoma is the third most common cause of death from cancer among males. Selection of appropriate therapy and evaluation of results is often difficult, since patients present at different stages of the disease. Methods of staging, diagnosis, treatment of localized tumor, radiation, surgery and treatment of metastases are described. PMID:21274084

  5. Virtual HDR{sup SM} CyberKnife Treatment for Localized Prostatic Carcinoma: Dosimetry Comparison With HDR Brachytherapy and Preliminary Clinical Observations

    SciTech Connect

    Fuller, Donald B. Naitoh, John; Lee, Charles; Hardy, Steven C.; Jin, Haoran

    2008-04-01

    Background: We tested our ability to approximate the dose (38 Gy), fractionation (four fractions), and distribution of high-dose-rate (HDR) brachytherapy for prostate cancer with CyberKnife (CK) stereotactic body radiotherapy (SBRT) plans. We also report early clinical observations of CK SBRT treatment. Methods and Materials: Ten patients were treated with CK. For each CK SBRT plan, an HDR plan was designed using common contour sets and simulated HDR catheters. Planning target volume coverage, intraprostatic dose escalation, and urethra, rectum, and bladder exposure were compared. Results: Planning target volume coverage by the prescription dose was similar for CK SBRT and HDR plans, whereas percent of volume of interest receiving 125% of prescribed radiation dose (V125) and V150 values were higher for HDR, reflecting higher doses near HDR source dwell positions. Urethra dose comparisons were lower for CK SBRT in 9 of 10 cases, suggesting that CK SBRT may more effectively limit urethra dose. Bladder maximum point doses were higher with HDR, but bladder dose falloff beyond the maximum dose region was more rapid with HDR. Maximum rectal wall doses were similar, but CK SBRT created sharper rectal dose falloff beyond the maximum dose region. Second CK SBRT plans, constructed by equating urethra radiation dose received by point of maximum exposure of volume of interest to the HDR plan, significantly increased V125 and V150. Clinically, 4-month post-CK SBRT median prostate-specific antigen levels decreased 86% from baseline. Acute toxicity was primarily urologic and returned to baseline by 2 months. Acute rectal morbidity was minimal and transient. Conclusions: It is possible to construct CK SBRT plans that closely recapitulate HDR dosimetry and deliver the plans noninvasively.

  6. Ultrasound-only dosimetry for prostate brachytherapy: preliminary phantom results

    NASA Astrophysics Data System (ADS)

    Wen, Xu; Salcudean, S. E.; Lawrence, P. D.; Morris, J.

    2007-03-01

    Accurate and fast seed localization plays a key role in computing dosimetry for prostate brachytherapy. Because transrectal ultrasound is the primary imaging modality providing the guidance for prostate brachytherapy, an ultrasound-only approach for dosimetry would offer many benefits. In this paper, we propose an ultrasound only dosimetry solution, in which the brachytherapy seeds are located in reflected power images computed from ultrasonic radio frequency signals and the boundary of the prostate is delineated from B-mode TRUS and vibroelastography images as the prostate is stiffer than the surrounding tissue. The location of the implanted seeds relative to the prostate boundary is thus obtained. As only one imaging modality, ultrasound, is used, image registration is easy to implement. A prostate phantom with seeds embedded within it was built to evaluate the proposed approach. To measure the seed localization accuracy in the reflected power images, the phantom was scanned by CT as well. Experimental results show that the implanted seeds can be successfully located in the reflected power images with high contrast and accuracy, and that the contour of the "prostate" can be detected in the ultrasound vibro-elastography images outside the shadow of the seeds.

  7. Transrectal Ultrasound of Prostatic Carcinoma

    PubMed Central

    Murray, Daniel J.; Cooperberg, Peter L.; Goldenberg, S. Larry; Toi, Ants

    1991-01-01

    The purpose of this paper is to review the indications for transrectal ultrasound; to briefly describe the sonographic technique; to describe the sonographic findings of prostatic carcinoma; to review the indications for transrectal sonographic-guided biopsy; and to discuss the controversles of routine screening and staging. ImagesFigures 1-3 PMID:21229044

  8. Sarcomatoid Carcinoma of the Prostate

    PubMed Central

    Açıkgöz, Onur; Gazel, Eymen; Zengin, Neslihan İnci; Kasap, Yusuf; Çamtosun, Ahmet; Yazıcıoğlu, Ahmet Hamdi

    2013-01-01

    Sarcomatoid carcinoma of the prostate is among the rarest malignant neoplasm types and has been well known for its aggressive clinical course. Patient was admitted with the symptoms of lower urinary tract. Transurethral resection of prostate (TUR-P) was carried out. Revealing Gleason 5 + 3 = 8 prostate adenocarcinoma in TUR-P material. Thereby, a Radical Prostatectomy procedure was planned. In operation, frozen examination revealed adenocarcinoma metastasis to the obturator lymph node. The operation was terminated. In the postoperative 3rd month, the patient was re-admitted with acute urinary system symptoms. A cystoscopy performed and complete resection of the mass was performed. The pathological examination reported that the tumor was compatible with undifferentiated adenocarcinoma owing to presence of poorly differentiated tumoral cells and detection of adenocarcinoma in a relatively small (<1%) focus. 4 month after the operation, the patient underwent another cyctoscopic examination which revealed the prostatic lounge and most of the bladder lumen to be filled with tumoral tissue. The tumoral tissues was resected incompletely. This material was diagnosed to be “Sarcomatoid Malignant Tumor” upon the new evidences of progressive dedifferentiation and predominant sarcomatoid appearance, compared with the former TUR-P materials. Subsequent PET-CT scan depicted multiple metastasis. The patient was referred to oncology department. In conclusion, sarcomatoid carcinoma is a malignant variant that brings along diagnostic and treatment difficulties. PMID:23691427

  9. Sarcomatoid carcinoma of the prostate.

    PubMed

    Açıkgöz, Onur; Gazel, Eymen; Zengin, Neslihan İnci; Kasap, Yusuf; Camtosun, Ahmet; Yazıcıoğlu, Ahmet Hamdi

    2013-01-01

    Sarcomatoid carcinoma of the prostate is among the rarest malignant neoplasm types and has been well known for its aggressive clinical course. Patient was admitted with the symptoms of lower urinary tract. Transurethral resection of prostate (TUR-P) was carried out. Revealing Gleason 5 + 3 = 8 prostate adenocarcinoma in TUR-P material. Thereby, a Radical Prostatectomy procedure was planned. In operation, frozen examination revealed adenocarcinoma metastasis to the obturator lymph node. The operation was terminated. In the postoperative 3rd month, the patient was re-admitted with acute urinary system symptoms. A cystoscopy performed and complete resection of the mass was performed. The pathological examination reported that the tumor was compatible with undifferentiated adenocarcinoma owing to presence of poorly differentiated tumoral cells and detection of adenocarcinoma in a relatively small (<1%) focus. 4 month after the operation, the patient underwent another cyctoscopic examination which revealed the prostatic lounge and most of the bladder lumen to be filled with tumoral tissue. The tumoral tissues was resected incompletely. This material was diagnosed to be "Sarcomatoid Malignant Tumor" upon the new evidences of progressive dedifferentiation and predominant sarcomatoid appearance, compared with the former TUR-P materials. Subsequent PET-CT scan depicted multiple metastasis. The patient was referred to oncology department. In conclusion, sarcomatoid carcinoma is a malignant variant that brings along diagnostic and treatment difficulties.

  10. Intra-Operative Dosimetry in Prostate Brachytherapy

    DTIC Science & Technology

    2008-04-01

    4 A INTRODUCTION For several decades, the definitive treatment for low and medium risk prostate cancer was radical prostatectomy or external...with reduced morbidity. In contemporary practice, however, faulty needle and source placement often cause insufficient dose to the cancer and/or...seeds if the pose of a C-arm is known. The algorithm was validated using phantom and clinical patient data. Index Terms— Tomosynthesis, prostate cancer

  11. Prostatic carcinoma in two cats.

    PubMed

    Caney, S M; Holt, P E; Day, M J; Rudorf, H; Gruffydd-Jones, T J

    1998-03-01

    Clinical, radiological and pathological features of two cats with prostatic carcinoma are reported. In both cats the presenting history included signs of lower urinary tract disease with haematuria and dysuria. Prostatomegaly was visible radiographically in one cat; an irregular intraprostatic urethra was seen on retrograde contrast urethrography in both cats. In one of the cats, neoplasia was suspected on the basis of a transurethral catheter biopsy. Following a poor response to palliative treatment in both cases, euthanasia was performed with histological confirmation of the diagnosis.

  12. [Single prostatic metastasis of a small cell lung carcinoma].

    PubMed

    Gonzalez Yañez, Isabel; Perez Lopez, Maria Eva; Rodriguez Lopez, Jose Angel; Arias Santos, Maria Dolores; Garcia Gomez, Jesus; Garcia Mata, Jesus

    2009-03-01

    To make the difference between two uncommon entities, small cell prostate carcinoma and prostatic metastasis of small cell lung cancer. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. We describe a case of single extrapulmonar metastasis in the prostate from small lung carcinoma. Clinical and radiographic findings and inmunohistochemistry allow differential diagnosis.

  13. Basal cell carcinoma of the prostate: unusual subtype of prostatic carcinoma.

    PubMed

    Komura, Kazumasa; Inamoto, Teruo; Tsuji, Motomu; Ibuki, Naokazu; Koyama, Kohei; Ubai, Takanobu; Azuma, Haruhito; Katsuoka, Yoji

    2010-12-01

    Basal cell carcinoma of the prostate, which has been generally considered to be indolent, is an unusual histological type of prostatic carcinoma and is extremely rare. This tumor has been classified according to the prevalent pattern of growth as adenoid cystic carcinoma or basaloid cell carcinoma (BCC), with the former growth pattern being considered to be the main feature of this entity. A 67-year-old Japanese man was admitted to a general hospital with obstructive urinary symptoms. His prostate was slightly enlarged, stony hard, and with a rough surface on digital rectal examination, while serum prostate-specific antigen and prostatic acid phosphatase concentrations were within the normal ranges (0.007 and 0.9 ng/mL, respectively). 2-Fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) exhibited multiple accumulations suspicious for cancer metastases. Specimens obtained by prostatic needle biopsy showed immunohistochemical reactivity for cytokeratin 34βE12 and P63, findings that were identical to those seen in basal cell carcinoma. Basal cell carcinoma of the prostate is a rare tumor, reported in 56 cases so far, and among all these, the pure form of BCC is extremely rare. Immunohistochemistry is indispensable to distinguish this neoplasm from other unusual histological types of prostatic carcinomas. Our findings reveal that tumors with a basaloid cell-predominant pattern have significant potential for a poor prognosis, in contrast with the conventional understanding regarding this neoplasm.

  14. Prostatic edema in {sup 125}I permanent prostate implants: Dynamical dosimetry taking volume changes into account

    SciTech Connect

    Leclerc, Ghyslain; Lavallee, Marie-Claude; Roy, Rene; Vigneault, Eric; Beaulieu, Luc

    2006-03-15

    The purpose of this study is to determine the impact of edema on the dose delivered to the target volume. An evaluation of the edema characteristics was first made, and then a dynamical dosimetry algorithm was developed and used to compare its results to a standard clinical (static) dosimetry. Source positions and prostate contours extracted from 66 clinical cases on images taken at different points in time (planning, implant day, post-implant evaluation) were used, via the mean interseed distance, to characterize edema [initial increase ({delta}r{sub 0}), half-life ({tau})]. An algorithm was developed to take into account the edema by summing a time series of dose-volume histograms (DVHs) with a weight based on the fraction of the dose delivered during the time interval considered. The algorithm was then used to evaluate the impact of edema on the dosimetry of permanent implants by comparing its results to those of a standard clinical dosimetry. The volumetric study yielded results as follows: the initial prostate volume increase was found to be 1.58 (ranging from 1.15 to 2.48) and the edema half-life, approximately 30 days (range: 3 to 170 days). The dosimetric differences in D{sub 90} observed between the dynamic dosimetry and the clinical one for a single case were up to 15 Gy and depended on the edema half-life and the initial volume increase. The average edema half-life, 30 days, is about 3 times longer than the previously reported 9 days. Dosimetric differences up to 10% of the prescription dose are observed, which can lead to differences in the quality assertion of an implant. The study of individual patient edema resorption with time might be necessary to extract meaningful clinical correlation or biological parameters in permanent implants.

  15. Dosimetry Modeling for Focal Low-Dose-Rate Prostate Brachytherapy

    SciTech Connect

    Al-Qaisieh, Bashar; Mason, Josh; Bownes, Peter; Henry, Ann; Dickinson, Louise; Ahmed, Hashim U.; Emberton, Mark; Langley, Stephen

    2015-07-15

    Purpose: Focal brachytherapy targeted to an individual lesion(s) within the prostate may reduce side effects experienced with whole-gland brachytherapy. The outcomes of a consensus meeting on focal prostate brachytherapy were used to investigate optimal dosimetry of focal low-dose-rate (LDR) prostate brachytherapy targeted using multiparametric magnetic resonance imaging (mp-MRI) and transperineal template prostate mapping (TPM) biopsy, including the effects of random and systematic seed displacements and interseed attenuation (ISA). Methods and Materials: Nine patients were selected according to clinical characteristics and concordance of TPM and mp-MRI. Retrospectively, 3 treatment plans were analyzed for each case: whole-gland (WG), hemi-gland (hemi), and ultra-focal (UF) plans, with 145-Gy prescription dose and identical dose constraints for each plan. Plan robustness to seed displacement and ISA were assessed using Monte Carlo simulations. Results: WG plans used a mean 28 needles and 81 seeds, hemi plans used 17 needles and 56 seeds, and UF plans used 12 needles and 25 seeds. Mean D90 (minimum dose received by 90% of the target) and V100 (percentage of the target that receives 100% dose) values were 181.3 Gy and 99.8% for the prostate in WG plans, 195.7 Gy and 97.8% for the hemi-prostate in hemi plans, and 218.3 Gy and 99.8% for the focal target in UF plans. Mean urethra D10 was 205.9 Gy, 191.4 Gy, and 92.4 Gy in WG, hemi, and UF plans, respectively. Mean rectum D2 cm{sup 3} was 107.5 Gy, 77.0 Gy, and 42.7 Gy in WG, hemi, and UF plans, respectively. Focal plans were more sensitive to seed displacement errors: random shifts with a standard deviation of 4 mm reduced mean target D90 by 14.0%, 20.5%, and 32.0% for WG, hemi, and UF plans, respectively. ISA has a similar impact on dose-volume histogram parameters for all plan types. Conclusions: Treatment planning for focal LDR brachytherapy is feasible. Dose constraints are easily met with a notable

  16. Dosimetry modeling for focal high-dose-rate prostate brachytherapy.

    PubMed

    Mason, Josh; Al-Qaisieh, Bashar; Bownes, Peter; Thwaites, David; Henry, Ann

    2014-01-01

    The dosimetry of focal high-dose-rate prostate brachytherapy was assessed. Dose volume histogram parameters, robustness to source position errors, and Monte Carlo (MC) simulations were compared for whole-gland (WG), hemi-gland (HEMI), and ultra-focal (UF) treatment plans. Tumor volumes were delineated based on MRI and template biopsy results for 9 patients. WG, HEMI, and UF plans were produced assuming 19 Gy single fraction monotherapy treatments. For UF plans, a 6-mm margin was applied to the visible tumor to create a focal-planning target volume (F-PTV). Systematic source position shifts of 1-4 mm were applied to assess plan robustness. The dosimetric impact of steel catheters was assessed using MC simulation. Mean D90 and V100 were 20.4 Gy and 97.9% for prostate in WG plans, 22.2 Gy and 98.1% for hemi-prostate in HEMI plans, and 23.0 Gy and 98.2% for F-PTV in UF plans. Mean urethra D10 was 20.3, 19.7, and 9.2 Gy in WG, HEMI, and UF plans, respectively. Mean rectal D2cc was 12.5, 9.8, and 4.6 Gy in WG, HEMI, and UF plans, respectively. Focal treatment plans were sensitive to source position errors-2 mm systematic shifts reduced mean prostate D90 by 0.7%, hemi-prostate D90 by 2.6%, and F-PTV D90 by 8.3% in WG, HEMI, and UF plans, respectively. MC simulation results were similar for all plan types with most dose volume histogram parameters reduced by <2%. HEMI and UF treatments can achieve higher D90 values compared with WG treatments with reduced organ at risk dose. Focal treatments are more sensitive to systematic source position errors than WG treatments. Copyright © 2014 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  17. Prostate brachytherapy postimplant dosimetry: Automatic plan reconstruction of stranded implants

    SciTech Connect

    Chng, N.; Spadinger, I.; Morris, W. J.; Usmani, N.; Salcudean, S.

    2011-01-15

    Purpose: Plan reconstruction for permanent implant prostate brachytherapy is the process of determining the correspondence between planned and implanted seeds in postimplant analysis. Plan reconstruction informs many areas of brachytherapy quality assurance, including the verification of seed segmentation, misplacement and migration assessment, implant simulations, and the dosimetry of mixed-activity or mixed-species implants. Methods: An algorithm has been developed for stranded implants which uses the interseed spacing constraints imposed by the suture to improve the accuracy of reconstruction. Seventy randomly selected clinical cases with a mean of 23.6 (range 18-30) needles and mean density of 2.0 (range 1.6-2.6) 2.0 (range 1.6-2.6) seeds/cm{sup 3} were automatically reconstructed and the accuracy compared to manual reconstructions performed using a custom 3D graphical interface. Results: Using the automatic algorithm, the mean accuracy of the assignment relative to manual reconstruction was found to be 97.7{+-}0.5%. Fifty-two of the 70 cases (74%) were error-free; of seeds in the remaining cases, 96.7{+-}0.3% were found to be attributed to the correct strand and 97.0{+-}0.3% were correctly connected to their neighbors. Any necessary manual correction using the interface is usually straightforward. For the clinical data set tested, neither the number of seeds or needles, average density, nor the presence of clusters was found to have an effect on reconstruction accuracy using this method. Conclusions: Routine plan reconstruction of stranded implants can be performed with a high degree of accuracy to support postimplant dosimetry and quality analyses.

  18. Secondary Signet Ring Cell Carcinoma of Prostate

    PubMed Central

    Khan, Kalyan; Bandyopadhyay, Arghya; Gangopadhyay, Mimi; Chakraborty, Subrata; Bera, Pranati

    2012-01-01

    True metastases to prostate from solid tumors are reported only in 0.2% of all surgical prostatic specimens and 2.9% of all male postmortems. Clinical context, morphological features, and immunohistochemical localization of prostate specific antigen (PSA) are supposed to clarify the differential diagnosis between a secondary and a primary tumor. We report an unusual and rare case of secondary signet ring cell carcinoma (SRCC) of prostate in which the clinical data and signet ring cell morphology pointed toward the diagnosis of a primary SRCC. Immunohistochemistry (IHC) for PSA not only proved the case to be a secondary SRCC but also initiated the process for diagnosis of the occult primary malignancy in the patient′s stomach. PMID:24027389

  19. Men of African Descent and Carcinoma of the Prostate Consortium

    Cancer.gov

    The Men of African Descent and Carcinoma of the Prostate Consortium collaborates on epidemiologic studies to address the high burden of prostate cancer and to understand the causes of etiology and outcomes among men of African ancestry.

  20. [Familial prostate carcinoma in Germany].

    PubMed

    Paiss, T; Herkommer, K; Chab, A; Häussler, J; Vogel, W; Gschwend, J E; Hautmann, R E

    2002-01-01

    Epidemiologic studies have shown that hereditary forms account for approximately 10% of all prostate cancers. The identification of several susceptibility loci harboring predisposing genes indicates the genetic heterogeneity of prostate cancer. The conflicting results of different linkage analyses may be explained by a varying contribution of each locus within different family collections and reflect differences of allele frequencies across different populations. In the present study we recorded the incidence of familial prostate cancer in Germany and performed descriptive analysis of the epidemiological data. In spite of a significant ascertainment bias, only 19% of all prostate cancers were familial. In 94% of families there were three affected relatives at most. Large prostate cancer families with at least five affected persons were rare (2%). Descriptive analysis revealed that only 42% of all pedigrees followed an autosomal-dominant pattern of transmission; the other pedigrees showed an X-chromosomal or recessive mode of inheritance. These data confirm the genetic heterogeneity of hereditary prostate cancer and imply that previously published epidemiological data cannot be transferred to the German population.

  1. The effect of obesity on rectal dosimetry after permanent prostate brachytherapy.

    PubMed

    Patil, Nikhilesh; Crook, Juanita; Saibishkumar, Elantholi P; Aneja, Manipdip; Borg, Jette; Pond, Greg; Ma, Clement

    2009-01-01

    Men with higher body mass index (BMI) tend to have more fatty tissue in prostate-rectum interface, which may reduce the rectal wall dose by the inverse square law. We hypothesized that men with higher BMI will have a lower dose to the rectal wall and less rectal toxicity after permanent prostate implant. Prospectively collected data on rectal dosimetry/toxicity and BMI of 407 patients who underwent iodine-125 ((125)I) prostate implant were analyzed. Postimplant dosimetry used CT-MRI fusion on Day 30. Rectal wall was contoured on all slices where seeds were seen. The volume of rectal wall receiving the prescribed dose (RV(100) in cm(3)) and the dose to 1cc of rectal wall (RD(1cc)) were reported. Other factors evaluated for association with rectal dosimetry and toxicity included age, diabetes, hypertension, smoking, use of neoadjuvant hormones, T stage, baseline prostate volume, 1 month prostate edema, seed type and activity, and prostate dosimetry factors (the isodose enclosing 90% of the prostate volume [D(90)], the percentage of the prostate volume enclosed by the prescription [V(100)], and the percentage of the prostate volume enclosed by the 150% isodose [V(150)]). Rectal toxicity was reported as per Radiation Therapy Oncology Group criteria. BMIs ranged from 15.9 to 46.8 (mean+/-standard deviation [SD]: 27.8+/-4.2). The mean+/-SD values for RV(100) and RD(1cc) were 0.79+/-0.49cm(3) and 128.2+/-27.8Gy, respectively. There was a significant negative association of BMI with RV(100) (p=0.007) and RD(1cc) (p=0.01) on univariate analysis. The mean RV(100) and RD(1cc) for men with higher BMI (>27.8) were lower compared with their slimmer counterparts (0.70 vs. 0.86cm(3) and 123.4 vs. 132.4Gy, respectively). On multivariate analysis for RV(100) and RD(1cc), BMI remained significant (p-values 0.004 and 0.01, respectively) along with prostate volume and V(150), suggesting that anatomic factors are important in rectal dosimetry in prostate brachytherapy. Overall the

  2. Comparison of CT and MR-CT Fusion for Prostate Post-Implant Dosimetry

    SciTech Connect

    Maletz, Kristina L.; Ennis, Ronald D.; Ostenson, Jason; Pevsner, Alexander; Kagen, Alexander; Wernick, Iddo

    2012-04-01

    Purpose: The use of T2 MR for postimplant dosimetry (PID) after prostate brachytherapy allows more anatomically accurate and precise contouring but does not readily permit seed identification. We developed a reproducible technique for performing MR-CT fusion and compared the resulting dosimetry to standard CT-based PID. Methods and Materials: CT and T1-weighted MR images for 45 patients were fused and aligned based on seed distribution. The T2-weighted MR image was then fused to the aligned T1. Reproducibility of the fusion technique was tested by inter- and intraobserver variability for 13 patients. Dosimetry was computed for the prostate as a whole and for the prostate divided into anterior and posterior sectors of the base, mid-prostate, and apex. Results: Inter- and intraobserver variability for the fusion technique showed less than 1% variation in D90. MR-CT fusion D90 and CT D90 were nearly equivalent for the whole prostate, but differed depending on the identification of superior extent of the base (p = 0.007) and on MR/CT prostate volume ratio (p = 0.03). Sector analysis showed a decrease in MR-CT fusion D90 in the anterior base (ratio 0.93 {+-}0.25, p < 0.05) and an increase in MR-CT fusion D90 in the apex (p < 0.05). The volume of extraprostatic tissue encompassed by the V100 is greater on MR than CT. Factors associated with this difference are the MR/CT volume ratio (p < 0.001) and the difference in identification of the inferior extent of the apex (p = 0.03). Conclusions: We developed a reproducible MR-CT fusion technique that allows MR-based dosimetry. Comparing the resulting postimplant dosimetry with standard CT dosimetry shows several differences, including adequacy of coverage of the base and conformity of the dosimetry around the apex. Given the advantage of MR-based tissue definition, further study of MR-based dosimetry is warranted.

  3. Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model

    NASA Astrophysics Data System (ADS)

    Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

    2016-02-01

    Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

  4. Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.

    PubMed

    Swartling, Johannes; Höglund, Odd V; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

    2016-02-01

    Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30  J/cm2.

  5. Segmental Urethral Dosimetry and Urinary Toxicity in Patients With No Urinary Symptoms Before Permanent Prostate Brachytherapy

    SciTech Connect

    Thomas, Carys; Keyes, Mira Liu, Mitchell; Moravan, Veronika

    2008-10-01

    Purpose: To determine whether segmental urethral dosimetry is predictive for the degree of urinary morbidity after prostate brachytherapy in patients with no urinary symptoms before prostate brachytherapy. Methods and Materials: Between May 2000 and November 2005, 1,107 patients underwent iodine-125 monotherapy with urethral sparing techniques. A total of 166 patients fulfilled the selection criteria: baseline (International Prostate Symptom Score) IPSS {<=}5, no androgen deprivation therapy, and prostate ultrasound planning volumes (PUTV) <45 mL. The median follow-up was 44 months. Urinary morbidity was defined by maximum increase in IPSS, time to IPSS resolution, maximum Radiation Therapy Oncology Group (RTOG) score, time to RTOG resolution, and urinary retention. Surrogate deviated urethra was contoured and doses calculated at the base, mid-prostate, apex, and urogenital diaphragm. Univariate and multivariate analysis was used to evaluate urethral and prostate dosimetry, age, PUTV, and number of needles for their association with urinary morbidity. Results: Urethral dose was fairly constant in all urethra segments except prostate base, where the variation in does was large. On multivariate analysis, higher urethral base D50, V100, and larger PUTV were predictive for higher maximum increase in IPSS. Higher urethral base V100 and larger PUTV predicted for prolonged IPSS resolution. Higher urethral base D50 and larger needle number predicted for longer RTOG resolution. Higher urethral base V100 predicted for RTOG {>=}2 toxicity. Conclusions: Radiation dose to the urethral base, larger PUTV, and needle number, predicted for increased urinary toxicity after prostate brachytherapy. Correlation between urinary morbidity and urethral base dosimetry may reflect a large variation in urethral dose observed at the prostate base.

  6. Hyaluronan Biosynthesis in Prostate Carcinoma

    DTIC Science & Technology

    2007-01-01

    the diagnosis and treatment of prostate cancer in the last several years, metastasis represents the major cause of frustration and failure in the...Malignant progression ultimately culminates in various degrees of visceral invasion and metastasis to lymph nodes and bone. Metastasis to bone is...when tumors become androgen-independent and resume growth. By defining factors that contribute to the growth and metastasis of androgen-independent

  7. Cyclin D1 expression in prostate carcinoma.

    PubMed

    Pereira, R A; Ravinal, R C; Costa, R S; Lima, M S; Tucci, S; Muglia, V F; Reis, R B dos; Silva, G E B

    2014-06-01

    The purpose of this study was to investigate the relationship between cyclin D1 expression and clinicopathological parameters in patients with prostate carcinoma. We assessed cyclin D1 expression by conventional immunohistochemistry in 85 patients who underwent radical prostatectomy for prostate carcinoma and 10 normal prostate tissue samples retrieved from autopsies. We measured nuclear immunostaining in the entire tumor area and based the results on the percentage of positive tumor cells. The preoperative prostate-specific antigen (PSA) level was 8.68±5.16 ng/mL (mean±SD). Cyclin D1 staining was positive (cyclin D1 expression in >5% of tumor cells) in 64 cases (75.4%) and negative (cyclin D1 expression in ≤5% of tumor cells) in 21 cases (including 15 cases with no immunostaining). Normal prostate tissues were negative for cyclin D1. Among patients with a high-grade Gleason score (≥7), 86% of patients demonstrated cyclin D1 immunostaining of >5% (P<0.05). In the crude analysis of cyclin D1 expression, the high-grade Gleason score group showed a mean expression of 39.6%, compared to 26.9% in the low-grade Gleason score group (P<0.05). Perineural invasion tended to be associated with cyclin D1 expression (P=0.07), whereas cyclin D1 expression was not associated with PSA levels or other parameters. Our results suggest that high cyclin D1 expression could be a potential marker for tumor aggressiveness.

  8. Results from a multicenter prostate IMRT dosimetry intercomparison for an OCOG-TROG clinical trial

    SciTech Connect

    Healy, B.; Frantzis, J.; Murry, R.; Martin, J.; Plank, A.; Middleton, M.; Catton, C.; Kron, T.

    2013-07-15

    Purpose: A multi-institution dosimetry intercomparison has been undertaken of prostate intensity modulated radiation therapy (IMRT) delivery. The dosimetry intercomparison was incorporated into the quality assurance for site credentialing for the Trans-Tasman Radiation Oncology Group Prostate Fractionated Irradiation Trial 08.01 clinical trial.Methods: An anthropomorphic pelvic phantom with realistic anatomy was used along with multiplanar dosimetry tools for the assessment. Nineteen centers across Australia and New Zealand participated in the study.Results: In comparing planned versus measured dose to the target at the isocenter within the phantom, all centers were able to achieve a total delivered dose within 3% of planned dose. In multiplanar analysis with radiochromic film using the gamma analysis method to compare delivered and planned dose, pass rates for a 5%/3 mm criterion were better than 90% for a coronal slice through the isocenter. Pass rates for an off-axis coronal slice were also better than 90% except for one instance with 84% pass rate.Conclusions: Strengths of the dosimetry assessment procedure included the true anthropomorphic nature of the phantom used, the involvement of an expert from the reference center in carrying out the assessment at every site, and the ability of the assessment to detect and resolve dosimetry discrepancies.

  9. CT-ultrasound fusion prostate brachytherapy: a dynamic dosimetry feedback and improvement method. A report of 54 consecutive cases.

    PubMed

    Fuller, Donald B; Jin, Haoran; Koziol, James A; Feng, Anne C

    2005-01-01

    The authors describe a prostate brachytherapy technique with dynamic dosimetry feedback, using coregistered CT and ultrasound (US) images, to map initial dosimetry deficiencies and guide remedial source placement. Fifty-four consecutive patients treated with this method were analyzed for coregistration accuracy and dosimetry outcomes by evaluating the prostate V100, V150, D90, and urethral D50 and D10. Dosimetric improvements created by remedial source placement and preplan/postplan prostate D90 agreement were evaluated. Median CT-US coregistration discrepancy with this technique ranged from 0 to 4mm, with the posterior midline prostate and base prostate providing the least consistent and the urethra providing the most consistent coregistration agreement. Final prostate V100 values ranged from 96.1% to 99.8% for all patients. The addition of remedial sources directed by CT-US fusion produced V100 and D90 improvements whose magnitude inversely correlated with the initial result and exceeded the effect of adding quantitatively identical randomly distributed increased millicuries. The final prostate D90 result agreed within (-) 5% to (+) 10% of the preplan result in 98% of all patients. CT-US fusion prostate brachytherapy represents a dynamic dosimetry feedback and remediation method that consistently produced high prostate V100 and D90 values with acceptably low urethra D50 and D10 values in our study. The degree of prostate V100 and D90 dosimetry improvement created by remedial source placement effectively matched the degree of initial dosimetry deficiency. This method produced a high level of correlation between the preplan and final prostate D90 values.

  10. Molecular Profiling of Intraductal Carcinoma of the Prostate

    DTIC Science & Technology

    2014-10-01

    diagnosed in needle biopsies because it has significant morphologic overlap with another intraepithelial lesion, high grade prostatic intraepithelial...protein as biomarkers of IDC-P in prostate needle biopsy specimens. 15. SUBJECT TERMS Prostate cancer, intraductal carcinoma, molecular profiling... needle biopsies results in the under-recognition of potentially aggressive prostate tumors. We have found that IDC-P and HGPIN may be readily

  11. System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer

    NASA Astrophysics Data System (ADS)

    Swartling, Johannes; Axelsson, Johan; Ahlgren, Göran; Kälkner, Karl Mikael; Nilsson, Sten; Svanberg, Sune; Svanberg, Katarina; Andersson-Engels, Stefan

    2010-09-01

    The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J/cm2.

  12. Correlation Between Pre- and Postimplant Dosimetry for Iodine-125 Seed Implants for Localized Prostate Cancer

    SciTech Connect

    Al-Qaisieh, Bashar; Witteveen, Thelma Carey, Brendan; Henry, Ann; Bottomley, David; Smith, Jonathan; Franks, Kevin; Bownes, Peter

    2009-10-01

    Purpose: In order to evaluate implant quality for permanent prostate brachytherapy in patients with localized prostate cancer, American Brachytherapy Society and ESTRO guidelines recommend that postimplant dosimetry should be performed. To understand more about the relationship between pre- and postimplant dosimetry, a comparison was made of patients who received iodine-125 ({sup 125}I) brachytherapy between March 1995 and the end of 2004, using a preplan technique. Methods and Materials: CT postimplant dosimetry was available for 707 patients. Detailed dose volume analysis was performed using both preimplant ultrasound and postimplant CT data sets for a subgroup of 445 patients. The following parameters were compared: prostate volume covered by 100% of the prescription dose (Vp100), Vp150, and Vp200 and dose to 90% (D90) of the prostate. In addition, volume implanted (Vi) parameters were used to compare pre- and postimplant dosimetry. Vi parameters describe dose levels inside the patient, based on number of seeds, seed activity, and their spatial distribution relative to each other, without reference to the actual prostate volume or position. Results: The mean {+-} standard deviation values of preimplant (34.7 {+-} 8.9 cm{sup 3}) and postimplant (36.7 {+-} 9.4 cm{sup 3}) prostate volumes were similar. The mean ({+-}standard deviation) planned D90 was 183.4 ({+-}12.1) Gy while the D90 that was achieved was 145.5 ({+-}20.4) Gy. Over the study period, there was a steady increase of the average D90. Postimplant CT D90 and Vp100 values correlated significantly (R = 0.84; p < 0.001). The Vi and Vp parameters all showed a strong correlation. Conclusions: In this study, we showed that there is a strong correlation between transrectal ultrasound-based preimplant and CT-based postimplant dosimetry. The excellent correlation between prostate D90 and V100 values demonstrates they are both equally valid quality indices. Vi parameters are an additional measure that can be used

  13. Systematic 5 region prostate biopsy is superior to sextant method for diagnosing carcinoma of the prostate.

    PubMed

    Eskew, L A; Bare, R L; McCullough, D L

    1997-01-01

    The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique. A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions. Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p < 0.05). Of these additional cancers 83% had Gleason scores of 6 or more. We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml.

  14. Photodynamic therapy in prostate cancer: optical dosimetry and response of normal tissue

    NASA Astrophysics Data System (ADS)

    Chen, Qun; Shetty, Sugandh D.; Heads, Larry; Bolin, Frank; Wilson, Brian C.; Patterson, Michael S.; Sirls, Larry T., II; Schultz, Daniel; Cerny, Joseph C.; Hetzel, Fred W.

    1993-06-01

    The present study explores the possibility of utilizing photodynamic therapy (PDT) in treating localized prostate carcinoma. Optical properties of ex vivo human prostatectomy specimens, and in vivo and ex vivo dog prostate glands were studied. The size of the PDT induced lesion in dog prostate was pathologically evaluated as a biological endpoint. The data indicate that the human normal and carcinoma prostate tissues have similar optical properties. The average effective attenuation depth is less in vivo than that of ex vivo. The PDT treatment generated a lesion size of up to 16 mm in diameter. The data suggest that PDT is a promising modality in prostate cancer treatment. Multiple fiber system may be required for clinical treatment.

  15. Coagulopathy, following medical therapy, for carcinoma of the prostate.

    PubMed

    Bern, Murray M

    2005-02-01

    Cancer of the prostate can be associated with coagulopathy characterized as primary fibrinolysis or diffuse intravascular coagulopathy (DIC) with secondary fibrinolysis. These complications are usually associated with surgical manipulation of the prostate or with advanced metastatic disease. This report describes a patient with DIC and fibrinolysis following medical management of advanced prostate cancer with gonadotropin-releasing hormone leuprolide, while receiving the androgen receptor blocking agent flutamide. This report suggests that release of procoagulant material from prostatic carcinoma may be so rapid following hormonal management that consumptive coagulopathy with fibrinolysis can follow. Shortened Abstract: Medical management with gonadotropin releasing hormone allowed the expression of consumptive coagulopathy in patients with metastatic prostate cancer.

  16. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma.

    PubMed

    Zardawi, Ibrahim; Chong, Peter

    2016-07-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  17. [Small cell prostatic carcinoma detected at the stage of metastases].

    PubMed

    Rabii, Redouane; Meziane, Anas; Taha, Abdelatif; Joual, Abdenabi; El Mrini, Mohamed

    2004-09-01

    Small cell prostatic carcinoma is rare, with a poor prognosis. The authors report a case of small cell prostatic carcinoma in a 30-year-old patient diagnosed at the stage of metastases. Immunohistochemistry showed positive anti-neuron-specific enolase (NSE.) and anti-synaptophysin antibodies, while serum PSA was normal (1.2 ng/ml). The patient was treated by cisplatin-etoposide combination chemotherapy, but died 20 days after the first course.

  18. Measurement uncertainty analysis of low-dose-rate prostate seed brachytherapy: post-implant dosimetry.

    PubMed

    Gregory, Kent J; Pattison, John E; Bibbo, Giovanni

    2015-03-01

    The minimal dose covering 90 % of the prostate volume--D 90--is arguably the most important dosimetric parameter in low-dose-rate prostate seed brachytherapy. In this study an analysis of the measurement uncertainties in D 90 from low-dose-rate prostate seed brachytherapy was conducted for two common treatment procedures with two different post-implant dosimetry methods. The analysis was undertaken in order to determine the magnitude of D 90 uncertainty, how the magnitude of the uncertainty varied when D 90 was calculated using different dosimetry methods, and which factors were the major contributors to the uncertainty. The analysis considered the prostate as being homogeneous and tissue equivalent and made use of published data, as well as original data collected specifically for this analysis, and was performed according to the Guide to the expression of uncertainty in measurement (GUM). It was found that when prostate imaging and seed implantation were conducted in two separate sessions using only CT images for post-implant analysis, the expanded uncertainty in D 90 values were about 25 % at the 95 % confidence interval. When prostate imaging and seed implantation were conducted during a single session using CT and ultrasound images for post-implant analysis, the expanded uncertainty in D 90 values were about 33 %. Methods for reducing these uncertainty levels are discussed. It was found that variations in contouring the target tissue made the largest contribution to D 90 uncertainty, while the uncertainty in seed source strength made only a small contribution. It is important that clinicians appreciate the overall magnitude of D 90 uncertainty and understand the factors that affect it so that clinical decisions are soundly based, and resources are appropriately allocated.

  19. Effect of Edema on Postimplant Dosimetry in Prostate Brachytherapy Using CT/MRI Fusion

    SciTech Connect

    Tanaka, Osamu Hayashi, Shinya; Matsuo, Masayuki; Nakano, Masahiro; Uno, Hiromi; Ohtakara, Kazuhiro; Miyoshi, Toshiharu; Deguchi, Takashi; Hoshi, Hiroaki

    2007-10-01

    Purpose: To investigate the time course of prostatic edema and the effect on the dose-volume histograms of the prostate for patients treated with brachytherapy. Methods and Materials: A total of 74 patients with prostate cancer were enrolled in this prospective study. A transrectal ultrasound-based preplan was performed 4 weeks before implantation and computed tomography/magnetic resonance imaging fusion-based postimplant dosimetry was performed on the day after implantation (Day 1) and 30 days after implantation (Day 30). The prostate volume, prostate volume covered by 100% of the prescription dose (V{sub 100}), and dose covering 90% of the prostate (D{sub 90}) were evaluated with prostatic edema over time. Results: Prostatic edema was greatest on Day 1, with the mean prostate volume 36% greater than the preplan transrectal ultrasound-based volume; it thereafter decreased over time. It was 9% greater than preplan volume on Day 30. The V{sub 100} increased 5.7% from Day 1 to Day 30, and the D{sub 90} increased 13.1% from Day 1 to Day 30. The edema ratio (postplan/preplan) on Day 1 of low-quality implants with a V{sub 100} of <80% was significantly greater than that of intermediate- to high-quality implants (>80% V{sub 100}; p = 0.0272). The lower V{sub 100} on Day 1 showed a greater increase from Day 1 to Day 30. A V{sub 100} on Day 1 of >92% is unlikely to increase >0% during the interval studied. Conclusion: Low-quality implants on Day 1 were highly associated with edema; however, such a low-quality implant on Day 1, with significant edema, tended to improve by Day 30. If a high-quality implant (V100 >92%) can be obtained on Day 1, a re-examination is no longer necessary.

  20. Resin versus Glass Microspheres for Yttrium-90 Transarterial Radioembolization: Comparing Survival in Unresectable Hepatocellular Carcinoma using Pretreatment Partition Model Dosimetry.

    PubMed

    VAN DER Gucht, Axel; Jreige, Mario; Denys, Alban; Blanc-Durand, Paul; Boubaker, Ariane; Pomoni, Anastasia; Mitsakis, Periklis; Silva-Monteiro, Marina; Gnesin, Silvano; Nicod-Lalonde, Marie; Duran, Rafael; Prior, John; Schaefer, Niklaus

    2017-01-12

    The aim of this study was to compare survival of patients treated for unresectable hepatocellular carcinoma (uHCC) with Yttrium-90 ((90)Y) transarterial radioembolization (TARE) using pretreatment partition model dosimetry (PMD).

  1. Improved dosimetry in prostate brachytherapy using high resolution contrast enhanced magnetic resonance imaging: a feasibility study

    PubMed Central

    Morancy, Tye; Kaplan, Irving; Qureshi, Muhammad M.; Hirsch, Ariel E.; Rofksy, Neil M.; Holupka, Edward; Oismueller, Renee; Hawliczek, Robert; Helbich, Thomas H.; Bloch, B. Nicolas

    2014-01-01

    Purpose To assess detailed dosimetry data for prostate and clinical relevant intra- and peri-prostatic structures including neurovascular bundles (NVB), urethra, and penile bulb (PB) from postbrachytherapy computed tomography (CT) versus high resolution contrast enhanced magnetic resonance imaging (HR-CEMRI). Material and methods Eleven postbrachytherapy prostate cancer patients underwent HR-CEMRI and CT imaging. Computed tomography and HR-CEMRI images were randomized and 2 independent expert readers created contours of prostate, intra- and peri-prostatic structures on each CT and HR-CEMRI scan for all 11 patients. Dosimetry data including V100, D90, and D100 was calculated from these contours. Results Mean V100 values from CT and HR-CEMRI contours were as follows: prostate (98.5% and 96.2%, p = 0.003), urethra (81.0% and 88.7%, p = 0.027), anterior rectal wall (ARW) (8.9% and 2.8%, p < 0.001), left NVB (77.9% and 51.5%, p = 0.002), right NVB (69.2% and 43.1%, p = 0.001), and PB (0.09% and 11.4%, p = 0.005). Mean D90 (Gy) derived from CT and HR-CEMRI contours were: prostate (167.6 and 150.3, p = 0.012), urethra (81.6 and 109.4, p = 0.041), ARW (2.5 and 0.11, p = 0.003), left NVB (98.2 and 58.6, p = 0.001), right NVB (87.5 and 55.5, p = 0.001), and PB (11.2 and 12.4, p = 0.554). Conclusions Findings of this study suggest that HR-CEMRI facilitates accurate and meaningful dosimetric assessment of prostate and clinically relevant structures, which is not possible with CT. Significant differences were seen between CT and HR-CEMRI, with volume overestimation of CT derived contours compared to HR-CEMRI. PMID:25834576

  2. Monte Carlo modelling of angular radiance in tissue phantoms and human prostate: PDT light dosimetry.

    PubMed

    Barajas, O; Ballangrud, A M; Miller, G G; Moore, R B; Tulip, J

    1997-09-01

    Photodynamic therapy (PDT) is a promising technique for destroying tumours. Photosensitizing drugs presently available are not sufficiently tumour specific; hence, light dosimetry is required in order to control light exposure and thereby restrict cell kill to the target tissue to avoid damage to healthy tissue. Current light dosimetry methods rely on tissue optical characterization by fluence measurements at several points. Fluence-based tissue characterization is impractical for tumours in organs such as prostate where access by optical probes is limited and the tumours are highly optically inhomogeneous. This paper explores the potential of radiance-based light dosimetry as an alternative. Correlation is found between Monte Carlo simulation of radiance in a tissue phantom and radiance measurements made using a new radiance probe. Radiance is sensitive to variations in the tissue optical parameters, absorption coefficient mu(a), scattering coefficient mu(s), and anisotropy factor g, and therefore is potentially useful for tissue characterization. Radiance measurements have several advantages over fluence measurements. Radiance measurements provide more information from a single location, better spatial resolution of the tissue optical parameters, and higher sensitivity in discriminating between different media. However, the Monte Carlo method is too slow to be of practical value for tissue characterization by correlation of measured and simulated radiance. An analytical solution to the transport equation for radiance would be desirable as this would facilitate and increase the speed of tissue characterization.

  3. Early Quality of Life in Patients with Localized Prostate Carcinoma

    PubMed Central

    Eton, David T.; Lepore, Stephen J.; Helgeson, Vicki S.

    2008-01-01

    BACKGROUND Men with localized prostate carcinoma are faced with important treatment decisions, and quality of life (QoL) information has become a crucial element of decision making. The first objective of this study was to compare the early, health-related QoL (HRQoL) of men with localized prostate carcinoma who were treated with radical prostatectomy, external beam radiotherapy, or brachytherapy. A second objective was to identify demographic and psychosocial variables that predict HRQoL. METHODS Two-hundred fifty-six men with localized prostate carcinoma were interviewed within 7 weeks of treatment initiation. The interview included measures of prostate-specific HRQoL (the University of California—Los Angeles Prostate Cancer Index), general HRQoL (the SF-36), and psychosocial variables. RESULTS After adjusting for covariates, treatment group differences were found for both prostate specific HRQoL and general HRQoL. Men who underwent prostatectomy reported more urinary and sexual problems and more general physical dysfunction compared with men who were treated with either form of radiation therapy. Men who were treated with brachytherapy reported the fewest problems in sexual function and the least general physical dysfunction. Few treatment group differences were found in mental functioning. Both demographic factors and psychosocial factors predicted HRQoL. Older men and African-American men reported more physical problems than younger men and Caucasian men, respectively. A supportive social environment, high self-efficacy, and high self-esteem were predictive of better HRQoL. CONCLUSIONS Shortly after undergoing treatment for localized prostate carcinoma, men who underwent radical prostatectomy, older men, and African-American men are at heightened risk for experiencing prostate-specific and general deficits in HRQoL. Having psychosocial resources from which to draw may enhance HRQoL. PMID:11745222

  4. Small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive prostatic carcinoma: a study of 7 cases.

    PubMed

    Lee, Stephen; Han, Jeong S; Chang, Alex; Ross, Hillary M; Montironi, Rodolfo; Yorukoglu, Kutsal; Lane, Zhaoli; Epstein, Jonathan I

    2013-03-01

    Small cell carcinoma of the prostate is associated with poor prognosis and different treatment from conventional acinar adenocarcinoma. Given the important clinicopathologic implications of a diagnosis of small cell carcinoma, we report 7 cases showing unusual, extensive small cell-like change in intraductal carcinoma and invasive carcinoma. Prostatic biopsies from 3 patients and radical prostatectomy specimens from 4 patients showed variably extensive small cell-like high-grade prostatic intraepithelial neoplasia and intraductal carcinoma. Five cases were associated with conventional acinar adenocarcinoma (2 cases with Gleason score 4 + 3 = 7; 3 cases with Gleason 3 + 4 = 7). No small cell carcinoma was seen. Small and large ducts with small cell-like change showed solid and cribriform proliferations of atypical cells with abrupt transition between centrally located populations of small cells and more typical large dysplastic cells at the duct periphery. Rosette-like formations were noted within some involved ducts. Small cell-like change was characterized by crowded cells with uniformly bland vesicular nuclei and minimal cytoplasm and no significant mitotic or apoptotic activity. In 3 cases, similar small cell-like morphology was noted focally in invasive carcinoma. The small cell-like areas were negative for synaptophysin and chromogranin, focally positive for TTF-1, and weakly positive for racemase. Ki-67 labeled less than 5% with predominant labeling of the larger atypical cells and minimal reactivity in the small cell-like population. In summary, small cell-like change in prostatic intraepithelial neoplasia, intraductal carcinoma, and invasive carcinoma is not associated with small cell carcinoma; shows no immunohistochemical evidence of neuroendocrine differentiation; and likely is not an adverse prognostic feature.

  5. Primary Signet Ring Cell Carcinoma of the Prostate

    PubMed Central

    Warner, Jonathan N.; Nakamura, Leah Y.; Pacelli, Anna; Humphreys, Mitchell R.; Castle, Erik P.

    2010-01-01

    Nine patients treated with primary signet ring cell carcinoma of the prostate were identified among 29,783 cases of prostate cancer evaluated at Mayo Clinic from January 15, 1970, until January 2, 2009. A PubMed search of the English-language literature published from January 1, 1980, to January 1, 2010, was then performed using the key words signet ring cell and prostate, identifying 42 cases. This study reviews those cases, along with the additional 9 reported herein, and evaluates clinical characteristics, histologic diagnoses, treatment modalities, and outcomes. Mean age at diagnosis was 68 years (range, 50-85 years), and mean prostate-specific antigen level was 95.3 ng/mL (range, 1.9-536.0 ng/mL; to convert to μg/L, multiply by 1). Most patients (66%) had non–stage IV carcinoma, the most common Gleason sum was 8 (33%), and mean survival was 29 months. The presence of a primary signet ring cell carcinoma of the prostate was best confirmed by negative findings on gastrointestinal work-up, a positive stain for prostate-specific acid phosphatase, and negative carcinoembryonic antigen test results. PMID:21123640

  6. Mining featured biomarkers associated with prostatic carcinoma based on bioinformatics.

    PubMed

    Piao, Guanying; Wu, Jiarui

    2013-11-01

    To analyze the differentially expressed genes and identify featured biomarkers from prostatic carcinoma. The software "Significance Analysis of Microarray" (SAM) was used to identify the differentially coexpressed genes (DCGs). The DCGs existed in two datasets were analyzed by GO (Gene Ontology) functional annotation. A total of 389 DCGs were obtained. By GO analysis, we found these DCGs were closely related with the acinus development, TGF-β receptor and signal transduction pathways. Furthermore, five featured biomarkers were discovered by interaction analysis. These important signal pathways and oncogenes may provide potential therapeutic targets for prostatic carcinoma.

  7. Pulmonary tumor thrombotic microangiopathy caused by prostate carcinoma

    PubMed Central

    Kuriyama, Keiko; Kinoshita, Tatsuya; Nagai, Keisuke; Hongyo, Hidenari; Kishimoto, Kentaro; Inoue, Atsuo; Takamura, Manabu; Choi, Soomi

    2016-01-01

    Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal malignancy-related condition that involves rapidly progressing hypoxia and pulmonary hypertension. We report a case of PTTM caused by prostate carcinoma, which was diagnosed before autopsy in an 81-year-old man. Computed tomography showed diffuse ground-glass opacities, consolidation, and small nodules in the peripheral regions of the lung. Autopsy showed adenocarcinoma cells embolizing small pulmonary arteries with fibrocellular intimal proliferation, which was consistent with PTTM caused by prostate carcinoma. PMID:27635254

  8. Deformable registration of x-ray to MRI for post-implant dosimetry in prostate brachytherapy

    NASA Astrophysics Data System (ADS)

    Park, Seyoun; Song, Danny Y.; Lee, Junghoon

    2016-03-01

    Post-implant dosimetric assessment in prostate brachytherapy is typically performed using CT as the standard imaging modality. However, poor soft tissue contrast in CT causes significant variability in target contouring, resulting in incorrect dose calculations for organs of interest. CT-MR fusion-based approach has been advocated taking advantage of the complementary capabilities of CT (seed identification) and MRI (soft tissue visibility), and has proved to provide more accurate dosimetry calculations. However, seed segmentation in CT requires manual review, and the accuracy is limited by the reconstructed voxel resolution. In addition, CT deposits considerable amount of radiation to the patient. In this paper, we propose an X-ray and MRI based post-implant dosimetry approach. Implanted seeds are localized using three X-ray images by solving a combinatorial optimization problem, and the identified seeds are registered to MR images by an intensity-based points-to-volume registration. We pre-process the MR images using geometric and Gaussian filtering. To accommodate potential soft tissue deformation, our registration is performed in two steps, an initial affine transformation and local deformable registration. An evolutionary optimizer in conjunction with a points-to-volume similarity metric is used for the affine registration. Local prostate deformation and seed migration are then adjusted by the deformable registration step with external and internal force constraints. We tested our algorithm on six patient data sets, achieving registration error of (1.2+/-0.8) mm in < 30 sec. Our proposed approach has the potential to be a fast and cost-effective solution for post-implant dosimetry with equivalent accuracy as the CT-MR fusion-based approach.

  9. Quantifying the effect of seed orientation in postplanning dosimetry of low-dose-rate prostate brachytherapy.

    PubMed

    Collins Fekete, Charles-Antoine; Plamondon, Mathieu; Martin, André-Guy; Vigneault, Éric; Verhaegen, Frank; Beaulieu, Luc

    2014-10-01

    Radioactive seed orientations are usually ignored in clinical brachytherapy dosimetry for prostate implants. Associated with the anisotropic dose distribution of seeds, these orientations could cause dose differences between the planning configurations and the clinical postplanning dosimetry. This study will quantify the impact of seed orientation on the dosimetry. 3D seed positions and θ and φ polar angles were obtained using five independent fluoroscopic images for 287 patients. Five dose calculation methods are compared: TG43-1D (1), TG43-2D parallel to implant axis (2) and with orientations (3), Monte Carlo (MC) simulations parallel (4), and MC simulations with orientations (5). GEANT4 v4.9.6 MC simulations were made in 1 mm(3) voxelized geometries based on the DICOM-RT information. Materials were assigned using thresholds based on the HU number, as recommended in TG186 reports. Seed voxels are overridden with prostatic materials and the layered mass geometry [Enger et al., Phys. Med. Biol. 57(19), 6269-6277 (2012)] allows subsequent placement of the source geometry. 500 million histories were used per patient. 3D dose and DVHs for each structure were calculated. The various seed orientations do not result in statistically significant differences on the dose metrics for the clinical target volume (CTV) or the urethra, based on the Student t-test p-value. Difference as low as -0.238% and 0.059% has been seen on the CTV D90, respectively, for the MC and the TG43. The difference between parallel and oriented calculations for the organs at risk (OARs) can differ by 2% on average. Based on the results from this study, seed orientations have no significant impact of CTV and urethra dose metrics but can affect OARs that are external to the CTV.

  10. In vivo detection of prostatic carcinoma with antibodies against prostatic acid phosphatase

    SciTech Connect

    De Land, F.H.; Goldenberg, D.M.

    1984-01-01

    Serum prostatic acid phosphates (PAP) immunoassay is used to evaluate patients with prostatic carcinoma; however, as with other tumor markers, the enzyme levels do not necessarily reflect the presence or extent of tumor. The authors investigated the use of radiolabeled PAP antibodies for the in vivo detection of prostatic carcinoma by external scintillation imaging. Nine patients with prostatic carcinoma were entered into the study. Each received from 2.0 to 2.5 mCi of I-131 labeled antibody to PAP, administered i.v. The immunogen (PAP) was purified from normal human seminal fluid. Antiserum was prepared in rabbits by injecting the purified PAP. The antibodies were labeled with I-131 by chloramine-T method (10 to 20 Ci/g of IgG). Total body images were obtained at 24 and 48 hrs following administration of the labeled antibody. Nontarget I-131 activity was diminished by computer processing. Tumor sites detected by I-131 antibodies were correlated with other diagnostic procedures. In 7 of 9 patients primary and metastatic sites of cancer were detected by antibody imaging, however, no bone lesions were detected (6 cases). In 3 patients with concomitant pulmonary tumors, one was identified as of prostate origin. The serum PAP was normal in 4 patients; however, the primary tumor was identified in 3 of these. These findings suggest that the localization of prostatic carcinoma by means of in-vivo imaging of labeled antibodies to PAP is feasible and offers diagnostic opportunities based upon the functional characteristics.

  11. Sequential Comparison of Seed Loss and Prostate Dosimetry of Stranded Seeds With Loose Seeds in {sup 125}I Permanent Implant for Low-Risk Prostate Cancer

    SciTech Connect

    Saibishkumar, Elantholi P.; Borg, Jette; Yeung, Ivan; Cummins-Holder, Cheryl; Landon, Angela; Crook, Juanita

    2009-01-01

    Purpose: To compare stranded seeds (SSs) with loose seeds (LSs) in terms of prostate edema, dosimetry, and seed loss after {sup 125}I brachytherapy. Methods and Materials: Two prospective cohorts of 20 men participated in an institutional review board-approved protocols to study postimplant prostate edema and its effect on dosimetry. The LS cohort underwent brachytherapy between September 2002 and July 2003 and the SS cohort between April 2006 and January 2007. Both cohorts were evaluated sequentially using computed tomography-magnetic resonance imaging fusion-based dosimetry on Days 0, 7, and 30. No hormonal therapy or supplemental beam radiotherapy was used. Results: Prostate edema was less in the SS cohort at all points (p = NS). On Day 0, all the prostate dosimetric factors were greater in the LS group than in the SS group (p = 0.003). However, by Days 7 and 30, the dosimetry was similar between the two cohorts. No seeds migrated to the lung in the SS cohort compared with a total of five seeds in 4 patients in the LS cohort. However, the overall seed loss was greater in the SS cohort (24 seeds in 6 patients; 1.1% of total vs. 0.6% for LSs), with most seeds lost through urine (22 seeds in 5 patients). Conclusion: Despite elimination of venous seed migration, greater seed loss was observed with SSs compared with LSs, with the primary site of loss being the urinary tract. Modification of the technique might be necessary to minimize this. Prostate dosimetry on Days 7 and 30 was similar between the SS and LS cohorts.

  12. Greater Postimplant Swelling in Small-Volume Prostate Glands: Implications for Dosimetry, Treatment Planning, and Operating Room Technique

    SciTech Connect

    Chung, Eugene; Stenmark, Matthew H.; Evans, Cheryl; Narayana, Vrinda; McLaughlin, Patrick W.

    2012-04-01

    Purpose: Postimplant prostatic edema has been implicated in suboptimal permanent implants, and smaller prostates have been reported to have worse dosimetric coverage. In this study we compare the degree of postimplant edema between larger and smaller prostates and examine the effects of prostate size on the dose delivered to 90% of the prostate (D90). Methods and Materials: From September 2003 to February 2006, 105 hormone-naive patients underwent permanent prostate brachytherapy with {sup 125}I Rapid Strand (Oncura Inc., Arlington Heights, IL). All patients underwent pelvic magnetic resonance imaging (MRI) within 3 weeks before implant, transrectal ultrasound at the time of implant, and both computed tomography and MRI 2.5 to 3 weeks after implant. Prostates were divided into 5 subgroups based on preimplant MRI volumes: less than 25 mL, 25 to 35 mL, 35 to 45 mL, 45 to 55 mL, and greater than 55 mL. Prostate swelling was assessed by use of preimplant and postimplant MRI volumes. Postimplant dosimetry was determined by MRI and compared between the subgroups. Results: All prostates showed postimplant swelling on MRI when compared with preimplant MRI, with a mean increase of 31% {+-} 31% (p < 0.0001). The greatest swelling was noted in small prostates (volume less than 25 mL), with a mean increase of 70% {+-} 36%. The degree of swelling in the group with a volume less than 25 mL was significantly larger than the degree of swelling in all other prostate subgroups (p < 0.003). Transrectal ultrasound significantly overestimates the prostate volume when compared with MRI by a mean of 15% {+-} 25% (p = 0.0006) and is more pronounced for smaller prostates. Although prostates with volumes less than 25 mL did not have significantly worse D90 compared with larger prostates, they had the largest percent of suboptimal implants by the standard ratio of D90 divided by the prescription dose. Conclusions: Although small prostates have the greatest postimplant edema, planning

  13. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma.

    PubMed

    Bishop, Justin A; Yonescu, Raluca; Epstein, Jonathan I; Westra, William H

    2015-08-01

    Adenoid cystic carcinoma (ACC) is a basaloid tumor consisting of myoepithelial and ductal cells typically arranged in a cribriform pattern. Adenoid cystic carcinoma is generally regarded as a form of salivary gland carcinoma, but it can arise from sites unassociated with salivary tissue. A rare form of prostate carcinoma exhibits ACC-like features; it is no longer regarded as a true ACC but rather as prostatic basal cell carcinoma (PBCC) and within the spectrum of basaloid prostatic proliferations. True ACCs often harbor MYB translocations resulting in the MYB-NFIB fusion protein. MYB analysis could clarify the true nature of prostatic carcinomas that exhibit ACC features and thus help refine the classification of prostatic basaloid proliferations. Twelve PBCCs were identified from the pathology consultation files of Johns Hopkins Hospital. The histopathologic features were reviewed, and break-apart fluorescence in situ hybridization for MYB was performed. All 12 cases exhibited prominent basaloid histology. Four were purely solid, 7 exhibited a cribriform pattern reminiscent of salivary ACC, and 1 had a mixed pattern. The MYB rearrangement was detected in 2 (29%) of 7 ACC-like carcinomas but in none (0%) of the 5 PBCCs with a prominent solid pattern. True ACCs can arise in the prostate as is evidenced by the presence of the characteristic MYB rearrangement. When dealing with malignant basaloid proliferations in the prostate, recommendations to consolidate ACCs with other tumor types may need to be reassessed, particularly in light of the rapidly advancing field of biologic therapy where the identification of tumor-specific genetic alterations presents novel therapeutic targets.

  14. An unusual cystic presentation of ductal carcinoma of the prostate.

    PubMed

    De Gobbi, Alberto; Morlacco, Alessandro; Valotto, Claudio; Vianello, Fabio; Zattoni, Filiberto

    2016-11-18

    A 74-year-old male came to our clinic for rectal tenesmus, lower urinary tract symptoms and a previous episode of acute retention of urine. Computed tomography (CT) and magnetic resonance imaging (MRI) scan of abdomen showed a multiloculated, cystic formation of 12 cm in the pelvic cavity to the left, with compression of the prostate, bladder, sigmoid and rectum, and its extension imprinted the back of the pubis and back bladder. Saturation prostate biopsy was negative for carcinoma. The histology of transurethral resection of bladder formation revealed flogistic tissue. Cistoprostatectomy and ureteroileal pouch with Wallace anastomosis, removal of the rectum and colostomy with Hartmann pouch were performed. The histopatology showed a ductal carcinoma of the prostate.

  15. The role of human papillomavirus infection in prostate carcinoma.

    PubMed

    Aghakhani, Arezoo; Hamkar, Rasool; Parvin, Mahmoud; Ghavami, Nastaran; Nadri, Mahsa; Pakfetrat, Attesa; Banifazl, Mohammad; Eslamifar, Ali; Izadi, Nabiollah; Jam, Sara; Ramezani, Amitis

    2011-01-01

    Human papillomavirus (HPV) infections are associated with benign and malignant lesions of the female and male anogenital tract. Currently the possible role of HPV infections in prostate carcinogenesis is a subject of great controversy. In this study we aimed to investigate the role of HPV infection in prostate carcinoma (PCa). The study included formalin-fixed paraffin-embedded tissue samples of 104 primary prostate adenocarcinoma cases and 104 control tissues of benign prostatic hyperplasia (BPH). HPV-DNA was purified and amplified through MY09/MY11 and GP5(+)/GP6(+) primers and subsequently subjected to sequencing. HPV-DNA was found in 13 of 104 (12.5%) PCa and 8 of 104 (7.7%) BPH samples. High-risk HPVs were detected in 10 of 13 (76.9%) PCa and 5 of 8 (62.5%) BPH samples with positive HPV-DNA. Low-risk HPVs were detected in 3 of 13 (23.1%) PCa and 3 of 8 (37.5%) BPH specimens with positive HPV-DNA. There was no significant difference between PCa and BPH specimens regarding HPV-DNA presence or the detection of high-risk and low-risk types of HPV. Our data do not support the role of HPV infection in prostate carcinoma. Further studies are required to elucidate the role of HPV infection in human prostate carcinogenesis.

  16. High-Dose-Rate Prostate Brachytherapy Consistently Results in High Quality Dosimetry

    SciTech Connect

    White, Evan C.; Kamrava, Mitchell R.; Demarco, John; Park, Sang-June; Wang, Pin-Chieh; Kayode, Oluwatosin; Steinberg, Michael L.; Demanes, D. Jeffrey

    2013-02-01

    Purpose: We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials: Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results: The mean prostate ultrasound volume was 38.7 {+-} 13.4 cm{sup 3} (range: 11.7-108.6 cm{sup 3}). The mean CTV was 75.1 {+-} 20.6 cm{sup 3} (range: 33.4-156.5 cm{sup 3}). The mean D90 was 109.2% {+-} 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% {+-} 0.05%, 99.5% {+-} 0.8%, 25.4% {+-} 4.2%, and 7.8% {+-} 1.4%. The mean dose to 0.1 cm{sup 3}, 1 cm{sup 3}, and 2 cm{sup 3} for organs at risk were: Urethra: 107.3% {+-} 3.0%, 101.1% {+-} 14.6%, and 47.9% {+-} 34.8%; bladder wall: 79.5% {+-} 5.1%, 69.8% {+-} 4.9%, and 64.3% {+-} 5.0%; bladder balloon: 70.3% {+-} 6.8%, 59.1% {+-} 6.6%, and 52.3% {+-} 6.2%; rectum: 76.3% {+-} 2.5%, 70.2% {+-} 3.3%, and 66.3% {+-} 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions: HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

  17. Detailed urethral dosimetry in the evaluation of prostate brachytherapy-related urinary morbidity

    SciTech Connect

    Allen, Zachariah A.; Merrick, Gregory S. . E-mail: gmerrick@wheelinghospital.com; Butler, Wayne M.; Wallner, Kent E.; Kurko, Brian; Anderson, Richard L.; Murray, Brian C.; Galbreath, Robert W.

    2005-07-15

    blockers and strict adherence to urethral-sparing techniques, detailed urethral dosimetry did not substantially improve the ability to predict urinary morbidity. Neither the average dose to the prostatic urethra nor urethral doses stratified into base, midprostate, apex, or urogenital diaphragm segments predicted for IPSS normalization. Radiation doses of 100%-140% minimum peripheral dose are well tolerated by all segments of the prostatic urethra with resultant tumorcidal doses to foci of periurethral cancer.

  18. Adherence to ICRU-83 reporting recommendations is inadequate in prostate dosimetry studies.

    PubMed

    Mohan, Aishling; Forde, Elizabeth

    2017-08-31

    This study aimed to investigate if the International Commission on Radiation Units and Measurements (ICRU) 83 recommendations for reporting dosimetric endpoints are followed in published prostate studies using modulated techniques. Prostate dosimetry studies using inverse planning techniques were identified through a search of PubMed and EMBASE databases. These studies were analyzed to determine if the endpoints reported followed the recommendations outlined in ICRU-83. A data collection form was completed and any alternative methods of reporting were recorded. Results were analyzed using frequencies, percentages, and Fisher exact tests. The ICRU-83 recommendations were not followed in the majority of studies. For the planning target volume, the dose received by 2% of the volume, the dose received by 98% of the volume, and the dose received by 50% of the volume were reported in 22.9%, 18.8%, and 8.3% of studies, respectively. The adherence to reporting for the clinical target volume was below 5% for all specifications. The mean dose, the dose received by a specified volume, and dose received by 2% of the volume for organs at risk were reported in 47.1%, 83.3%, and 16.7%, respectively. The homogeneity index was used in 14.6% of studies. Conformity was discussed in 45.8% of studies. Confidence intervals were included in 37.5% of studies. The reporting recommendations of ICRU-83 were not adhered to in the majority of the dosimetry studies reviewed, highlighting the need for greater diligence for authors and reviewers when publishing planning outcomes for modulated techniques. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  19. Prostate brachytherapy postimplant dosimetry: Seed orientation and the impact of dosimetric anisotropy in stranded implants

    SciTech Connect

    Chng, Nicholas; Spadinger, Ingrid; Rasoda, Rosey; Morris, W. James; Salcudean, Septimiu

    2012-02-15

    Purpose: In postimplant dosimetry for prostate brachytherapy, dose is commonly calculated using the TG-43 1D formalism, because seed orientations are difficult to determine from CT images, the current standard for the procedure. However, the orientation of stranded seeds soon after implantation is predictable, as these seeds tend to maintain their relative spacing, and orient themselves along the implant trajectory. The aim of this study was to develop a method for determining seed orientations from reconstructed strand trajectories, and to use this information to investigate the dosimetric impact of applying the TG-43 2D formalism to clinical postimplant analysis. Methods: Using in-house software, the preplan to postimplant seed correspondence was determined for a cohort of 30 patients during routine day-0 CT-based postimplant dosimetry. All patients were implanted with stranded-seed trains. Spline curves were fit to each set of seeds composing a strand, with the requirement that the distance along the spline between seeds be equal to the seed spacing within the strand. The orientations of the seeds were estimated by the tangents to the spline at each seed centroid. Dose distributions were then determined using the 1D and 2D TG-43 formalisms. These were compared using the TG-137 recommended dose metrics for the prostate, prostatic urethra, and rectum. Results: Seven hundred and sixty one strands were analyzed in total. Defining the z-axis to be cranial-positive and the x-axis to be left-lateral positive in the CT coordinate system, the average seed had an inclination of 21 deg. {+-} 10 deg. and an azimuth of -81 deg. {+-} 57 deg. These values correspond to the average strand rising anteriorly from apex to base, approximately parallel to the midsagittal plane. Clinically minor but statistically significant differences in dose metrics were noted. Compared to the 2D calculation, the 1D calculation underestimated prostate V100 by 1.1% and D90 by 2.3 Gy, while

  20. [Intraoperative and post-implant dosimetry in patients treated with permanent prostate implant brachytherapy].

    PubMed

    Herein, András; Ágoston, Péter; Szabó, Zoltán; Jorgo, Kliton; Markgruber, Balázs; Pesznyák, Csilla; Polgár, Csaba; Major, Tibor

    2015-06-01

    The purpose of our work was to compare intraoperative and four-week post-implant dosimetry for loose and stranded seed implants for permanent prostate implant brachytherapy. In our institute low-dose-rate (LDR) prostate brachytherapy is performed with encapsulated I-125 isotopes (seeds) using transrectal ultrasound guidance and metal needles. The SPOT PRO 3.1 (Elekta, Sweden) system is used for treatment planning. In this study the first 79 patients were treated with loose seed (LS) technique, the consecutive patients were treated with stranded seed (SS) technique. During intraoperative planning the dose constraints were the same for both techniques. All LSs were placed inside the prostate capsule, while with SS a 2 mm margin around the prostate was allowed for seed positioning. The prescribed dose for the prostate was 145 Gy. This study investigated prostate dose coverage in 30-30 randomly selected patients with LS and SS. Four weeks after the implantation native CT and MRI were done and CT/MRI image fusion was performed. The target was contoured on MRI and the plan was prepared on CT data. To assess the treatment plan dose-volume histograms were used. For the target coverage V100, V90, D90, D100, for the dose inhomogeneity V150, V200, and the dose-homogeneity index (DHI), for dose conformality the conformal index (COIN) were calculated. Intraoperative and postimplant plans were compared. The mean V100 values decreased at four-week plan for SS (97% vs. 84%) and for LS (96% vs. 80%) technique, as well. Decrease was observed for all parameters except for the DHI value. The DHI increased for SS (0.38 vs. 0.41) and for LS (0.38 vs. 0.47) technique, as well. The COIN decreased for both techniques at four-week plan (SS: 0.63 vs. 0.57; LS: 0.67 vs. 0.50). All differences were significant except for the DHI value at SS technique. The percentage changes were not significant, except the COIN value. The dose coverage of the target decreased significantly at four-week plans

  1. Comprehensive I-125 multi-seed comparison for prostate brachytherapy: dosimetry and visibility analysis.

    PubMed

    Al-Qaisieh, Bashar; Smith, David W; Brearley, Elizabeth; St Clair, Shaun; Bownes, Peter

    2007-08-01

    To compare the visibility of different manufacturers I-125, seeds, and to investigate the effect of differences in dosimetry on treatment planning. Oncura Oncoseed, Oncura Echoseed, IBT Intersource, Bebig Isoseed and Nucletron Selectseed were investigated. The point dose at increasing distances from each seed type was calculated for three different angles; theta=0 degrees, 45 degrees and 90 degrees (where theta=0 degrees lies parallel to seed length). 10 patient plans were used to assess the effect of a change in dosimetry on treatment planning and quality of prostate and rectum implant indices such as Vp100, Vp200, Dp90, Vr100 and Vr69. All implant indices and dosimetry data were compared to Oncoseed. Visibility under X-ray, fluoroscopy, CT and MRI was investigated using prostate phantoms created in-house. Statistical significance was calculated using paired two-tailed t-tests. Dosimetric analysis was carried out for seeds of the same source strength. Differences in dose increase closer to the centre of each source, with the largest changes occurring for the angle theta=0 degrees. Selectseed and Isoseed seed types provide a consistently lower dose in all three directions. Changes to Vp100 are small and statistically insignificant for all seeds except Selectseed which shows a statistically significant decrease of 0.04% (p=0.02). Changes to Vp150 and Vp200 are statistically significant (p<0.01), with Intersource showing the greatest increase in both values. Selectseed shows a decrease in both Vp150 and Vp200. Echoseed shows an increase in both Vp150 and Vp200. Changes to D90 are statistically significant (p<0.01), with Intersource showing the greatest increase, followed by Isoseed then Echoseed. Selectseed shows a decrease in D90. For Vr100 there is no statistically significant change for any seed type. However, all seeds except Selectseed show a statistically significant increase in the value of Vr69, with Intersource showing the greatest increase. On fluoroscopy

  2. Dose fractionation and biological optimization in carcinoma of the prostate.

    PubMed

    Perez, Carlos A

    2004-01-01

    Three-dimensional conformal radiation therapy (3-D CRT) or intensity-modulated radiation therapy (IMRT) have been increasingly used as an alternative to radical prostatectomy in patients with localized carcinoma of the prostate and in patients at high risk, in combination with hormonal therapy. To better understand the implications of dose-time and fractionation in prostate cancer, it is important to be familiar with some laboratory investigations dealing with the cell kinetics characteristics of this tumor. Biological and clinical considerations of dose fractionation, total dose of irradiation and local tumor control, elapsed overall treatment time and sequelae of irradiation are illustrated, based on an exhaustive review of the literature.

  3. Transperineal in vivo fluence-rate dosimetry in the canine prostate during SnET2-mediated PDT

    NASA Astrophysics Data System (ADS)

    Lilge, Lothar; Pomerleau-Dalcourt, Natalie; Douplik, Alexander; Selman, Steven H.; Keck, Rick W.; Szkudlarek, Maria; Pestka, Maciej; Jankun, Jerzy

    2004-07-01

    Advances in photodynamic therapy (PDT) treatment for prostate cancer can be achieved either by improving selectivity of the photosensitizer towards prostate gland tissue or improving the dosimetry by means of individualized treatment planning using currently available photosensitizers. The latter approach requires the ability to measure, among other parameters, the fluence rate at different positions within the prostate and the ability to derive the tissue optical properties. Here fibre optic probes are presented capable of measuring the fluence rate throughout large tissue volumes and a method to derive the tissue optical properties for different volumes of the prostate. The responsivity of the sensors is sufficient to detect a fluence rate of 0.1 mW cm-2. The effective attenuation coefficient in the canine prostate at 660 nm is higher at the capsule (2.15 ± 0.19 cm-1) than in proximity of the urethra (1.84 ± 0.36 cm-1). Significant spatial and temporal intra- and inter-canine variability in the tissue optical properties was noted, highlighting the need for individualized monitoring of the fluence rate for improved dosimetry.

  4. Thermoluminescence dosimetry for in-vivo verification of high dose rate brachytherapy for prostate cancer.

    PubMed

    Das, R; Toye, W; Kron, T; Williams, S; Duchesne, G

    2007-09-01

    It was the aim of the study to verify dose delivered in urethra and rectum during High Dose Rate brachytherapy boost (HDRBB) of prostate cancer patients. During the first fraction of HDRBB measurement catheters were placed in the urethra and rectum of prostate cancer patients. These contained LiF:Mg,Ti Thermoluminescence Dosimetry (TLD) rods of 1 mm diameter, with up to 11 detectors positioned every 16 mm separated by radio-opaque markers. A Lorentzian peak function was used to fit the data. Measurements from 50 patients were evaluated and measured doses were compared with predictions from the treatment planning system (Plato Vs 13.5 to 14.1). Prospective urinary and rectal toxicity scores were collected following treatment. In more than 90% of cases, the Lorentzian peak function provided a good fit to both experimental and planning urethral data (r2 > 0.9). In general there was good agreement between measured and predicted doses with the average difference between measured and planned maximum dose being 0.1 Gy. No significant association between dose and any clinical endpoints was observed in 43 patients available for clinical evaluation. An average inferior shift of 2 mm between the plan and the measurement performed approximately 1 hour after the planning CT scan was found for the dose distribution in the cohort of patients for the urethra measurements. Rectal measurements proved to be more difficult to interpret as there is more variability of TLD position between planning and treatment. TLD in-vivo measurements are easily performed in urethra and rectum during HDR brachytherapy of prostate patients. They verify the delivery and provide information about the dose delivered to critical structures. The latter may be of particular interest if higher doses are to be given per fraction such as in HDR monotherapy.

  5. Comparison of 3 different postimplant dosimetry methods following permanent {sup 125}I prostate seed brachytherapy

    SciTech Connect

    Marcu, Loredana G.; Gowda, Raghu

    2013-10-01

    Postimplant dosimetry (PID) after Iodine-125 ({sup 125}I) implant of the prostate should offer a reliable qualitative assessment. So far, there is no consensus regarding the optimum PID method, though the latest literature is in favor of magnetic resonance imaging (MRI). This study aims to simultaneously compare 3 PID techniques: (1) MRI-computed tomography (CT) fusion; (2) ultrasound (US)-CT fusion; and (3) manual target delineation on CT. The study comprised 10 patients with prostate cancer. CT/MR scans with urinary catheters in place for PID were done either on day 0 or day 1 postimplantation. The main parameter evaluated and compared among methods was target D90. The results show that CT-based D90s are lower than US-CT D90s (median difference,−6.85%), whereas MR-CT PID gives higher D90 than US-CT PID (median difference, 4.25%). Manual contouring on CT images tends to overestimate the prostate volume compared with transrectal ultrasound (TRUS) (median difference, 23.33%), whereas on US images the target is overestimated compared with MR-based contouring (median difference, 13.25%). Although there are certain differences among the results given by various PID techniques, the differences are statistically insignificant for this small group of patients. Any dosimetric comparison between 2 PID techniques should also account for the limitations of each technique, to allow for an accurate quantification of data. Given that PID after permanent radioactive seed implant is mandatory for quality assurance, any imaging method–based PID (MR-CT, US-CT, and CT) available in a radiotherapy department can be indicative of the quality of the procedure.

  6. Unusual Presentation of Prostate Carcinoma: A Case Report

    PubMed Central

    Maheshwari, Anuradha; Yadav, Sher Singh; Tomar, Vinay

    2017-01-01

    Prostate cancer is a common cancer in elderly men and it frequently metastasizes to regional lymph nodes and sometimes to bone. Very rarely in some of the cases it also shows involvement of non-regional lymph nodes like supra-diaphragmatic lymph nodes. In our report, we present a 60-year-old male, initially misdiagnosed as Chronic Obstructive Pulmonary Disease (COPD) with cervical lymph node involvement may be due to infective region or inflammatory pathology, which was later found to have prostatic adenocarcinoma metastatic to supraclavicular lymph nodes. Very less case reports are present which have shown similar presentations. So we would like to highlight that prostatic carcinoma can be present in an atypical form also.

  7. Comparison between real-time intra-operative ultrasound-based dosimetry and CT-based dosimetry for prostate brachytherapy using cesium-131.

    PubMed

    Jacobs, B L; Gibbons, E P; Smith, R P; Beriwal, S; Komanduri, K; Benoit, R M

    2008-12-01

    The purpose of this study was to evaluate the correlation between real-time intra-operative ultrasound-based dosimetry (USD) and day 0 post-implant CT dosimetry (CTD) (131)Cs permanent prostate brachytherapy. Fifty-two consecutive patients who underwent prostate brachytherapy with (131)Cs were evaluated. Real time operating room planning was performed using VariSeed 7.1 software. Post-needle placement prostate volume was used for real-time planning. Targets for dosimetry were D(90) >110%, V(100) >90%, V(150) <50%, and V(200) <20%. The CT scan for post-operative dosimetry was obtained on day 0. The mean values for USD, CTD, and the linear correlation, respectively, were, for D(90): 114.0%, 105.61%, and 0.15; for V(100): 95.1%, 91.6%, and 0.22; for V(150): 51.5%, 46.4%, and 0.40; and for V(200): 15.8%, 17.9%, and 0.42. The differences between the mean values for USD and CTD for D(90) (p<0.01), V(100) (p<0.01), and V(150) (p<0.05) were statistically significant. For D(90), 30.8% of patients had a >15% difference between USD and CTD and 51.9% of patients had a >10% difference between these values. In contrast, the USD and CTD for V(100) were within 5% in 55.8% of patients and within 10% in 86.5% of patients. This study demonstrates a correlation between the mean intra-operative USD and post-implant day 0 CTD values only for V(200). Significant variation in D(90), V(150), and V(200) values existed for individual patients between USD and CTD. These results suggest that real-time intra-operative USD does not serve as a surrogate for post-operative CTD, and that post-operative CTD is still necessary.

  8. Diet, vegetarian food and prostate carcinoma among men in Taiwan.

    PubMed

    Chen, Y C; Chiang, C I; Lin, R S; Pu, Y S; Lai, M K; Sung, F-C

    2005-10-31

    In a case-control study in a veterans hospital in Taiwan, we compared 237 histology-confirmed prostate carcinoma cases with 481 controls, frequency matched by age, for their consumption of vegetarian food, namely soybean products, rice, wheat protein and other vegetables. The multivariable logistic regression analysis showed a significant association with such food (odds ratio (OR)=0.67, 95% confidence interval (CI)=0.47, 0.94). This beneficial effect presented for men with body mass index (BMI) < or =25 kg m(-2) (OR=0.50, 95% CI=0.32, 0.76) but not for men with greater BMI. The OR of prostate carcinoma for men with BMI < or =25 kg m(-2) was 1.74 (95% CI=1.21, 2.51), compared with men with higher BMI (>25 kg m(-2)). Other significant risk factors associated with the disease included higher income (OR=2.40, 95% CI=1.07, 5.42), physical activity (OR=1.75, 95% CI=1.08, 2.83), being married (OR=2.49, 95% CI=1.40, 4.43) and coffee consumption (OR=1.88, 95% CI=1.07, 3.30). Stratified analysis also showed that the consumption of fish/shellfish had an adverse association for men with higher BMI. This study suggests that the intake of the low fat local vegetarian food has a protective effect against prostate carcinoma for thin men in this study population.

  9. TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate.

    PubMed

    Guo, Charles C; Dancer, Jane Y; Wang, Yan; Aparicio, Ana; Navone, Nora M; Troncoso, Patricia; Czerniak, Bogdan A

    2011-01-01

    Recent studies have shown that most prostate cancers carry the TMPRSS2-ERG gene fusion. Here we evaluated the TMPRSS2-ERG gene fusion in small cell carcinoma of the prostate (n = 12) in comparison with small cell carcinoma of the urinary bladder (n = 12) and lung (n = 11). Fluorescence in situ hybridization demonstrated rearrangement of the ERG gene in 8 cases of prostatic small cell carcinoma (67%), and the rearrangement was associated with deletion of the 5' ERG gene in 7 cases, but rearrangement of the ERG gene was not present in any small cell carcinoma of the urinary bladder or lung. Next we evaluated the TMPRSS2-ERG gene fusion in nude mouse xenografts that were derived from 2 prostatic small cell carcinomas carrying the TMPRSS2-ERG gene fusion. Two transcripts encoded by the TMPRSS2-ERG gene fusion were detected by reverse transcriptase polymerase chain reaction, and DNA sequencing demonstrated that the 2 transcripts were composed of fusions of exon 1 of the TMPRSS2 gene to exon 4 or 5 of the ERG gene. Our study demonstrates the specific presence of TMPRSS2-ERG gene fusion in prostatic small cell carcinoma, which may be helpful in distinguishing small cell carcinoma of prostatic origin from nonprostatic origins. The high prevalence of the TMPRSS2-ERG gene fusion in prostatic small cell carcinoma as well as adenocarcinoma implies that small cell carcinoma may share a common pathogenic pathway with adenocarcinoma in the prostate.

  10. Testosterone metabolism of fibroblasts grown from prostatic carcinoma, benign prostatic hyperplasia and skin fibroblasts

    SciTech Connect

    Schweikert, H.U.; Hein, H.J.; Romijn, J.C.; Schroeder, F.H.

    1982-02-01

    The metabolism of (1,2,6,7-3H)testosterone was assessed in fibroblast monolayers derived from tissue of 5 prostates with benign hyperplasia (BPH), 4 prostates with carcinoma (PC), and 3 biopsy samples of skin, 2 nongenital skin (NG) and 1 genital skin. The following metabolites could be identified: androstanedione androstenedione, dihydrotestosterone, androsterone, epiandrosterone, androstane-3 alpha, 17 beta-diol and androstane-3 beta, 17 beta-diol. Testosterone was metabolized much more rapidly in fibroblasts originating from prostatic tissue than in fibroblasts derived from NG. A significantly higher formation of 5 alpha-androstanes and 3 alpha-hydroxysteroids could be observed in fibroblasts from BPH as compared to PC. 17-ketosteroid formation exceeded 5 alpha-androstane formation in BPH, whereas 5 alpha-reduction was the predominant pathway in fibroblasts grown from PC and NG. Since testosterone metabolism in fibroblasts of prostatic origin therefore resembles in many aspects that in whole prostatic tissue, fibroblasts grown from prostatic tissues might be a valuable tool for further investigation of the pathogenesis of human BPH and PC.

  11. Pharmacological studies on androgen suppression in therapy of prostate carcinoma.

    PubMed

    Sandow, J; von Rechenberg, W; Engelbart, K

    1988-01-01

    In hormone-dependent prostate carcinoma, androgens can be suppressed into the castrate range by LHRH agonists. Testosterone secretion is blocked at two levels: testicular androgens and adrenal androgens. In humans, the contribution of testicular androgens is about 95%, whereas in the rat, the adrenal androgen secretion is negligible. Pharmacological studies were performed on the suppressive effect of the LHRH agonist, buserelin on androgen-dependent organs in adult rats. The reduction in pituitary and testicular binding capacity was monitored during treatment by injection, or by long-term infusion. Marked differences in suppressive mechanisms activated by the different regimens were observed. Changes in testicular steroid biosynthesis were analysed by incubation of testes after treatment with HCG, measuring the spectrum of C21/C19-steroids in incubation media. In particular, the levels of intraprostatic androgens were determined during treatment with daily buserelin injections, or with sustained release formulations of buserelin. The tissue content of testosterone and 5-alpha-dihydrotestosterone (DHT) were both markedly lowered. In castrate rats, stimulation of adrenal function by ACTH infusion had no effect on the prostate weight or intratesticular T/DHT content. Combination therapy during the initial phase of treatment by an androgen receptor blocker (cyproterone acetate) and buserelin (infusion or implants) was more effective to suppress prostate weight and intra-prostatic T/DHT content than therapy with the single compounds alone. Spermatogenesis and fertility were suppressed after prolonged treatment periods of 6-12 months; the testicular atrophy was not reversible in these long-term injection studies. Similar studies in dogs and monkeys have shown a different result: inhibition of spermatogenesis was fully reversible. It is concluded that studies on the mechanism of androgen suppression by LHRH agonists and the effects on androgen dependent organs provide

  12. Education concerning carcinoma of prostate and its early detection

    PubMed Central

    Jędrzejewska, Sylwia

    2011-01-01

    Introduction and objectives Prostate cancer is the most common male cancer. Insufficient knowledge of PCa among men causes its low detection. Lack of essential actions in health education and widely understood prophylaxis, the need of the latter are maybe responsible for the increasing mortality rate. According to our assumption, educating men increase their awareness on the need of screening tests and results in increasing reporting to physical examinations. This in turn allows for an early detection of the disease. Material and methods A research was conducted between the years 2003-2009 on the knowledge of PCa among 260 men. They were divided into two groups. Group A – 63 patients treated for carcinoma of prostate and group B – 197 men reporting spontaneously to screening tests. In order to check the adopted hypothesis, we prepared an educational material and test of knowledge – test with a questionnaire. Knowledge was evaluated before (test I) and after the education process (test II). Until 2009, we were monitoring the number of patients from group B reporting to screening tests and their knowledge was once again checked (test III). Two subgroups C and D were created from group B – 117 healthy men and 80 with diagnosed diseases respectively (70 with benign prostatic hyperplasia, 7 with prostatitis, and 3 with carcinoma of prostate). Patients with prostatitis and PCa and 3 patients from group C not reporting to the tests were excluded from further monitoring. Maths statistics with the use of SPSS 12.0 PL program and Statistica 6.0 constituted the base for working out the results. Results We observed a higher knowledge about carcinoma of prostate in group A than in group B (p <0.0001) and it increased after 5 years in group D (p <0.0001) in comparison to group C. Patients aged >40 from groups C and D were interested in health care (p<0.01) as much as patients aged 40-49, 50-59 and 60-69. In men >70 a lower level of motivation was observed. The interest

  13. Novel trends in transrectal ultrasound imaging of prostate gland carcinoma.

    PubMed

    Szopiński, Tomasz; Nowicki, Andrzej; Záťura, František; Gołąbek, Tomasz; Chłosta, Piotr

    2014-09-01

    Carcinoma of the prostate gland is the most common neoplasm in men. Its treatment depends on multiple factors among which local staging plays a significant role. The basic method is transrectal ultrasound imaging. This examination enables imaging of the prostate gland and its abnormalities, but it also allows ultrasound-guided biopsies to be conducted. A conventional gray-scale ultrasound examination enables assessment of the size, echostructure and outlines of the anatomic capsule, but in many cases, neoplastic lesions cannot be observed. For this reason, new sonographic techniques are implemented in order to facilitate detectability of cancer. The usage of contrast agents during transrectal ultrasound examination must be emphasized since, in combination with color Doppler, it facilitates detection of cancerous lesions by visualizing flow which is not observable without contrast enhancement. Elastography, in turn, is a different solution. It uses the differences in tissue elasticity between a neoplastic region and normal prostatic parenchyma that surrounds it. This technique facilitates detection of lesions irrespective of their echogenicity and thereby supplements conventional transrectal examinations. However, the size of the prostate gland and its relatively far location from the transducer may constitute limitations to the effectiveness of elastography. Moreover, the manner of conducting such an examination depends on the examiner and his or her subjective assessment. Another method, which falls within the novel, popular trend of combining imaging methods, is fusion of magnetic resonance imaging and transrectal sonography. The application of multidimensional magnetic resonance imaging, which is currently believed to be the best method for prostate cancer staging, in combination with the availability of a TRUS examination and the possibility of monitoring biopsies in real-time sonography is a promising alternative, but it is associated with higher costs and

  14. Novel trends in transrectal ultrasound imaging of prostate gland carcinoma

    PubMed Central

    Nowicki, Andrzej; Záťura, František; Gołąbek, Tomasz; Chłosta, Piotr

    2014-01-01

    Carcinoma of the prostate gland is the most common neoplasm in men. Its treatment depends on multiple factors among which local staging plays a significant role. The basic method is transrectal ultrasound imaging. This examination enables imaging of the prostate gland and its abnormalities, but it also allows ultrasound-guided biopsies to be conducted. A conventional gray-scale ultrasound examination enables assessment of the size, echostructure and outlines of the anatomic capsule, but in many cases, neoplastic lesions cannot be observed. For this reason, new sonographic techniques are implemented in order to facilitate detectability of cancer. The usage of contrast agents during transrectal ultrasound examination must be emphasized since, in combination with color Doppler, it facilitates detection of cancerous lesions by visualizing flow which is not observable without contrast enhancement. Elastography, in turn, is a different solution. It uses the differences in tissue elasticity between a neoplastic region and normal prostatic parenchyma that surrounds it. This technique facilitates detection of lesions irrespective of their echogenicity and thereby supplements conventional transrectal examinations. However, the size of the prostate gland and its relatively far location from the transducer may constitute limitations to the effectiveness of elastography. Moreover, the manner of conducting such an examination depends on the examiner and his or her subjective assessment. Another method, which falls within the novel, popular trend of combining imaging methods, is fusion of magnetic resonance imaging and transrectal sonography. The application of multidimensional magnetic resonance imaging, which is currently believed to be the best method for prostate cancer staging, in combination with the availability of a TRUS examination and the possibility of monitoring biopsies in real-time sonography is a promising alternative, but it is associated with higher costs and

  15. Dynamic dosimetry and edema detection in prostate brachytherapy: a complete system

    NASA Astrophysics Data System (ADS)

    Jain, A.; Deguet, A.; Iordachita, I.; Chintalapani, G.; Blevins, J.; Le, Y.; Armour, E.; Burdette, C.; Song, D.; Fichtinger, G.

    2008-03-01

    Purpose: Brachytherapy (radioactive seed insertion) has emerged as one of the most effective treatment options for patients with prostate cancer, with the added benefit of a convenient outpatient procedure. The main limitation in contemporary brachytherapy is faulty seed placement, predominantly due to the presence of intra-operative edema (tissue expansion). Though currently not available, the capability to intra-operatively monitor the seed distribution, can make a significant improvement in cancer control. We present such a system here. Methods: Intra-operative measurement of edema in prostate brachytherapy requires localization of inserted radioactive seeds relative to the prostate. Seeds were reconstructed using a typical non-isocentric C-arm, and exported to a commercial brachytherapy delivery system. Technical obstacles for 3D reconstruction on a non-isocentric C-arm include pose-dependent C-arm calibration; distortion correction; pose estimation of C-arm images; seed reconstruction; and C-arm to TRUS registration. Results: In precision-machined hard phantoms with 40-100 seeds and soft tissue phantoms with 45-87 seeds, we correctly reconstructed the seed implant shape with an average 3D precision of 0.35 mm and 0.24 mm, respectively. In a DoD Phase-1 clinical trial on 6 patients with 48-82 planned seeds, we achieved intra-operative monitoring of seed distribution and dosimetry, correcting for dose inhomogeneities by inserting an average of 4.17 (1-9) additional seeds. Additionally, in each patient, the system automatically detected intra-operative seed migration induced due to edema (mean 3.84 mm, STD 2.13 mm, Max 16.19 mm). Conclusions: The proposed system is the first of a kind that makes intra-operative detection of edema (and subsequent re-optimization) possible on any typical non-isocentric C-arm, at negligible additional cost to the existing clinical installation. It achieves a significantly more homogeneous seed distribution, and has the potential to

  16. Prostatic sarcomatoid carcinoma in a dog: cytologic and immunohistochemical findings.

    PubMed

    Pinto da Cunha, Nazarél; Ghisleni, Gabriele; Romussi, Stefano; Caniatti, Mario

    2007-12-01

    An 8-year-old neutered male Boxer was presented with tenesmus, hemorrhagic urethral discharge, and dysuria. Abdominal ultrasound and radiographic examinations revealed irregular prostatic enlargement. Laparotomy was performed and intraoperative cytology was done on imprint smears of a biopsy specimen obtained from a prostatic mass. The cytologic preparation was highly cellular and contained a predominant population of atypical, large, loosely cohesive spindle cells, with rare multinucleated cells and mitotic figures. The cytologic findings were consistent with undifferentiated sarcoma. At necropsy, a large cystic prostatic mass and numerous satellite nodules in the soft tissues around the pelvis were found. On histologic examination the tumor was composed primarily of bundles of neoplastic spindle cells. Rare pseudo-acinar structures and signet-ring cells also were observed. On immunohistochemical examination, the neoplastic cells co-expressed cytokeratin and vimentin. Based on histologic and immunohistochemical findings, the tumor was diagnosed as primary prostatic sarcomatoid carcinoma. This is a rare tumor in dogs, in which biphasic morphology of epithelial and mesenchymal cells can complicate the diagnosis, requiring immunochemical stains for confirmation.

  17. Modeling the impact of prostate edema on LDR brachytherapy: a Monte Carlo dosimetry study based on a 3D biphasic finite element biomechanical model

    NASA Astrophysics Data System (ADS)

    Mountris, K. A.; Bert, J.; Noailly, J.; Rodriguez Aguilera, A.; Valeri, A.; Pradier, O.; Schick, U.; Promayon, E.; Gonzalez Ballester, M. A.; Troccaz, J.; Visvikis, D.

    2017-03-01

    Prostate volume changes due to edema occurrence during transperineal permanent brachytherapy should be taken under consideration to ensure optimal dose delivery. Available edema models, based on prostate volume observations, face several limitations. Therefore, patient-specific models need to be developed to accurately account for the impact of edema. In this study we present a biomechanical model developed to reproduce edema resolution patterns documented in the literature. Using the biphasic mixture theory and finite element analysis, the proposed model takes into consideration the mechanical properties of the pubic area tissues in the evolution of prostate edema. The model’s computed deformations are incorporated in a Monte Carlo simulation to investigate their effect on post-operative dosimetry. The comparison of Day1 and Day30 dosimetry results demonstrates the capability of the proposed model for patient-specific dosimetry improvements, considering the edema dynamics. The proposed model shows excellent ability to reproduce previously described edema resolution patterns and was validated based on previous findings. According to our results, for a prostate volume increase of 10-20% the Day30 urethra D10 dose metric is higher by 4.2%-10.5% compared to the Day1 value. The introduction of the edema dynamics in Day30 dosimetry shows a significant global dose overestimation identified on the conventional static Day30 dosimetry. In conclusion, the proposed edema biomechanical model can improve the treatment planning of transperineal permanent brachytherapy accounting for post-implant dose alterations during the planning procedure.

  18. Biodistribution and Radiation Dosimetry for a Probe Targeting Prostate-Specific Membrane Antigen for Imaging and Therapy

    PubMed Central

    Herrmann, Ken; Bluemel, Christina; Weineisen, Martina; Schottelius, Margret; Wester, Hans-Jürgen; Czernin, Johannes; Eberlein, Uta; Beykan, Seval; Lapa, Constantin; Riedmiller, Hubertus; Krebs, Markus; Kropf, Saskia; Schirbel, Andreas; Buck, Andreas K.; Lassmann, Michael

    2016-01-01

    Prostate-specific membrane antigen (PSMA) is a promising target for diagnosis and treatment of prostate cancer. EuK-Subkff-68Ga-DOTAGA (68Ga-PSMA Imaging & Therapy [PSMA I&T]) is a recently introduced PET tracer for imaging PSMA expression in vivo. Whole-body distribution and radiation dosimetry of this new probe were evaluated. Methods Five patients with a history of prostate cancer were injected intravenously with 91–148 MBq of 68Ga-PSMA I&T (mean ± SD, 128 ± 23 MBq). After an initial series of rapid whole-body scans, 3 static whole-body scans were acquired at 1, 2, and 4 h after tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses were calculated using OLINDA/EXM. Results Injection of 150 MBq of 68Ga-PSMA I&T resulted in an effective dose of 3.0 mSv. The kidneys were the critical organ (33 mGy), followed by the urinary bladder wall and spleen (10 mGy each), salivary glands (9 mGy each), and liver (7 mGy). Conclusion 68Ga-PSMA I&T exhibits a favorable dosimetry, delivering organ doses that are comparable to (kidneys) or lower than those delivered by 18F-FDG. PMID:25883128

  19. Adipocyte secreted factors enhance aggressiveness of prostate carcinoma cells.

    PubMed

    Moreira, Ângela; Pereira, Sofia S; Costa, Madalena; Morais, Tiago; Pinto, Ana; Fernandes, Rúben; Monteiro, Mariana P

    2015-01-01

    Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade.

  20. Adipocyte Secreted Factors Enhance Aggressiveness of Prostate Carcinoma Cells

    PubMed Central

    Moreira, Ângela; Pereira, Sofia S.; Costa, Madalena; Morais, Tiago; Pinto, Ana; Fernandes, Rúben; Monteiro, Mariana P.

    2015-01-01

    Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1) and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01). Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01). Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05). Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade. PMID:25928422

  1. Activity of Artemisia annua and artemisinin derivatives, in prostate carcinoma.

    PubMed

    Michaelsen, Friedrich-Wilhelm; Saeed, Mohamed E M; Schwarzkopf, Jörg; Efferth, Thomas

    2015-12-15

    Artemisia annua L, artemisinin and artesunate reveal profound activity not only against malaria, but also against cancer in vivo and clinical trials. Longitudinal observations on the efficacy of A. annua in patients are, however missing as of yet. Clinical diagnosis was performed by imaging techniques (MRT, scintigraphy, SPECT/CT) and blood examinations of standard parameters from clinical chemistry. Immunohistochemistry of formalin-fixed, paraffin-embedded tumor material was performed to determine the expression of several biomarkers (cycloxygenase-2 (COX2), epidermal growth factor receptor (EGFR), glutathione S-transferase P1 (GSTP1), Ki-67, MYC, oxidized low density lipoprotein (lectin-like) receptor 1 (LOX1), p53, P-glycoprotein, transferrin receptor (TFR, CD71), vascular endothelial growth factor (VEGF), von Willebrand factor (CD31)). The immunohistochemical expression has been compared with the microarray-based mRNA expression of these markers in two prostate carcinoma cell lines (PC-3, DU-145). A patient with prostate carcinoma (pT3bN1M1, Gleason score 8 (4+4)) presented with a prostate specific antigen (PSA) level >800 µg/l. After short-term treatment with bacalitumide (50 mg/d for 14 days) and long-term oral treatment with A. annua capsules (continuously 5 × 50 mg/d), the PSA level dropped down to 0.98 µg/l. MRT, scintigraphy and SPECT/CT verified tumor remission. Seven months later, PSA and ostase levels increased, indicating tumor recurrence and skeletal metastases. Substituting A. annua capsules by artesunate injections (2 × 150 mg twice weekly i.v.) did not prohibit tumor recurrence. PSA and ostase levels rose to 1245 µg/l and 434 U/l, respectively, and MRT revealed progressive skeletal metastases, indicating that the tumor acquired resistance. The high expression of MYC, TFR, and VEGFC in the patient biopsy corresponded with high expression of these markers in the artemisinin-sensitive PC-3 cells compared to artemisinin-resistant DU-145 cells

  2. SU-D-BRF-07: Ultrasound and Fluoroscopy Based Intraoperative Image-Guidance System for Dynamic Dosimetry in Prostate Brachytherapy

    SciTech Connect

    Kuo, N; Le, Y; Deguet, A; Prince, J; Song, D; Lee, J; Dehghan, E; Burdette, E; Fichtinger, G

    2014-06-01

    Purpose: Prostate brachytherapy is a common treatment method for low-risk prostate cancer patients. Intraoperative treatment planning is known to improve the treatment procedure and the outcome. The current limitation of intraoperative treatment planning is the inability to localize the seeds in relation to the prostate. We developed an image-guidance system to fulfill this need to achieve intraoperative dynamic dosimetry in prostate brachytherapy. Methods: Our system is based on standard imaging equipments available in the operating room, including the transrectal ultrasound (TRUS) and the mobile C-arm. A simple fiducial is added to compute the C-arm pose. Three fluoroscopic images and an ultrasound volume of the seeds and the prostate are acquired and processed by four image processing algorithms: seed segmentation, fiducial detection with pose estimation, seed reconstruction, and seeds-to-TRUS registration. The updated seed positions allow the physician to assess the quality of implantation and dynamically adjust the treatment plan during the course of surgery to achieve improved exit dosimetry. Results: The system was tested on 10 phantoms and 37 patients. Seed segmentation resulted in a 1% false negative and 2% false positive rates. Fiducial detection with pose estimation resulted in a detection rate of 98%. Seed reconstruction had a mean reconstruction error of 0.4 mm. Seeds-to-TRUS registration had a mean registration error of 1.3 mm. The total processing time from image acquisition to registration was approximately 1 minute. Conclusion: We present an image-guidance system for intraoperative dynamic dosimetry in prostate brachytherapy. Using standard imaging equipments and a simple fiducial, our system can be easily adopted in any clinics. Robust image processing algorithms enable accurate and fast computation of the delivered dose. Especially, the system enables detection of possible hot/cold spots during the surgery, allowing the physician to address these

  3. Economics of screening for carcinoma of the prostate.

    PubMed

    Optenberg, S A; Thompson, I M

    1990-11-01

    The proposition of whether to adopt a system of mass screening for carcinoma of the prostate in the U.S. is well suited to the clinical decision analysis approach. The authors demonstrate this by using available data, which suggest that offering a screening program to all men ages 50 to 70 would be prohibitively expensive. The method also permits calculation of the eventual morbidity of screening and its costs. This analysis demonstrates the importance of attempting to predict ultimate patient outcomes before implementing any health care strategy as standard.

  4. Dosimetric differences between intraoperative and postoperative plans using Cs-131 in transrectal ultrasound–guided brachytherapy for prostatic carcinoma

    SciTech Connect

    Jones, Andrew; Treas, Jared; Yavoich, Brian; Dean, Douglas; Danella, John; Yumen, Omar

    2014-01-01

    The aim of the study was to investigate the differences between intraoperative and postoperative dosimetry for transrectal ultrasound–guided transperineal prostate implants using cesium-131 ({sup 131}Cs). Between 2006 and 2010, 166 patients implanted with {sup 131}Cs had both intraoperative and postoperative dosimetry studies. All cases were monotherapy and doses of 115 were prescribed to the prostate. The dosimetric properties (D{sub 90}, V{sub 150}, and V{sub 100} for the prostate) of the studies were compared. Two conformity indices were also calculated and compared. Finally, the prostate was automatically sectioned into 6 sectors (anterior and posterior sectors at the base, midgland, and apex) and the intraoperative and postoperative dosimetry was compared in each individual sector. Postoperative dosimetry showed statistically significant changes (p < 0.01) in every dosimetric value except V{sub 150}. In each significant case, the postoperative plans showed lower dose coverage. The conformity indexes also showed a bimodal frequency distribution with the index indicating poorer dose conformity in the postoperative plans. Sector analysis revealed less dose coverage postoperatively in the base and apex sectors with an increase in dose to the posterior midgland sector. Postoperative dosimetry overall and in specific sectors of the prostate differs significantly from intraoperative planning. Care must be taken during the intraoperative planning stage to ensure complete dose coverage of the prostate with the understanding that the final postoperative dosimetry will show less dose coverage.

  5. Customized dose prescription for permanent prostate brachytherapy: insights from a multicenter analysis of dosimetry outcomes.

    PubMed

    Stone, Nelson N; Potters, Louis; Davis, Brian J; Ciezki, Jay P; Zelefsky, Michael J; Roach, Mack; Fearn, Paul A; Kattan, Michael W; Stock, Richard G

    2007-12-01

    To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group. Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. (125)I was used in 2,293 (58%), (103)Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140-200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log-rank test. The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate-, and high-dose group, respectively (p < 0

  6. Customized Dose Prescription for Permanent Prostate Brachytherapy: Insights From a Multicenter Analysis of Dosimetry Outcomes

    SciTech Connect

    Stone, Nelson N. Potters, Louis; Davis, Brian J.; Ciezki, Jay P.; Zelefsky, Michael J.; Roach, Mack; Fearn, Paul A. B.A.; Kattan, Michael W.; Stock, Richard G.

    2007-12-01

    Purpose: To investigate the biochemical control rate in patients undergoing permanent prostate brachytherapy as a function of the biologically effective dose (BED) and risk group. Methods and Materials: Six centers provided data on 3,928 permanent brachytherapy patients with postimplant dosimetry results. The mean prostate-specific antigen level was 8.9 ng/mL. {sup 125}I was used in 2,293 (58%), {sup 103}Pd in 1,635, and supplemental external beam radiotherapy in 882 (22.5%) patients. The patients were stratified into low- (n = 2,188), intermediate- (n = 1,188), and high- (n = 552) risk groups and into three BED groups of < 140 Gy (n = 524), 140-200 Gy (n = 2284), and >200 Gy (n = 1,115). Freedom from biochemical disease progression (biochemical freedom from failure [bFFF]) was determined using the American Society for Therapeutic Radiology Oncology and Phoenix definitions and calculated using the Kaplan-Meier method, with factors compared using the log-rank test. Results: The 10-year prostate-specific antigen bFFF rate for the American Society for Therapeutic Radiology Oncology and Phoenix definitions was 79.2% and 70%, respectively. The corresponding bFFF rates for the low-, intermediate-, and high-risk groups was 84.1% and 78.1%, 76.8% and 63.6%, and 64.4% and 58.2%, respectively (p < 0.0001). The corresponding bFFF rate for the three BED groups was 56.1% and 41.4%, 80% and 77.9%, and 91.1% and 82.9% (p < 0.0001). The corresponding bFFF rate for the low-risk patients by dose group was 69.8% and 49.8%, 86% and 85.2%, and 88.1% and 88.3% for the low-, intermediate, and high-dose group, respectively (p <0.0001). The corresponding bFFF rate for the intermediate-risk patients by dose group was 52.9% and 23.1%, 74.1% and 77.7%, and 94.3% and 88.8% for the low-, intermediate-, and high-dose group, respectively (p < 0.0001). The corresponding bFFF rate for high-risk patients by dose group was 19.2% and 41.7%, 61.8% and 53.2%, and 90% and 69.6% for the low-, intermediate

  7. A Vector-Based Short Hairpin RNA Targeting Aurora B Suppresses Human Prostatic Carcinoma Growth.

    PubMed

    Cao, Mei; Qi, Panpan; Chen, Chong; Song, Liju; Wang, Xuege; Li, Ningzhe; Wu, Daoyan; Hu, Guoku; Zhao, Jian

    2017-02-01

    Aurora kinase B, playing a vital, important role in mitosis, is frequently detected to be overexpressed in many cancer cell lines and various tumor tissues, including prostatic carcinoma. Given the essential function of Aurora kinase B in mitosis and its association with tumorigenesis, it might be a drug target for prostatic carcinoma treatment. In our study, short hairpin RNA targeting Aurora kinase B was cloned into a pGPU6 plasmid vector and then transfected into human prostatic carcinoma cells. The expression level of Aurora kinase B was verified by reverse transcription-polymerase chain reaction and Western blot. At the same time, cell apoptosis was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide, fluorescent staining, and flow cytometric analysis. Furthermore, prostate carcinoma cells were injected into mice to establish a tumor xenograft model. Previous studies have shown the effect of pGPU6-shAURKB plasmid on tumor growth in a prostate carcinoma xenogenic implantation model. From the study, we knew that the Aurora kinase B was significantly downregulated in prostate carcinoma cells, and cell apoptosis was also detected higher in treated groups than that in control groups. Moreover, in the prostate carcinoma xenogenic implantation model, compared with the control groups, the tumor growth was inhibited about 78.7% in the pGPU6-shAURKB plasmid-treated group, and cell apoptosis in the experimental group was notably higher than that in control groups. The average duration of tumor-bearing mice was prolonged to about 35 days. The results of experiment indicated that specific knockdown of Aurora kinase B led to prostate carcinoma cells apoptosis and inhibited tumor growth. Our data clearly confirmed that specific knockdown of Aurora kinase B expression by vector-based short hairpin RNA/liposome may be a potential new approach to treat human prostatic carcinoma.

  8. [177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer].

    PubMed

    Fendler, Wolfgang P; Kratochwil, Clemens; Ahmadzadehfar, Hojjat; Rahbar, Kambiz; Baum, Richard P; Schmidt, Matthias; Pfestroff, Andreas; Lützen, Ulf; Prasad, Vikas; Heinzel, Alexander; Heuschkel, Martin; Ruf, Juri; Bartenstein, Peter; Krause, Bernd J

    2016-06-28

    Radioligand therapy (RLT) using 177Lu labelled inhibitors of the prostate-specific membrane antigen (177Lu-PSMA) is performed in patients with metastatic castration-resistant prostate cancer (mCRPC) after exhaustion of other options. German University Clinics offer RLT since 2013 on a compassionate use basis. The present consensus document includes recommendations for RLT with 177Lu-PSMA-617. These consensus statements were developed by an expert panel formed by the German Society of Nuclear Medicine (DGN) in December 2015. Statements include recommendations for indication, baseline tests, therapy protocol, concomitant therapy, dosimetry, and follow-up. Consensus recommendations aim to inform the attending medical staff, standardize 177Lu-PSMA-617 RLT, and improve quality of individual patient care.

  9. Sarcomatoid carcinoma of the prostate: ductal adenocarcinoma and stromal sarcoma-like appearance: a rare association.

    PubMed

    Parada, David; Peña, Karla B; Riu, Francesc

    2011-01-01

    Sarcomatoid carcinoma (SC) of prostate gland is a rare biphasic tumour. In about half of cases, initial diagnosis is acinar adenocarcinoma, followed by nonsurgical therapy, with a subsequent diagnosis of SC. The survival rate is lower. We report a case of an 59-years-old man with unusual histopathologic finding of prostate sarcomatoid carcinoma, showing characteristics of ductal prostatic adenocarcinoma and prostatic stromal sarcoma-like appearance. Ductal adenocarcinoma was characterized by tall columnar cells with abundant amphophilic to eosinophil cytoplasm. Pleomorphic sarcoma was characterized to have overall glandular growth pattern, simulating a malignant phyllodes tumour. Estrogen and progesterone receptors showed nuclear immunostaining in mesenchymal multinucleated giant cells. In conclusion, SC of the prostate is an exceedingly rare tumour. Retrospective analyses render prostate SC as one of the most aggressive prostate malignancies. The prognosis is dismal regardless of other histologic or clinical findings.

  10. Evaluation of MENT on primary cell cultures from benign prostatic hyperplasia and prostate carcinoma.

    PubMed

    Mendoza, Patricia; Sánchez, Catherine; Contreras, Héctor R; Vergara, Jorge; Acevedo, Cristian; Cabezas, Juan; Huidobro, Christian; Noé, Gabriela; Castellón, Enrique A

    2009-12-01

    7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.

  11. Bony expansion in skeletal metastases from carcinoma of the prostate as seen by bone scintigraphy

    SciTech Connect

    Resnik, C.S.; Garver, P.; Resnick, D.

    1984-10-01

    Carcinoma of the prostate often metastasizes to the skeletal system, the usual radiologic pattern being widespread patchy areas of increased density without change in the contour of the involved bones. Radionuclide correlation generally shows multiple foci of increased tracer activity. Less commonly, there is bony sclerosis with expansion of the diameter of the involved bone. Several cases of expansile skeletal metastases from carcinoma of the prostate have appeared in the literature but we know of no published descriptions of the radionuclide findings. We present three patients with carcinoma of the prostate who had skeletal metastases with evidence of bony expansion on both roentgenographic and radionuclide examination. 15 references, 8 figures.

  12. EpCAM Expression in Lymph Node and Bone Metastases of Prostate Carcinoma: A Pilot Study

    PubMed Central

    Campos, Anna K.; Hoving, Hilde D.; Rosati, Stefano; van Leenders, Geert J. L. H.; de Jong, Igle J.

    2016-01-01

    There is an urgent need for new imaging modalities in prostate carcinoma staging. A non-invasive modality that can assess lymph node and bone metastases simultaneously is preferred. Epithelial cell adhesion molecule (EpCAM) is a membranous protein of interest as an imaging target since it is overexpressed in prostatic carcinoma compared with benign prostate epithelium and compared with stroma. However, EpCAM expression in lymph node metastases is sparsely available in the literature and EpCAM expression in bone metastases is yet unknown. The current study evaluates the expression of EpCAM in prostate carcinoma lymph nodes, in matched normal lymph nodes, in prostate carcinoma bone metastases, and in normal bone by immunohistochemistry. EpCAM was expressed in 100% of lymph node metastases (21 out of 21), in 0% of normal lymph nodes (0 out of 21), in 95% of bone metastases (19 out of 20), and in 0% of normal bone (0 out of 14). Based on these results, EpCAM may be a feasible imaging target in prostate carcinoma lymph node and bone metastases. Prospective clinical trials are needed to confirm current results. Preoperative visualization of prostate carcinoma metastases will improve disease staging and will prevent unnecessary invasive surgery. PMID:27690012

  13. 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

  14. Which patients benefit from post-implant CT dosimetry after real-time intraoperative planning for low dose rate prostate brachytherapy? Case series and systematic literature review.

    PubMed

    Mitina, Natalia; Christie, David; Hill, Brendan; Middlebrook, Nigel; Nadezhdin, Nikita

    2016-04-01

    At present, post-implant CT-based dosimetry is a standard quality assurance practice following low dose rate (LDR) prostate brachytherapy. However, it rarely influences management and involves radiation exposure, costs and inconvenience. The purpose of our study was to assess the need for post-implant CT-based dosimetry through correlation with pre-implant and real-time dosimetry and review its place in the management of patients treated with LDR brachytherapy, so that it could be undertaken more selectively. The real-time dosimetry parameters of 34 consecutive patients who underwent LDR brachytherapy were compared with day 30 post-implant CT-based dosimetry. To validate our results against the world practice, we performed a meta-analysis of six relevant published studies, which combined data from 699 patients. The Student's t-test was performed to verify whether our dosimetric parameters significantly differ from the results of the meta-analysis. In our case series, the mean target volume on real-time-planned US and post-implant CT was 33.9 and 32.7 cc, respectively (P > 0.05). The dose-volume histogram (DVH) parameters were significantly different between real-time-planned and post-implant dosimetry, but re-implantation was not needed for any patients. The literature review demonstrated that there is no consensus on measures being reported. Comparison showed that our cohort had significantly smaller prostate volumes, but the DVHs were similar to other series. Post-implant CT and dosimetry did not alter patients' management after real-time intraoperative planning. However, we recommend that it still be employed for difficult cases or if there are any concerns identified in real-time planned dosimetry. © 2015 The Royal Australian and New Zealand College of Radiologists.

  15. Prostate carcinoma, presenting with a solitary osteolytic bone lesion to the right hip.

    PubMed

    Agheli, Aref; Patsiornik, Yelena; Chen, Yu; Chaudhry, M Rashid; Gerber, Howard; Wang, Jen C

    2009-01-01

    Prostate cancer is the most common malignancy and the second most common cause of cancer-associated mortality in males. Bone metastasis is frequent and generally multiple and osteoblastic. Presentation of a pure osteolytic and solitary metastasis from a prostate carcinoma is extremely rare. We report a case of prostate cancer in a 70-year-old man who presented with progressive severe right hip pain and stiffness with no urinary symptom. A whole-body bone scan revealed a solitary metastasis to the right hip. A prostate biopsy revealed prostate adenocarcinoma. We believe this is the first reported case of presentation of a solitary osteolytic bone metastasis in the pelvis from carcinoma of the prostate.

  16. Primary squamous cell carcinoma of the prostate: a case report of a rare clinical entity.

    PubMed

    Biswas, Tithi; Podder, Tarun; Lepera, Pamela A; Walker, Paul

    2015-11-01

    Primary squamous cell carcinoma of the prostate is a unique and rare clinicopathological entity with fewer than 100 cases reported in the literature. Because of its rarity, the optimal management is not well known. Here, we report a case of primary squamous cell carcinoma of the prostate which was treated with definitive concurrent chemo-radiotherapy with excellent outcome along with a brief review of the literature.

  17. Primary squamous cell carcinoma of the prostate: a case report of a rare clinical entity

    PubMed Central

    Biswas, Tithi; Podder, Tarun; Lepera, Pamela A; Walker, Paul

    2015-01-01

    Primary squamous cell carcinoma of the prostate is a unique and rare clinicopathological entity with fewer than 100 cases reported in the literature. Because of its rarity, the optimal management is not well known. Here, we report a case of primary squamous cell carcinoma of the prostate which was treated with definitive concurrent chemo-radiotherapy with excellent outcome along with a brief review of the literature. PMID:28031893

  18. Successful treatment of metastatic androgen-independent prostate carcinoma in a transsexual patient.

    PubMed

    Dorff, Tanya B; Shazer, Ronald L; Nepomuceno, Edward M; Tucker, Steven J

    2007-06-01

    The occurrence of prostate carcinoma in transsexual patients has rarely been reported. These cases present a unique challenge in that such patients are effectively receiving androgen deprivation therapy. By definition, their disease is androgen-independent prostate cancer, and the role of local therapy is undefined. We report on a male-to-female transsexual patient with metastatic prostate cancer treated successfully with combination chemotherapy after previous standard therapy failed.

  19. Localization of linked {sup 125}I seeds in postimplant TRUS images for prostate brachytherapy dosimetry

    SciTech Connect

    Xue Jinyu . E-mail: Jinyu.Xue@mail.tju.edu; Waterman, Frank; Handler, Jay; Gressen, Eric

    2005-07-01

    Purpose: To demonstrate that {sup 125}I seeds can be localized in transrectal ultrasound (TRUS) images obtained with a high-resolution probe when the implant is performed with linked seeds and spacers. Adequate seed localization is essential to the implementation of TRUS-based intraoperative dosimetry for prostate brachytherapy. Methods and Materials: Thirteen preplanned peripherally loaded prostate implants were performed using {sup 125}I seeds and spacers linked together in linear arrays that prevent seed migration and maintain precise seed spacing. A set of two-dimensional transverse images spaced at 0.50-cm intervals were obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. The image set extended from 1.0 cm superior to the base to 1.0 cm inferior to the apex. The visible echoes along each needle track were first localized and then compared with the known construction of the implanted array. The first step was to define the distal and proximal ends of each array. The visible echoes were then identified as seeds or spacers from the known sequence of the array. The locations of the seeds that did not produce a visible echo were interpolated from their known position in the array. A CT scan was obtained after implantation for comparison with the TRUS images. Results: On average, 93% (range, 86-99%) of the seeds were visible in the TRUS images. However, it was possible to localize 100% of the seeds in each case, because the locations of the missing seeds could be determined from the known construction of the arrays. Two factors complicated the interpretation of the TRUS images. One was that the spacers also produced echoes. Although weak and diffuse, these echoes could be mistaken for seeds. The other was that the number of echoes along a needle track sometimes exceeded the number of seeds and spacers implanted. This was attributed to the overall length of the array, which was approximately 0.5 cm

  20. Perturbation of NK cell peripheral homeostasis accelerates prostate carcinoma metastasis

    PubMed Central

    Liu, Gang; Lu, Shengjun; Wang, Xuanjun; Page, Stephanie T.; Higano, Celestia S.; Plymate, Stephen R.; Greenberg, Norman M.; Sun, Shaoli; Li, Zihai; Wu, Jennifer D.

    2013-01-01

    The activating receptor NK cell group 2 member D (NKG2D) mediates antitumor immunity in experimental animal models. However, whether NKG2D ligands contribute to tumor suppression or progression clinically remains controversial. Here, we have described 2 novel lines of “humanized” bi-transgenic (bi-Tg) mice in which native human NKG2D ligand MHC class I polypeptide-related sequence B (MICB) or the engineered membrane-restricted MICB (MICB.A2) was expressed in the prostate of the transgenic adenocarcinoma of the mouse prostate (TRAMP) model of spontaneous carcinogenesis. Bi-Tg TRAMP/MICB mice exhibited a markedly increased incidence of progressed carcinomas and metastasis, whereas TRAMP/MICB.A2 mice enjoyed long-term tumor-free survival conferred by sustained NKG2D-mediated antitumor immunity. Mechanistically, we found that cancer progression in TRAMP/MICB mice was associated with loss of the peripheral NK cell pool owing to high serum levels of tumor-derived soluble MICB (sMICB). Prostate cancer patients also displayed reduction of peripheral NK cells and high sMIC levels. Our study has not only provided direct evidence in “humanized” mouse models that soluble and membrane-restricted NKG2D ligands pose opposite impacts on cancer progression, but also uncovered a mechanism of sMIC-induced impairment of NK cell antitumor immunity. Our findings suggest that the impact of soluble NKG2D ligands should be considered in NK cell–based cancer immunotherapy and that our unique mouse models should be valuable for therapy optimization. PMID:24018560

  1. Genetic and Molecular Mechanisms in Assessing Response in Patients With Prostate Cancer Receiving Enzalutamide Therapy

    ClinicalTrials.gov

    2017-08-23

    Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma in the Soft Tissue; Metastatic Prostatic Adenocarcinoma; Prostate Carcinoma Metastatic in the Bone; PSA Progression; Recurrent Prostate Carcinoma; Stage III Prostate Adenocarcinoma; Stage IV Prostate Adenocarcinoma

  2. An immunohistochemical assessment of hypoxia in prostate carcinoma using pimonidazole: Implications for radioresistance

    SciTech Connect

    Carnell, Dawn M. . E-mail: peterhoskin@nhs.net; Smith, Rowena E.; Daley, Frances; Saunders, Michele I.; Bentzen, Soren M.; Hoskin, Peter J.

    2006-05-01

    Purpose: To investigate the presence of hypoxia in human prostate carcinoma by using pimonidazole immunohistochemical labeling in radical prostatectomy specimens. Methods and Materials: Forty-three patients (median age, 69 years; range, 49-83 years) with localized prostate adenocarcinoma received 0.5 gm/m{sup 2} i.v. pimonidazole 16-24 h before radical prostatectomy. Hypoxia was detected with a monoclonal antibody directed against pimonidazole and scored in formalin-fixed, paraffin-embedded sections. Median and maximal vessel counts were measured with CD34. Results: Thirty-seven patients completed the study. Pimonidazole binding was present in prostate carcinomas in 34 of 37 patients (92%) and in benign prostatic hyperplasia in 35 of 37 patients (95%). A positive correlation of 3+ pimonidazole binding with Gleason score was demonstrated (Spearman's rank, p = 0.044). Vascularity scores did not correlate with hypoxic status or clinical prognostic parameters. Conclusion: Prostate carcinoma and benign prostatic hyperplasia have significant areas of hypoxia; greater hypoxia scores are seen with more aggressive prostate cancer. It is postulated that a hypoxic microenvironment within the prostate might be responsible for the promotion of secondary genetic alterations and angiogenic stimulation, leading to malignant progression, a more aggressive cell phenotype, and greater radioresistance. Modification of radiation regimens to specifically target hypoxia might improve local tumor control.

  3. Unusual Cushing's Syndrome and Hypercalcitoninaemia due to a Small Cell Prostate Carcinoma

    PubMed Central

    Magnani, Elena; Nuzzo, Fiorella

    2016-01-01

    A 75-year-old man was hospitalized because of severe hypokalaemia due to ACTH dependent Cushing's syndrome. Total body computed tomography (TBCT) and 68 Gallium DOTATATE PET/CT localized a voluminous prostate tumour. A subsequent transurethral prostate biopsy documented a small cell carcinoma positive for ACTH and calcitonin and negative for prostatic specific antigen (PSA) at immunocytochemical study; serum prostatic specific antigen (PSA) was normal. Despite medical treatments, Cushing's syndrome was not controlled and the patient's clinical condition progressively worsened. Surgical resection was excluded; the patient underwent a cycle of chemotherapy followed by febrile neutropenia and fatal intestinal perforation. This case report describes a rare case of Cushing's syndrome and hypercalcitoninaemia due to a small cell carcinoma of the prostate, a rare tumour with very few therapeutic options and negative prognosis. PMID:28044110

  4. Intraductal Carcinoma of the Prostate on Diagnostic Needle Biopsy Predicts Prostate Cancer Mortality: A Population-Based Study.

    PubMed

    Saeter, Thorstein; Vlatkovic, Ljiljana; Waaler, Gudmund; Servoll, Einar; Nesland, Jahn M; Axcrona, Karol; Axcrona, Ulrika

    2017-06-01

    Intraductal carcinoma of the prostate (IDC-P) is a distinct histopathologic feature associated with high-grade, advanced prostate cancer. Although studies have shown that IDC-P is a predictor of progression following surgical or radiation treatment for prostate cancer, there are sparse data regarding IDC-P on diagnostic needle biopsy as a prognosticator of prostate cancer mortality. This was a population-based study of all prostate cancer patients diagnosed using needle biopsy and without evidence of systemic disease between 1991 and 1999 within a defined geographic region of Norway. Patients were identified by cross-referencing the Norwegian Cancer Registry. Of 318 eligible patients, 283 had biopsy specimens available for central pathology review. Clinical data were obtained from medical charts. We examined whether IDC-P on diagnostic needle biopsy was associated with adverse clinicopathological features and prostate cancer mortality. Patients with IDC-P on diagnostic needle biopsy had a more advanced stage and a higher Gleason score compared to patients without IDC-P. IDC-P was also associated with an intensively reactive stroma. The 10-year prostate cancer-specific survival was 69% for patients with IDC-P on diagnostic needle biopsy and 89% for patients without IDC-P (Log rank P-value < 0.005). The presence of IDC-P on diagnostic needle biopsy remained an independent predictor of prostate cancer mortality after adjustments for clinical prognostic factors and treatment. After adjustment for the newly implemented Grade Group system of prostate cancer, IDC-P showed a strong tendency toward statistical significance. However, IDC-P did not remain a statistically significant predictor in the multivariable analysis. IDC-P on diagnostic needle biopsy is an indicator of prostate cancer with a high risk of mortality. Accordingly, a diagnosis of IDC-P on needle biopsy should be reported and considered a feature of high-risk prostate cancer. Moreover, the association

  5. Radiation, hormonotherapy, survival and local control in prostatic carcinoma.

    PubMed

    Cellini, N; Luzi, S; Morganti, A G; Smaniotto, D; Niespolo, R M; Valentini, V

    1998-01-01

    The combination of concomitant external beam radiotherapy (ERT) and neoadjuvant hormonotherapy was shown to be able to significantly improve local control and disease-free survival in locally advanced prostatic carcinoma. (RTOG study 8610). Aim of this analysis was to assess the clinical results observed in a population of patients undergoing this combined treatment and, more particularly, to examine the prognostic impact of local control. 84 patients (T2: 47%, T3: 49.4%, T4: 3.6%) underwent concomitant ERT (dose to pelvic volume: 45 Gy; mean dose to prostatic volume: 65 Gy) and neoadjuvant hormonotherapy (flutamide: 250 mg three times/daily for 30 days; LH-RH analogue: 1 oral dose every 28 days starting 2 months prior to radiotherapy and for its whole duration). With a median follow-up of 36 months, 3.6% of patients were deceased; hematogenous metastases and local disease progression were recorded in 16.7% and 4.8% of patients, respectively. Local disease progression was shown to be significantly correlated with the incidence of metastases. In fact, the actuarial incidence of metastases at 5 years was 100% and 27% in patients with and without local recurrence (p = 0.0043) respectively. Overall, metastases-free local and biochemical recurrence-free survival was 89.2%, 66.5%, 85.0% and 41.9% respectively. At univariate analysis (logrank) the clinical stage (T) was shown to be significantly correlated with the incidence of metastases (p = .0004) and local progression (p < .0001). In conclusion, this study has confirmed the low rate of local progression with the combination of hormonotherapy and radiotherapy and the significant correlation of local control with the incidence of hematogenous metastases.

  6. Potential impact of prostate edema on the dosimetry of permanent seed implants using the new {sup 131}Cs (model CS-1) seeds

    SciTech Connect

    Chen Zhe; Deng Jun; Roberts, Kenneth; Nath, Ravinder

    2006-04-15

    Our aim in this work was to study the potential dosimetric effect of prostate edema on the accuracy of conventional pre- and post-implant dosimetry for prostate seed implants using the newly introduced {sup 131}Cs seed, whose radioactive decay half-life ({approx}9.7 days) is directly comparable to the average edema resolution half-life ({approx}10 days) observed previously by Waterman et al. for {sup 125}I implants [Int. J. Radiat. Oncol. Biol. Phys. 41, 1069-1077 (1998)]. A systematic calculation of the relative dosimetry effect of prostate edema on the {sup 131}Cs implant was performed by using an analytic solution obtained previously [Int. J. Radiat. Oncol. Biol. Phys. 47, 1405-1419 (2000)]. It was found that conventional preimplant dosimetry always overestimates the true delivered dose as it ignores the temporary increase of the interseed distance caused by edema. The overestimation for {sup 131}Cs implants ranged from 1.2% (for a small edema with a magnitude of 10% and a half-life of 2 days) to approximately 45% (for larger degree edema with a magnitude of 100% and a half-life of 25 days). The magnitude of pre- and post-implant dosimetry error for {sup 131}Cs implants was found to be similar to that of {sup 103}Pd implants for typical edema characteristics (magnitude <100%, and half-life <25 days); both of which are worse compared to {sup 125}I implants. The preimplant dosimetry error for {sup 131}Cs implants cannot be compensated effectively without knowing the edema characteristics before the seed implantation. On the other hand, the error resulted from a conventional post-implant dosimetry can be minimized (to within {+-}6%) for {sup 131}Cs implants if the post-implant dosimetry is performed at 10{+-}2 days post seed implantation. This 'optimum' post-implant dosimetry time is shorter than those determined previously for the {sup 103}Pd and {sup 125}I implants at 16{+-}4 days and 6{+-}1 weeks, respectively.

  7. MiRNA regulation of TRAIL expression exerts selective cytotoxicity to prostate carcinoma cells.

    PubMed

    Huo, Wei; Jin, Ning; Fan, Li; Wang, Weihua

    2014-03-01

    Prostate carcinoma is the most common cancer for men and among the leading cancer-related causes. Many evidences have shown that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) potently induces apoptosis in cancer cells, and thus, is a promising biologic agent for prostate carcinoma therapy. However, TRAIL expression mediated by the current vectors lacks tumor specificity, thereby exerting cytotoxicity to normal cells. To solve this problem, we inserted miRNA response elements (MREs), miR-143 and miR-145, expression levels of which were reduced in prostate carcinoma, as well as that of miR-122, which is specifically expressed in hepatic cells, into adenoviral vectors to control TRAIL expression (Ad-TRAIL-M3). qPCR data confirmed that miR-143, miR-145, and miR-122 levels were all decreased in prostate carcinoma cell lines and prostate cancer samples from patients. Luciferase assays showed that MREs-regulated luciferase expression was potently suppressed in normal cells, but not in prostate cancer cells. Ad-TRAIL-M3, which expresses TRAIL in a MREs-regulated manner, produced high level of TRAIL and suppressed the survival of prostate cancer cells by inducing apoptosis, while Ad-TRAIL-M3 had no TRAIL expression in normal cells and thus exerted no cytotoxicity to them. The studies on PC-3 tumor xenograft in mice further confirmed that Ad-TRAIL-M3 was able to inhibit the growth of tumors and possessed high biosafety. In conclusion, we successfully generated an adenoviral vector that expresses TRAIL in miRNA-regulated mechanism. This miRNA-based gene therapy may be promising for prostate carcinoma treatment.

  8. An evaluation of the contouring abilities of medical dosimetry students for the anatomy of a prostate cancer patient

    SciTech Connect

    Collins, Kevin S.

    2012-10-01

    Prostate cancer is one of the most common diseases treated in a radiation oncology department. One of the major predictors of the treatment outcome and patient side effects is the accuracy of the anatomical contours for the treatment plan. Therefore, the purpose of this study was to determine which anatomical structures are most often contoured correctly and incorrectly by medical dosimetry students. The author also wanted to discover whether a review of the contouring rules would increase contouring accuracy. To achieve this, a male computed tomography dataset consisting of 72 transverse slices was sent to students for contouring. The students were instructed to import this dataset into their treatment planning system and contour the following structures: skin, bladder, rectum, prostate, penile bulb, seminal vesicles, left femoral head, and right femoral head. Upon completion of the contours, the contour file was evaluated against a 'gold standard' contour set using StructSure software (Standard Imaging, Inc). A review of the initial contour results was conducted and then students were instructed to contour the dataset a second time. The results of this study showed significant differences between contouring sessions. These results and the standardization of contouring rules should benefit all individuals who participate in the treatment planning of cancer patients.

  9. Real-time in vivo rectal wall dosimetry using plastic scintillation detectors for patients with prostate cancer

    PubMed Central

    Wootton, Landon; Kudchadker, Rajat; Lee, Andrew; Beddar, Sam

    2014-01-01

    We designed and constructed an in vivo dosimetry system using plastic scintillation detectors (PSDs) to monitor dose to the rectal wall in patients undergoing intensity-modulated radiation therapy for prostate cancer. Five patients were enrolled in an Institutional Review Board–approved protocol for twice weekly in vivo dose monitoring with our system, resulting in a total of 142 in vivo dose measurements. PSDs were attached to the surface of endorectal balloons used for prostate immobilization to place the PSDs in contact with the rectal wall. Absorbed dose was measured in real time and the total measured dose was compared with the dose calculated by the treatment planning system on the daily CT image dataset. The mean difference between measured and calculated doses for the entire patient population was −0.4% (standard deviation 2.8%). The mean difference between daily measured and calculated doses for each patient ranged from −3.3% to 3.3% (standard deviation ranged from 5.6% to 7.1% for 4 patients and was 14.0% for the last, for whom optimal positioning of the detector was difficult owing to the patient’s large size). Patients tolerated the detectors well and the treatment workflow was not compromised. Overall, PSDs performed well as in vivo dosimeters, providing excellent accuracy, real-time measurement, and reusability. PMID:24434775

  10. Accuracy of dose planning for prostate radiotherapy in the presence of metallic implants evaluated by electron spin resonance dosimetry

    PubMed Central

    Alves, G.G.; Kinoshita, A.; de Oliveira, H.F.; Guimarães, F.S.; Amaral, L.L.; Baffa, O.

    2015-01-01

    Radiotherapy is one of the main approaches to cure prostate cancer, and its success depends on the accuracy of dose planning. A complicating factor is the presence of a metallic prosthesis in the femur and pelvis, which is becoming more common in elderly populations. The goal of this work was to perform dose measurements to check the accuracy of radiotherapy treatment planning under these complicated conditions. To accomplish this, a scale phantom of an adult pelvic region was used with alanine dosimeters inserted in the prostate region. This phantom was irradiated according to the planned treatment under the following three conditions: with two metallic prostheses in the region of the femur head, with only one prosthesis, and without any prostheses. The combined relative standard uncertainty of dose measurement by electron spin resonance (ESR)/alanine was 5.05%, whereas the combined relative standard uncertainty of the applied dose was 3.35%, resulting in a combined relative standard uncertainty of the whole process of 6.06%. The ESR dosimetry indicated that there was no difference (P>0.05, ANOVA) in dosage between the planned dose and treatments. The results are in the range of the planned dose, within the combined relative uncertainty, demonstrating that the treatment-planning system compensates for the effects caused by the presence of femur and hip metal prostheses. PMID:26017344

  11. [Complete remission of endobronchial, parenchymal and hilar lymphatic lung metastases of prostatic carcinoma after anti-androgenic hormotherapy].

    PubMed

    Morrone, N; Volpe, V L; Dourado, A M; Coletta, E N

    1996-01-01

    A 65 year old male Negro had respiratory and urinary symptoms for the last 5 months. The work-up disclosed a prostatic carcinoma with metastases in bones, bronchus, lung parenchyma and hilar lymphnodes. Prostatic and bronchial biopsies revealed carcinoma; specific prostatic antigen was detected in both. A prostatectomy with bilateral orchiectomy was performed followed by anti-androgenic hormotherapy. Complete remission of metastatic bronchial, lung parenchyma and lymphatic lesions was observed; bone lesions did not change. lung and bronchial metastases of prostatic carcinoma may resemble primitive bronchial tumor; complete remission with anti-androgenic therapy is possible, saving the patient from unnecessary radio and/or chemotherapy.

  12. Investigation of the gold nanoparticles effects on the prostate dose distribution in brachytherapy: gel dosimetry and Monte Carlo method

    PubMed Central

    Hashemi, Bijan; Rahmani, Faezeh; Ebadi, Ahmad

    2016-01-01

    Purpose In this work, gold nanoparticles (GNPs) were embedded in the MAGIC-f polymer gel irradiated with the 192Ir brachytherapy sources. Material and methods At the first plexiglas phantom was made as the human pelvis. The GNPs were synthesized with 15 nm in diameter and 0.1 mM (0.0197 mg/ml) in concentration by using a chemical reduction method. Then, the MAGIC-f gel was synthesized. The fabricated gel was poured into the tubes located at the prostate (with and without the GNPs) locations of the phantom. The phantom was irradiated with 192Ir brachytherapy sources for prostate cancer. After 24 hours, the irradiated gels was read by using Siemens 1.5 Tesla MRI scanner. Following the brachytherapy practices, the absolute doses at the reference points and isodose curves were extracted and compared by experimental measurements and Monte Carlo (MC) simulations. Results The mean absorbed doses in the presence of the GNPs in prostate were 14% higher than the corresponding values without the GNPs in the brachytherapy. The gamma index analysis (between gel and MC) using 7%/7 mm was also applied to the data and a high pass rate achieved (91.7% and 86.4% for analysis with/without GNPs, respectively). Conclusions The real three-dimensional analysis shows the comparison of the dose-volume histograms measured for planning volumes and the expected one from the MC calculation. The results indicate that the polymer gel dosimetry method, which developed and used in this study, could be recommended as a reliable method for investigating the dose enhancement factor of GNPs in brachytherapy. PMID:27895684

  13. An analysis of intraoperative versus post-operative dosimetry with CT, CT-MRI fusion and XMR for the evaluation of permanent prostate brachytherapy implants.

    PubMed

    Acher, Peter; Puttagunta, Srikanth; Rhode, Kawal; Morris, Stephen; Kinsella, Janette; Gaya, Andrew; Dasgupta, Prokar; Deehan, Charles; Beaney, Ronald; Popert, Rick; Keevil, Stephen

    2010-08-01

    To assess the agreement between intraoperative and post-operative dosimetry and to identify factors that influence dose calculations of prostate brachytherapy implants. Patients treated with prostate brachytherapy implants underwent post-operative CT and XMR (combined X-ray and MR) imaging. Dose-volume histograms were calculated from CT, XMR and CT-MR fusion data and compared with intraoperative values for two observers. Multiple linear regression models assessed the influences of intraoperative D90, gland oedema, gland volume, source loss and migration, and implanted activity/volume prostate on post-operative D90. Forty-nine patients were studied. The mean D90 differences (95% confidence limits) between intraoperative and post-operative CT, XMR and CT-MR fusion assessments were: 11 Gy (-22, 45), 18 Gy (-13, 49) and 20 Gy (-17, 58) for Observer 1; and 15 Gy (-34, 63), 13 Gy (-29, 55) and 14 Gy (-27, 54) for Observer 2. Multiple linear regression modelling showed that the observed oedema and intraoperative D90 were significant independent variables for the prediction of post-operative D90 values for both observers using all modalities. This is the first study to report Bland-Altman agreement analysis between intraoperative and post-operative dosimetry. Agreement is poor. Post-operative dosimetry is dependent on the intraoperative D90 and the subjectively outlined gland volume. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  14. F-18 labelled PSMA-1007: biodistribution, radiation dosimetry and histopathological validation of tumor lesions in prostate cancer patients.

    PubMed

    Giesel, Frederik L; Hadaschik, B; Cardinale, J; Radtke, J; Vinsensia, M; Lehnert, W; Kesch, C; Tolstov, Y; Singer, S; Grabe, N; Duensing, S; Schäfer, M; Neels, O C; Mier, W; Haberkorn, U; Kopka, K; Kratochwil, C

    2017-04-01

    The prostate-specific membrane antigen (PSMA) targeted positron-emitting-tomography (PET) tracer (68)Ga-PSMA-11 shows great promise in the detection of prostate cancer. However, (68)Ga has several shortcomings as a radiolabel including short half-life and non-ideal energies, and this has motivated consideration of (18)F-labelled analogs. (18)F-PSMA-1007 was selected among several (18)F-PSMA-ligand candidate compounds because it demonstrated high labelling yields, outstanding tumor uptake and fast, non-urinary background clearance. Here, we describe the properties of (18)F-PSMA-1007 in human volunteers and patients. Radiation dosimetry of (18)F-PSMA-1007 was determined in three healthy volunteers who underwent whole-body PET-scans and concomitant blood and urine sampling. Following this, ten patients with high-risk prostate cancer underwent (18)F-PSMA-1007 PET/CT (1 h and 3 h p.i.) and normal organ biodistribution and tumor uptakes were examined. Eight patients underwent prostatectomy with extended pelvic lymphadenectomy. Uptake in intra-prostatic lesions and lymph node metastases were correlated with final histopathology, including PSMA immunostaining. With an effective dose of approximately 4.4-5.5 mSv per 200-250 MBq examination, (18)F-PSMA-1007 behaves similar to other PSMA-PET agents as well as to other (18)F-labelled PET-tracers. In comparison to other PSMA-targeting PET-tracers, (18)F-PSMA-1007 has reduced urinary clearance enabling excellent assessment of the prostate. Similar to (18)F-DCFPyL and with slightly slower clearance kinetics than PSMA-11, favorable tumor-to-background ratios are observed 2-3 h after injection. In eight patients, diagnostic findings were successfully validated by histopathology. (18)F-PSMA-1007 PET/CT detected 18 of 19 lymph node metastases in the pelvis, including nodes as small as 1 mm in diameter. (18)F-PSMA-1007 performs at least comparably to (68)Ga-PSMA-11, but its longer half-life combined with its superior energy

  15. Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells.

    PubMed

    Pastori, M; Pfander, H; Boscoboinik, D; Azzi, A

    1998-09-29

    The effect of lycopene alone or in association with other antioxidants was studied on the growth of two different human prostate carcinoma cell lines (the androgen insensitive DU-145 and PC-3). It was found that lycopene alone was not a potent inhibitor of prostate carcinoma cell proliferation. However, the simultaneous addition of lycopene together with alpha-tocopherol, at physiological concentrations (less than 1 microM and 50 microM, respectively), resulted in a strong inhibitory effect of prostate carcinoma cell proliferation, which reached values close to 90 %. The effect of lycopene with alpha-tocopherol was synergistic and was not shared by beta-tocopherol, ascorbic acid and probucol. Copyright 1998 Academic Press.

  16. Metastatic superscan in prostate carcinoma on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography scan.

    PubMed

    Agarwal, Krishan Kant; Tripathi, Madhavi; Kumar, Rajeev; Bal, Chandrasekhar

    2016-01-01

    We describe the imaging features of a metastatic superscan on gallium-68 Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as gallium-68-prostate-specific membrane antigen ((68)Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging. (68)Ga-PSMA is novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. This patient had a superscan of metastases on conventional bone scintigraphy and was referred for (68)Ga-PSMA PET/CT to evaluate the feasibility of (177)Lu-PSMA therapy.

  17. Tissue composition and density impact on the clinical parameters for (125)I prostate implants dosimetry.

    PubMed

    Oliveira, Susana Maria; Teixeira, Nuno José; Fernandes, Lisete; Teles, Pedro; Vieira, Guy; Vaz, Pedro

    2014-11-01

    The MCNPX code was used to calculate the TG-43U1 recommended parameters in water and prostate tissue in order to quantify the dosimetric impact in 30 patients treated with (125)I prostate implants when replacing the TG-43U1 formalism parameters calculated in water by a prostate-like medium in the planning system (PS) and to evaluate the uncertainties associated with Monte Carlo (MC) calculations. The prostate density was obtained from the CT of 100 patients with prostate cancer. The deviations between our results for water and the TG-43U1 consensus dataset values were -2.6% for prostate V100, -13.0% for V150, and -5.8% for D90; -2.0% for rectum V100, and -5.1% for D0.1; -5.0% for urethra D10, and -5.1% for D30. The same differences between our water and prostate results were all under 0.3%. Uncertainties estimations were up to 2.9% for the gL(r) function, 13.4% for the F(r,θ) function and 7.0% for Λ, mainly due to seed geometry uncertainties. Uncertainties in extracting the TG-43U1 parameters in the MC simulations as well as in the literature comparison are of the same order of magnitude as the differences between dose distributions computed for water and prostate-like medium. The selection of the parameters for the PS should be done carefully, as it may considerably affect the dose distributions. The seeds internal geometry uncertainties are a major limiting factor in the MC parameters deduction. Copyright © 2014. Published by Elsevier Ltd.

  18. Olaparib With or Without Cediranib in Treating Patients With Metastatic Castration-Resistant Prostate Cancer

    ClinicalTrials.gov

    2017-09-12

    Castration Levels of Testosterone; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma With Focal Neuroendocrine Differentiation; Prostate Carcinoma Metastatic in the Bone; Prostate Small Cell Carcinoma; PSA Progression; Stage IV Prostate Adenocarcinoma

  19. Intraductal carcinoma of the prostate: a distinct histopathological entity with important prognostic implications.

    PubMed

    Henry, P C; Evans, A J

    2009-07-01

    Intraductal carcinoma of the prostate (IDCP) has been described as a lesion associated with poor prognostic features in prostate cancer. Its recognition and reporting in prostate specimens, particularly in needle biopsies, is critical as it carries significant implications for patient management. Recent histological definitions have been proposed to assist in the recognition of IDCP and to help distinguish it from lesions with similar appearance, but different clinical behaviour. In this review, a historical overview of the description of IDCP will be presented followed by a summary of the current histological diagnostic criteria and the recommendations for management and reporting of IDCP.

  20. Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil

    PubMed Central

    Araujo-Neto, Ari P.; Ferreira-Fernandes, Hygor; Amaral, Carolina M.M.; Santos, Lina G.; Freitas, Antônio C.; Silva-Neto, Jacinto C.; Rey, Juan A.; Burbano, Rommel R.; da Silva, Benedito B.; Yoshioka, France K.N.; Pinto, Giovanny R.

    2016-01-01

    Abstract Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied. PMID:27007894

  1. Lack of detection of human papillomavirus DNA in prostate carcinomas in patients from northeastern Brazil.

    PubMed

    Araujo-Neto, Ari P; Ferreira-Fernandes, Hygor; Amaral, Carolina M M; Santos, Lina G; Freitas, Antônio C; Silva-Neto, Jacinto C; Rey, Juan A; Burbano, Rommel R; Silva, Benedito B da; Yoshioka, France K N; Pinto, Giovanny R

    2016-03-01

    Prostate cancer is the second most common cancer among men in western populations, and despite its high mortality, its etiology remains unknown. Inflammatory processes are related to the etiology of various types of tumors, and prostate inflammation, in particular, has been associated with prostate cancer carcinogenesis and progression. Human papillomavirus (HPV) is associated with benign and malignant lesions in the anogenital tract of both females and males. The possible role of HPV in prostate carcinogenesis is a subject of great controversy. In this study, we aimed to examine the prevalence of HPV infections in prostate carcinomas of patients from northeastern Brazil. This study included 104 tissue samples from primary prostate carcinoma cases. HPV DNA was purified and then amplified using MY09/11 and GP5+/GP6+ degenerate primer sets that detect a wide range of HPV types, and with specific PCR primers sets for E6 and E7 HPV regions to detect HPV 16. None of the samples showed amplification products of HPV DNA for primer sets MY09/11 and GP5+/GP6+, or the specific primer set for the E6 and E7 HPV regions. HPV infection, thus, does not seem to be one of the causes of prostate cancer in the population studied.

  2. Membrane testosterone binding sites in prostate carcinoma as a potential new marker and therapeutic target: Study in paraffin tissue sections

    PubMed Central

    Dambaki, Constantina; Kogia, Christina; Kampa, Marilena; Darivianaki, Katherine; Nomikos, Michael; Anezinis, Ploutarchos; Theodoropoulos, Panayiotis A; Castanas, Elias; Stathopoulos, Efstathios N

    2005-01-01

    Background Steroid action is mediated, in addition to classical intracellular receptors, by recently identified membrane sites, that generate rapid non-genomic effects. We have recently identified a membrane androgen receptor site on prostate carcinoma cells, mediating testosterone rapid effects on the cytoskeleton and secretion within minutes. Methods The aim of this study was to investigate whether membrane androgen receptors are differentially expressed in prostate carcinomas, and their relationship to the tumor grade. We examined the expression of membrane androgen receptors in archival material of 109 prostate carcinomas and 103 benign prostate hyperplasias, using fluorescein-labeled BSA-coupled testosterone. Results We report that membrane androgen receptors are preferentially expressed in prostate carcinomas, and they correlate to their grade using the Gleason's microscopic grading score system. Conclusion We conclude that membrane androgen receptors may represent an index of tumor aggressiveness and possibly specific targets for new therapeutic regimens. PMID:16293185

  3. Influence of source batch S{sub K} dispersion on dosimetry for prostate cancer treatment with permanent implants

    SciTech Connect

    Nuñez-Cumplido, E. Hernandez-Armas, J.; Perez-Calatayud, J.; Casares-Magaz, O.

    2015-08-15

    Purpose: In clinical practice, specific air kerma strength (S{sub K}) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with {sup 125}I and {sup 103}Pd sources; in fact, commercial TPS provide only one S{sub K} input value for all implanted sources and the certified shipment average is typically used. However, the value for S{sub K} is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their S{sub K} values. The purpose of this work is to examine the impact of S{sub K} dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). Methods: The authors have developed a new algorithm to compute dose distributions with different S{sub K} values for each source. Three different prostate volumes (20, 30, and 40 cm{sup 3}) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for {sup 125}I sources; for the palladium, typical implants were simulated. To assess the many different possible S{sub K} values for each source belonging to a class, the authors assigned an S{sub K} value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform S{sub K} value for all the implanted sources. The authors analyzed several dose coverage (V{sub 100} and D{sub 90}) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and

  4. The 1999 patterns of care study of radiotherapy in localized prostate carcinoma: a comprehensive survey of prostate brachytherapy in the United States.

    PubMed

    Lee, W Robert; Moughan, Jennifer; Owen, Jean B; Zelefsky, Michael J

    2003-11-01

    The objective of the current study was to provide descriptive information on a representative national sample of patients with prostate carcinoma who were treated with prostate brachytherapy (PB) in calendar year 1999. A random survey was conducted by the Patterns of Care Study in radiation oncology of 59 facilities (1 facility had no eligible patients) that treated patients with prostate carcinoma in 1999 in the United States. A weighted sample size of 36,496 patients with prostate cancer was included in the 1999 survey (unweighted sample size, 554 patients). The main measures were the clinical characteristics of men prior to treatment and the technical characteristics of PB. Patients were classified into three prognostic groups according to T stage, pretreatment prostate specific antigen (PSA) level, and Gleason score. A weighted sample size of 13,293 patients (36%; unweighted sample size, 162 patients) was treated with PB. Compared with a weighted sample size of 23,203 patients (64%; unweighted sample size, 392 patients) was treated with external beam radiotherapy (EB), patients who received PB were significantly younger (mean age: PB group, 67.7 years; EB group, 70.8 years; P = 0.0006). The mean pretreatment PSA level for the PB group was lower compared with the EB group (9.9 ng/mL vs. 13.33 ng/mL; P = 0.0015). The prognostic groupings were more favorable for patients in the PB group compared with patients in EB group (P = 0.0365). The utilization of androgen deprivation therapy (ADT) in the PB group was similar to the utilization of ADT in the EB group (40.4% vs. 51.3%; P = 0.2282). The vast majority of men who were treated with PB received low-dose-rate, permanent sources (89%). Fifty-four percent of men received PB monotherapy (PBM), and the remaining 46% were treated with EB in addition to PB (EBPB). The prognostic groupings were more favorable for patients in the PBM group compared with patients in the EBPB group (P = 0.0037). Of the men who were treated

  5. Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer.

    PubMed

    Evans, Andrew J; Humphrey, Peter A; Belani, Jay; van der Kwast, Theodorus H; Srigley, John R

    2006-06-01

    Neuroendocrine (NE) differentiation in prostate cancer is typically detected by immunohistochemistry as single cells in conventional adenocarcinoma. Prostatic NE tumors, such as carcinoid or small cell carcinoma, are rare and large cell NE carcinoma (LCNEC) is described only in case reports. We identified 7 cases of LCNEC and compiled their clinicopathologic characteristics. In 6 cases, there was a history of adenocarcinoma treated with hormone therapy for a mean of 2.4 years (range: 2 to 3 y). The remaining case was de novo LCNEC. LCNEC was incidentally diagnosed in palliative transurethral resection specimens in 5 cases. The mean patient age at diagnosis with LCNEC was 67 years (range: 43 to 81 y). LCNEC comprised solid sheets and ribbons of cells with abundant pale to amphophilic cytoplasm, large nuclei with coarse chromatin and prominent nucleoli along with brisk mitotic activity and foci of necrosis. In 6 cases, there were foci of admixed adenocarcinoma, 4 of which showed hormone therapy effects. LCNEC was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S/alpha methylacyl CoA racemase. There was strong bcl-2 overexpression, expression of MIB1, and p53 in >50% of nuclei, focally positive staining for prostate specific antigen and prostatic acid phosphatase and negative androgen receptor staining. Follow-up was available for 6 patients, all of who died with metastatic disease at mean of 7 months (range: 3 to 12 mo) after platinum-based chemotherapy. LCNEC of prostate is a distinct clinicopathologic entity that typically manifests after long-term hormonal therapy for prostatic adenocarcinoma and likely arises through clonal progression under the selection pressure of therapy.

  6. Monte Carlo Simulations for Dosimetry in Prostate Radiotherapy with Different Intravesical Volumes and Planning Target Volume Margins

    PubMed Central

    Lv, Wei; Yu, Dong; He, Hengda; Liu, Qian

    2016-01-01

    In prostate radiotherapy, the influence of bladder volume variation on the dose absorbed by the target volume and organs at risk is significant and difficult to predict. In addition, the resolution of a typical medical image is insufficient for visualizing the bladder wall, which makes it more difficult to precisely evaluate the dose to the bladder wall. This simulation study aimed to quantitatively investigate the relationship between the dose received by organs at risk and the intravesical volume in prostate radiotherapy. The high-resolution Visible Chinese Human phantom and the finite element method were used to construct 10 pelvic models with specific intravesical volumes ranging from 100 ml to 700 ml to represent bladders of patients with different bladder filling capacities during radiotherapy. This series of models was utilized in six-field coplanar 3D conformal radiotherapy simulations with different planning target volume (PTV) margins. Each organ’s absorbed dose was calculated using the Monte Carlo method. The obtained bladder wall displacements during bladder filling were consistent with reported clinical measurements. The radiotherapy simulation revealed a linear relationship between the dose to non-targeted organs and the intravesical volume and indicated that a 10-mm PTV margin for a large bladder and a 5-mm PTV margin for a small bladder reduce the effective dose to the bladder wall to similar degrees. However, larger bladders were associated with evident protection of the intestines. Detailed dosimetry results can be used by radiation oncologists to create more accurate, individual water preload protocols according to the patient’s anatomy and bladder capacity. PMID:27441944

  7. Canine prostate carcinoma: epidemiological evidence of an increased risk in castrated dogs.

    PubMed

    Teske, E; Naan, E C; van Dijk, E M; Van Garderen, E; Schalken, J A

    2002-11-29

    The present retrospective study investigated the frequency of prostate carcinoma (PCA) among prostate abnormalities in dogs and determined whether castration influences the incidence of PCA in dogs. During the years 1993-1998, 15,363 male dogs were admitted to the Utrecht University Clinic of Companion Animals, and of these dogs 225 were diagnosed with prostatic disease. In addition, another 206 male dogs were diagnosed as having prostatic disease based on cytologic examination of aspiration biopsies submitted by referring veterinarians. Benign prostatic hyperplasia was diagnosed in 246 dogs (57.1%), prostatitis in 83 dogs (19.3%), and PCA in 56 dogs (13%). Dogs with PCA were significantly older (mean age=9.9 years) than dogs with other prostatic diseases (mean age=8.4 years). The Bouvier des Flandres breed had an increased risk (odds ratio (OR)=8.44; 95% CI 4.38-16.1) of having PCA. Castration (26/56) increased the risk (OR=4.34; 95% CI 2.48-7.62) of PCA. The mean age at diagnosis of PCA in castrated dogs and in intact male dogs was not significantly different. The interval between castration and onset of prostatic problems was highly variable, suggesting that castration does not initiate the development of PCA in the dog, but it does favour tumor progression.

  8. Diagnosis of prostatic neuroendocrine carcinoma: Two cases report and literature review

    PubMed Central

    He, Hai-Qing; Fan, Shu-Feng; Xu, Qiong; Chen, Zhen-Jing; Li, Zheng

    2015-01-01

    Two cases of prostatic neuroendocrine carcinoma (PNEC) imaged by computed tomography (CT) and magnetic resonance imaging (MRI), and literature review are presented. Early enhanced CT, MRI, especially diffusion-weighted image were emphasized, the complementary roles of ultrasound, CT, MRI, clinical and laboratory characteristic’s features in achieving accurate diagnosis were valued in the preoperative diagnosis of PNEC. PMID:26029353

  9. Tumour-to-tumour metastases: prostate carcinoma metastasising to a renal oncocytoma.

    PubMed

    Petts, Gemma; Rashid, Tina; Hrouda, David; Ngo, Nye-Thane

    2013-01-09

    This is a case report of prostate carcinoma metastasising to a renal oncocytoma. The report demonstrates the unusual presentation of metastases from a common cancer to a common benign tumour, and reviews the rare phenomenon of tumour-to-tumour metastases.

  10. Associations of Prostate-Specific Antigen, Prostate Carcinoma Tissue Gleason Score, and Androgen Receptor Expression with Bone Metastasis in Patients with Prostate Carcinoma.

    PubMed

    Chen, Yehui; Lin, Yun; Nie, Pin; Jiang, Wen; Liu, Yanqing; Yuan, Runqiang; Li, Miaoyuan; Zhao, Shijia; Lin, Huaxin; Li, Penghui; Zhang, Jinxiang; Hu, Zhiwen; Xu, Jin; Zhu, Xusheng

    2017-04-12

    BACKGROUND Prostate carcinoma (PCa) is often not diagnosed until advanced disease with bone metastasis. Predictive factors for bone metastasis are required to improve patient outcomes. The study aimed to analyze the factors associated with bone metastases in newly diagnosed patients with PCa. MATERIAL AND METHODS This was a retrospective study of 80 patients newly diagnosed with PCa by pathological examination between January 2012 and December 2014. Bone metastases were diagnosed by positron emission computed tomography. Clinical data, serological laboratory results, and pathological examination results were collected. RESULTS Among the 80 patients, 45 (56%) had bone metastases. Age, serum alkaline phosphatase, prostate-specific antigen (PSA), erythrocyte sedimentation rate, PCa tissue Gleason score, androgen receptor (AR) expression, and Ki-67 expression were higher in patients with bone metastasis compared with those without (all P<0.05). Multivariate logistic regression showed that PSA (OR: 1.005; 95%CI: 1.001-1.010; P=0.016), Gleason score (OR: 4.095; 95%CI: 1.592-10.529; P=0.003), and AR expression (OR: 14.023; 95%CI: 3.531-55.6981; P=0.005) were independently associated with bone metastases. Cut-off values for PSA, Gleason score, and AR expression were 67.1 ng/ml (sensitivity: 55.6%; specificity: 97.1%), 7.5 (sensitivity: 75.6%; specificity: 82.9%), and 2.5 (sensitivity: 84.0%; specificity: 91.4%), respectively. CONCLUSIONS PSA, Gleason score, and AR expression in PCa tissues were independently associated with PCa bone metastases. These results could help identifying patients with PCa at high risk of bone metastases.

  11. Establishing an in vivo model of canine prostate carcinoma using the new cell line CT1258

    PubMed Central

    Fork, Melani AM; Escobar, Hugo Murua; Soller, Jan T; Sterenczak, Katharina A; Willenbrock, Saskia; Winkler, Susanne; Dorsch, Martina; Reimann-Berg, Nicola; Hedrich, Hans J; Bullerdiek, Jörn; Nolte, Ingo

    2008-01-01

    Background Prostate cancer is a frequent finding in man. In dogs, malignant disease of the prostate is also of clinical relevance, although it is a less common diagnosis. Even though there are numerous differences in origin and development of the disease, man and dog share many similarities in the pathological presentation. For this reason, the dog might be a useful animal model for prostate malignancies in man. Although prostate cancer is of great importance in veterinary medicine as well as in comparative medicine, there are only few cell lines available. Thus, it was the aim of the present study to determine whether the formerly established prostate carcinoma cell line CT1258 is a suitable tool for in vivo testing, and to distinguish the growth pattern of the induced tumours. Methods For characterisation of the in vivo behaviour of the in vitro established canine prostate carcinoma cell line CT1258, cells were inoculated in 19 NOD.CB17-PrkdcScid/J (in the following: NOD-Scid) mice, either subcutaneously or intraperitoneally. After sacrifice, the obtained specimens were examined histologically and compared to the pattern of the original tumour in the donor. Cytogenetic investigation was performed. Results The cell line CT 1258 not only showed to be highly tumourigenic after subcutaneous as well as intraperitoneal inoculation, but also mimicked the behaviour of the original tumour. Conclusion Tumours induced by inoculation of the cell line CT1258 resemble the situation in naturally occurring prostate carcinoma in the dog, and thus could be used as in vivo model for future studies. PMID:18706092

  12. TERE1, a novel gene affecting growth regulation in prostate carcinoma.

    PubMed

    McGarvey, Terence W; Nguyen, Trang; Puthiyaveettil, Raghunath; Tomaszewski, John E; Malkowicz, S Bruce

    2003-02-01

    Recently, we isolated a ubiquitously expressed gene designated TERE1, which has a significant effect on the growth regulation in bladder cancer. The TERE1 gene maps to chromosome 1p36.11-1p36.33 between the micro-satellite markers D1S2667 and D1S434, a chromosome locus that has been identified by loss of heterozygosity studies as a site of a putative tumor suppressor gene or genes for multiple tumor types including prostate carcinoma. The expression of the TERE1 transcript and protein was examined in a series of thirty microdissected prostate tumors by semi-quantitative RT/PCR and immunohistochemistry. There was a significant 61% decrease in the TERE1 transcript in prostate carcinoma (CaP) and a distinct loss of the TERE1 protein in metstatic prostate. Though a loss of heterozygosity at chromosome 1p36 was found in 25% of these prostate tumors, there appeared to be no TERE1 mutations present in these tumor samples. Induced TERE1 expression after transduction or transfection of TERE1 constructs into two prostate carcinoma (LNCaP and PC-3) cell lines significantly decreased proliferation up to 80% with a significant increase in the number of cells in G1. Serum factors but not DHT (dihydrotestosterone) appear to regulate the amount of TERE1 protein in the androgen responsive LNCaP cell line. Additionally, we have identified by microarray analysis various growth regulatory genes that are down-regulated or up-regulated in TERE1-transduced PC-3 cells. Altogether, these data suggest that TERE1 maybe significant in prostate cancer growth regulation and the down regulation or absence of TERE1 may be an important component of the phenotype of advanced disease.

  13. In vivo dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer--a phantom study.

    PubMed

    Anton, Mathias; Wagner, Daniela; Selbach, Hans-Joachim; Hackel, Thomas; Hermann, Robert Michael; Hess, Clemens Friedrich; Vorwerk, Hilke

    2009-05-07

    A phantom study for dosimetry in the urethra using alanine/ESR during (192)Ir HDR brachytherapy of prostate cancer is presented. The measurement method of the secondary standard of the Physikalisch-Technische Bundesanstalt had to be slightly modified in order to be able to measure inside a Foley catheter. The absorbed dose to water response of the alanine dosimetry system to (192)Ir was determined with a reproducibility of 1.8% relative to (60)Co. The resulting uncertainty for measurements inside the urethra was estimated to be 3.6%, excluding the uncertainty of the dose rate constant Lambda. The applied dose calculated by a treatment planning system is compared to the measured dose for a small series of (192)Ir HDR irradiations in a gel phantom. The differences between the measured and applied dose are well within the limits of uncertainty. Therefore, the method is considered to be suitable for measurements in vivo.

  14. In vivo dosimetry in the urethra using alanine/ESR during 192Ir HDR brachytherapy of prostate cancer—a phantom study

    NASA Astrophysics Data System (ADS)

    Anton, Mathias; Wagner, Daniela; Selbach, Hans-Joachim; Hackel, Thomas; Hermann, Robert Michael; Hess, Clemens Friedrich; Vorwerk, Hilke

    2009-05-01

    A phantom study for dosimetry in the urethra using alanine/ESR during 192Ir HDR brachytherapy of prostate cancer is presented. The measurement method of the secondary standard of the Physikalisch-Technische Bundesanstalt had to be slightly modified in order to be able to measure inside a Foley catheter. The absorbed dose to water response of the alanine dosimetry system to 192Ir was determined with a reproducibility of 1.8% relative to 60Co. The resulting uncertainty for measurements inside the urethra was estimated to be 3.6%, excluding the uncertainty of the dose rate constant Λ. The applied dose calculated by a treatment planning system is compared to the measured dose for a small series of 192Ir HDR irradiations in a gel phantom. The differences between the measured and applied dose are well within the limits of uncertainty. Therefore, the method is considered to be suitable for measurements in vivo.

  15. A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells.

    PubMed

    Sharpe, Benjamin; Alghezi, Dhafer A; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D

    2017-05-01

    of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness. © 2017 Wiley Periodicals, Inc.

  16. Preclinical Evaluation of 86Y-Labeled Inhibitors of Prostate-Specific Membrane Antigen for Dosimetry Estimates

    PubMed Central

    Banerjee, Sangeeta Ray; Foss, Catherine A.; Pullambhatla, Mrudula; Wang, Yuchuan; Srinivasan, Senthamizhchelvan; Hobbs, Robert F.; Baidoo, Kwamena E.; Brechbiel, Martin W.; Nimmagadda, Sridhar; Mease, Ronnie C.; Sgouros, George; Pomper, Martin G.

    2016-01-01

    86Y (half-life = 14.74 h, 33% β+) is within an emerging class of positron-emitting isotopes with relatively long physical half-lives that enables extended imaging of biologic processes. We report the synthesis and evaluation of 3 low-molecular-weight compounds labeled with 86Y for imaging the prostate-specific membrane antigen (PSMA) using PET. Impetus for the study derives from the need to perform dosimetry estimates for the corresponding 90Y-labeled radiotherapeutics. Methods Multistep syntheses were used in preparing 86Y-4–6. PSMA inhibition constants were evaluated by competitive binding assay. In vivo characterization using tumor-bearing male mice was performed by PET/CT for 86Y-4–6 and by biodistribution studies of 86Y-4 and 86Y-6 out to 24 h after injection. Quantitative whole-body PET scans were recorded to measure the kinetics for 14 organs in a male baboon using 86Y-6. Results Compounds 86Y-4–6 were obtained in high radiochemical yield and purity, with specific radioactivities of more than 83.92 GBq/µmol. PET imaging and biodistribution studies using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu tumor-bearing mice revealed that 86Y-4–6 had high site-specific uptake in PSMA-positive PC-3 PIP tumor starting at 20 min after injection and remained high at 24 h. Compound 86Y-6 demonstrated the highest tumor uptake and retention, with 32.17 ± 7.99 and 15.79 ± 6.44 percentage injected dose per gram (%ID/g) at 5 and 24 h, respectively. Low activity concentrations were associated with blood and normal organs, except for the kidneys, a PSMA-expressing tissue. PET imaging in baboons reveals that all organs have a 2-phase (rapid and slow) clearance, with the highest uptake (8 %ID/g) in the kidneys at 25 min. The individual absolute uptake kinetics were used to calculate radiation doses using the OLINDA/EXM software. The highest mean absorbed dose was received by the renal cortex, with 1.9 mGy per MBq of 86Y-6. Conclusion Compound 86Y-6 is a promising

  17. Semiconductor nanocrystal-aptamer bioconjugate probes for specific prostate carcinoma cell targeting

    NASA Astrophysics Data System (ADS)

    Shieh, Felice; Lavery, Laura; Chu, Chitai T.; Richards-Kortum, Rebecca; Ellington, Andrew D.; Korgel, Brian A.

    2005-04-01

    Cancer of the prostate affects approximately 1 in 11 men. Current early screening for prostate cancer utilizes digital rectal examinations to detect anomalies in the prostate gland and blood test screenings for upregulated levels of prostate specific antigen (PSA). Many of these tests are invasive and can often be inconclusive as PSA levels may be heightened due to benign factors. Prostate specific membrane antigen (PSMA), a well-characterized integral membrane protein, is expressed in virtually all prostate cancers and often correlates with cancer aggressiveness. Therefore, it may be used as an indicator of cancer growth and metastases. PSMA-specific antibodies have been identified and conjugated to fluorescent markers for cancer cell targeting; however, both the antibodies and markers possess significant limitations in their pharmaceutical and diagnostic value. Here we report the use of semiconductor nanocrystals bioconjugated to PSMA-specific aptamer recognition molecules for prostate carcinoma cell targeting. The nanocrystal/aptamer bioconjugates are small biocompatible probes with the potential for color-tunability for multicolor imaging. Ongoing in vitro and in vivo research seeks to introduce these nanoparticle bioconjugates into medical diagnostics.

  18. Pim1 kinase synergizes with c-MYC to induce advanced prostate carcinoma

    PubMed Central

    Wang, Jie; Kim, Jongchan; Roh, Meejeon; Franco, Omar E.; Hayward, Simon W.; Wills, Marcia L.; Abdulkadir, Sarki A.

    2010-01-01

    The oncogenic PIM1 kinase has been implicated as a cofactor for c-MYC in prostate carcinogenesis. Here we show that in human prostate tumors, coexpression of c-MYC and PIM1 is associated with higher Gleason grades. Using a tissue recombination model coupled with lentiviral-mediated gene transfer we find that Pim1 is weakly oncogenic in naïve adult mouse prostatic epithelium. However, it cooperates dramatically with c-MYC to induce prostate cancer within 6-weeks. Importantly, c-MYC/Pim1 synergy is critically dependent on Pim1 kinase activity. c-MYC/Pim1 tumors showed increased levels of the active serine-62 (S62) phosphorylated form of c-MYC. Grafts expressing a phosphomimetic c-MYCS62D mutant had higher rates of proliferation than grafts expressing wild type c-MYC but did not form tumors like c-MYC/Pim1 grafts, indicating that Pim1 cooperativity with c-MYC in vivo involves additional mechanisms other than enhancement of c-MYC activity by S62 phosphorylation. c-MYC/Pim1-induced prostate carcinomas demonstrate evidence of neuroendocrine (NE) differentiation. Additional studies, including the identification of tumor cells coexpressing androgen receptor and NE cell markers synaptophysin and Ascl1 suggested that NE tumors arose from adenocarcinoma cells through transdifferentiation. These results directly demonstrate functional cooperativity between c-MYC and PIM1 in prostate tumorigenesis in vivo and support efforts for targeting PIM1 in prostate cancer. PMID:20140016

  19. Dosimetry verification on VMAT and IMRT radiotherapy techniques: In the case of prostate cancer

    NASA Astrophysics Data System (ADS)

    Maulana, A.; Pawiro, S. A.

    2016-03-01

    Radiotherapy treatment depends on the accuracy of the dose delivery to patients, the purpose of the study is to verify the dose in IMRT and VMAT technique in prostate cancer cases correspond to TPS dose using phantom base on ICRU No.50. The dose verification of the target and OAR was performed by placing the TLD Rod LiF100 and EBT2 Gafchromic film at slab hole of pelvic part of the Alderson RANDO phantom for prostate cancer simulation. The Exposed TLDs was evaluated using the TLD Reader Harshaw while EBT2 film was scanned using Epson scanner. The point dose measurements were compared between planned dose and measured dose at target volume and OAR. The result is the dose difference at target volume, bladder and rectum for IMRT and VMAT are less than 5%. On the other hand, the dose difference at the Femoral head is more than 5% for both techniques because the location of OAR already in low gradient dose. Furthermore, the difference dose of the target volume for IMRT technique tends to be smaller than VMAT either for TLD and EBT2 film detectors. From the measurement showed that the delivered dose on the phantom simulation match with ICRU No.50 criteria.

  20. Proton Radiotherapy for Pediatric Bladder/Prostate Rhabdomyosarcoma: Clinical Outcomes and Dosimetry Compared to Intensity-Modulated Radiation Therapy

    SciTech Connect

    Cotter, Shane E.; Herrup, David A.; Friedmann, Alison; Macdonald, Shannon M.; Pieretti, Raphael V.; Robinson, Gregoire; Adams, Judith; Tarbell, Nancy J.; Yock, Torunn I.

    2011-12-01

    Purpose: In this study, we report the clinical outcomes of 7 children with bladder/prostate rhabdomyosarcoma (RMS) treated with proton radiation and compare proton treatment plans with matched intensity-modulated radiation therapy (IMRT) plans, with an emphasis on dose savings to reproductive and skeletal structures. Methods and Materials: Follow-up consisted of scheduled clinic appointments at our institution or direct communication with the treating physicians for referred patients. Each proton radiotherapy plan used for treatment was directly compared to an IMRT plan generated for the study. Clinical target volumes and normal tissue volumes were held constant to facilitate dosimetric comparisons. Each plan was optimized for target coverage and normal tissue sparing. Results: Seven male patients were treated with proton radiotherapy for bladder/prostate RMS at the Massachusetts General Hospital between 2002 and 2008. Median age at treatment was 30 months (11-70 months). Median follow-up was 27 months (10-90 months). Four patients underwent a gross total resection prior to radiation, and all patients received concurrent chemotherapy. Radiation doses ranged from 36 cobalt Gray equivalent (CGE) to 50.4 CGE. Five of 7 patients were without evidence of disease and with intact bladders at study completion. Target volume dosimetry was equivalent between the two modalities for all 7 patients. Proton radiotherapy led to a significant decrease in mean organ dose to the bladder (25.1 CGE vs. 33.2 Gy; p = 0.03), testes (0.0 CGE vs. 0.6 Gy; p = 0.016), femoral heads (1.6 CGE vs. 10.6 Gy; p = 0.016), growth plates (21.7 CGE vs. 32.4 Gy; p = 0.016), and pelvic bones (8.8 CGE vs. 13.5 Gy; p = 0.016) compared to IMRT. Conclusions: This study provides evidence of significant dose savings to normal structures with proton radiotherapy compared to IMRT and is well tolerated in this patient population. The long-term impact of these reduced doses can be tested in future studies

  1. Metastasis in urothelial carcinoma mimicking prostate cancer metastasis in Ga-68 prostate-specific membrane antigen positron emission tomography-computed tomography in a case of synchronous malignancy.

    PubMed

    Gupta, Manoj; Choudhury, Partha Sarathi; Gupta, Gurudutt; Gandhi, Jatin

    2016-01-01

    Prostate cancer is the second most common cancer in man. It commonly presents with urinary symptoms, bone pain, or diagnosed with elevated prostate-specific antigen.(PSA) levels. Correct staging and early diagnosis of recurrence by a precise imaging tool are the keys for optimum management. Molecular imaging of prostate cancer with Ga-68 prostate-specific membrane antigen.(PSMA), positron emission tomography-computed tomography.(PET-CT) has recently received significant attention and frequently used with a signature to prostate cancer-specific remark. However, this case will highlight the more cautious use of it. A-72-year-old male treated earlier for synchronous double malignancy.(invasive papillary urothelial carcinoma right ureter and carcinoma prostate) presented with rising PSA.(0.51.ng/ml) and referred for Ga-68 PSMA PET-CT, which showed a positive enlarged left supraclavicular lymph node. Lymph node biopsy microscopic and immunohistochemistry examination revealed metastatic carcinoma favoring urothelial origin. Specificity of PSMA scan to prostate cancer has been seen to be compromised in a certain situation mostly due to neoangiogenesis, and false positives emerged in renal cell cancer, differentiated thyroid cancer, glioblastoma, breast cancer brain metastasis, and paravertebral schwannomas. Understanding the causes of false positive will further enhance the confidence of interpretating PSMA scans.

  2. Laser-induced thermotherapy of renal cell carcinoma in man: dosimetry, ultrasound, and histopathologic correlation

    NASA Astrophysics Data System (ADS)

    Williams, J. C.; Swischuk, Peter N.; Morrison, Patricia M.; Chiao, Joseph

    2000-05-01

    Laser-induced thermoterapy (LITT), is the interstitial application of laser energy to achieve tissue coagulation by a thermal process. This is achieved by implanting the laser delivery fiber directly into the target tissue and firing the laser. LITT is being investigated and evaluated clinically as a treatment for renal tumors. The objective of this study was to determine if ultrasound could be used as a real-time monitoring modality of LITT during the coagulation process. Ultrasound characterization was correlated with histopathologic changes and dosimetry. In addition, temperature was monitored and correlated as well.

  3. Multi-institutional retrospective analysis of learning curves on dosimetry and operation time before and after introduction of intraoperatively built custom-linked seeds in prostate brachytherapy.

    PubMed

    Ishiyama, Hiromichi; Satoh, Takefumi; Yorozu, Atsunori; Saito, Shiro; Kataoka, Masaaki; Hashine, Katsuyoshi; Nakamura, Ryuji; Tanji, Susumu; Masui, Koji; Okihara, Koji; Ohashi, Toshio; Momma, Tetsuo; Aoki, Manabu; Miki, Kenta; Kato, Masako; Morita, Masashi; Katayama, Norihisa; Nasu, Yasutomo; Kawanaka, Takashi; Fukumori, Tomoharu; Ito, Fumitaka; Shiroki, Ryoichi; Baba, Yuji; Inadome, Akito; Yoshioka, Yasuo; Takayama, Hitoshi; Hayakawa, Kazushige

    2016-01-01

    This multi-institutional retrospective analysis examined learning curves for dosimetric parameters and operation time after introduction of intraoperatively built custom-linked (IBCL) seeds. Data from consecutive patients treated with seed implantation before and after introduction of IBCL seeds (loose seed, n = 428; IBCL seed, n = 426) were collected from 13 centers. Dose-volume histogram parameters, operation times, and seed migration rates were compared before and after introduction of IBCL seeds. At the 1-month CT analysis, no significant differences were seen in dose to 90% of prostate volume between before and after IBCL seed introduction. No learning curve for dosimetry was seen. Prostate and rectal volume receiving at least 150% of prescription dose (V150 and RV150) were higher in the loose-seed group than in the IBCL-seed group. Operation time was extended by up to 10 min when IBCL seeds were used, although there was a short learning curve of about five patients. The percentage of patients with seed migration in the IBCL-seed group was one-tenth that in the loose-seed group. Our study revealed no dosimetric demerits, no learning curve for dosimetry, and a slightly extended operation time for IBCL seeds. A significant reduction in the rate of seed migration was identified in the IBCL-seed group.

  4. SU-E-T-257: Development of a New Endorectal Balloon with An Unfoldable Radiochromic Film for In-Vivo Rectal Dosimetry During Prostate Cancer Radiotherapy

    SciTech Connect

    Jeang, E; Lim, Y; Cho, K; Hwang, U; Jeong, J; Kim, H; Kim, S; Lee, S; Shin, D; Park, J; Kim, J; Kwak, J; Choi, S

    2015-06-15

    Purpose: We developed an endorectal balloon for in-vivo rectal dosimetry in two-dimensions, and evaluated its dosimetric properties for the radiation treatment of prostate cancer. Methods: The endorectal balloon for in-vivo rectal dosimetry is equipped with a radiochromic film so that two-dimensional dose distribution can be measured in the rectal wall. The film is unrolled as the balloon is inflated, and it is rolled as the balloon is deflated. The outer diameter of the balloon is about 14 mm before inflating it, but its outer diameter can be increased up to about 50 mm after inflating it with 80 ml distilled water. The size of the film is 80(L) x 64(W) mm2, so large as to measure a dose distribution of an anterior half of the rectal wall. After it was inserted into a fabricated rectal phantom, the phantom was scanned by a CT scanner and 5 Gy was delivered to a target inside the phantom with a 15 MV photon beam in AP direction. Finally, the dose distribution measured in the endorectal balloon was compared with that of the treatment plan. Results: The two dose distributions were compared each other in the parallel and the perpendicular directions along an axis of the balloon. The two dose profiles analyzed from the radiochromic film agreed well with the plan within 3% for 15 MV photon beam. Conclusion: An endorectal balloon for two-dimensional in-vivo rectal dosimetry was developed and its dosimetric effectiveness was evaluated for the radiation treatment of prostate cancer. The measured dose distributions showed good agreement with the plans.

  5. [The 2014 consensus conference of the ISUP on Gleason grading of prostatic carcinoma].

    PubMed

    Kristiansen, G; Egevad, L; Amin, M; Delahunt, B; Srigley, J R; Humphrey, P A; Epstein, J I

    2016-02-01

    In 2005 the International Society of Urological Pathology (ISUP) held a concensus conference on Gleason grading in order to bring this grading system up to the current state of contemporary practice; however, it became clear that further modifications on the grading of prostatic carcinoma were necessary. The International Society of Urological Pathology therefore held a further consensus conference in 2014 to clarify these points. This article presents the essential results of the Chicago grading meeting.

  6. Fast dose kernel interpolation using Fourier transform with application to permanent prostate brachytherapy dosimetry

    SciTech Connect

    Liu, Derek Sloboda, Ron S.

    2014-05-15

    Purpose: Boyer and Mok proposed a fast calculation method employing the Fourier transform (FT), for which calculation time is independent of the number of seeds but seed placement is restricted to calculation grid points. Here an interpolation method is described enabling unrestricted seed placement while preserving the computational efficiency of the original method. Methods: The Iodine-125 seed dose kernel was sampled and selected values were modified to optimize interpolation accuracy for clinically relevant doses. For each seed, the kernel was shifted to the nearest grid point via convolution with a unit impulse, implemented in the Fourier domain. The remaining fractional shift was performed using a piecewise third-order Lagrange filter. Results: Implementation of the interpolation method greatly improved FT-based dose calculation accuracy. The dose distribution was accurate to within 2% beyond 3 mm from each seed. Isodose contours were indistinguishable from explicit TG-43 calculation. Dose-volume metric errors were negligible. Computation time for the FT interpolation method was essentially the same as Boyer's method. Conclusions: A FT interpolation method for permanent prostate brachytherapy TG-43 dose calculation was developed which expands upon Boyer's original method and enables unrestricted seed placement. The proposed method substantially improves the clinically relevant dose accuracy with negligible additional computation cost, preserving the efficiency of the original method.

  7. Molecular Profiling of Intraductal Carcinoma of the Prostate

    DTIC Science & Technology

    2016-12-01

    or 12.5%). In order to confirm that the ERG-positive foci did not represent occult infiltrating cancer with a HGPIN- like morphology, 4 of the...prostate is entirely submitted for histologic examination to ex- clude the possibility of occult invasive cancer in some cases. However, overall, it is

  8. Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.

    PubMed

    Delker, Andreas; Fendler, Wolfgang Peter; Kratochwil, Clemens; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Tritschler, Stefan; Stief, Christian Georg; Kopka, Klaus; Haberkorn, Uwe; Bartenstein, Peter; Böning, Guido

    2016-01-01

    Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand (177)Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) (177)Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for

  9. [Mediterranean diet, micronutrients and prostate carcinoma: a rationale approach to primary prevention of prostate cancer].

    PubMed

    Miano, Lucio

    2003-09-01

    Cancer of the prostate is one of the most commonly diagnosed solid malignancies and the fourth leading cause of cancer-related deaths in men living in Italy. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an impelling need to prevent the onset of the cancer or delay the progression of carcinogenesis in this organ. The chemoprevention of cancer is a relatively new concept defined as the administration of pharmacological agents (drug or diet-derived supplements) to prevent, delay or reverse the carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of dietary factors may be protective. There is increasing evidence that diet (particularly dietary fat intake) may play a significant role in early prostate carcinogenesis. Dietary micronutrients and antioxidants are under intense scrutiny. These factors include the vitamin D and E, lycopene, selenium, zinc, poliphenols, isoflavonoids, and phytoestrogens (especially soy products and green tea). The old Mediterranean diet (based on cereals, vegetables, polyunsaturated fats, fruits, fish and low quantities of dairy products and meat) is now sparingly adopted because of the globalisation of the food chain which now involves also our country. Nevertheless, our traditional dietary habits are considered of great value in the prevention of cardiovascular or cancerous diseases and particularly of prostate cancer.

  10. Diffuse reflectance spectroscopy can differentiate high grade and low grade prostatic carcinoma.

    PubMed

    Werahera, Priya N; Jasion, Edward A; David Crawford, E; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; David Port, J; Daily, John W; Rosa, Francisco G La; Werahera, Priya N; Jasion, Edward A; Crawford, E David; Lucia, M Scott; van Bokhoven, Adrie; Sullivan, Holly T; Kim, Fernando J; Maroni, Paul D; Port, J David; Daily, John W; La Rosa, Francisco G; Daily, John W; Van Bokhoven, Adrie; Crawford, E David; Port, J David; Werahera, Priya N; Lucia, M Scott; Sullivan, Holly T; Maroni, Paul D; Jasion, Edward A; La Rosa, Francisco G; Kim, Fernando J

    2016-08-01

    Prostate tumors are graded by the revised Gleason Score (GS) which is the sum of the two predominant Gleason grades present ranging from 6-10. GS 6 cancer exclusively with Gleason grade 3 is designated as low grade (LG) and correlates with better clinical prognosis for patients. GS >7 cancer with at least one of the Gleason grades 4 and 5 is designated as HG indicate worse prognosis for patients. Current transrectal ultrasound guided prostate biopsies often fail to correctly diagnose HG prostate cancer due to sampling errors. Diffuse reflectance spectra (DRS) of biological tissue depend on tissue morphology and architecture. Thus, DRS could potentially differentiate between HG and LG prostatic carcinoma. A 15-gauge optical biopsy needle was prototyped to take prostate biopsies after measuring DRS with a laboratory fluorometer. This needle has an optical sensor that utilizes 8×100 μm optical fibers for tissue excitation and a single 200 μm central optical fiber to measure DRS. Tissue biopsy cores were obtained from 20 surgically excised prostates using this needle after measuring DRS at 5 nm intervals between 500-700 nm wavelengths. Tissue within a measurement window was histopathologically classified as either benign, LG, or HG and correlated with DRS. Partial least square analysis of DRS identified principal components (PC) as potential classifiers. Statistically significant PCs (p<;0.05) were tested for their ability to classify biopsy tissue using support vector machine and leave-one-out cross validation method. There were 29 HG and 49 LG cancers among 187 biopsy cores included in the study. Study results show 76% sensitivity, 80% specificity, 93% negative predictive value, and 50% positive predictive value for HG versus benign, and 76%, 73%, 84%, and 63%, for HG versus LG prostate tissue classification. DRS failed to diagnose 7/29 (24%) HG cancers. This study demonstrated that an optical biopsy needle guided by DRS has sufficient accuracy to differentiate HG

  11. Do HOXB13 and P63 have a role in differentiating poorly differentiated prostatic carcinoma from urothelial high-grade carcinoma?

    PubMed

    Alshenawy, Hanan AlSaeid; Saied, Eman

    2015-09-01

    Poorly differentiated prostatic carcinoma may overlap with high-grade urothelial carcinoma; a distinction is a must as treatments differ. This study aims to evaluate traditional (PSA and HMWCK) and relatively novel (P63 and HOXB13) markers in distinguishing them; and to evaluate their role in the diagnosis of challenging cases. Sections from: diagnosed group includes 65 prostatic and urothelial carcinoma cases were stained with PSA, HMWCK, P63, and HOXB13. Sensitivity, specificity, and accuracy were evaluated. The second group includes 25 challenging cases which were stained first by PSA and HMWCK, then solved the problematic cases with P63 and HOXB13. PSA and HMWCK were sensitive and specific for prostatic and urothelial carcinomas, respectively, but the sensitivity and accuracy were higher for P63 and HOXB13. By using the traditional markers, 17 cases were diagnosed in the second group while the remaining eight cases need the novel markers to be diagnosed. A confident diagnosis can be established in the majority of cases of poorly differentiated carcinoma in either prostatic or urothelial by using a panel of PSA and HMWCK. In some problematic cases, an extended panel including P63 and HOXB13 is helpful in resolving the diagnosis.

  12. Prostate carcinoma in liver transplant recipients: Think about it!

    PubMed

    Tillou, Xavier; Chiche, Laurence; Guleryuz, Kerem; Hervé, Sophie; Bensadoun, Henri; Doerfler, Arnaud

    2015-06-01

    To analyze retrospectively our series of prostate cancer (PC) in liver transplant recipients (LTRs) given an increase in frequency in an aging recipient population when no studies were reported in literature. We conducted a retrospective analysis of LTRs in a single institution. After liver transplantation, all patients were followed up in our institution with an annual digital rectal examination by a urologist and prostate-specific antigen measurement after the age of 50 years. Between 1995 and 2013, among 361 male LTRs, 12 (3.3%) had PC. The mean age at diagnosis was 62.8 years, and the time lapse between liver transplantation and diagnosis was 55.7 months. The median initial prostate-specific antigen level was 7.4ng/ml. In total, 9 patients underwent radical prostatectomy. Histological findings showed 5 pT2 and 4 pT3 cancers. A patient showed invasion in the lymph nodes and was treated with hormonotherapy. Another patient had a biochemical recurrence at 10 months and underwent salvage radiotherapy. After 32.9 months of follow-up, no other patients showed any recurrence. Moreover, 1 patient was treated by radiohormonotherapy for high-risk PC with no recurrence at 65 months, and 1 patient was treated with high-intensity focal ultrasound. There was 1 patient with metastatic disease who received hormonotherapy and died 5 months after diagnosis. Our incidence of intermediate- and high-risk PCs in LTRs was slightly higher than in the general population. In the absence of any recommendations, individual screening should be proposed to LTRs. The treatment of choice remains surgery or radiotherapy to ensure a good carcinologic control. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Proposal of Gleason-like grading system of canine prostate carcinoma in veterinary pathology practice.

    PubMed

    Palmieri, Chiara; Grieco, Valeria

    2015-12-01

    Gleason grading - the most useful predictor of prognosis for prostate cancer in men - was updated at a 2005 consensus conference by the International Society of Urological Pathology. Since Gleason-like growth patterns have been recognised in dogs, this study aimed to apply the modified Gleason grading to 45 canine prostate carcinomas. A single primary growth pattern was observed in 28 cases, a secondary pattern in 11 cases and a tertiary pattern in 6 cases. Cribriform, solid and small acinar/ductal were the most common primary, secondary and tertiary morphological patterns, respectively. The highest Gleason score (GS10) was obtained in 46.7% of cases. Nine of 14 metastasizing cases were classified as GS10. Gleason pattern 5 was present in 33 of cases. This study suggests that the modified Gleason grading, based on specific histological growth patterns existing in canine prostate carcinomas, may be accepted as a grading system for histopathology in the practice settings in order to complete the clinical assessment for the best management of the patient.

  14. Stereotactic body radiation therapy salvage reirradiation of radiorecurrent prostatic carcinoma relapsed in the prostatic bed.

    PubMed

    Arcangeli, Stefano; Gambardella, Pasquale; Agolli, Linda; Monaco, Alessia; Dognini, Jessica; Regine, Giovanni; Donato, Vittorio

    2015-04-28

    A 67-year-old man presented with a slow increase of prostate-specific antigen value after radical prostatectomy and postoperative radiotherapy for prostate cancer. The patient had received 3D conformal radiotherapy to a total dose of 66 Gy in 33 fractions of 2 Gy each on the prostatic bed. Three years later, a macroscopic local failure was diagnosed at the apical region. The patient could not receive androgenic deprivation therapy or other types of treatment owing to comorbid conditions. Thus, stereotactic body radiation therapy with helical image-guided tomotherapy was administered. The total dose was 30 Gy in 5 consecutive fractions of 6 Gy each to the site of the local failure. The treatment was preceded by a transperineal-guided injection of a self-absorbable hydrogel into the prostatic bed, between rectum and bladder, in order to preserve the rectal wall, which already had received significant doses from the first radiation course. Radiation therapy was well-tolerated. After a follow-up period of 6 months, the patient remains healthy, and there has been no further evidence of metastatic spread or recurrence.

  15. Responsiveness of human prostate carcinoma bone tumors to interleukin-2 therapy in a mouse xenograft tumor model.

    PubMed

    Kocheril, S V; Grignon, D J; Wang, C Y; Maughan, R L; Montecillo, E J; Talati, B; Tekyi-Mensah, S; Pontes, J e; Hillman, G G

    1999-01-01

    We have tested an immunotherapy approach for the treatment of metastatic prostate carcinoma using a bone tumor model. Human PC-3 prostate carcinoma tumor cells were heterotransplanted into the femur cavity of athymic Balb/c nude mice. Tumor cells replaced marrow cells in the bone cavity, invaded adjacent bone and muscle tissues, and formed a palpable tumor at the hip joint. PC-3/IF cell lines, generated from bone tumors by serial in vivo passages, grew with faster kinetics in the femur and metastasized to inguinal lymph nodes. Established tumors were treated with systemic interleukin-2 (IL-2) injections. IL-2 significantly inhibited the formation of palpable tumors and prolonged mouse survival at nontoxic low doses. Histologically IL-2 caused vascular damage and infiltration of polymorphonuclear cells and lymphocytes in the tumor as well as necrotic areas with apoptotic cells. These findings suggest destruction of tumor cells by systemic IL-2 therapy and IL-2 responsiveness of prostate carcinoma bone tumors.

  16. Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-kappaB activation and invasive prostate carcinoma.

    PubMed

    Fernandez-Marcos, Pablo J; Abu-Baker, Shadi; Joshi, Jayashree; Galvez, Anita; Castilla, Elias A; Cañamero, Marta; Collado, Manuel; Saez, Carmen; Moreno-Bueno, Gema; Palacios, Jose; Leitges, Michael; Serrano, Manuel; Moscat, Jorge; Diaz-Meco, Maria T

    2009-08-04

    Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-kappaB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-kappaB. These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-kappaB pathway as a critical event in prostate tumorigenesis.

  17. Simultaneous inactivation of Par-4 and PTEN in vivo leads to synergistic NF-κB activation and invasive prostate carcinoma

    PubMed Central

    Fernandez-Marcos, Pablo J.; Abu-Baker, Shadi; Joshi, Jayashree; Galvez, Anita; Castilla, Elias A.; Cañamero, Marta; Collado, Manuel; Saez, Carmen; Moreno-Bueno, Gema; Palacios, Jose; Leitges, Michael; Serrano, Manuel; Moscat, Jorge; Diaz-Meco, Maria T.

    2009-01-01

    Prostate cancer is one of the most common neoplasias in men. The tumor suppressor Par-4 is an important negative regulator of the canonical NF-κB pathway and is highly expressed in prostate. Here we show that Par-4 expression is lost in a high percentage of human prostate carcinomas, and this occurs in association with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) loss. Par-4 null mice, similar to PTEN-heterozygous mice, only develop benign prostate lesions, but, importantly, concomitant Par-4 ablation and PTEN-heterozygosity lead to invasive prostate carcinoma in mice. This strong tumorigenic cooperation is anticipated in the preneoplastic prostate epithelium by an additive increase in Akt activation and a synergistic stimulation of NF-κB. These results establish the cooperation between Par-4 and PTEN as relevant for the development of prostate cancer and implicate the NF-κB pathway as a critical event in prostate tumorigenesis. PMID:19470463

  18. Evaluation of artificial neural networks for the prediction of pathologic stage in prostate carcinoma.

    PubMed

    Han, M; Snow, P B; Brandt, J M; Partin, A W

    2001-04-15

    Currently, the standard for predicting pathologic stage from information available at the time of prostate biopsy is the "Partin nomograms" that were derived using logistic regression analysis. The authors retrospectively reviewed a large series of men with clinically localized prostate carcinoma who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy. They then utilized pathologic and clinical data at the time of prostate biopsy to develop and test an artificial neural network (ANN) to predict the final pathologic stage for this group of men. They then compared the results of ANN with the previous nomograms. Five thousand seven hundred forty-four men were treated at the authors' institution from 1985 to 1998. An ANN was developed using two randomly selected training and validation sets for predicting pathologic stage. Input variables included age, preoperative serum prostate specific antigen level, clinical TNM (tumor, lymph node, and metastasis) classification, and Gleason score from the biopsy specimen. Outcomes included organ confinement and lymph node involvement status. The ANN was slightly superior to the nomograms in predicting pathologic stage, such as organ confinement and lymph node involvement status. In predicting organ confinement and lymph node involvement status, ANN was more accurate and had a larger area under ROC than the nomograms based on the logistic regression method. Artificial neural network models can be developed and used to better predict final pathologic stage when preoperative pathologic and clinical features are known. Copyright 2001 American Cancer Society.

  19. Resveratrol and propolis as necrosis or apoptosis inducers in human prostate carcinoma cells.

    PubMed

    Scifo, Christian; Cardile, Venera; Russo, Alessandra; Consoli, Rosanna; Vancheri, Carlo; Capasso, Francesco; Vanella, Angelo; Renis, Marcella

    2004-01-01

    Vegetables and fruit help the prevention and the therapy of several kinds of cancer because they contain micronutrients, a class of substances that have been shown to exhibit chemopreventive and chemotherapeutic activities. In the present study the effects of resveratrol (100 and 200 microM), a phytoalexin found in grapes, and of the ethanolic extract of propolis (50 and 100 microg/ml), a natural honeybee hive product, were tested in androgen-resistant prostate cancer cells (DU145), a cell line resembling the last stage of prostate carcinoma. A comparison between the activity of these micronutrients and vinorelbine bitartrate (Navelbine), a semi-synthetic drug normally used in the therapy of prostate cancer, was conducted. Several biochemical parameters were tested, such as cell viability (MTT assay), cell membrane integrity (lactate dehydrogenase release), cell redox status (nitric oxide formation, reactive oxygen species production, reduced glutathione levels), genomic DNA fragmentation (COMET assay) with special attention on the presence of apoptotic DNA damage (TUNEL test), and possible mitochondrial transmembrane potential alteration (deltapsi). Our results point out the anticancer activity of resveratrol and propolis extract in human prostate cancer, exerting their cytotoxicity through two different types of cell death: necrosis and apoptosis, respectively. The data obtained suggest the possible use of these micronutrients both in alternative to classic chemotherapy, and in combination with very low dosage of vinorelbine (5 microM).

  20. Effect of Gold Nanoparticles on Prostate Dose Distribution under Ir-192 Internal and 18 MV External Radiotherapy Procedures Using Gel Dosimetry and Monte Carlo Method

    PubMed Central

    Khosravi, H.; Hashemi, B.; Mahdavi, S. R.; Hejazi, P.

    2015-01-01

    Background Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. Objective The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. Method A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. Results The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15% and 8 % higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 % and 7 % due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. Conclusion There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external

  1. Nevirapine restores androgen signaling in hormone-refractory human prostate carcinoma cells both in vitro and in vivo.

    PubMed

    Landriscina, Matteo; Bagalà, Cinzia; Piscazzi, Annamaria; Schinzari, Giovanni; Quirino, Michela; Fabiano, Annarita; Bianchetti, Sara; Cassano, Alessandra; Sica, Gigliola; Barone, Carlo

    2009-05-15

    Prostate carcinomas are androgen-dependent neoplasms which progress toward a hormone-independent phenotype during hormone-deprivation therapy. We evaluated nevirapine, a reverse transcriptase inhibitor, as a new treatment in hormone-refractory prostate carcinoma cells with the aim of restoring the androgen-dependency of tumor cells, the rationale being that endogenous reverse transcriptase is up-regulated in transformed cells and reverse transcriptase inhibitors exert a differentiating activity in human tumors. Nevirapine induced extensive reprogramming of gene expression in vitro with up-regulation of genes that might be silenced during prostate tumor progression (i.e., K18, PSA and androgen receptor) and down-regulation of genes involved in the progression toward an androgen-independent phenotype (i.e., K5, EGFR1, EGF and VEGF-A). Furthermore, nevirapine down-regulated the growth of prostate carcinoma xenografts in athymic mice and induced a differentiated phenotype in vivo with increased K18 expression. Interestingly, the drug restored androgen signaling by enhancing the ability of tumor cells to respond to dihydrotestosterone stimulation and to the antiproliferative activity of the androgen receptor blocker bicalutamide. Finally, nevirapine pretreatment increased the susceptibility of tumor cells to docetaxel, by enhancing their ability to undergo apoptosis. These data suggest that nevirapine may be clinically tested in human hormone-refractory prostate carcinoma to restore the susceptibility to androgen deprivation therapy or to docetaxel. 2009 Wiley-Liss, Inc.

  2. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line.

    PubMed

    Ahmad, Mohammad; Sahabjada, -; Akhtar, Juber; Hussain, Arshad; Badaruddeen, -; Arshad, Md; Mishra, Anuradha

    2017-01-01

    Biological effects of rutin bioactive are limited due to its poor oral bioavailability and its degradation in aqueous environments. For the purpose of bioenhancement, different nanoemulsion systems of rutin were developed by aqueous titration method using water as dispersion media. The nanoemulsion systems were characterized for surface morphology, droplet size, polydispersity index, zeta potential, in vitro release profile and the formulations were optimized. The anticancer potential of optimized nanoemulsion was evaluated by cells viability (MTT) assay, nuclear condensation, and ROS activity using human prostate cancer (PC3) cell line. On the basis of cell viability data the inhibitory concentration (IC50) value for optimized nanoemulsion formulation on PC3 cancer cells was found to be 11.8 μM. Fluorescent microscopic analysis and intracellular ROS generation demonstrated significant ROS induction that might lead to triggering the apoptosis pathway. In conclusion, developed nanoemulsion displayed significant efficacy against prostate carcinoma cells.

  3. Development of a new rutin nanoemulsion and its application on prostate carcinoma PC3 cell line

    PubMed Central

    Ahmad, Mohammad; Sahabjada, -; Akhtar, Juber; Hussain, Arshad; Badaruddeen, -; Arshad, Md; Mishra, Anuradha

    2017-01-01

    Biological effects of rutin bioactive are limited due to its poor oral bioavailability and its degradation in aqueous environments. For the purpose of bioenhancement, different nanoemulsion systems of rutin were developed by aqueous titration method using water as dispersion media. The nanoemulsion systems were characterized for surface morphology, droplet size, polydispersity index, zeta potential, in vitro release profile and the formulations were optimized. The anticancer potential of optimized nanoemulsion was evaluated by cells viability (MTT) assay, nuclear condensation, and ROS activity using human prostate cancer (PC3) cell line. On the basis of cell viability data the inhibitory concentration (IC50) value for optimized nanoemulsion formulation on PC3 cancer cells was found to be 11.8 μM. Fluorescent microscopic analysis and intracellular ROS generation demonstrated significant ROS induction that might lead to triggering the apoptosis pathway. In conclusion, developed nanoemulsion displayed significant efficacy against prostate carcinoma cells. PMID:28694767

  4. SU-E-J-166: Sensitivity of Clinically Relevant Dosimetric Parameters to Contouring Uncertainty During Post Implant Dosimetry of Prostate Permanent Seed Implants

    SciTech Connect

    Mashouf, S; Ravi, A; Morton, G; Song, W

    2015-06-15

    Purpose: There is a strong evidence relating post-implant dosimetry for permanent seed prostate brachytherpy to local control rates. The delineation of the prostate on CT images, however, represents a challenge as it is difficult to confidently identify the prostate borders from soft tissue surrounding it. This study aims at quantifying the sensitivity of clinically relevant dosimetric parameters to prostate contouring uncertainty. Methods: The post-implant CT images and plans for a cohort of 43 patients, who have received I–125 permanent prostate seed implant in our centre, were exported to MIM Symphony LDR brachytherapy treatment planning system (MIM Software Inc., Cleveland, OH). The prostate contours in post-implant CT images were expanded/contracted uniformly for margins of ±1.00mm, ±2.00mm, ±3.00mm, ±4.00mm and ±5.00mm (±0.01mm). The values for V100 and D90 were extracted from Dose Volume Histograms for each contour and compared. Results: The mean value of V100 and D90 was obtained as 92.3±8.4% and 108.4±12.3% respectively (Rx=145Gy). V100 was reduced by −3.2±1.5%, −7.2±3.0%, −12.8±4.0%, −19.0±4.8%, − 25.5±5.4% for expanded contours of prostate with margins of +1mm, +2mm, +3mm, +4mm, and +5mm, respectively, while it was increased by 1.6±1.2%, 2.4±2.4%, 2.7±3.2%, 2.9±4.2%, 2.9±5.1% for the contracted contours. D90 was reduced by −6.9±3.5%, −14.5±6.1%, −23.8±7.1%, − 33.6±8.5%, −40.6±8.7% and increased by 4.1±2.6%, 6.1±5.0%, 7.2±5.7%, 8.1±7.3% and 8.1±7.3% for the same set of contours. Conclusion: Systematic expansion errors of more than 1mm may likely render a plan sub-optimal. Conversely contraction errors may Result in labeling a plan likely as optimal. The use of MRI images to contour the prostate should results in better delineation of prostate organ which increases the predictive value of post-op plans. Since observers tend to overestimate the prostate volume on CT, compared with MRI, the impact of the

  5. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas.

    PubMed

    Kleb, Brittany; Estécio, Marcos R H; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M; Tahir, Salahaldin; Marquez, Victor E; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

    2016-03-03

    Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor-derived xenografts (PDX) revealed that AR-negative SCPC (AR(-)SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR-positive castration-resistant adenocarcinomas (AR(+)ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR(-) and AR(+) PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR(-)SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR(-)SCPC cell lines. We conclude that the epigenome of AR(-) is distinct from that of AR(+) castration-resistant prostate carcinomas, and that the AR(-) phenotype can be reversed with epigenetic drugs.

  6. The landscape of somatic chromosomal copy number aberrations in GEM models of prostate carcinoma.

    PubMed

    Bianchi-Frias, Daniella; Hernandez, Susana A; Coleman, Roger; Wu, Hong; Nelson, Peter S

    2015-02-01

    Human prostate cancer is known to harbor recurrent genomic aberrations consisting of chromosomal losses, gains, rearrangements, and mutations that involve oncogenes and tumor suppressors. Genetically engineered mouse (GEM) models have been constructed to assess the causal role of these putative oncogenic events and provide molecular insight into disease pathogenesis. While GEM models generally initiate neoplasia by manipulating a single gene, expression profiles of GEM tumors typically comprise hundreds of transcript alterations. It is unclear whether these transcriptional changes represent the pleiotropic effects of single oncogenes, and/or cooperating genomic or epigenomic events. Therefore, it was determined whether structural chromosomal alterations occur in GEM models of prostate cancer and whether the changes are concordant with human carcinomas. Whole genome array-based comparative genomic hybridization (CGH) was used to identify somatic chromosomal copy number aberrations (SCNA) in the widely used TRAMP, Hi-Myc, Pten-null, and LADY GEM models. Interestingly, very few SCNAs were identified and the genomic architecture of Hi-Myc, Pten-null, and LADY tumors were essentially identical to the germline. TRAMP neuroendocrine carcinomas contained SCNAs, which comprised three recurrent aberrations including a single copy loss of chromosome 19 (encoding Pten). In contrast, cell lines derived from the TRAMP, Hi-Myc, and Pten-null tumors were notable for numerous SCNAs that included copy gains of chromosome 15 (encoding Myc) and losses of chromosome 11 (encoding p53). Chromosomal alterations are not a prerequisite for tumor formation in GEM prostate cancer models and cooperating events do not naturally occur by mechanisms that recapitulate changes in genomic integrity as observed in human prostate cancer. ©2014 American Association for Cancer Research.

  7. Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas

    PubMed Central

    Kleb, Brittany; Estécio, Marcos R.H.; Zhang, Jiexin; Tzelepi, Vassiliki; Chung, Woonbok; Jelinek, Jaroslav; Navone, Nora M.; Tahir, Salahaldin; Marquez, Victor E.; Issa, Jean-Pierre; Maity, Sankar; Aparicio, Ana

    2016-01-01

    ABSTRACT Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor–derived xenografts (PDX) revealed that AR–negative SCPC (AR−SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR–positive castration-resistant adenocarcinomas (AR+ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR− and AR+ PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR−SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR−SCPC cell lines. We conclude that the epigenome of AR− is distinct from that of AR+ castration-resistant prostate carcinomas, and that the AR− phenotype can be reversed with epigenetic drugs. PMID:26890396

  8. Androgen deprivation therapy and fracture risk in Chinese patients with prostate carcinoma

    PubMed Central

    Lee, Chi-Ho; Huang, Gang; Chan, Pak-Hei; Hai, Jojo; Yeung, Chun-Yip; Fong, Carol Ho-Yi; Woo, Yu-Cho; Ho, Kwan Lun; Yiu, Ming-Kwong; Leung, Frankie; Lau, Tak-Wing; Tse, Hung-Fat; Lam, Karen Siu-Ling; Siu, Chung-Wah

    2017-01-01

    Objective Androgen deprivation therapy (ADT) increases fracture risk in men with carcinoma of the prostate, but little is known about the fracture risk for different types of ADT. We studied the fracture risk amongst Chinese patients with carcinoma of the prostate prescribed different ADT regimens. Subjects and methods This was a single-centered observational study that involved 741 patients with carcinoma of the prostate from January 2001 to December 2011. Results After a median follow-up of 5 years, 71.7% of the study cohort received ADT and the incidence rate of fracture was 8.1%. Multivariable Cox regression analysis revealed that use of ADT was significantly associated with risk of incident fracture (Hazard Ratio [HR] 3.60; 95% Confidence Interval [95% CI] 1.41–9.23; p = 0.008), together with aged >75 years and type 2 diabetes. Compared with no ADT, all three types of ADT were independently associated with the risk of incident fracture: anti-androgen monotherapy (HR 4.47; 95% CI 1.47–13.7; p = 0.009), bilateral orchiectomy ± anti-androgens (HR 4.01; 95% CI 1.46–11.1; p = 0.007) and luteinizing hormone-releasing hormone agonists ± anti-androgens (HR 3.16; 95% CI 1.18–8.43; p = 0.022). However, there was no significant difference in the relative risks among the three types of ADT. Conclusions Fracture risk increases among all types of ADT. Clinicians should take into account the risk-benefit ratio when prescribing ADT, especially in elderly patients with type 2 diabetes. PMID:28158241

  9. Pathophysiology and Natural History of Anorectal Sequelae Following Radiation Therapy for Carcinoma of the Prostate

    SciTech Connect

    Yeoh, Eric K.; Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle J.; Di Matteo, Addolorata C.; Butters, Julie

    2012-12-01

    Purpose: To characterize the prevalence, pathophysiology, and natural history of chronic radiation proctitis 5 years following radiation therapy (RT) for localized carcinoma of the prostate. Methods and Materials: Studies were performed in 34 patients (median age 68 years; range 54-79) previously randomly assigned to either 64 Gy in 32 fractions over 6.4 weeks or 55 Gy in 20 fractions over 4 weeks RT schedule using 2- and later 3-dimensional treatment technique for localized prostate carcinoma. Each patient underwent evaluations of (1) gastrointestinal (GI) symptoms (Modified Late Effects in Normal Tissues Subjective, Objective, Management and Analytic scales including effect on activities of daily living [ADLs]); (2) anorectal motor and sensory function (manometry and graded balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before RT, at 1 month, and annually for 5 years after its completion. Results: Total GI symptom scores increased after RT and remained above baseline levels at 5 years and were associated with reductions in (1) basal anal pressures, (2) responses to squeeze and increased intra-abdominal pressure, (3) rectal compliance and (4) rectal volumes of sensory perception. Anal sphincter morphology was unchanged. At 5 years, 44% and 21% of patients reported urgency of defecation and rectal bleeding, respectively, and 48% impairment of ADLs. GI symptom scores and parameters of anorectal function and anal sphincter morphology did not differ between the 2 RT schedules or treatment techniques. Conclusions: Five years after RT for prostate carcinoma, anorectal symptoms continue to have a significant impact on ADLs of almost 50% of patients. These symptoms are associated with anorectal dysfunction independent of the RT schedules or treatment techniques reported here.

  10. A phase II trial with new triptorelin sustained release formulations in prostatic carcinoma.

    PubMed

    Minkov, N K; Zozikov, B I; Yaneva, Z; Uldry, P A

    2001-01-01

    The objectives were to assess if a single intramuscular (i.m.) injection of the GnRH agonist triptorelin, as pamoate Sustained Release (RS) 11.25 mg, was able to induce pharmacological castration and to maintain the plasma testosterone levels in the castrate range (< 1.735 nmol/l) up to 3 months in prostatic carcinoma. Two different formulations of triptorelin pamoate 11.25 mg were assessed in 2 groups of 10 patients suffering from prostatic carcinoma. Each patient received one i.m. injection of triptorelin pamoate SR 11.25 mg. Triptorelin and testosterone levels were measured over 3 months. Pain, micturition difficulties, performance status, local and general tolerance, and the occurrence of adverse events were evaluated. Both formulations were able to induce castration levels (<1.735 nmol/l) of testosterone within 3 to 4 weeks post-injection, and to maintain levels below 1.735 nmol/l till the end of 3rd month. The bioavailability of one formulation (DLGSD-3-95-21) tended to be greater. This may explain the quicker onset of castration and the slight better maintenance of low testosterone levels during the 3rd month observed with this formulation. In terms of clinical end-points, the local tolerance of both formulations was excellent. No serious adverse events were recorded except transient hot flushes in 2 cases and slight bone pain in one. Triptorelin pamoate 11.25 mg given in microgranules is a 3-month sustained-release administration form which appears to be safe and effective in advanced prostatic carcinoma. Based on the findings of this study, the formulation with greater bioavailability (DLGSD-3-95-21) was selected as formulation of choice to be used for clinical treatments and further clinical investigation.

  11. [Basic features of the ISUP prostate carcinoma Gleason grading system: a preliminary analysis].

    PubMed

    Wang, Gong-Wei; Shen, Dan-Hua

    2014-06-01

    To explore the basic features of the prostate carcinoma Gleason grading system of the International Society of Urological Pathology (ISUP). We analyzed the means and proportions of the Gleason score (GS), primary grade (PG), secondary grade (SG) and third grade (TG) of 667 cases of prostate carcinoma. The means of GS, PG, SG and TG were 7.06 +/- 1.10, 3.53 +/- 0.66, 3.53 +/- 0.72 and 4.30 +/- 0.96, respectively. The cases with GS 5, 6, 7, 8, 9 and 10 accounted for 0.4% (3/677), 37.2% (252/677), 34.4% (233/677), 13.7% (93/677), 12.0% (81/677) and 2.2% (15/677), respectively; those with GS < or = 6 and > or = 7 constituted 37.7% (255/677) and 62.3% (422/677); those with GS3 + 3, 4 + 3 and 3 + 4 made up 37.2% (252/677), 19.2% (130/677) and 15.2% (103/677); and the TG cases held 10.3% (70/677), including 30.0% (21/70) of grade 3, 10% (7/70) of grade 4 and 60.0% (42/70) of grade 5. Our study showed a high proportion of GS, a low proportion of GS < or = 6, and a high proportion of GS > or = 7 in the ISUP prostate carcinoma Gleason grading system. TG of GS needs to be further understood.

  12. Anorectal Function After Three- Versus Two-Dimensional Radiation Therapy for Carcinoma of the Prostate

    SciTech Connect

    Yeoh, Eric K. Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle; Di Matteo, Addolorata; Moore, James W.; Schoeman, Mark N.; Bartholomeusz, Dylan L.

    2009-01-01

    Purpose: To compare the effects of (three-dimensional) 3D vs. two-dimensional (2D) radiation therapy (RT) for carcinoma of the prostate on the prevalence and pathophysiology of anorectal dysfunction. Methods and Materials: Anorectal symptoms, motility, sensory function, and anal sphincter morphology were evaluated before and up to 2 years after randomly assigned hypofractionated vs. conventionally fractionated RT in 67 patients (median age, 69 years; range, 54-82 years) with localized prostate carcinoma, using either a 3D (n = 29) or 2D (n = 38) treatment technique. Results: Anorectal symptoms increased 4 to 6 weeks after RT and persisted in both patient groups. At 2 years, abnormalities included increased stool frequency (55% vs. 53%, p = NS), urgency of defecation (72% vs. 47%, p < 0.05), fecal incontinence (28% vs. 26%, p = NS), and rectal bleeding (38% and 42%, p = NS). Anorectal motility and sensory function deteriorated after RT in both groups with reductions in basal anal pressures, anal pressures in response to squeeze, rectal compliance, and rectal volumes associated with the desire to defecate. External but not internal sphincter thickness changed in the treatment groups although in different directions. However no differences in motility or sensory function were detected between the groups. Baseline anorectal motility but not treatment technique and the hypofracionated schedule were of independent prognostic significance for anorectal motor dysfunction and rectal bleeding respectively at 2 years. Conclusion: The prevalence and pathophysiology of anorectal dysfunction 2 years after RT for prostate carcinoma was largely independent of the treatment techniques used in this study.

  13. Disturbed Colonic Motility Contributes to Anorectal Symptoms and Dysfunction After Radiotherapy for Carcinoma of the Prostate

    SciTech Connect

    Yeoh, Eric K.; Bartholomeusz, Dylan L.; Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle; Di Matteo, Addolorata; Moore, James W.; Schoeman, Mark N.

    2010-11-01

    Purpose: To evaluate the role of colonic motility in the pathogenesis of anorectal symptoms and dysfunction after radiotherapy (RT) for carcinoma of the prostate. Patients and Methods: Thirty-eight patients, median age 71 (range, 50-81) years with localized prostate carcinoma randomized to one of two radiation dose schedules underwent colonic transit scintigraphy and assessment of anorectal symptoms (questionnaire), anorectal function (manometry), and anal sphincteric morphology (endoanal ultrasound) before and at 1 month and 1 year after RT. Results: Whole and distal colonic transit increased 1 month after RT, with faster distal colonic transit only persisting at 1 year. Frequency and urgency of defecation, fecal incontinence, and rectal bleeding increased 1 month after RT and persisted at 1 year. Basal anal pressures remained unchanged, but progressive reductions occurred in anal squeeze pressures and responses to increased intra-abdominal pressure. Rectal compliance decreased progressively in the patients, although no changes in anorectal sensory function ensued. Radiotherapy had no effect on the morphology of the internal and external anal sphincters. Distal colonic retention was weakly related to rectal compliance at 1 month, but both faster colonic transit and reduced rectal compliance were more frequent with increased fecal urgency. At 1 year, a weak inverse relationship existed between colonic half-clearance time and frequency of defecation, although both faster whole-colonic transit and reduced rectal compliance occurred more often with increased stool frequency. Conclusion: Colonic dysmotility contributes to anorectal dysfunction after RT for carcinoma of the prostate. This has implications for improving the management of anorectal radiation sequelae.

  14. Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate.

    PubMed

    Sundar, Santhanam; Dickinson, Peter D

    2012-02-25

    The authors report the case of an 80-year-old man who had heavily pretreated castration refractory carcinoma of the prostate and heart failure. Following the introduction of spironolactone to manage his heart failure, the patient experienced clinical and biochemical progression of his prostate cancer. Within 2 weeks of withdrawing spironolactone the patient's prostate-specific antigen returned its previous level. This is the first reported case of clinical and biochemical progression of prostate cancer following the introduction of spironolactone. The authors propose that spironolactone is a selective androgen receptor modulator. Spironolactone should be used in caution with men with prostate cancer, and should not be used to treat oedema, hypokalaemia and hypertension associated with the newly licensed hormonal therapy abiraterone acetate.

  15. Spironolactone, a possible selective androgen receptor modulator, should be used with caution in patients with metastatic carcinoma of the prostate

    PubMed Central

    Sundar, Santhanam; Dickinson, Peter D

    2012-01-01

    The authors report the case of an 80-year-old man who had heavily pretreated castration refractory carcinoma of the prostate and heart failure. Following the introduction of spironolactone to manage his heart failure, the patient experienced clinical and biochemical progression of his prostate cancer. Within 2 weeks of withdrawing spironolactone the patient’s prostate-specific antigen returned its previous level. This is the first reported case of clinical and biochemical progression of prostate cancer following the introduction of spironolactone. The authors propose that spironolactone is a selective androgen receptor modulator. Spironolactone should be used in caution with men with prostate cancer, and should not be used to treat oedema, hypokalaemia and hypertension associated with the newly licensed hormonal therapy abiraterone acetate. PMID:22665559

  16. Evaluation of RET Tyrosine Kinase as a Novel Driver of Prostatic Small Cell Neuroendocrine Carcinoma

    DTIC Science & Technology

    2015-08-01

    author( s ) and should not be construed as an official Department of the Army position, policy or decision unless so designated by other documentation...GRANT NUMBER W81XWH-14-1-0148 Prostatic Small Cell Neuroendocrine Carcinoma 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) Justin Drake and Owen Witte 5d...PROJECT NUMBER 5e. TASK NUMBER E-Mail: jdrake@mednet.ucla.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME( S ) AND ADDRESS(ES) 8

  17. Effects of external beam radiotherapy on endocrine function in patients with carcinoma of the prostate

    SciTech Connect

    Grigsby, P.W.; Perez, C.A.

    1986-04-01

    Serum levels of testosterone, dihydrotestosterone, and follicle-stimulating and luteinizing hormones were determined prospectively in 59 patients with carcinoma of the prostate treated curatively with external beam radiotherapy. Hormone levels were determined before the initiation of therapy and up to 2 years following completion of therapy. Testosterone levels remained unchanged but dihydrotestosterone levels decreased slightly. Follicle-stimulating and luteinizing hormone levels increased significantly during therapy and remained elevated for up to 2 years after therapy. These findings are consistent with low dose irradiation of the testis.

  18. Targeting prostate carcinoma by G3-C12 peptide conjugated N-(2-hydroxypropyl)methacrylamide copolymers.

    PubMed

    Yang, Yang; Li, Lian; Zhou, Zhou; Yang, Qingqing; Liu, Chong; Huang, Yuan

    2014-10-06

    Prostate carcinoma is the second leading cause of cancer-related deaths. Increased expression of membrane-bound galectin-3 by prostate carcinoma cell has been found to correlate with more poorly differentiated and increased metastatic potential. In the present study, different amount of galectin-3-binding peptide, G3-C12 (the sequence ANTPCGPYTHDCPVKR), was attached to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers as targeting moiety. The results of qPCR and competitive binding test indicated that the expression level of galectin-3 in two metastatic prostate carcinoma cell lines (PC-3 and DU145 cells) could be significantly suppressed by the addition of G3-C12-modified HPMA copolymers (PG1 and PG2), demonstrating the high affinity of PG1 and PG2 to galectin-3. Due to the multivalent effects of moieties, the uptake of copolymers was remarkably enhanced with the increasing amount of conjugated G3-C12 peptide. A higher internalization of PG1 and PG2 occurred in PC-3 cells via caveolin- and clathrin-mediated endocytosis, whereas a clathrin-mediated uptake process was involved in DU145 cells. The in vivo biodistribution and pharmacokinetics of nonmodified ((131)I-pHPMA) and G3-C12-modified ((131)I-PG1 and (131)I-PG2) copolymers were estimated on a well-established mice model bearing PC-3 xenografts by (131)I-SPECT-imaging. Higher tumor accumulation of (131)I-PG1 (1.60 ± 0.08% ID/g, p < 0.05) and (131)I-PG2 (1.54 ± 0.06% ID/g, p < 0.05) was observed compared with (131)I-pHPMA (1.19 ± 0.04% ID/g) at 2 h post-intravenous injection. Although the amount of conjugated G3-C12 peptide performed a remarkable in vitro effect on the affinity and internalization of HPMA copolymers to the galectin-3 overexpressed prostate carcinoma cells, the molecular weight and ligand modification all play important roles on their in vivo tumor accumulation.

  19. Radium-223 chloride: a new treatment option for metastatic castration-resistant prostate carcinoma.

    PubMed

    Pinto, Alvaro; Cruz, Patricia

    2012-12-01

    In the last few years, the treatment of castration-resistant prostate carcinoma (CRPC) has changed completely. The approval of docetaxel and subsequent investigation in this field have led to development of new agents that have demonstrated an improvement in overall survival in the post-docetaxel setting, such as cabazitaxel and abiraterone. Radium-223 chloride is a radioisotope that has recently shown efficacy after docetaxel and in patients unfit for docetaxel, with improvements in overall survival and the time to the first skeletal-related event, compared with placebo, without increasing toxicity. These findings have made this agent a new option for treatment of these patients in the near future.

  20. (99m)Tc-labeled PSMA inhibitor: Biokinetics and radiation dosimetry in healthy subjects and imaging of prostate cancer tumors in patients.

    PubMed

    Santos-Cuevas, Clara; Davanzo, Jenny; Ferro-Flores, Guillermina; García-Pérez, Francisco O; Ocampo-García, Blanca; Ignacio-Alvarez, Eleazar; Gómez-Argumosa, Edgar; Pedraza-López, Martha

    2017-09-01

    The prostate-specific membrane antigen (PSMA) is expressed in epithelial cells of the prostate and highly overexpressed in 95% of advanced prostate cancers. The aims of this study was to estimate the biokinetics and dosimetry of (99m)Tc-EDDA/HYNIC-iPSMA ((99m)Tc-labeled PSMA inhibitor) in eight healthy subjects and evaluate its usefulness as a tumor-imaging agent in eight prostate cancer patients. (99m)Tc-EDDA/HYNIC-iPSMA was obtained from a lyophilized formulation with radiochemical purities >98%, determined by reversed-phase HPLC and ITLC-SG analyses. Whole-body images from eight healthy subjects were acquired at 20min, and at 2, 6 and 24h after (99m)Tc-EDDA/HYNIC-iPSMA administration. Regions of interest (ROIs) were drawn around the source organs on each time frame. Each ROI was corrected by background, attenuation, scattered radiation and physical decay. The image sequence was used to extrapolate the (99m)Tc-EDDA/HYNIC-iPSMA time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation doses. In eight prostate cancer patients with histologically confirmed cancer, whole-body SPECT/CT images were obtained at 3h. The blood activity showed a half-life value of 4.98min for the fast component (T1/2α=ln2/8.34), 2.49h for the first slow component (T1/2β=ln2/0.278), and 9.24h for the second slow component (T1/2γ=ln2/0.076). Images from patients showed an average tumor/background ratio of 8.99±3.27 at 3h. The average equivalent doses calculated for a study using 740MBq were 3.80, 7.06, 9.69, 10.70, and 28.80mSv for the breast, spleen, salivary glands, liver, and kidneys respectively, with an effective dose of 3.42±0.78mSv. All the absorbed doses were comparable to those known for most of the (99m)Tc studies. (99m)Tc-EDDA/HYNIC-iPSMA obtained from kit formulations showed high tumor uptake in

  1. Post-therapeutic dosimetry of 177Lu-DKFZ-PSMA-617 in the treatment of patients with metastatic castration-resistant prostate cancer.

    PubMed

    Yadav, Madhav P; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant A; Sahoo, Ranjit K; Seth, Amlesh; Bal, Chandrasekhar

    2017-01-01

    Lu-DKFZ-PSMA-617, a urea-based compound, binds to the extracellular domain of prostate-specific membrane antigen, thus providing an effective target for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Before its therapeutic use, it is necessary that the radiation dosimetry of this radiopharmaceutical be studied to determine the safe activity that can be administered in patients to prevent haematological, renal and liver toxicity. The present study thus aimed to assess the pharmacokinetics and dosimetry of Lu-DKFZ-PSMA-617 in CRPC patients. After obtaining ethical clearance from the institute ethics review board, we enrolled mCRPC patients who were positive on a Glu-NH-CO-NH-Lys-(Ahx)-[Ga(HBED-CC)] PET/CT scan. For kidney protection, a cocktail of lysine and arginine diluted in 2 litres of normal saline was infused, starting from 30 to 60 min before Lu-DKFZ-PSMA-617 infusion. The mean administered activity in the overall population was 2.52±1.3 GBq. For the purpose of dosimetry, each patient underwent nine planar whole-body scans along with blood and urine sample collection at 0.5, 3.5, 24, 48, 72, 96, 120, 144 and 168 h, respectively. SPECT/CT was performed to derive the volume of salivary glands (parotid and submandibular glands) and tumour. Dosimetric evaluation was carried out using the OLINDA/EXM 1.0 software. A total of 26 mCRPC patients with a mean age of 66.30±9.95 years (range: 38-81 years) were recruited. Normal physiological uptake was observed in all the patients in the lacrimal glands, salivary glands (parotid glands and submandibular glands), liver, spleen, kidneys, intestines and urinary bladder. Organs with the highest absorbed doses were the salivary glands, followed by the kidneys, receiving 1.24±0.26 and 0.99±0.31 mGy/MBq, respectively. The mean absorbed doses to the liver, urinary bladder and red marrow were 0.36±0.10, 0.243±0.09 and 0.048±0.05 mGy/MBq, respectively. The mean whole-body dose was 0.016±0

  2. SU-E-J-215: Towards MR-Only Image Guided Identification of Calcifications and Brachytherapy Seeds: Application to Prostate and Breast LDR Implant Dosimetry

    SciTech Connect

    Elzibak, A; Fatemi-Ardekani, A; Soliman, A; Mashouf, S; Safigholi, H; Ravi, A; Morton, G; Song, WY; Han, D

    2015-06-15

    Purpose: To identify and analyze the appearance of calcifications and brachytherapy seeds on magnitude and phase MRI images and to investigate whether they can be distinguished from each other on corrected phase images for application to prostate and breast low dose rate (LDR) implant dosimetry. Methods: An agar-based gel phantom containing two LDR brachytherapy seeds (Advantage Pd-103, IsoAid, 0.8mm diameter, 4.5mm length) and two spherical calcifications (large: 7mm diameter and small: 4mm diameter) was constructed and imaged on a 3T Philips MR scanner using a 16-channel head coil and a susceptibility weighted imaging (SWI) sequence (2mm slices, 320mm FOV, TR/ TE= 26.5/5.3ms, 15 degree flip angle). The phase images were unwrapped and corrected using a 32×32, 2D Hanning high pass filter to remove background phase noise. Appearance of the seeds and calcifications was assessed visually and quantitatively using Osirix (http://www.osirix-viewer.com/). Results: As expected, calcifications and brachytherapy seeds appeared dark (hypointense) relative to the surrounding gel on the magnitude MRI images. The diameter of each seed without the surrounding artifact was measured to be 0.1 cm on the magnitude image, while diameters of 0.79 and 0.37 cm were measured for the larger and smaller calcifications, respectively. On the corrected phase images, the brachytherapy seeds and the calcifications appeared bright (hyperintense). The diameter of the seeds was larger on the phase images (0.17 cm) likely due to the dipole effect. Conclusion: MRI has the best soft tissue contrast for accurate organ delineation leading to most accurate implant dosimetry. This work demonstrated that phase images can potentially be useful in identifying brachytherapy seeds and calcifications in the prostate and breast due to their bright appearance, which helps in their visualization and quantification for accurate dosimetry using MR-only. Future work includes optimizing phase filters to best identify

  3. Primary Hyperfibrinolysis as a Presentation of Extended Prostate Carcinoma.

    PubMed

    Ruiz-Sada, Pablo; Nahia, Arostegui-Uribe; Iker, Garay-Hidalgo; Katalin, Uriarte-Elguezabal

    2016-09-01

    Primary hyperfibrinolysis States are rare entities associated with different clinical scenarios and can be sometimes their first presentation. PHS outcome relies on the underlying cause. We introduce the case of a man presenting with a complex clotting abnormality malignancy related. Not having an accurate diagnosis hindered us to give an easy solution and compromised the prognosis overall. Misdiagnosing a severe entity often leads to fatal outcomes. We want to highlight the rarity of our case, the challenging differential diagnosis and the importance of being aware of PHS. Because our patient appeared to have an extended carcinoma, definitive treatment was not an option on our case.When an uncommon and challenging disease is presented, having all the clues is mandatory to succeed.

  4. Simplified Irradiation Dosimetry in Carcinoma of the Cervix (External Irradiation and One Radium Insertion)

    PubMed Central

    Allen, William E.; Reddi, Raghunath P.

    1980-01-01

    Gynecologic radiation oncologists have long desired a single unit by which radiation doses to specific reference points in the pelvis can be summed. The Patterns of Care Studies, Marcial's 1976 report to the Conference on Radiation Oncology of the American Cancer Society, and other radiation oncologists advise summed doses to Point A, Point B, or the pelvic side wall. Since there is a difference in the biologic effect of high intensity, long time interval teletherapy and low intensity, short time interval brachytherapy, the rad dose obtained from each modality cannot be simply added. Ellis and Sorenson in the Nominal Standard Dose (NSD) concept have described radium conversion factors that can be used to normalize brachytherapy rads at selected reference points to equivalent teletherapy rad. The two rad doses can then be summed. A simple method found useful in 50 cases of carcinoma of the cervix, and used with a computer or readily available reference tables and with any radium system, is described and discussed. Further clinical uses of the method are suggested. PMID:7365825

  5. Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma.

    PubMed

    Priemer, David S; Wang, Mingsheng; Zhang, Shaobo; Lopez-Beltran, Antonio; Kouba, Erik; Montironi, Rodolfo; Davidson, Darrell D; MacLennan, Gregory T; Wang, Lisha; Osunkoya, Adeboye O; Deng, Youping; Emerson, Robert E; Cheng, Liang

    2017-03-31

    Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non-small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  6. Targeted α-Therapy of Metastatic Castration-Resistant Prostate Cancer with (225)Ac-PSMA-617: Dosimetry Estimate and Empiric Dose Finding.

    PubMed

    Kratochwil, Clemens; Bruchertseifer, Frank; Rathke, Hendrik; Bronzel, Marcus; Apostolidis, Christos; Weichert, Wilko; Haberkorn, Uwe; Giesel, Frederik L; Morgenstern, Alfred

    2017-10-01

    The aim of this study was to develop a treatment protocol for (225)Ac-PSMA-617 α-radiation therapy in advanced-stage, metastatic castration-resistant prostate cancer patients with prostate-specific membrane antigen (PSMA)-positive tumor phenotype. Methods: A dosimetry estimate was calculated on the basis of time-activity curves derived from serially obtained (177)Lu-PSMA-617 scans extrapolated to the physical half-life of (225)Ac, assuming instant decay of unstable daughter nuclides. Salvage therapies empirically conducted with 50 (n = 4), 100 (n = 4), 150 (n = 2), and 200 kBq/kg (n = 4) of (225)Ac-PSMA-617 were evaluated retrospectively regarding toxicity and treatment response. Eight of 14 patients received further cycles in either 2- or 4-mo intervals with identical or deescalated activities. Results: Dosimetry estimates for 1 MBq of (225)Ac-PSMA-617 assuming a relative biologic effectiveness of 5 revealed mean doses of 2.3 Sv for salivary glands, 0.7 Sv for kidneys, and 0.05 Sv for red marrow that are composed of 99.4% α, 0.5% β, and 0.1% photon radiation, respectively. In clinical application, severe xerostomia became the dose-limiting toxicity if treatment activity exceeded 100 kBq/kg per cycle. At 100 kBq/kg, the duration of prostate-specific antigen decline was less than 4 mo, but if therapy was repeated every 2 mo patients experienced additive antitumor effects. Treatment activities of 50 kBq/kg were without toxicity but induced insufficient antitumor response in these high-tumor-burden patients. Remarkable antitumor activity by means of objective radiologic response or tumor marker decline was observed in 9 of 11 evaluable patients. Conclusion: For advanced-stage patients, a treatment activity of 100 kBq/kg of (225)Ac-PSMA-617 per cycle repeated every 8 wk presents a reasonable trade-off between toxicity and biochemical response. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  7. Anti-tumor activity of oxypeucedanin from Ostericum koreanum against human prostate carcinoma DU145 cells.

    PubMed

    Kang, Tae Jin; Lee, Sook Yeon; Singh, Rana P; Agarwal, Rajesh; Yim, Dong Sool

    2009-01-01

    Oxypeucedanin has been reported to have various biological activities. We investigated the efficacy of a coumarin compound, oxypeucedanin, from Ostericum koreanum against the human prostate carcinoma cell line DU145. Oxypeucedanin (C(16)H(14)O(5), mw: 286) was isolated through silica gel chromatography and characterized by NMR. The cells were treated with oxypeucedanin (25, 50, and 100 microM) for 24-72 hours, and cell growth and death were then assayed. The cell cycle progression and apoptotic effects were also assessed by western blotting. Treatment with oxypeucedanin inhibited cell growth and induced cell death in DU145 cells. Furthermore, oxypeucedanin-induced cell growth inhibition was associated with an increase in G2-M arrest in cell cycle progression in DU145 cells in a dose and time-dependent manner. G2-M arrest by oxypeucedanin was associated with decreased levels of cyclin A, cyclin B1, Cdc2, and pCdc2. Oxypeucedanin-induced cell death was associated with significant increases in apoptosis and cleaved caspase-3 and poly-(ADP-ribose) polymerase. These finding suggest a novel anticancer effect for oxypeucedanin, mediated via induction of G2-M cell cycle arrest and apoptosis in human prostate carcinoma DU145 cells.

  8. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells.

    PubMed

    Qiu, Y; Ravi, L; Kung, H J

    1998-05-07

    Interleukin-6 (IL-6) is a cytokine that was initially recognized as a regulator of immune and inflammatory responses, but it also regulates the growth of many tumour cells, including prostrate carcinoma. Overexpression of the growth-factor receptors ErbB2/neu and ErbB3 has been implicated in the neoplastic transformation of prostate carcinoma. Here we show that treatment of the prostate cancer cell line LNCaP with IL-6 induces tyrosine phosphorylation of ErbB2 and ErbB3, but not ErbB1/EGFR. We also show that ErbB2 forms a complex with the gp130 subunit of the IL-6 receptor in an IL-6-dependent manner. This association is important because the inhibition of ErbB2 activity results in abrogation of IL-6-induced MAPK activation. Thus ErbB2 is a critical component of IL-6 signalling through the MAP kinase pathway. These data show how a cytokine receptor can diversify its signalling pathways by engaging with a growth-factor receptor kinase.

  9. [Trends in Gleason scores of Chinese prostate carcinoma from 1995 to 2014].

    PubMed

    Wang, G W; Shen, D H; Zhang, W Y; Xu, K X; Xu, T; Hu, H

    2016-10-18

    To assess the changing trends in Gleason score (GS) of Chinese prostate carcinoma (PCa) from January 1995 to December 2014. In the study, 875 patients admitted to hospital from January 1995 to December 2004 (1995-2004) and from January 2005 to December 2014 (2005-2014) were divided into two groups. The mean levels and proportions of GS, primary and secondary grades were studied. The patients were divided into four groups according to age: <60, 60-69, 70-79 and ≥80 years. Types of specimen included needle biopsy (NB), transurethral resection of the prostate (TURP) and radical prostatectomy (RP). Histological types were made up by acinar carcinoma and other types (including atrophic, pseudohyperplastic, foam, signet ring cell and ductal carcinoma, and so on). The total prostate-specific antigen (tPSA) involved groups of <20.0 μg/L and ≥20.0 μg/L. We observed the mean levels and proportions of GS in age, types of specimen, histological types and total prostate-specific antigen in different periods, and used SPSS 17.0 software for statistical analysis. Compared with 1995-2004, the mean levels of GS, primary and secondary grades decreased 0.32 (P=0.003), 0.19 (P=0.001) and 0.12 (P=0.016) in 2005-2014, respectively. The proportions of ≤6 in GS increased 10.9% (P=0.003), and ≥8 decreased 14.0% (P<0.001). The difference of GS 7 was not statistically significant. In the primary grade, the ratio of grades≤3 increased 12.8% (P=0.001), and grade 4 decreased 7.4% (P=0.037), grade 5 decreased 5.5% (P=0.007). The ratio of secondary grades ≤3 increased 7.6% (P=0.037). The difference of grades 4 and 5 was not statistically significant. GS in Chinese patients with PCa showed a downward trend, which is one of the notable features in the past 20 years in China. The types of specimen and age are important factors in GS, while the histological types and tPSA have less impact on the GS.

  10. Perforation of an Occult Carcinoma of the Prostate as a Rare Differential Diagnosis of Subcutaneous Emphysema of the Leg

    PubMed Central

    Hockertz, Thomas

    2016-01-01

    We report a case of subcutaneous emphysema caused by perforation of the rectum due to a carcinoma of the prostate. Although rare, an abdominal cause must always be considered as a rare differential diagnosis of subcutaneous emphysema. As a matter of fact adequate diagnostic with rapid treatment is essential for the outcome. PMID:27597913

  11. Early Response of Prostate Carcinoma Xenografts to Docetaxel Chemotherapy Monitored With Diffusion MRI

    PubMed Central

    Jennings, Dominique; Hatton, B Nicholas; Guo, Jingyu; Galons, Jean-Philippe; Trouard, Theodore P; Raghunand, Natarajan; Marshall, James; Gillies, Robert J

    2002-01-01

    Abstract For many anticancer therapies, it would be desirable to accurately monitor and quantify tumor response early in the treatment regimen. This would allow oncologists to continue effective therapies or discontinue ineffective therapies early in the course of treatment, and hence, reduce morbidity. This is especially true for second-line therapies, which have reduced response rates and increased toxicities. Previous works by others and ourselves have shown that water mobility, measured by diffusion-weighted magnetic resonance imaging (DW-MRI), increases early in tumors destined to respond to therapies. In the current communication, we further characterize the utility of DW-MRI to predict response of prostate cancer xenografts to docetaxel in SCID mice in a preclinical setting. The current data illustrate that tumor volumes and secreted prostate-specific antigen both respond strongly to docetaxel in a dose-responsive manner, and the apparent diffusion coefficient of water (ADCw) increases significantly by 2 days even at the lowest doses (10 mg/kg). The ADCw data were parsed by histogram analyses. Our results indicate that DW-MRI can be used for early detection of prostate carcinoma xenograft response to docetaxel chemotherapy. PMID:11988845

  12. Strontium-89 therapy for the treatment of huge osseous metastases in prostate carcinoma: A case report.

    PubMed

    Zhang, Wenjie; Zhao, Weiwei; Jia, Zhiyun; Deng, Houfu

    2013-02-01

    Prostate cancer is a growing public health problem. The palliation of pain in patients with painful bone metastases is of primary importance in the clinical management of advanced cancer. Internal therapy with radionuclides, which concentrate at sites of increased bone turnover, is used to control pain and improve quality of life as an alternative to conventional therapies. In the present study, we report the case of a 52-year-old male who had been diagnosed with prostate cancer. The patient presented with severe pain in multiple areas, but particularly in the right hip. A whole-body bone scan revealed that the right hip, ilium and ischium were covered with huge metastatic lesions. Treatment with radionuclide strontium-89 chloride ((89)Sr) resulted in a partial response which was confirmed by the successful relief of pain and other imaging modalities. No significant change in the leukocyte or thrombocyte levels was observed. The results of the present study indicate that systemic radionuclide therapy using (89)Sr is an effective, well-tolerated and safe palliative treatment in patients with huge osseous metastases in prostate carcinoma.

  13. Matrix protein CCN1 is critical for prostate carcinoma cell proliferation and TRAIL-induced apoptosis.

    PubMed

    Franzen, Carrie A; Chen, Chih-Chiun; Todorović, Viktor; Juric, Vladislava; Monzon, Ricardo I; Lau, Lester F

    2009-07-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays an important role in immune surveillance and preferentially induces apoptosis in cancer cells over normal cells, suggesting its potential in cancer therapy. However, the molecular basis for its selective killing of cancer cells is not well understood. Recent studies have identified the CCN family of integrin-binding matricellular proteins as important regulators of cell behavior, including cell adhesion, proliferation, migration, differentiation, and survival. We show here that CCN1 (CYR61) supports the adhesion of prostatic carcinoma cells as an adhesion substrate through integrins and heparan sulfate proteoglycans. Knockdown of CCN1 expression in PC-3 and DU-145 androgen-independent prostate cancer cells strongly inhibited their proliferation without causing apoptosis, indicating that CCN1 promotes their growth. However, CCN1 also significantly enhances TRAIL-induced apoptosis through interaction with integrins alphavbeta3 and alpha6beta4 and the cell-surface heparan sulfate proteoglycan syndecan-4, acting through a protein kinase Calpha-dependent mechanism without requiring de novo protein synthesis. Knockdown of CCN1 expression in PC-3, DU-145, and LNCaP cells severely blunted their sensitivity to TRAIL, an effect that was reversed by exogenously added CCN1 protein. These findings reveal a functional dichotomy for CCN1 in prostate carcinoma cells, because it contributes to both cell proliferation and TRAIL-induced cell death and suggest that CCN1 expression status may be an important parameter in assessing the efficacy of TRAIL-dependent cancer therapy.

  14. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells.

    PubMed

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antczak, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J; Guindani, Michele; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-04-01

    The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication networks

  15. A Network Biology Approach Identifies Molecular Cross-Talk between Normal Prostate Epithelial and Prostate Carcinoma Cells

    PubMed Central

    Trevino, Victor; Cassese, Alberto; Nagy, Zsuzsanna; Zhuang, Xiaodong; Herbert, John; Antzack, Philipp; Clarke, Kim; Davies, Nicholas; Rahman, Ayesha; Campbell, Moray J.; Bicknell, Roy; Vannucci, Marina; Falciani, Francesco

    2016-01-01

    Abstract The advent of functional genomics has enabled the genome-wide characterization of the molecular state of cells and tissues, virtually at every level of biological organization. The difficulty in organizing and mining this unprecedented amount of information has stimulated the development of computational methods designed to infer the underlying structure of regulatory networks from observational data. These important developments had a profound impact in biological sciences since they triggered the development of a novel data-driven investigative approach. In cancer research, this strategy has been particularly successful. It has contributed to the identification of novel biomarkers, to a better characterization of disease heterogeneity and to a more in depth understanding of cancer pathophysiology. However, so far these approaches have not explicitly addressed the challenge of identifying networks representing the interaction of different cell types in a complex tissue. Since these interactions represent an essential part of the biology of both diseased and healthy tissues, it is of paramount importance that this challenge is addressed. Here we report the definition of a network reverse engineering strategy designed to infer directional signals linking adjacent cell types within a complex tissue. The application of this inference strategy to prostate cancer genome-wide expression profiling data validated the approach and revealed that normal epithelial cells exert an anti-tumour activity on prostate carcinoma cells. Moreover, by using a Bayesian hierarchical model integrating genetics and gene expression data and combining this with survival analysis, we show that the expression of putative cell communication genes related to focal adhesion and secretion is affected by epistatic gene copy number variation and it is predictive of patient survival. Ultimately, this study represents a generalizable approach to the challenge of deciphering cell communication

  16. [Prostate carcinoma (PC)--an organ-related specific pathological neoplasm].

    PubMed

    Massmann, J; Funk, A; Altwein, J; Praetorius, M

    2003-06-01

    The organ- and tumour-related specific characteristics of prostate carcinoma (PC) are presented in an overview under various aspects. It is the key for understanding pathological changes, including PC, to consider the subdivision of the prostate into anatomically and functionally distinguishable zones, especially the transitional zone (TZ) and the peripheral zone (PZ). The pseudoneoplastic hyperplasia of the TZ, combined with inflammatory consequences and age-related changes, forms a differential diagnostic challenge to both clinico-radiological diagnosis and macroscopic and microscopic examination. High-degree prostatic intra-epithelial neoplasia (PIN III) and atypical adenomatous hyperplasia (AAH) are presented as precursor lesions of PC with varying significance and assessment. Moreover, there are discussed the following characteristic features of PC: localisation types, focality, volume, progression, double-graduation according to Gleason, tumour stage, and prognosis. The most important prognosis factors of PC (category I) include the categories of the TNM system, such as stage, surgical marginal situation, degree and also the preoperative PSA level as a (poor) substitute for the tumour volume. Potential prognosis parameters (category II) show the tumour volume and the DNS ploidy, while there continues to exist a large number of non-established parameters (category III). The prognostic validity of the pathological examinations depends, on the one hand, on the tissue extent (needle biopsy, transurethral resection (TURP), so-called simple prostatectomy, radical prostatectomy (RPE)) and the prostate zones covered. On the other hand, the prognostic certainty also depends on the tumour-adequate macroscopic and microscopic assessment of an RPE that can only be a partial or complete handling in transversal large-area sections.

  17. Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma.

    PubMed

    Diamandis, Eleftherios P; Okui, Akira; Mitsui, Shinichii; Luo, Liu-Ying; Soosaipillai, Antoninus; Grass, Linda; Nakamura, Terukazu; Howarth, David J C; Yamaguchi, Nozomi

    2002-01-01

    Human kallikrein 11 (hK11) is a putative serine protease of the human kallikrein gene family. Currently, no methods are available for measuring hK11 in biological fluids and tissues. Our aim was to develop immunological reagents and assays for measuring hK11 and examine if the concentration of this kallikrein is altered in disease states. We produced recombinant hK11 protein in a baculovirus system and used it to develop monoclonal and polyclonal antibodies against hK11. We then developed an immunofluorometric procedure for measuring hK11 in biological fluids and tissue extracts with high sensitivity and specificity. We further quantified hK11 in various biological fluids and in serum of patients with various cancers. The hK11 immunofluorometric assay is highly sensitive (detection limit, 0.1 microg/l) and specific (no detectable cross-reactivity for other homologous kallikreins). We established the tissue expression pattern of hK11 at the protein level and found the highest levels in the prostate, followed by stomach, trachea, skin, and colon. We have immunohistochemically localized hK11 in epithelial cells of various organs. We further detected hK11 in amniotic fluid, milk of lactating women, cerebrospinal fluid, follicular fluid, and breast cancer cytosols. However, highest levels were seen in prostatic tissue extracts and seminal plasma. hK11 in seminal plasma and prostatic extracts is present at approximately 300-fold lower levels than prostate-specific antigen and at approximately the same levels as hK2. hK11 expression in breast cancer cell lines is up-regulated by estradiol. Elevated serum levels of hK11 were found in 70% of women with ovarian cancer and in 60% of men with prostate cancer. This is the first reported immunological assay for hK11. Analysis of this biomarker in serum may aid in the diagnosis and monitoring of ovarian and prostatic carcinoma.

  18. Quality of treatment plans and accuracy of in vivo portal dosimetry in hybrid intensity-modulated radiation therapy and volumetric modulated arc therapy for prostate cancer.

    PubMed

    Bedford, James L; Smyth, Gregory; Hanson, Ian M; Tree, Alison C; Dearnaley, David P; Hansen, Vibeke N

    2016-08-01

    Delivering selected parts of volumetric modulated arc therapy (VMAT) plans using step-and-shoot intensity modulated radiotherapy (IMRT) beams has the potential to increase plan quality by allowing specific aperture positioning. This study investigates the quality of treatment plans and the accuracy of in vivo portal dosimetry in such a hybrid approach for the case of prostate radiotherapy. Conformal and limited-modulation VMAT plans were produced, together with five hybrid IMRT/VMAT plans, in which 0%, 25%, 50%, 75% or 100% of the segments were sequenced for IMRT, while the remainder were sequenced for VMAT. Integrated portal images were predicted for the plans. The plans were then delivered as a single hybrid beam using an Elekta Synergy accelerator with Agility head to a water-equivalent phantom and treatment time, isocentric dose and portal images were measured. Increasing the IMRT percentage improves dose uniformity to the planning target volume (p<0.01 for 50% IMRT or more), substantially reduces the volume of rectum irradiated to 65Gy (p=0.02 for 25% IMRT) and increases the monitor units (p<0.001). Delivery time also increases substantially. All plans show accurate delivery of dose and reliable prediction of portal images. Hybrid IMRT/VMAT can be efficiently planned and delivered as a single beam sequence. Beyond 25% IMRT, the delivery time becomes unacceptably long, with increased risk of intrafraction motion, but 25% IMRT is an attractive compromise. Integrated portal images can be used to perform in vivo dosimetry for this technique. Copyright © 2016 The Royal Marsden NHS Foundation Trust. Published by Elsevier Ireland Ltd.. All rights reserved.

  19. Genetic polymorphisms of estrogen receptor alpha and catechol-O-methyltransferase genes in Turkish patients with familial prostate carcinoma

    PubMed Central

    Pazarbasi, Ayfer; Yilmaz, M. Bertan; Alptekin, Davut; Luleyap, Umit; Tansug, Zuhtu; Ozpak, Lutfiye; Izmirli, Muzeyyen; Onatoglu-Arikan, Dilge; Kocaturk-Sel, Sabriye; Erkoc, Mehmet Ali; Turgut, Ozgur; Bereketoglu, Ceyhun; Tunc, Erdal; Akbal, Eylul

    2013-01-01

    OBJECTIVES: Estrogen is one of the most crucial hormones participating in the proliferation and carcinogenesis of the prostate glands. Genetic polymorphisms in the estrogen metabolism pathway might be involved in the risk of prostate carcinoma development. We evaluated the association between genetic polymorphisms in estrogen receptor alpha (ESR1) and catechol-O-methyltransferase (COMT) genes and the risk of developing familial prostate carcinoma. MATERIALS AND METHODS: In this study, 34 cases with prostate carcinoma whose first-degree relatives had prostate carcinoma and 30 healthy age-matched male controls were enrolled. The genotypes of ESR1 and COMT genes were analyzed employing polymerase chain reaction-restriction fragment length polymorphism method. 34 cases with prostate carcinoma, whose first degree relatives had prostate carcinoma and 14 age-matched male controls were enrolled to analyze the genotype of these two genes. RESULTS: Among control patients, the ESR1 PvuII genotypes of C/C, C/T and T/T were observed in 37%, 26% and 37%, respectively, whereas the C/C, C/T and T/T genotypes were observed in 18%, 41% and 41% of case patients, respectively. Among controls, the ESR1 PvuII allele frequencies of C and T were equally observed, whereas the C and T allele frequencies were observed in 38% and 62% of patients, respectively. Among ESR1 PvuII genotypes there were not any significant difference in terms of genotype (P = 0.199) and allele (P = 0.181) frequencies. Among controls, the ESR1 XbaI genotypes of G/G, G/A and A/A were observed in 33%, 37% and 33%, respectively, whereas the G/G, G/A and A/A genotypes were observed in 12%, 47% and 41% of patients, respectively. Among controls, the ESR1 XbaI allele frequencies of A and G were observed equally, respectively, whereas the A and G frequencies were observed in 65% and 35% of patients, respectively. Among ESR1 Χ baI, there was not any significant difference in terms of genotype (P = 0.111) and allele (P = 0

  20. SU-E-J-214: MR Protocol Development to Visualize Sirius MRI Markers in Prostate Brachytherapy Patients for MR-Based Post-Implant Dosimetry

    SciTech Connect

    Lim, T; Wang, J; Frank, S; Stafford, R; Bruno, T; Bathala, T; Mahmood, U; Pugh, T; Ibbott, G; Kudchadker, R

    2015-06-15

    Purpose: The current CT-based post-implant dosimetry allows precise seed localization but limited anatomical delineation. Switching to MR-based post-implant dosimetry is confounded by imprecise seed localization. One approach is to place positive-contrast markers (Sirius) adjacent to the negative-contrast seeds. This patient study aims to assess the utility of a 3D fast spoiled gradient-recalled echo (FSPGR) sequence to visualize Sirius markers for post-implant dosimetry. Methods: MRI images were acquired in prostate implant patients (n=10) on Day 0 (day-of-implant) and Day 30. The post-implant MR protocol consisted of 3D T2-weighted fast-spin-echo (FSE), T2-weighted 2D-FSE (axial) and T1-weighted 2D-FSE (axial/sagittal/coronal). We incorporated a 3D-FSPGR sequence into the post-implant MR protocol to visualize the Sirius markers. Patients were scanned with different number-of-excitations (6, 8, 10), field-of-view (10cm, 14cm, 18cm), slice thickness (1mm, 0.8mm), flip angle (14 degrees, 20 degrees), bandwidth (122.070 Hz/pixel, 325.508 Hz/pixel, 390.625 Hz/pixel), phase encoding steps (160, 192, 224, 256), frequency-encoding direction (right/left, anterior/posterior), echo-time type (minimum-full, out-of-phase), field strength (1.5T, 3T), contrast (with, without), scanner vendor (Siemens, GE), coil (endorectal-coil only, endorectal-and-torso-coil, torsocoil only), endorectal-coil filling (30cc, 50cc) and endorectal-coil filling type (air, perfluorocarbon [PFC]). For post-implant dosimetric evaluation with greater anatomical detail, 3D-FSE images were fused with 3D-FSPGR images. For comparison with CT-based post-implant dosimetry, CT images were fused with 3D-FSPGR images. Results: The 3D-FSPGR sequence facilitated visualization of markers in patients. Marker visualization helped distinguish signal voids as seeds versus needle tracks for more definitive MR-based post-implant dosimetry. On the CT-MR fused images, the distance between the seed on CT to MR images was 3

  1. TU-AB-201-11: A Novel Theoretical Framework for MRI-Only Image Guided LDR Prostate and Breast Brachytherapy Implant Dosimetry

    SciTech Connect

    Soliman, A; Elzibak, A; Fatemi, A; Safigholi, H; Ravi, A; Morton, G; Song, W; Han, D

    2015-06-15

    Purpose: To propose a novel framework for accurate model-based dose calculations using only MR images for LDR prostate and breast seed implant brachytherapy. Methods: Model-based dose calculation methodologies recommended by TG-186 require further knowledge about specific tissue composition, which is challenging with MRI. However, relying on MRI-only for implant dosimetry would reduce the soft tissue delineation uncertainty, costs, and uncertainties associated with multi-modality registration and fusion processes. We propose a novel framework to address this problem using quantitative MRI acquisitions and reconstruction techniques. The framework includes three steps: (1) Identify the locations of seeds(2) Identify the presence (or absence) of calcification(s)(3) Quantify the water and fat content in the underlying tissueSteps (1) and (2) consider the sources that limit patient dosimetry, particularly the inter-seed attenuation and the calcified regions; while step (3) targets the quantification of the tissue composition to consider the heterogeneities in the medium. Our preliminary work has shown that the seeds and the calcifications can be identified with MRI using both the magnitude and the phase images. By employing susceptibility-weighted imaging with specific post-processing techniques, the phase images can be further explored to distinguish the seeds from the calcifications. Absolute quantification of tissue, water, and fat content is feasible and was previously demonstrated in phantoms and in-vivo applications, particularly for brain diseases. The approach relies on the proportionality of the MR signal to the number of protons in an image volume. By employing appropriate correction algorithms for T1 - and T2*-related biases, B1 transmit and receive field inhomogeneities, absolute water/fat content can be determined. Results: By considering calcification and interseed attenuation, and through the knowledge of water and fat mass density, accurate patient

  2. Partition Model-Based 99mTc-MAA SPECT/CT Predictive Dosimetry Compared with 90Y TOF PET/CT Posttreatment Dosimetry in Radioembolization of Hepatocellular Carcinoma: A Quantitative Agreement Comparison.

    PubMed

    Gnesin, Silvano; Canetti, Laurent; Adib, Salim; Cherbuin, Nicolas; Silva Monteiro, Marina; Bize, Pierre; Denys, Alban; Prior, John O; Baechler, Sebastien; Boubaker, Ariane

    2016-11-01

    (90)Y-microsphere selective internal radiation therapy (SIRT) is a valuable treatment in unresectable hepatocellular carcinoma (HCC). Partition-model predictive dosimetry relies on differential tumor-to-nontumor perfusion evaluated on pretreatment (99m)Tc-macroaggregated albumin (MAA) SPECT/CT. The aim of this study was to evaluate agreement between the predictive dosimetry of (99m)Tc-MAA SPECT/CT and posttreatment dosimetry based on (90)Y time-of-flight (TOF) PET/CT. We compared the (99m)Tc-MAA SPECT/CT results for 27 treatment sessions (25 HCC patients, 41 tumors) with (90)Y SIRT (7 glass spheres, 20 resin spheres) and the posttreatment (90)Y TOF PET/CT results. Three-dimensional voxelized dose maps were computed from the (99m)Tc-MAA SPECT/CT and (90)Y TOF PET/CT data. Mean absorbed dose ([Formula: see text]) was evaluated to compute the predicted-to-actual dose ratio ([Formula: see text]) in tumor volumes (TVs) and nontumor volumes (NTVs) for glass and resin spheres. The Lin concordance ([Formula: see text]) was used to measure accuracy ([Formula: see text]) and precision (ρ). Administered activity ranged from 0.8 to 1.9 GBq for glass spheres and from 0.6 to 3.4 GBq for resin spheres, and the respective TVs ranged from 2 to 125 mL and from 6 to 1,828 mL. The mean dose [Formula: see text] was 240 Gy for glass and 122 Gy for resin in TVs and 72 Gy for glass and 47 Gy for resin in NTVs. [Formula: see text] was 1.46 ± 0.58 (0.65-2.53) for glass and 1.16 ± 0.41 (0.54-2.54) for resin, and the respective values for [Formula: see text] were 0.88 ± 0.15 (0.56-1.00) and 0.86 ± 0.2 (0.58-1.35). DR variability was substantially lower in NTVs than in TVs. The Lin concordance between [Formula: see text] and [Formula: see text] (resin) was significantly better for tumors larger than 150 mL than for tumors 150 mL or smaller ([Formula: see text] = 0.93 and [Formula: see text] = 0.95 vs. [Formula: see text] = 0.57 and [Formula: see text] = 0.93; P < 0.05). In (90)Y

  3. Pre-therapeutic dosimetry of normal organs and tissues of (177)Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer.

    PubMed

    Kabasakal, Levent; AbuQbeitah, Mohammad; Aygün, Aslan; Yeyin, Nami; Ocak, Meltem; Demirci, Emre; Toklu, Turkay

    2015-12-01

    (177)Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of (177)Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected (177)Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that (177)Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion

  4. Prostatitis

    PubMed Central

    Domingue, Gerald J.; Hellstrom, Wayne J. G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (controversial) leukocytes or bacteria in the expressed prostatic secretions. Despite these diagnostic criteria, the etiology of chronic idiopathic prostatitis is unknown. While this review covers the entire spectrum of microbially caused acute prostatitis (including common and uncommon bacteria, viruses, fungi, and parasites) and microbially associated chronic prostatitis, a special focus has been given to chronic idiopathic prostatitis. The idiopathic syndrome is commonly diagnosed in men but is poorly treated. Recent data convincingly suggests a possible bacterial etiology for the condition. Provocative molecular studies have been published reporting the presence of 16S rRNA bacterial sequences in prostate biopsy tissue that is negative for ordinary bacteria by routine culture in men with chronic idiopathic prostatitis. Additionally, special culture methods have indicated that difficult-to-culture coryneforms and coagulase-negative staphylococci are present in expressed prostatic secretions found to be negative by routine culture techniques. Treatment failures are not uncommon in chronic prostatitis. Literature reports suggest that antimicrobial treatment failures in chronic idiopathic prostatitis caused by organisms producing extracellular slime might result from the virulent properties of coagulase-negative staphylococci or other bacteria. While it is difficult to definitively extrapolate from animal models, antibiotic pharmokinetic studies with a murine model have

  5. Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus

    PubMed Central

    Sarwar, Shahana; Nyamath, Parveen; Ishaq, Mohammed

    2017-01-01

    Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50–85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease. PMID:28168057

  6. Biomarkers of Prostatic Cancer: An Attempt to Categorize Patients into Prostatic Carcinoma, Benign Prostatic Hyperplasia, or Prostatitis Based on Serum Prostate Specific Antigen, Prostatic Acid Phosphatase, Calcium, and Phosphorus.

    PubMed

    Sarwar, Shahana; Adil, Mohammed Abdul Majid; Nyamath, Parveen; Ishaq, Mohammed

    2017-01-01

    Prostatitis, BPH, and P.Ca are the most frequent pathologies of the prostate gland that are responsible for morbidity in men. Raised levels of PSA are seen in different pathological conditions involving the prostate. PAP levels are altered in inflammatory or infectious or abnormal growth of the prostate tissue. Serum calcium and phosphorus levels were also found to be altered in prostate cancer and BPH. The present study was carried out to study the levels of PSA, PAP, calcium, and phosphorus in serum of patients with Prostatitis, BPH, or P.Ca and also to evaluate the relationship between them. Males in the age group of 50-85 years with LUTS disease symptoms and with PSA levels more than 4 ng/mL were included. A total of 114 patients were analyzed including 30 controls. Prostatitis in 35.7% of cases, BPH in 35.7% of the cases, and P.Ca in 28.57% of the cases were observed. Thus, the nonmalignant cases constitute a majority. PSA, a marker specific for prostatic conditions, was significantly high in all the diseases compared to controls. A rise in serum PSA and PAP indicates prostatitis or, in combination with these two tests, decreased serum calcium shows advanced disease.

  7. Extrapulmonary Small Cell Carcinoma of the Seminal Vesicles and Prostate Demonstrated on 18F-FDG Positron Emission Tomography/Computed Tomography.

    PubMed

    Tabrizipour, Amir Iravani; Shen, Lily; Mansberg, Robert; Chuong, Bui

    2016-02-05

    Extrapulmonary primary small cell carcinomas arising from the urogenital tract is infrequent. It can rarely arise from the prostate and even more rarely from the seminal vesicles. We present a 79-year-old male who was admitted due to acute renal failure with a history of radical radiotherapy for prostate adenocarcinoma 13 years ago. The prostate specific antigen level was not elevated. An abdominopelvic computed tomography (CT) scan showed markedly enlarged seminal vesicles causing bilateral ureteral obstruction and a mildly enlarged prostate. Further evaluation with fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography/CT demonstrated extensive 18F-FDG uptake in the pelvis with diffuse involvement of both seminal vesicles and the prostate without pathologic uptake in the lungs or elsewhere in the body. Core biopsies of the prostate and both seminal vesicles revealed diffuse involvement by small cell carcinoma. Therapy could not be instituted due to a rapid deterioration in the patient's clinical condition.

  8. Loss of heterozygosity in human primary prostate carcinomas: a possible tumor suppressor gene at 7q31.1.

    PubMed

    Zenklusen, J C; Thompson, J C; Troncoso, P; Kagan, J; Conti, C J

    1994-12-15

    We studied loss of heterozygosity (LOH) on human chromosome 7q to determine the location of a putative tumor suppressor gene (TSG) in human primary prostate carcinomas. Samples were obtained from 16 primary prostate carcinomas surgically removed from patients at The University of Texas M. D. Anderson Cancer Center. Paired normal and tumor DNAs were used as template for PCR amplification of a set of 14 CA microsatellite repeats on 7q21-qter. Twelve of 16 cases studied had LOH at one or more loci on 7q. Eighty-three percent LOH (five of six informative cases) was detected with D7S522 at 7q31.1-7q31.2. Percentage of LOH was normally distributed around D7S522. The high incidence of LOH in primary prostate carcinomas suggests that there is a TSG relevant to the development of prostate cancers at 7q31.1-31.2, confirming our previous functional evidence for a TSG at this location. Further research needs to be conducted to establish the identity and function of this putative TSG.

  9. An Unusual Case of Resistant Hypokalaemia in a Patient with Large Bowel Obstruction Secondary to Neuroendocrine Carcinoma of the Prostate

    PubMed Central

    Bagul, A.; Gupta, A.

    2017-01-01

    Neuroendocrine Carcinoma of the Prostate (NECP) is rare and only few cases have been reported, constituting less than 0.5% of prostatic malignancies. We report a rare case of large bowel obstruction from NECP posing a further challenge in management due to resistant hypokalaemia. A 70-year-old man presented with clinical signs of large bowel obstruction who was known to have prostatic carcinoma three years ago, treated initially with hormone therapy then chemoradiation. The blood profile showed a severe hypokalaemia and CT scan revealed liver and lung metastases apart from confirming large bowel obstruction from local invasion of NECP. Severe hypokalaemia was believed to be caused by paraneoplastic syndrome from tumor burden or by recent administration of Etoposide. Intensive potassium correction through a central venous access in maximal doses of 150 mmol/24 hours under cardiac monitoring finally raised serum potassium to 3.8 mmol/L. This safe period allowed us to perform a trephine colostomy at the left iliac fossa. The postoperative period was relatively uneventful. This first case report is presenting a rare cause of large bowel obstruction from a neuroendocrine carcinoma of prostate and highlights the importance of an early, intensive correction of electrolytes in patients with large tumor burden from NECP. PMID:28386507

  10. Internal jugular venous thrombosis due to Trousseau's syndrome as the presenting feature of metastatic prostate carcinoma: a case report.

    PubMed

    Bandara, Asela Rasika; Wimalarathna, Harith; Kalupahana, Ranjith; Gunathilake, Sonali Sihindi Chapa

    2016-04-21

    Internal jugular vein thrombosis is a rare vascular event with a potentially fatal outcome. Of the known etiologies, internal malignancies, either known or occult, are well described. Even though malignancies are known to present with internal jugular vein thrombosis, it rarely occurs due to prostate carcinoma. Many cases of jugular vein and superior vena cava thrombosis secondary to malignancies are due to metastatic compression of veins. Recurrent and unusual vascular thrombosis due to hypercoagulability associated with malignancies is also known as Trousseau's syndrome. Here we report a rare case of a patient with internal jugular vein thrombosis as a presenting feature of metastatic prostate carcinoma, which is a case of Trousseau's syndrome. A 75-year-old Sri Lankan man with hypertension, hyperlipidemia, and past history of spontaneous intracranial hemorrhage presented with a short history of painless swelling in his left supraclavicular fossa. An examination revealed the swelling was due to a thickened left external jugular vein. A duplex ultrasound scan revealed left-sided internal jugular, external jugular, and brachiocephalic venous thrombosis. Surveillance into underlying malignancies showed an irregular, hard prostate gland suspicious of prostate carcinoma, which was proven with histology, and biochemically. A computed tomography scan found extensive vertebral, pelvic bone, intra-abdominal lymph node metastasis, and a single right-sided lower lung metastatic lesion, with no direct involvement of the jugular vein. Spontaneous thrombosis of the internal jugular vein due to Trousseau's syndrome is rare and unusual. Clinicians should promptly investigate for malignancies as it can be the first presentation of underlying occult malignancies. Although prostate carcinomas are rare to present with internal jugular vein thrombosis, this case illustrates the importance of having a high degree of suspicion in the appropriate clinical setting.

  11. Constitutive Activation of NF-kappaB in Prostate Carcinoma Cells Through a Positive Feedback Loop: Implication of Inducible IKK-Related Kinase (IKKi)

    DTIC Science & Technology

    2006-08-01

    strongly suggests that GR is constitutively active in both normal and hyperplastic prostate glands. In contrast, GR levels were low or below detection... BPH ; (b) PC (Gleason score 7); (c) HGPIN and (d) prostate stroma. Note: Low GR expression in PC (B1) and high GR expression in apparently normal...was increased in human prostate carcinomas in comparison to BPH samples (see progress report for FY02), these recent results suggest an important

  12. miR-96 promotes the growth of prostate carcinoma cells by suppressing MTSS1.

    PubMed

    Xu, Libo; Zhong, Jiateng; Guo, Baofeng; Zhu, Qi; Liang, Hang; Wen, Naiyan; Yun, Wenjing; Zhang, Ling

    2016-09-01

    Prostate carcinoma (PC) is one of the most common cancers for males. However, the molecular mechanisms of PC progression are still to be uncovered. MicroRNA (miRNA) has been shown to be associated with the initiation and progression of prostate cancer. Among the identified tumor-promoting miRNAs, miR-96 has been well established to contribute to PC by reducing FOXO1 expression. This study is aimed to study if miR-96 can promote the progression of PC through other pathways. Our data reinforced the finding that the level of miR-96 was higher in PC samples and cell lines than in non-cancerous tissues and normal prostate epithelial cells. In addition, serum miR-96 abundance was also found to be elevated in PC patients. Decreasing miR-96 expression was able to suppress the proliferation, clonogenicity, and invasion of PC cells. Overexpressing miR-96 led to increased proliferation and colony formation of normal prostate epithelial cells. miR-96 level was found to be inversely associated with the abundance of metastasis suppressor protein 1 (MTSS1) messenger RNA (mRNA), which has been proved to be a tumor suppressor for PC. Predictive analysis indicated that there was a potential miRNA response elements (MREs) located within 3'UTR of MTSS1 mRNA. The changes in miR-96 expression can affect the levels of MTSS1 both at mRNA and protein levels. miR-96 also suppressed the activity of luciferase reporter under the regulation of 3'UTR of MTSS1. Further studies showed that MTSS1 restoration accounted for the effect of miR-96 reduction on PC cells. The overexpression of a recombinant MTSS1 resistant against miRNA regulation was also demonstrated to abolish the transforming effect of miR-96 on prostate epithelial cells. Taken together, we found that miR-96 has a higher abundance in serum samples of PC patients than healthy controls, implying that it may be used as a prognostic marker. MTSS1 is a new authentic target of miR-96 in PC. The above findings suggested that targeting mi

  13. Comparative treatment planning on localized prostate carcinoma conformal photon- versus proton-based radiotherapy.

    PubMed

    Mock, Ulrike; Bogner, Joachim; Georg, Dietmar; Auberger, Thomas; Pötter, Richard

    2005-07-01

    To assess the potential benefit of proton-beam therapy in comparison to 3-D conformal photon therapy and photon- based intensity-modulated radiotherapy (IMRT) in prostate carcinoma for various stages of disease. In five patients a 3-D conformal proton-based (two lateral beams) irradiation technique was compared with 3-D conformal photon-beam radiotherapy (four-field box) and IMRT (seven beams). For each patient different target volumes (CTVs) were defined according to early, intermediate and advanced stages of disease: CTV I consisted of the prostate gland, CTV II encompassed prostate and basis of seminal vesicles, and CTV III the prostate and seminal vesicles. Corresponding planning target volumes PTV I-III were defined by uniformly adding a margin of 5 mm to CTV I-III. Dose-volume histograms (DVHs) were analyzed for the different PTVs and various organs at risk (OARs), i.e., rectal wall, bladder, both femoral heads. In addition, maximum and mean doses were derived for the various structures and irradiated non-target tissue volumes were compared for PTV I-III and the different irradiation techniques. Finally, dose conformity and target dose homogeneity were assessed. With photon- and proton-based radiotherapy techniques similar dose distributions were determined for PTV I-III: mean and maximum PTV dose values were between 99-104% and 102-107% of the normalized total doses (70 Gy), respectively. Conformity indices varied from 1.4 to 1.5 for the photon techniques, whereas for proton-beam radiotherapy values ranged from 1.1 to 1.4. Both the 3-D conformal and the IMRT photon treatment technique resulted in increased mean doses (approximately 40-80%) for OARs when compared to protons. With both photon techniques non-target tissue volumes were irradiated to higher doses (mean dose difference > or = 70%) compared to proton-beam radiotherapy. Differences occurred mainly at the low and medium dose levels, whereas in high dose levels similar values were obtained. In

  14. Good response of an aggressive rare variant of signet ring cell carcinoma of prostate with hormonal therapy.

    PubMed

    Tiwari, Deviprasad; Nayak, Brusabhanu; Seth, Amlesh

    2017-03-08

    Primary signet ring cell carcinoma (SRCC) of the prostate is a rare entity, characterised by its aggressive nature and dismal prognosis. We report a case of an advanced SRCC of the prostate presenting as a large pelvic mass with obstructive uropathy and rectal involvement managed by complete androgen blockade. At 24 months follow-up, the patient has no evidence of progression or metastasis. Aggressive management with multimodality approach combining surgery, radiation and hormonal ablation can result in long disease-free survival in some patients, despite the aggressive nature of this disease.

  15. Effects of herbal preparation Equiguard on hormone-responsive and hormone-refractory prostate carcinoma cells: mechanistic studies.

    PubMed

    Hsieh, Tze-Chen; Lu, Xiaohua; Guo, Junqiao; Xiong, Wen; Kunicki, Jan; Darzynkiewicz, Zbigniew; Wu, Joseph M

    2002-04-01

    The Equiguard is a dietary supplement comprised of standardized extracts from nine herbs, respectively, Herba epimedium brevicornum Maxim (stem and leaves), Radix morindae officinalis (root), Fructus rosa laevigatae michx (fruit), Rubus chingii Hu (fruit), Schisandra chinensis (Turz.) Baill (fruit), Ligustrum lucidum Ait (fruit), Cuscuta chinensis Lam (seed), Psoralea corylifolia L. (fruit), and Astragalus membranaceus (Fisch.) Bge (root). This proprietary product, formulated according to Chinese traditional medicinal concepts, is aimed at restoring harmony in the of the kidney, an organ which Chinese medicinal principles consider to be vital for invigorating as well as maintaining balance of the entire urological system. As the prostate is an integral component of the urological system, we performed in vitro studies to test the effects of ethanol extracts of Equiguard to modulate prostate growth and gene expression. These studies used prostate cancer cells mimicking the androgen-dependent (AD) and androgen-independent (AI) states of prostate carcinogenesis. Results show that Equiguard significantly reduced cancer cell growth, induced apoptosis, suppressed expression of the androgen receptor (AR) and lowered intracellular and secreted prostate specific antigen (PSA), and almost completely abolished colony forming abilities of prostate cancer cells. These data support the interpretation that this herbal formulation contains ingredients that collectively may be efficacious in preventing or treating AD and AI prostate carcinoma. The anti-prostatic activities of Equiguard may stem from its complex composition capable of targeting multiple signal transduction/metabolic pathways, to effectively correct, counteract or circumvent the impaired or dysfunctional mechanisms accompanying different stages of prostate carcinogenesis.

  16. PEG spacer gel and adaptive planning vs single plan in external prostate radiotherapy—clinical dosimetry evaluation

    PubMed Central

    2015-01-01

    Objective: Spacer gel is used to reduce the rectal dose in prostate radiotherapy. It is injected to increase the distance between the prostate and rectum. During the course of external radiotherapy treatment, physiological changes in rectal volume exist. When using polyethylene glycol material, such as DuraSeal® (Covidien, Mansfield, MA), gel resorption also occurs. Together, these factors alter the original dose plan distribution. Methods: External dose planning and calculations were simulated using images acquired from 10 patients who were treated with brachytherapy and gel. The CT series was taken relative to gel injection: pre 1 day, post 1 day, post 1 month and post 2 months. Adaptive planning was compared with a single plan. Results: Adaptive planning shows better results compared with the single plan used in the total treatment course; however, the effect is minor. Conclusion: Gel usage is clearly favourable to rectal DVH. Using adaptive planning with gel improves rectal DVH but is not necessary according to this study. Advances in knowledge: Spacer gel is used in prostate radiotherapy to increase distance between the prostate and the rectum, thus reducing the rectal doses. During the treatment course, gel resorption exists which affects the rectal doses. The usefulness of adaptive planning to compensate this resorption effect has not been studied before. PMID:26370300

  17. INITIAL SYMPTOMATIC PITUITARY METASTASIS IN A PATIENT WITH PROSTATE FOAMY GLAND CARCINOMA: TAILORING SAFE AND EFFECTIVE THERAPY.

    PubMed

    Prpić, Marin; Fröbe, Ana; Zadravec, Dijana; Pažanin, Leo; Jakšić, Blanka; Bolanča, Ante; Kusić, Zvonko

    2015-06-01

    Metastases to pituitary gland are unusual and mostly asymptomatic, presenting with local symptoms in one of ten patients, and only 3%-5% of them are of prostate origin. Here we report and evaluate the effectiveness and safety of multimodal treatment in a patient with pituitary metastasis of a prostate foamy gland carcinoma. A 78-year-old male patient presented with blurred vision and headache without a previous history of malignancy. Magnetic resonance imaging scans revealed a large sellar mass, with infiltration of the surrounding structures. Maximal transsphenoidal reduction of pituitary metastasis was performed, with a histologic finding of metastatic prostate foamy gland adenocarcinoma. Evaluation of the prostate specific antigen revealed a very high level (1461 ng/mL) and foamy gland carcinoma was found on prostate needle biopsy. The patient received 3D conformal external beam radiotherapy with 6 MV photons to the sellar and parasellar region with a tumor dose of 44 Gy, followed by androgen deprivation therapy. Follow up magnetic resonance imaging done after radiotherapy showed shrinkage of the tumor process, with rapid prostate specific antigen decline to 0.3 ng/mL. The visual function was fully established and headache resolved. On the last follow up 14 months after the diagnosis, the patient was alive and free from clinical signs of disease. Tailored treatment, including limited radiotherapy in a higher palliative dose, in a patient with foamy gland symptomatic pituitary metastatic disease resulted in good local and systemic control of the disease. In older male patients with clinical and/or radiologic characteristics suggestive of metastatic pituitary disease, the prostate specific antigen test should be included as part of the work-up.

  18. The heterogeneous Gleason 7 carcinoma of the prostate: analyses of low and high grade (risk) carcinomas with criteria of the International Society of Urological Pathology (ISUP).

    PubMed

    Helpap, Burkhard; Ringli, Daniel; Shaikhibrahim, Zaki; Wernert, Nicolas; Kristiansen, Glen

    2013-03-01

    Prostate carcinoma (PCa) with Gleason score (GS) 7 has to be examined differentially regarding its prognosis. Using the criteria of ISUP and supplementations, we attempted to analyze the heterogeneity of PCa with GS 7 of biopsy and corresponding specimens of radical prostatectomies (RP). PCa of 530 patients were graded according to Gleason under additional consideration of the state of the nucleoli. Investigating the biopsy specimens, we determined the pattern of Gleason 4 of GS 7, the extension of the tumors in percent, and the number of biopsies containing tumor. In the corresponding specimens of RP, the grading and the state of TNM with margins were assessed. Carcinomas with GS 7 (4+3) in biopsy and RP specimens were unequivocally assigned to the group of high-grade tumors. Carcinomas with GS 7 (3+4) were significantly different from carcinomas with GS 6 when only few and small nucleoli in GS 6 were present (low grade type, p≤0.0001), but were similar to the GS 6 group when nucleoli were prominent (intermediary type, p=0.71). The intermediary group showed an upgrading rate of 36% from GS 6 to GS 7. Furthermore the correlation between organ-confined and non-organ-confined growth showed differences of 63% and 37% in the intermediary group (p=0.0001). The values of grading, staging, margins and metastases indicate that carcinomas of the prostate with the Gleason 3+4 pattern correspond to an intermediary group of carcinomas in contrast to high-grade (high risk) carcinomas with GS 7 and pattern 4+3. Copyright © 2013 Elsevier GmbH. All rights reserved.

  19. Interphase cytogenetic analysis of prostatic carcinomas by use of nonisotopic in situ hybridization.

    PubMed

    Baretton, G B; Valina, C; Vogt, T; Schneiderbanger, K; Diebold, J; Löhrs, U

    1994-08-15

    To gain a better understanding of chromosomal aberrations in direct correlation with histology, we studied tumor material from 35 patients (36 regions) with primary prostate carcinoma by nonisotopic in situ hybridization. Nine biotinylated DNA probes were used on serial paraffin sections (centromer-specific probes for X, Y, 1, 7, 8, 10, 17, and 18, and a telomer-specific probe for 1p; ONCOR). Of the 324 hybridized sections, 94% were suitable for evaluation. In 34 of the 35 cases (35 of 36 regions) 1-8 chromosomal aberrations were detected. Chromosome X showed supernumerary centromer copies in 44% of cases. The probes for chromosomes 1, 1p, 10, and 18 demonstrated deletions in 25, 23, 40 and 58% of cases, respectively. Gains as well as deletions were present for Y, 7, 8, and 17 in 31, 25, 36, and 58% of cases, respectively. In 27% of cases discordant copy numbers of the centromer- and the telomer-specific probes for chromosome 1 were observed. No aberration which might be specific for prostate cancer could be established. The rate of aneusomy increased significantly with histological grade. Intratumoral heterogeneity of chromosomal aberrations was revealed in one case. Due to the higher sensitivity of nonisotopic in situ hybridization, aneusomic cases outnumbered cases with cytometrically determined DNA aneuploidy. In view of published results of metaphase preparations, the high frequency of aneusomy and some of the chromosomal aberrations detected by nonisotopic in situ hybridization were unexpected.

  20. Experience with interstitial implantation of iodine 125 in the treatment of prostatic carcinoma.

    PubMed

    Sogani, P C; Whitmore, W F; Hilaris, B S; Batata, M A

    1980-01-01

    Between February 1970 and April 1977 300 patients with localized prostatic carcinoma were treated with I-125 implantation and bilateral pelvic lymphadenectomy at Memorial Sloan-Kettering Cancer Center (MSKCC). 68% had clinical Stage B (T-1 and T-2) and 32% had Stage C (T-3) neoplasms. Pelvic lymph nodes were histologically positive in 38% of the patients. Five-year survival for all patients was 73%. Five-year survival for Stage B disease was 100% and Stage C 65%. Lymph node metastases implied a poor prognosis. While 92% of patients with negative nodes survived five years, only 46% of the patients with positive nodes did so. Supplemental external radiation to pelvic and periaortic region in 28 patients with positive nodes did not improve survival or disease free interval or reduce distal or local recurrence but rather increased the incidence of radiation morbidity. The complications and morbidity as a consequence of I-125 implantation are minimal. The ultimate role of I-125 implantation in the management of localized prostatic cancer is yet to be determined. The early experience with this technique, however, suggests that it may be as effective as alternative modalities for comparable stages in terms of patient survival and may prove superior in terms of the quality of survival.

  1. Interobserver consistency of digital rectal examination in clinical staging of localized prostatic carcinoma.

    PubMed

    Angulo, J C; Montie, J E; Bukowsky, T; Chakrabarty, A; Grignon, D J; Sakr, W; Shamsa, F H; Edson Pontes, J

    1995-01-01

    A prospective study was undertaken to determine the reproducibility of clinical staging based on digital rectal examination (DRE) in prostate carcinoma. We evaluated 48 consecutive patients diagnosed with localized prostatic cancer. Four urologists performed DRE and sorted the patients according to the 1992 American Joint Committee on Cancer Classification for prostate cancer. Both the percentage observed total agreement among each couple of two different observers and the interobserver variability (Kappa index) were analyzed. The percentage observed total agreement among observers in distinguishing five clinical subcategories (T1c, T2a, T2b, T2c, and T3a) ranged between 38-60% (mean 49%) and the Kappa index showed interobserver agreement was poor (overall Kappa = 0.3 1). All four examiners agreed in assigning the same subcategory in only 21 % of cases, and 90% of them were T I. If only categories are distinguished (T I, T2, or T3), the percentage observed total agreement rises to 60-71% (mean 66%) and the interexaminer agreement improves to good (overall Kappa = 0.4 1). Accurate pathologic staging was obtained in every patient and the percentage observed agreement between every examiner and the pathologist was calculated, excluding cases interpreted as T I c. Regarding subcategories, clinicopathologic agreement ranges between 17-46%. If only categories T2 and9T3 are distinguished, agreement rises to 57-69%. In summary, the ability to reproduce clinical staging based on DRE among multiple examiners is disappointingly low and understandably correlates poorly with pathologic stage.

  2. Dosimetry and preliminary acute toxicity in the first 100 men treated for prostate cancer on a randomized hypofractionation dose escalation trial

    SciTech Connect

    Pollack, Alan . E-mail: Alan.Pollack@FCCC.edu; Hanlon, Alexandra L.; Horwitz, Eric M.; Feigenberg, Steven J.; Konski, Andre A.; Movsas, Benjamin; Greenberg, Richard E.; Uzzo, Robert G.; Ma, C.-M. Charlie; McNeeley, Shawn W.; Buyyounouski, Mark K.; Price, Robert A.

    2006-02-01

    Purpose: The {alpha}/{beta} ratio for prostate cancer is postulated to be between 1 and 3, giving rise to the hypothesis that there may be a therapeutic advantage to hypofractionation. The dosimetry and acute toxicity are described in the first 100 men enrolled in a randomized trial. Patients and Methods: The trial compares 76 Gy in 38 fractions (Arm I) to 70.2 Gy in 26 fractions (Arm II) using intensity modulated radiotherapy. The planning target volume (PTV) margins in Arms I and II were 5 mm and 3 mm posteriorly and 8 mm and 7 mm in all other dimensions. The PTV D95% was at least the prescription dose. Results: The mean PTV doses for Arms I and II were 81.1 and 73.8 Gy. There were no differences in overall maximum acute gastrointestinal (GI) or genitourinary (GU) toxicity acutely. However, there was a slight but significant increase in Arm II GI toxicity during Weeks 2, 3, and 4. In multivariate analyses, only the combined rectal DVH parameter of V65 Gy/V50 Gy was significant for GI toxicity and the bladder volume for GU toxicity. Conclusion: Hypofractionation at 2.7 Gy per fraction to 70.2 Gy was well tolerated acutely using the planning conditions described.

  3. Biodistribution and radiation dosimetry of (68)Ga-PSMA HBED CC-a PSMA specific probe for PET imaging of prostate cancer.

    PubMed

    Pfob, Christian H; Ziegler, Sibylle; Graner, Frank Philipp; Köhner, Markus; Schachoff, Sylvia; Blechert, Birgit; Wester, Hans-Jürgen; Scheidhauer, Klemens; Schwaiger, Markus; Maurer, Tobias; Eiber, Matthias

    2016-10-01

    Positron emission tomography (PET) agents targeting the prostate-specific membrane antigen (PSMA) are currently under broad clinical and scientific investigation. (68)Ga-PSMA HBED-CC constitutes the first (68)Ga-labelled PSMA-inhibitor and has evolved as a promising agent for imaging PSMA expression in vivo. The aim of this study was to evaluate the whole-body distribution and radiation dosimetry of this new probe. Five patients with a history or high suspicion of prostate cancer were injected intravenously with a mean of 139.8 ± 13.7 MBq of (68)Ga-PSMA HBED-CC (range 120-158 MBq). Four static skull to mid-thigh scans using a whole-body fully integrated PET/MR-system were performed 10 min, 60 min, 130 min, and 175 min after the tracer injection. Time-dependent changes of the injected activity per organ were determined. Mean organ-absorbed doses and effective doses (ED) were calculated using OLINDA/EXM. Injection of a standard activity of 150 MBq (68)Ga-PSMA HBED-CC resulted in a median effective dose of 2.37 mSv (Range 1.08E-02 - 2.46E-02 mSv/MBq). The urinary bladder wall (median absorbed dose 1.64E-01 mGv/MBq; range 8.76E-02 - 2.91E-01 mGv/MBq) was the critical organ, followed by the kidneys (median absorbed dose 1.21E-01 mGv/MBq; range 7.16E-02 - 1.75E-01), spleen (median absorbed dose 4.13E-02 mGv/MBq; range 1.57E-02 - 7.32E-02 mGv/MBq) and liver (median absorbed dose 2.07E-02 mGv/MBq; range 1.80E-02 - 2.57E-02 mGv/MBq). No drug-related pharmacological effects occurred. The use of (68)Ga-PSMA HBED-CC results in a relatively low radiation exposure, delivering organ doses that are comparable to those of other (68)Ga-labelled PSMA-inhibitors used for PET-imaging. Total effective dose is lower than for other PET-agents used for prostate cancer imaging (e.g. (11)C- and (18)F-Choline).

  4. Thermal dosimetry analysis combined with patient-specific thermal modeling of clinical interstitial ultrasound hyperthermia integrated within HDR brachytherapy for treatment of locally advanced prostate cancer

    NASA Astrophysics Data System (ADS)

    Salgaonkar, Vasant A.; Wootton, Jeff; Prakash, Punit; Scott, Serena; Hsu, I. C.; Diederich, Chris J.

    2017-03-01

    This study presents thermal dosimetry analysis from clinical treatments where ultrasound hyperthermia (HT) was administered following high-dose rate (HDR) brachytherapy treatment for locally advanced prostate cancer as part of a clinical pilot study. HT was administered using ultrasound applicators from within multiple 13-g brachytherapy catheters implanted along the posterior periphery of the prostate. The heating applicators were linear arrays of sectored tubular transducers (˜7 MHz), with independently powered array elements enabling energy deposition with 3D spatial control. Typical heat treatments employed time-averaged peak acoustic intensities of 1 - 3 W/cm2 and lasted for 60 - 70 minutes. Throughout the treatments, temperatures at multiple points were monitored using multi-junction thermocouples, placed within available brachytherapy catheters throughout mid-gland prostate and identified as the hyperthermia target volume (HTV). Clinical constraints allowed placement of 8 - 12 thermocouple sensors in the HTV and patient-specific 3D thermal modeling based on finite element methods (FEM) was used to supplement limited thermometry. Patient anatomy, heating device positions, orientations, and thermometry junction locations were obtained from patient CT scans and HDR and hyperthermia planning software. The numerical models utilized the applied power levels recorded during the treatments. Tissue properties such as perfusion and acoustic absorption were varied within physiological ranges such that squared-errors between measured and simulated temperatures were minimized. This data-fitting was utilized for 6 HT treatments to estimate volumetric temperature distributions achieved in the HTV and surrounding anatomy devoid of thermocouples. For these treatments, the measured and simulated T50 values in the hyperthermia target volume (HTV) were between 40.1 - 43.9 °C and 40.3 - 44.9 °C, respectively. Maximum temperatures between 46.8 - 49.8 °C were measured during

  5. Co-culturing human prostate carcinoma cells with hepatocytes leads to increased expression of E-cadherin

    PubMed Central

    Yates, C C; Shepard, C R; Stolz, D B; Wells, A

    2007-01-01

    Metastasis is a multi-step process wherein tumour cells detach from the primary mass, migrate through barrier matrices, gain access to conduits to disseminate, and subsequently survive and proliferate in an ectopic site. During the initial invasion stage, prostate carcinoma cells undergo epithelial–mesenchymal-like transition with gain of autocrine signalling and loss of E-cadherin, hallmarks that appear to enable invasion and dissemination. However, some metastases express E-cadherin, and we found close connections between prostate carcinoma cells and hepatocytes in a liver microtissue bioreactor. We hypothesise that phenotypic plasticity occurs late in prostate cancer progression at the site of ectopic seeding. Immunofluorescence staining for E-cadherin in co-cultures of hepatocytes and DU-145 prostate cancer cells revealed E-cadherin upregulation at peripheral sites of contact by day 2 of co-culture; E-cadherin expression also increased in PC-3 cells in co-culture. These carcinoma cells bound to hepatocytes in an E-cadherin-dependent manner. Although the signals by which the hepatocytes elicited E-cadherin expression remain undetermined, it appeared related to downregulation of epidermal growth factor receptor (EGFR) signalling. Inhibition of autocrine EGFR signalling increased E-cadherin expression and cell–cell heterotypic adhesion; further, expression of a downregulation-resistant EGFR variant prevented E-cadherin upregulation. These findings were supported by finding E-cadherin and catenins but not activated EGFR in human prostate metastases to the liver. We conclude that the term epithelial–mesenchymal transition only summarises the transient downregulation of E-cadherin for invasion with re-expression of E-cadherin being a physiological consequence of metastatic seeding. PMID:17406365

  6. Small cell carcinoma of the prostate presenting with Cushing Syndrome. A narrative review of an uncommon condition.

    PubMed

    Rueda-Camino, José Antonio; Losada-Vila, Beatriz; De Ancos-Aracil, Cristina Lucía; Rodríguez-Lajusticia, Laura; Tardío, Juan Carlos; Zapatero-Gaviria, Antonio

    2016-01-01

    Small cell carcinoma (SCC) of the prostate is an uncommon condition; there are very few cases in which presenting symptoms are consistent with Cushing Syndrome (CS). We report a new case in which CS triggers the suspicion of an SCC of the prostate and a review of the published cases of SCC of the prostate presenting with CS. The origin of these neoplasms is still unclear. It may be suspected when laboratory features appear in patients diagnosed with prostatic adenocarcinoma which becomes resistant to specific therapy. SCC usually occurs after the 6th decade. Patients suffering SCC of the prostate presenting with CS usually present symptoms such as hypertension, hyperglycemia, alkalosis or hypokalemia; cushingoid phenotype is less frequent. Cortisol and ACTH levels are often high. Prostatic-specific antigen levels are usually normal. CT scan is the preferred imaging test to localize the lesion, but its performance may be improved by adding other tests, such as FDG-PET scan. All patients have metastatic disease at the time of diagnosis. Lymph nodes, liver and bone are the most frequent metastases sites. Surgery and Ketokonazole are the preferred treatments for CS. The prognosis is very poor: 2- and 5-year survival rates are 27.5 and 14.3%, respectively. Key messages When a patient presents with ectopic Cushing Syndrome but lungs are normal, an atypical localization should be suspected. We should suspect a prostatic origin if Cushing Syndrome is accompanied by obstructive inferior urinary tract symptoms or in the setting of a prostatic adenocarcinoma with rapid clinical and radiological progression with relatively low PSA levels. Although no imaging test is preferred to localize these tumors, FDG-PET-TC can be very useful. Hormone marker scintigraphy (e.g. somatostatin) could be used too. As Cushing Syndrome is a paraneoplastic phenomenon, treatment of the underlying disease may help control hypercortisolism manifestations. These tumors are usually metastatic by the

  7. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    PubMed

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  8. Small Cell Carcinoma of the Prostate in an Elderly Patient: A Case Report and Review of the Literature

    PubMed Central

    Whitaker, Dale Alan; Miller, Daniel H.; Jagadesh, Niveditha; Strong, Gerald W.; Hintenlang, Lauren; Schenk, William B.; Broderick, Gregory A.; Tzou, Katherine S.; Buskirk, Steven J.

    2016-01-01

    Prostate cancer is the most common malignancy of men in the United States. Small-cell carcinoma (SCC), which typically presents as an aggressive lung malignancy, is a rare diagnosis within the setting of prostate cancer pathology. Due to its limited prevalence, little information regarding the treatment and prognosis of this disease in large populations is available. To date our current knowledge base is largely limited to case reports and retrospective case reviews. The mainstay of treatment for this particular histology most often involves a multimodality approach utilizing chemotherapy in conjunction with radiation therapy, androgen deprivation therapy, or prostatectomy. Here we present the case of an elderly 89-year-old Caucasian male who was diagnosed with SCC of the prostate. Despite proceeding with a course of definitive radiotherapy, the patient experienced rapid progression of disease and ultimately elected to discontinue radiation therapy and receive hospice care. PMID:28191295

  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. Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

    PubMed

    Yoshida, K I; Honda, M; Arai, K; Hosoya, Y; Moriguchi, H; Sumi, S; Ueda, Y; Kitahara, S

    1997-08-01

    Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

  11. Metastatic small cell carcinoma of the prostate: Population-based analysis of patient characteristics and treatment paradigms.

    PubMed

    Cohen, Andrew; Richards, Kyle A; Patel, Sanjay; Weiner, Adam; Eggener, Scott E; Szmulewitz, Russell Z

    2015-02-01

    Small cell carcinoma of the prostate is a rare malignancy comprising<1% of prostate cancers. Little is known about population-based treatment patterns for metastatic small cell carcinoma of the prostate. We evaluated clinical characteristics, treatment patterns, and survival outcomes. Using the National Cancer Database, we identified patients between 1998 and 2011 diagnosed with pure small cell carcinoma of the prostate as their only malignancy who presented with nodal involvement or distant metastasis. Treatment information was available for 379 patients. Of them, 122 (32.5%) underwent chemotherapy (CT) alone, 25 (6.7%) received hormonal therapy (androgen-deprivation therapy) alone, 10 (2.7%) underwent radiation therapy alone, 3 (1%) underwent radical prostatectomy, and 167 (44.4%) underwent combination therapy. The 1- and 3-year survival rates were 35.3% and 4.4%, respectively. Those receiving any CT as part of their treatment had a median survival of 9.3 vs. 3.2 months for those not receiving it (P<0.001). Those receiving CT, androgen-deprivation therapy, and radiation had a median survival of 15.1 vs. 7 months for those receiving CT alone (P<0.001). On multivariable analysis (controlling for age, Charlson comorbidity index, extent of metastasis, prostate-specific antigen level, and type of treatment), older age (hazard ratio [HR] = 3.87; 95% CI: 1.41-9.34; P = 0.007) and distant metastatic disease (HR = 7.17; 95% CI: 1.62-31.8; P = 0.010) increased risk of death, whereas receipt of CT (HR = 0.15; 95% CI: 0.05-0.44; P = 0.001) decreased risk of death. Men presenting with metastatic small cell carcinoma of the prostate have poor overall survival. Older patients and those presenting with distant metastases have an increased risk of death. It appears that patients receiving CT experience a modest survival benefit. The role of hormonal therapy in this population remains unclear. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Quantification of activity by alpha-camera imaging and small-scale dosimetry within ovarian carcinoma micrometastases treated with targeted alpha therapy.

    PubMed

    Chouin, N; Lindegren, S; Jensen, H; Albertsson, P; Bäck, T

    2012-12-01

    Targeted alpha therapy (TAT) a promising treatment for small, residual, and micrometastatic diseases has questionable efficacy against malignant lesions larger than the α-particle range, and likely requires favorable intratumoral activity distribution. Here, we characterized and quantified the activity distribution of an alpha-particle emitter radiolabelled antibody within >100-µm micrometastases in a murine ovarian carcinoma model. Nude mice bearing ovarian micrometastases were injected intra-peritoneally with 211At-MX35 (total injected activity 6 MBq, specific activity 650 MBq/mg). Animals were sacrificed at several time points, and peritoneal samples were excised and prepared for alpha-camera imaging. Spatial and temporal activity distributions within micrometastases were derived and used for small-scale dosimetry. We observed two activity distribution patterns: uniform distribution and high stable uptake (>100% IA/g at all time points) in micrometastases with no visible stromal compartment, and radial distribution (high activity on the edge and poor uptake in the core) in tumor cell lobules surrounded by fibroblasts. Activity distributions over time were characterized by a peak (140% IA/g at 4 h) in the outer tumor layer and a sharp drop beyond a depth of 50 µm. Small-scale dosimetry was performed on a multi-cellular micrometastasis model, using time-integrated activities derived from the experimental data. With injected activity of 400 kBq, tumors exhibiting uniform activity distribution received <25 Gy (EUD=13 Gy), whereas tumors presenting radial activity distribution received mean absorbed doses of <8 Gy (EUD=5 Gy). These results provide new insight into important aspects of TAT, and may explain why micrometastases >100 µm might not be effectively treated by the examined regimen.

  13. Effect of different breathing patterns in the same patient on stereotactic ablative body radiotherapy dosimetry for primary renal cell carcinoma: A case study

    SciTech Connect

    Pham, Daniel; Kron, Tomas; Foroudi, Farshad; Siva, Shankar

    2013-10-01

    Stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) targets requires motion management strategies to verify dose delivery. This case study highlights the effect of a change in patient breathing amplitude on the dosimetry to organs at risk and target structures. A 73-year-old male patient was planned for receiving 26 Gy of radiation in 1 fraction of SABR for a left primary RCC. The patient was simulated with four-dimensional computed tomography (4DCT) and the tumor internal target volume (ITV) was delineated using the 4DCT maximum intensity projection. However, the initially planned treatment was abandoned at the radiation oncologist's discretion after pretreatment cone-beam CT (CBCT) motion verification identified a greater than 50% reduction in superior to inferior diaphragm motion as compared with the planning 4DCT. This patient was resimulated with respiratory coaching instructions. To assess the effect of the change in breathing on the dosimetry to the target, each plan was recalculated on the data set representing the change in breathing condition. A change from smaller to larger breathing showed a 46% loss in planning target volume (PTV) coverage, whereas a change from larger breathing to smaller breathing resulted in an 8% decrease in PTV coverage. ITV coverage was similarly reduced by 8% in both scenarios. This case study highlights the importance of tools to verify breathing motion prior to treatment delivery. 4D image guided radiation therapy verification strategies should focus on not only verifying ITV margin coverage but also the effect on the surrounding organs at risk.

  14. Effect of different breathing patterns in the same patient on stereotactic ablative body radiotherapy dosimetry for primary renal cell carcinoma: a case study.

    PubMed

    Pham, Daniel; Kron, Tomas; Foroudi, Farshad; Siva, Shankar

    2013-01-01

    Stereotactic ablative body radiotherapy (SABR) for primary renal cell carcinoma (RCC) targets requires motion management strategies to verify dose delivery. This case study highlights the effect of a change in patient breathing amplitude on the dosimetry to organs at risk and target structures. A 73-year-old male patient was planned for receiving 26Gy of radiation in 1 fraction of SABR for a left primary RCC. The patient was simulated with four-dimensional computed tomography (4DCT) and the tumor internal target volume (ITV) was delineated using the 4DCT maximum intensity projection. However, the initially planned treatment was abandoned at the radiation oncologist's discretion after pretreatment cone-beam CT (CBCT) motion verification identified a greater than 50% reduction in superior to inferior diaphragm motion as compared with the planning 4DCT. This patient was resimulated with respiratory coaching instructions. To assess the effect of the change in breathing on the dosimetry to the target, each plan was recalculated on the data set representing the change in breathing condition. A change from smaller to larger breathing showed a 46% loss in planning target volume (PTV) coverage, whereas a change from larger breathing to smaller breathing resulted in an 8% decrease in PTV coverage. ITV coverage was similarly reduced by 8% in both scenarios. This case study highlights the importance of tools to verify breathing motion prior to treatment delivery. 4D image guided radiation therapy verification strategies should focus on not only verifying ITV margin coverage but also the effect on the surrounding organs at risk.

  15. [Planned 3-dimensional low-volume conformal irradiation of a local prostatic carcinoma].

    PubMed

    Wachter, S; Gerstner, N; Dieckmann, K; Stampfer, M; Hawliczek, R; Pötter, R

    1997-05-01

    Recent data have shown a significant reduction of acute side effects by means of a three-dimensional planned conformal radiotherapy of carcinoma of the prostate compared to treatment techniques used before. Theoretically, an optimized field coverage of the planning target volume should result in a reduction of treated bladder and rectum volumes. We studied the effects of individualized blocks on treatment volumes, planning target volumes, irradiated bladder and rectum volumes on basis of three-dimensional treatment planning by means of beam's-eye-view technique. We compared dose-volume-histograms of 2 different planning models, a (fictitious) open 4-field-box-technique and a technique with conformal blocked fields designed from the beam's-eye-view display (prescribed dose 66 Gy, daily single fraction 2 Gy). Plans of 115 patients with localized prostate cancer treated from January 1994 to February 1996 were analyzed. Using individualized fields treatment volume (covered by the 90%-isodose) was reduced by 23% on the average in comparison to the planning model without blocks. The averaged difference of treated volume and planning target volume, as a grade of efficiency of conformation, was reduced by 38% (496 cm3 303 cm3) using individualized blocks. 23% of the treated bladder volume and 13% of the treated rectum volume had been saved on the average. Nevertheless, at least 11.5% of the bladder volume and 27.6% of the contoured rectum volume were treated with the prescribed dose (55 Gy = 100%). The comparison of dose-volume-histogram-data showed that especially high dose volumes of organs at risk had been saved by means of individualized blocks created from the beam's-eye-view. The blocks did not affect the dose distribution of the planning target volume adversely. Consequently the impact of these data on the extent of side effects and local tumor control has to be proven.

  16. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation.

    PubMed

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S; Maclean, Fiona; Oto, Aytekin

    2016-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. Online supplemental material is available for this article. ©RSNA, 2015.

  17. Benign Conditions That Mimic Prostate Carcinoma: MR Imaging Features with Histopathologic Correlation1

    PubMed Central

    Kitzing, Yu Xuan; Prando, Adilson; Varol, Celi; Karczmar, Gregory S.; Maclean, Fiona; Oto, Aytekin

    2017-01-01

    Multiparametric magnetic resonance (MR) imaging combines anatomic and functional imaging techniques for evaluating the prostate and is increasingly being used in diagnosis and management of prostate cancer. A wide spectrum of anatomic and pathologic processes in the prostate may masquerade as prostate cancer, complicating the imaging interpretation. The histopathologic and imaging findings of these potential mimics are reviewed. These entities include the anterior fibromuscular stroma, surgical capsule, central zone, periprostatic vein, periprostatic lymph nodes, benign prostatic hyperplasia (BPH), atrophy, necrosis, calcification, hemorrhage, and prostatitis. An understanding of the prostate zonal anatomy is helpful in distinguishing the anatomic entities from prostate cancer. The anterior fibromuscular stroma, surgical capsule, and central zone are characteristic anatomic features of the prostate with associated low T2 signal intensity due to dense fibromuscular tissue or complex crowded glandular tissue. BPH, atrophy, necrosis, calcification, and hemorrhage all have characteristic features with one or more individual multiparametric MR imaging modalities. Prostatitis constitutes a heterogeneous group of infective and inflammatory conditions including acute and chronic bacterial prostatitis, infective and noninfective granulomatous prostatitis, and malacoplakia. These entities are associated with variable clinical manifestations and are characterized by the histologic hallmark of marked inflammatory cellular infiltration. In some cases, these entities are indistinguishable from prostate cancer at multiparametric MR imaging and may even exhibit extraprostatic extension and lymphadenopathy, mimicking locally advanced prostate cancer. It is important for the radiologists interpreting prostate MR images to be aware of these pitfalls for accurate interpretation. PMID:26587887

  18. Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife

    PubMed Central

    Fukuda, Shoichi; Seo, Yuji; Shiomi, Hiroya; Yamada, Yuji; Ogata, Toshiyuki; Morimoto, Masahiro; Konishi, Koji; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2014-01-01

    The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm3 for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm3 (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted. PMID:24957754

  19. Dosimetry analyses comparing high-dose-rate brachytherapy, administered as monotherapy for localized prostate cancer, with stereotactic body radiation therapy simulated using CyberKnife.

    PubMed

    Fukuda, Shoichi; Seo, Yuji; Shiomi, Hiroya; Yamada, Yuji; Ogata, Toshiyuki; Morimoto, Masahiro; Konishi, Koji; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2014-11-01

    The purpose of this study was to perform dosimetry analyses comparing high-dose-rate brachytherapy (HDR-BT) with simulated stereotactic body radiotherapy (SBRT). We selected six consecutive patients treated with HDR-BT monotherapy in 2010, and a CyberKnife SBRT plan was simulated for each patient using computed tomography images and the contouring set used in the HDR-BT plan for the actual treatment, but adding appropriate planning target volume (PTV) margins for SBRT. Then, dosimetric profiles for PTVs of the rectum, bladder and urethra were compared between the two modalities. The SBRT plan was more homogenous and provided lower dose concentration but better coverage for the PTV. The maximum doses in the rectum were higher in the HDR-BT plans. However, the HDR-BT plan provided a sharper dose fall-off around the PTV, resulting in a significant and considerable difference in volume sparing of the rectum with the appropriate PTV margins added for SBRT. While the rectum D5cm(3) for HDR-BT and SBRT was 30.7 and 38.3 Gy (P < 0.01) and V40 was 16.3 and 20.8 cm(3) (P < 0.01), respectively, SBRT was significantly superior in almost all dosimetric profiles for the bladder and urethra. These results suggest that SBRT as an alternative to HDR-BT in hypofractionated radiotherapy for prostate cancer might have an advantage for bladder and urethra dose sparing, but for the rectum only when proper PTV margins for SBRT are adopted.

  20. Comparison of PSMA-HBED and PSMA-I&T as diagnostic agents in prostate carcinoma.

    PubMed

    McCarthy, Michael; Langton, Tiffany; Kumar, Divesh; Campbell, Andrew

    2017-08-01

    Gallium(68)-labelled prostate-specific membrane antigen (PSMA) radiopharmaceuticals can be used to detect prostate cancer (PCa) cells due the their over expression of PSMA. The (68)Ga HBED-PSMA (PSMA-HBED) ligand has been most widely used and can be considered the current gold standard agent. Further PSMA ligands based on the DOTAGA and DOTA conjugates have more recently been developed. These agents (PSMA-I&T and PSMA-617) have potential theranostic capabilities as they can be conjugated with therapeutic radioisotopes. In this study, we examine whether PSMA-I&T has comparative efficacy, such that it could replace PSMA-HBED as a diagnostic agent in prostate carcinoma. 19 patients with PCa referred for (68)Ga-PSMA imaging were imaged with PSMA-HBED and PSMA-I&T PET-CT imaging within a 2-week period. The two pharmaceuticals were synthesised using click chemistry. Imaging was performed using the same standardised methodology on a Siemens Biograph mCT. All sites of PSMA binding thought to represent PCa (probable or definite) were included in a lesion analysis that examined lesion concordance and lesional binding efficiency (SUVpeak) between the two radiopharmaceuticals. For each patient, SUVmean of the LV cavity blood pool, bone, muscle and liver were determined as image background measures. Across all patients, PSMA uptake was observed in 47 lesions (10 bone lesions, 19 nodal lesions, 18 high-grade intraprostatic binding). Lesions were concordant between the agents in all except for two small (<4 mm) nodal lesions which were not visualised with PSMA-I&T. SUVpeak assessment showed significantly greater overall lesion binding with HBED (paired t test, p = 0.0001). LV blood pool and bone marrow SUVmean were significantly higher for I&T than HBED (paired t test, blood pool p < 1 × 10-5, bone marrow p < 0.005). Intra-patient comparative imaging demonstrates higher lesional PSMA-HBED binding than PSMA-I&T and that the HBED agent is likely to have better lesion

  1. External Beam Radiation and Brachytherapy for Prostate Cancer: Is It a Possible Trigger of Large Cell Neuroendocrine Carcinoma of the Urinary Bladder?

    PubMed

    Zakaria, Ali; Al Share, Bayan; Kollepara, Sri; Vakhariya, Cynthia

    2017-01-01

    Neuroendocrine tumors commonly involve the respiratory and gastrointestinal systems. Primary genitourinary neuroendocrine tumors are rare, accounting for less than 1% of all bladder carcinomas. Four histopathologic subtypes have been described. Among those, large cell neuroendocrine carcinoma (LCNEC) is the least common, is more aggressive, and generally presents in an advanced stage with poor prognosis compared to transitional cell bladder carcinoma. There is no standardized treatment regimen because of the rarity of the disease. Herein, we present a case of 72-year-old male patient with previously treated prostate cancer, who received external beam radiation therapy and high dose brachytherapy, presenting with intermittent hematuria. Cystoscopy and transurethral resection of bladder tumor (TURBT) were performed. The histopathology and immunohistochemistry were consistent with large cell neuroendocrine carcinoma (LCNEC). Further studies are required to proof the higher risk of neuroendocrine carcinoma of the bladder in patients treated with external beam radiation therapy and brachytherapy for prostate cancer.

  2. [Cycle arrest of prostate carcinoma DU-145 cells induced by pseudolaric acid B].

    PubMed

    Mai, Xia; Xu, Zhong-Wei; Chen, Xiao-Yi; Cao, Bo; Xu, Rui-Cheng

    2012-11-01

    To study the effect of pseudolaric acid B (PLAB) on cell proliferation and cycle of human prostate carcinoma DU-145 cells. method: Its inhibitory effect on the cell growth was measured by MTT method. Characteristics of cell death were determined by Hoechest 33342 staining. The cell cycle was detected by flow cytometry. The expressions of cyclin B1, cyclin D1 and CDK1 were detected by Real time-PCR and Western blot, respectively. PLAB notably inhibited DU-145 cell growth in a dose- and time dependent manner (P < 0.05). Its IC50 values of PLAB for DU-145 cells for 24, 48 and 72 h were 4.53, 2.39 and 2.08 micromol x L(-1), respectively. Having been treated with 5 micromol x L(-1) PLAB for 24 h, the cells showed such apoptosis characteristics as nuclei chromatin condensation and apoptotic body. With the increase in PLAB concentration, the proportion of G2/M phase cells strikingly increased in a dose- and time dependent manner (P < 0.05), meanwhile cyclin B1 and CDK1 showed over-expressions (P < 0.05), and the cyclin D1 showed under-expression (P < 0.05). PLAB can inhibit the growth of DU-145 cells and induce the cell cycle G2/M arrest, accompanied with the over-expression of cyclin B1 and CDK1, which may be related with its regulation cycle-associated protein degradation.

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

    SciTech Connect

    Jacobsson, H.; Naeslund, I. )

    1991-06-01

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

  4. Disease-related effects of perioperative blood transfusions associated with sup 125 I seed implantation for prostate carcinoma

    SciTech Connect

    Petersen, J.P.; Schellhammer, P.F.; el-Mahdi, A.M. )

    1990-08-01

    In some retrospective studies perioperative transfusions during oncologic surgery have been shown to decrease the time interval between surgery and local and/or distant recurrence of cancer. This study examines the disease-related effect, if any, of perioperative blood transfusions among 108 patients with localized carcinoma of the prostate treated by radioactive iodine-125 seed implantation of the prostate and lymphadenectomy. When all subjects were analyzed, there was no statistical difference of local and distant failure between the transfused and nontransfused groups. Patients with well-differentiated tumors had statistically fewer local recurrences (0% vs 22%, p = 0.036) if they were transfused perioperatively. However, the difference in distant metastases (0% vs 11%) was not statistically significant (p = 0.21). In contrast, patients with moderately and poorly differentiated disease receiving transfusions had more local recurrences and metastases, though this was not statistically significant. Our data suggest that there is no obvious evidence that perioperative blood transfusions have an adverse effect on local recurrence or distant metastases for iodine-125 seed implantation of carcinoma of the prostate.

  5. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken's embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  6. Computer-Aided Image Analysis and Fractal Synthesis in the Quantitative Evaluation of Tumor Aggressiveness in Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    The subjective evaluation of tumor aggressiveness is a cornerstone of the contemporary tumor pathology. A large intra- and interobserver variability is a known limiting factor of this approach. This fundamental weakness influences the statistical deterministic models of progression risk assessment. It is unlikely that the recent modification of tumor grading according to Gleason criteria for prostate carcinoma will cause a qualitative change and improve significantly the accuracy. The Gleason system does not allow the identification of low aggressive carcinomas by some precise criteria. The ontological dichotomy implies the application of an objective, quantitative approach for the evaluation of tumor aggressiveness as an alternative. That novel approach must be developed and validated in a manner that is independent of the results of any subjective evaluation. For example, computer-aided image analysis can provide information about geometry of the spatial distribution of cancer cell nuclei. A series of the interrelated complexity measures characterizes unequivocally the complex tumor images. Using those measures, carcinomas can be classified into the classes of equivalence and compared with each other. Furthermore, those measures define the quantitative criteria for the identification of low- and high-aggressive prostate carcinomas, the information that the subjective approach is not able to provide. The co-application of those complexity measures in cluster analysis leads to the conclusion that either the subjective or objective classification of tumor aggressiveness for prostate carcinomas should comprise maximal three grades (or classes). Finally, this set of the global fractal dimensions enables a look into dynamics of the underlying cellular system of interacting cells and the reconstruction of the temporal-spatial attractor based on the Taken’s embedding theorem. Both computer-aided image analysis and the subsequent fractal synthesis could be performed

  7. Computational dosimetry

    SciTech Connect

    Siebert, B.R.L.; Thomas, R.H.

    1996-01-01

    The paper presents a definition of the term ``Computational Dosimetry`` that is interpreted as the sub-discipline of computational physics which is devoted to radiation metrology. It is shown that computational dosimetry is more than a mere collection of computational methods. Computational simulations directed at basic understanding and modelling are important tools provided by computational dosimetry, while another very important application is the support that it can give to the design, optimization and analysis of experiments. However, the primary task of computational dosimetry is to reduce the variance in the determination of absorbed dose (and its related quantities), for example in the disciplines of radiological protection and radiation therapy. In this paper emphasis is given to the discussion of potential pitfalls in the applications of computational dosimetry and recommendations are given for their avoidance. The need for comparison of calculated and experimental data whenever possible is strongly stressed.

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

    ClinicalTrials.gov

    2017-05-18

    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

  9. Preventive and therapeutic vaccination with PAP-3, a novel human prostate cancer peptide, inhibits carcinoma development in HLA transgenic mice.

    PubMed

    Machlenkin, Arthur; Azriel-Rosenfeld, Ronit; Volovitz, Ilan; Vadai, Ezra; Lev, Avital; Paz, Adrian; Goldberger, Ofir; Reiter, Yoram; Tzehoval, Esther; Benhar, Itai; Eisenbach, Lea

    2007-02-01

    Conventional treatment of recurrent and metastasized prostate cancer (CaP) remains inadequate; this fact mandates development of alternative therapeutic modalities, such as specific active or passive immunotherapy. Previously, we reported the identification of a novel highly immunogenic HLA-A*0201-restricted Prostatic Acid Phosphatase-derived peptide (PAP-3) by a two-step in vivo screening in an HLA-transgenic (HHD) mouse system. In the present study we aimed at elucidating the efficiency of PAP-3-based vaccine upon active antitumor immunization. To this end we established preventive and therapeutic carcinoma models in HHD mice. The 3LL murine Lewis lung carcinoma clone D122 transduced to express HLA-A*0201 and PAP served as a platform for these models. The HLA-A*0201-PAP-3 complex specific recombinant single chain scFV-PAP-3 antibodies were generated and used to confirm an endogenous PAP processing resulting in PAP-3 presentation by HLA-A*0201. PAP-3 based vaccines significantly decreased tumor incidence in a preventive immunization setting. Therapeutic vaccination of HHD mice with PAP-3 led to rejection of early established tumors and to increase of mouse survival. These results strongly support a therapeutic relevance of the identified CTL epitope upon active antitumor immunization. The newly established carcinoma model presented herein might be a useful tool for cancer vaccine design and optimization.

  10. Extended transurethral resection and Nd:YAG laser ablation of the prostate (TURLAP) for carcinoma: a pilot study

    NASA Astrophysics Data System (ADS)

    Childs, Stacy J.

    1993-05-01

    Transurethral resection of the prostate (TURP) has been combined with Nd:YAG application for the treatment of prostatic carcinoma for a decade. The inability to deliver the energy at right angles has made the procedure technically difficult, but results have been encouraging. A pilot study was begun in 1991 on ten patients who refused or were not candidates for radical prostatectomy. The protocol consisted of transrectal ultrasound imaging (TRUS) during extended TURP (EXTURP) followed immediately by Nd:YAG energy applied to the prostate bed and capsule. A second laser application under real time TRUS followed in eight weeks and a third (or fourth in one patient) was undertaken eight weeks later. Energy of 30,000- 85,000 Joules was applied during each procedure with the right angle urolase fiber (Bard) at 60 watts. Lesions were created for 30-60 seconds in each area of remaining tissue documented on TRUS. A thermocoupler was used to monitor rectal temperature. Complications include urinary retention, gross hematuria, bladder neck contracture, early incontinence, late incontinence, and probable permanent incontinence. Of the only four potent patients preoperatively, all (100%) are impotent now. TURLAP appears to be a safe and effective method of killing prostate malignant tissue and should be further studied perhaps in combination with interstitial laser irradiation to increase efficacy and lessen complications.

  11. Biodistribution, Tumor Detection, and Radiation Dosimetry of 18F-DCFBC, a Low-Molecular-Weight Inhibitor of Prostate-Specific Membrane Antigen, in Patients with Metastatic Prostate Cancer

    PubMed Central

    Cho, Steve Y.; Gage, Kenneth L.; Mease, Ronnie C.; Senthamizhchelvan, Srinivasan; Holt, Daniel P.; Jeffrey-Kwanisai, Akimosa; Endres, Christopher J.; Dannals, Robert F.; Sgouros, George; Lodge, Martin; Eisenberger, Mario A.; Rodriguez, Ronald; Carducci, Michael A.; Rojas, Camilo; Slusher, Barbara S.; Kozikowski, Alan P.; Pomper, Martin G.

    2013-01-01

    Prostate-specific membrane antigen (PSMA) is a type II integral membrane protein expressed on the surface of prostate cancer (PCa) cells, particularly in androgen-independent, advanced, and metastatic disease. Previously, we demonstrated that N-[N-[(S)-1,3-dicarboxypropyl]carbamoyl]-4-18F-fluorobenzyl-Lcysteine (18F-DCFBC) could image an experimental model of PSMA-positive PCa using PET. Here, we describe the initial clinical experience and radiation dosimetry of 18F-DCFBC in men with metastatic PCa. Methods Five patients with radiologic evidence of metastatic PCa were studied after the intravenous administration of 370 MBq (10 mCi) of 18F-DCFBC. Serial PET was performed until 2 h after administration. Time- activity curves were generated for selected normal tissues and metastatic foci. Radiation dose estimates were calculated using OLINDA/EXM 1.1. Results Most vascular organs demonstrated a slow decrease in radioactivity concentration over time consistent with clearance from the blood pool, with primarily urinary radiotracer excretion. Thirty-two PET-positive suspected metastatic sites were identified, with 21 concordant on both PET and conventional imaging for abnormal findings compatible with metastatic disease. Of the 11 PET-positive sites not identified on conventional imaging, most were within the bone and could be considered suggestive for the detection of early bone metastases, although further validation is needed. The highest mean absorbed dose per unit administered radioactivity (µGy/MBq) was in the bladder wall (32.4), and the resultant effective dose was 19.9 ± 1.34 µSv/MBq (mean ± SD). Conclusion Although further studies are needed for validation, our findings demonstrate the potential of 18F-DCFBC as a new positron-emitting imaging agent for the detection of metastatic PCa. This study also provides dose estimates for 18F-DCFBC that are comparable to those of other PET radiopharmaceuticals such as 18F-FDG. PMID:23203246

  12. Molecular evidence that invasive adenocarcinoma can mimic prostatic intraepithelial neoplasia (PIN) and intraductal carcinoma through retrograde glandular colonization.

    PubMed

    Haffner, Michael C; Weier, Christopher; Xu, Meng Meng; Vaghasia, Ajay; Gürel, Bora; Gümüşkaya, Berrak; Esopi, David M; Fedor, Helen; Tan, Hsueh-Li; Kulac, Ibrahim; Hicks, Jessica; Isaacs, William B; Lotan, Tamara L; Nelson, William G; Yegnasubramanian, Srinivasan; De Marzo, Angelo M

    2016-01-01

    Prostate cancer often manifests as morphologically distinct tumour foci and is frequently found adjacent to presumed precursor lesions such as high-grade prostatic intraepithelial neoplasia (HGPIN). While there is some evidence to suggest that these lesions can be related and exist on a pathological and morphological continuum, the precise clonal and temporal relationships between precursor lesions and invasive cancers within individual tumours remain undefined. Here, we used molecular genetic, cytogenetic, and histological analyses to delineate clonal, temporal, and spatial relationships between HGPIN and cancer lesions with distinct morphological and molecular features. First, while confirming the previous finding that a substantial fraction of HGPIN lesions associated with ERG-positive cancers share rearrangements and overexpression of ERG, we found that a significant subset of such HGPIN glands exhibit only partial positivity for ERG. This suggests that such ERG-positive HGPIN cells either rapidly invade to form adenocarcinoma or represent cancer cells that have partially invaded the ductal and acinar space in a retrograde manner. To clarify these possibilities, we used ERG expression status and TMPRSS2-ERG genomic breakpoints as markers of clonality, and PTEN deletion status to track temporal evolution of clonally related lesions. We confirmed that morphologically distinct HGPIN and nearby invasive cancer lesions are clonally related. Further, we found that a significant fraction of ERG-positive, PTEN-negative HGPIN and intraductal carcinoma (IDC-P) lesions are most likely clonally derived from adjacent PTEN-negative adenocarcinomas, indicating that such PTEN-negative HGPIN and IDC-P lesions arise from, rather than give rise to, the nearby invasive adenocarcinoma. These data suggest that invasive adenocarcinoma can morphologically mimic HGPIN through retrograde colonization of benign glands with cancer cells. Similar clonal relationships were also seen for

  13. Hypofractionated versus conventionally fractionated radiation therapy for prostate carcinoma: Updated results of a phase III randomized trial

    SciTech Connect

    Yeoh, Eric E. . E-mail: eyeoh@mail.rah.sa.gov.au; Holloway, Richard H.; Fraser, Robert J.; Botten, Rochelle J.; Di Matteo, Addolorata C.; Butters, Julie; Weerasinghe, Sujeeva; Abeysinghe, Prasad

    2006-11-15

    Purpose: The aim of this study was to compare the toxicity and efficacy of radiation therapy (RT) for localized carcinoma of the prostate, using a hypofractionated (55 Gy/20 fractions/4 weeks) vs. a conventionally fractionated (64 Gy/32 fractions/6.5 weeks) dose schedule. Methods and Materials: A total of 217 patients were randomized to either the hypofractionated (108 patients) or the conventional (109 patients) dose schedule, with planning with two-dimensional (2D) CT scan planning methodology in the majority of cases. All patients were followed for a median of 48 (6-108) months. Gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated before RT and after its completion using modified late effects of normal tissue-subjective, objective, management, analytic (LENT-SOMA) scales and the European Organization for Research and Treatment of Cancer sexual function questionnaire. Efficacy of RT based on clinical, radiologic, and prostate-specific antigen data were also evaluated at baseline and after RT. Results: Gastrointestinal and GU toxicity persisted 5 years after RT and did not differ between the two dose schedules other than in regard to urgency of defecation. However, 1-month GI toxicity was not only worse in patients with the hypofractionated RT schedule but also adversely affected daily activities. Nadir prostate-specific antigen values occurred at a median of 18.0 (3.0-54.0) months after RT. A total of 76 biochemical relapses, with or without clinical relapses, have occurred since; of these, 37 were in the hypofractionated and 39 in the conventional schedule. The 5-year biochemical {+-} clinical relapse-free and overall survival was 55.9% and 85.3% respectively for all patients, and did not differ between the two schedules. Conclusions: Radiation therapy for prostate carcinoma causes persistent GI toxicity that is largely independent of the two dose schedules. The hypofractionated schedule is equivalent in efficacy to the conventional schedule.

  14. Celastrol blocks interleukin-6 gene expression via downregulation of NF-κB in prostate carcinoma cells.

    PubMed

    Chiang, Kun-Chun; Tsui, Ke-Hung; Chung, Li-Chuan; Yeh, Chun-Nan; Chen, Wen-Tsung; Chang, Phei-Lang; Juang, Horng-Heng

    2014-01-01

    Interleukin-6 (IL-6), a multifunctional cytokine, contributes to proliferation or differentiation of prostate carcinoma cells in a highly cell type-specific manner. Celastrol (3-hydroxy-24-nor-2oxo-1(10),3,5,7-friedelatetrane-29-oic acid), also named as tripterine, is extracted from root of Chinese traditional herb Tripterygiumwilfordii Hook f with potent anti-inflammatory and anti-cancer activities. In this study, we evaluated the molecular mechanisms of celastrol on cell proliferation and IL-6 gene expression in prostate carcinoma cells. 3H-thymidine incorporation and flow cytometric analysis indicated that celastrol treatments arrested the cell cycle at the G0/G1 phase, thus attenuating cell proliferation in prostate carcinoma PC-3 cells; moreover, celastrol induced cell apoptosis at higher dosage. Knockdown of IL-6 attenuated the anti-proliferative effect of celastrol on PC-3 cells. Results from ELISA and 5'-deletion transient gene expression assays indicated that celastrol treatment decreased IL-6 secretion and gene expression, and this effect is dependent on the NF-κB response element within IL-6 promoter area since mutation of the NF-κB response element from AAATGTCCCATTTTCCC to AAATGTTACATTTTCCC by site-directed mutagenesis abolished the inhibition of celastrol on the IL-6 promoter activity. Celastrol also attenuated the activation of PMA and TNFα on the gene expression and secretion of IL-6 in PC-3 cells. Immunoblot assays revealed that celastrol treatment downregulated the expressions of IKKα, p50 and p65, supporting the 5'-deletion transient gene expression assay result that celastrol blocked IL-6 expression through the NF-κB pathway in PC-3 cells. For the first time, our results concluded that celastrol attenuates PC-3 cell proliferation via downregulation of IL-6 gene expression through the NF-κB-dependent pathway.

  15. Hormono-radiotherapy in prostatic carcinoma: prognostic factors and implications for combined modality treatment.

    PubMed

    Cellini, Numa; Luzi, Stefano; Morganti, Alessio Giuseppe; Mantini, Giovanna; Valentini, Vincenzo; Racioppi, Marco; Leone, Mariavittoria; Mattiucci, Gian Carlo; Di Gesù, Cinzia; Giustacchini, Mario; Destito, Antonio; Smaniotto, Daniela; Alcini, Eugenio

    2002-01-01

    The aim of this study was to evaluate the prognostic role of several clinical variables in a patient population undergoing neoadjuvant hormonotherapy (NHT) with external beam radiotherapy (ERT) to identify subsets of patients with an unfavorable prognosis who require intensified therapy. Eighty-four patients (mean age, 68.2 +/- 6.1 years; range, 52-81 years) underwent ERT (45 Gy to pelvic volume; 65 Gy mean dose to prostate volume) and NHT (oral flutamide: 250 mg three times daily for 30 days; LH-RH analogue: one vial every 28 days starting two months before radiotherapy and for its entire duration). The distribution according to clinical stage was T2: 46.4%, T3: 50.0%, T4: 3.6%. The distribution according to the Gleason score was grade 2-4: 17.9%; grade 5-7: 53.6%; grade 8-10: 28.5%. The distribution according to pretreatment PSA levels (in ng/mL) was 0-4: 5.9%; 4-10: 26.2%; 10-20:16.7%; > or = 20: 51.2%. With a median follow-up of 36 months, 3.6% of patients died; hematogenous metastases and local disease progression were found in 16.7% and 6% of patients, respectively. Overall, the incidence of disease progression was 17.9%. 32.9% of patients showed biochemical failure during followup. Overall, metastasis-free, local progression-free and biochemical failure-free actuarial survival at five years was 89.2%, 66.5%, 85.0% and 41.9%, respectively. At univariate analysis (log-rank) clinical stage (cT) was shown to be significantly correlated with the incidence of metastasis (P = 0.0004), local progression (P < 0.0001) and disease-free survival (P = 0.0005). At multivariate analysis (Cox) the correlations between clinical stage and metastasis (P = 0.0175), local progression (P = 0.0200) and disease-free survival (P = 0.0175) were confirmed. Gleason score and pretreatment PSA levels did not show any significant correlation with these endpoints. These results confirm the indications of the recent literature, which, in prostate carcinoma at higher clinical stages, suggest

  16. Dosimetry of a thyroid uptake detected in seed migration survey following a patient's iodine-125 prostate implant and in vitro measurements of intentional seed leakages

    SciTech Connect

    Chen Qinsheng; Russell, John L. Jr.; Macklis, Roger R.; Weinhous, Martin S.; Blair, Henry F.

    2006-07-15

    As a quality control procedure, a post-implant seed migration survey has been accomplished on 340 prostate cancer patients since November 2001. Pulmonary seed embolization and intracardiac seed embolization have been detected. A case of thyroid uptake due to leaking iodine-125 (I-125) sources was also seized. In order to determine the dose to the thyroid, a dosimetry method was developed to link in vivo measurements and the cumulated dose to the thyroid. The calculated source leakage half-life in the case was approximately 15 days based on the measurements and the estimated cumulated dose to thyroid was 204 cGy. It is concluded that one seed was leaking. In order to verify the in vivo measurements, intentional in vitro seed leakage tests were performed. A seed was cut open and placed in a sealed glass container filled with a given volume of saline. The I-125 concentration in the saline was subsequently measured over a period of six months. Consistent in vivo and in vitro results were obtained. Recent incidents of seed leaks reported from other centers have drawn practitioners' attention to this problem. In order to make the measurements more useful, the seed leakage tests were expanded to include I-125 seeds from six other vendors. The results show that the leakage half-lives of those seeds varied from nine days to a half-year. Two seed models demonstrated least leakage. Since the measurements lasted for six months, the escape of iodine resulted from oxidation of iodide in the saline was a concern for the measurement accuracy. As a reference, another set of leakage tests were performed by adding sodium thiosulfate salt (Na{sub 2}S{sub 2}O{sub 3}{center_dot}5H{sub 2}O) to the saline. Sodium thiosulfate is a reducing agent that prevents the conversion of iodide to iodate so as to minimize I-125 evaporation. As a result, significantly shortened leakage half-lives were observed in this group. Seed agitation was also performed and no significant deviations of the

  17. Altered beta-tubulin isotype expression in paclitaxel-resistant human prostate carcinoma cells.

    PubMed Central

    Ranganathan, S.; Benetatos, C. A.; Colarusso, P. J.; Dexter, D. W.; Hudes, G. R.

    1998-01-01

    To investigate the role of beta-tubulin isotype composition in resistance to paclitaxel, an anti-microtubule agent, human prostate carcinoma (DU-145) cells were intermittently exposed to increasing concentrations of paclitaxel. Cells that were selected and maintained at 10 nM paclitaxel (Pac-10) were fivefold resistant to the drug. Pac-10 cells accumulated radiolabelled paclitaxel to the same extent as DU-145 cells and were negative for MDR-1. Analysis of Pac-10 and DU-145 cells by flow cytometry showed similar cell cycle patterns. Immunofluorescent staining revealed an overall increase of alpha- and beta-tubulin levels in Pac-10 cells compared with DU-145 cells. Examination of beta-tubulin isotype composition revealed a significant increase in betaIII isotype in the resistant cells, both by immunofluorescence and by western blot analysis. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of the isotypes confirmed the increase observed for the betaIII by exhibiting ninefold higher betaIII mRNA levels and also showed fivefold increase of the betaIVa transcript. In addition, analysis of paclitaxel-resistant cells that were selected at increasing levels of the drug (Pac 2, 4, 6, 8 and 10) exhibited a positive correlation between increasing betaIII levels and increasing resistance to paclitaxel. Increased expression of specific beta-tubulin isotypes and subsequent incorporation into microtubules may alter cellular microtubule dynamics, providing a defence against the anti-microtubule effects of paclitaxel and other tubulin-binding drugs. Images Figure 1 Figure 2 Figure 4 PMID:9484812

  18. Genetic variants in cell cycle control pathway confer susceptibility to aggressive prostate carcinoma.

    PubMed

    Kibel, Adam S; Ahn, Jiyoung; Isikbay, Masis; Klim, Aleksandra; Wu, William S; Hayes, Richard B; Isaacs, William B; Daw, E Warwick

    2016-04-01

    Because a significant number of patients with prostate cancer (PCa) are diagnosed with disease unlikely to cause harm, genetic markers associated with clinically aggressive PCa have potential clinical utility. Since cell cycle checkpoint dysregulation is crucial for the development and progression of cancer, we tested the hypothesis that common germ-line variants within cell cycle genes were associated with aggressive PCa. Via a two-stage design, 364 common sequence variants in 88 genes were tested. The initial stage consisted of 258 aggressive PCa patients and 442 controls, and the second stage added 384 aggressive PCa Patients and 463 controls. European-American and African-American samples were analyzed separately. In the first stage, SNPs were typed by Illumina Goldengate assay while in the second stage SNPs were typed by Pyrosequencing assays. Genotype frequencies between cases and controls were compared using logistical regression analysis with additive, dominant and recessive models. Eleven variants within 10 genes (CCNC, CCND3, CCNG1, CCNT2, CDK6, MDM2, SKP2, WEE1, YWHAB, YWHAH) in the European-American population and nine variants in 7 genes (CCNG1, CDK2, CDK5, MDM2, RB1, SMAD3, TERF2) in the African-American population were found to be associated with aggressive PCa using at least one model. Of particular interest, CCNC (rs3380812) was associated with risk in European-American cohorts from both institutions. CDK2 (rs1045435) and CDK5 (rs2069459) were associated with risk in the African-American cohorts from both institutions. Lastly, variants within MDM2 and CCNG1 were protective for aggressive PCa in both ethnic groups. This study confirms that polymorphisms within cell cycle genes are associated with clinically aggressive PCa. Validation of these markers in additional populations is necessary, but these markers may help identify patients at risk for potentially lethal carcinoma. © 2015 Wiley Periodicals, Inc.

  19. Five-point Likert scaling on MRI predicts clinically significant prostate carcinoma.

    PubMed

    Harada, Taisuke; Abe, Takashige; Kato, Fumi; Matsumoto, Ryuji; Fujita, Hiromi; Murai, Sachiyo; Miyajima, Naoto; Tsuchiya, Kunihiko; Maruyama, Satoru; Kudo, Kohsuke; Shinohara, Nobuo

    2015-09-04

    To clarify the relationship between the probability of prostate cancer scaled using a 5-point Likert system and the biological characteristics of corresponding tumor foci. The present study involved 44 patients undergoing 3.0-Tesla multiparametric MRI before laparoscopic radical prostatectomy. Tracing based on pathological and MRI findings was performed. The relationship between the probability of cancer scaled using the 5-point Likert system and the biological characteristics of corresponding tumor foci was evaluated. A total of 102 tumor foci were identified histologically from the 44 specimens. Of the 102 tumors, 55 were assigned a score based on MRI findings (score 1: n = 3; score 2: n = 3; score 3: n = 16; score 4: n = 11 score 5: n = 22), while 47 were not pointed out on MRI. The tracing study revealed that the proportion of >0.5 cm(3) tumors increased according to the upgrade of Likert scores (score 1 or 2: 33%; score 3: 68.8%; score 4 or 5: 90.9%, χ(2) test, p < 0.0001). The proportion with a Gleason score >7 also increased from scale 2 to scale 5 (scale 2: 0%; scale 3: 56.3%; scale 4: 72.7%; 5: 90.9%, χ(2) test, p = 0.0001). On using score 3 or higher as the threshold of cancer detection on MRI, the detection rate markedly improved if the tumor volume exceeded 0.5 cm(3) (<0.2 cm(3): 10.3%; 0.2-0.5 cm(3): 25%; 0.5-1.0 cm(3): 66.7%; 1.0 < cm(3): 92.1%). Each Likert scale favobably reflected the corresponding tumor's volume and Gleason score. Our observations show that "score 3 or higher" could be a useful threshold to predict clinically significant carcinoma when considering treatment options.

  20. Epid Dosimetry

    NASA Astrophysics Data System (ADS)

    Greer, Peter B.; Vial, Philip

    2011-05-01

    Electronic portal imaging devices (EPIDs) were introduced originally for patient position verification. The idea of using EPIDs for dosimetry was realised in the 1980s. Little was published on the topic until the mid 1990's, when the interest in EPIDs for dosimetry increased rapidly and continues to grow. The increasing research on EPID dosimetry coincided with the introduction of intensity modulated radiation therapy (IMRT). EPIDs are well suited to IMRT dosimetry because they are high resolution, two-dimensional (2D) digital detectors. They are also pre-existing on almost all modern linear accelerators. They generally show a linear response to increasing dose. Different types of EPIDs have been clinically implemented, and these have been described in several review papers. The current generation of commercially available EPIDs are indirect detection active matrix flat panel imagers, also known as amorphous silicon (a-Si) EPIDs. Disadvantages of a-Si EPIDs for dosimetry include non-water equivalent construction materials, and the energy sensitivity and optical scatter of the phosphor scintillators used to create optical signal from the megavoltage beam. This report discusses current knowledge regarding a-Si EPIDs for dosimetry.

  1. Effects of oridonin nanosuspension on cell proliferation and apoptosis of human prostatic carcinoma PC-3 cell line.

    PubMed

    Zhang, Zhen; Zhang, Xiumei; Xue, Wei; Yangyang, Yuna; Xu, Derong; Zhao, Yunxue; Lou, Haiyan

    2010-10-05

    This study aims to investigate the inhibitory effects of oridonin nanosuspension on human prostatic carcinoma PC-3 cell line in vitro. The PC-3 cells were incubated with increasing concentrations of oridonin solution and nanosuspensions for 12 hours, 24 hours, and 36 hours. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay was performed to measure cellular viability and investigate the effect of oridonin on cell growth of PC-3. Annexin V-FITC/PI staining method was used to determine the effect of oridonin by fluorescence microscope and flow cytometry, respectively. Nanosuspension on early apoptosis of PC-3 cells was also evaluated. Oridonin significantly inhibited the growth of PC-3 cells after 12 hours, 24 hours, and 36 hours of treatment in a dose-dependent manner (P < 0.05). Compared with the same concentration of oridonin solution, oridonin nanosuspension enhanced the inhibition ratio of proliferation. The observation of propidium iodide fluorescence staining confirmed the MTT assay results. The cell proportion of PC-3 at the G2/M phase in the nanosuspension treatment group was upregulated compared with that of the control and oridonin solution groups. Both oridonin solution and nanosuspension promoted the early apoptosis of PC-3 cells. Furthermore, while improving the ratio of early apoptosis, oridonin nanosuspensions also enhanced growth suppression, and induced apoptosis of PC-3 cells. This shows great potential in the treatment of androgen-independent carcinoma of prostate by oridonin nanosuspensions.

  2. Withanolides from Aeroponically Grown Physalis peruviana and Their Selective Cytotoxicity to Prostate Cancer and Renal Carcinoma Cells.

    PubMed

    Xu, Ya-Ming; Wijeratne, E M Kithsiri; Babyak, Ashley L; Marks, Hanna R; Brooks, Alan D; Tewary, Poonam; Xuan, Li-Jiang; Wang, Wen-Qiong; Sayers, Thomas J; Gunatilaka, A A Leslie

    2017-07-28

    Investigation of aeroponically grown Physalis peruviana resulted in the isolation of 11 new withanolides, including perulactones I-L (1-4), 17-deoxy-23β-hydroxywithanolide E (5), 23β-hydroxywithanolide E (6), 4-deoxyphyperunolide A (7), 7β-hydroxywithanolide F (8), 7β-hydroxy-17-epi-withanolide K (9), 24,25-dihydro-23β,28-dihydroxywithanolide G (10), and 24,25-dihydrowithanolide E (11), together with 14 known withanolides (12-25). The structures of 1-11 were elucidated by the analysis of their spectroscopic data, and 12-25 were identified by comparison of their spectroscopic data with those reported. All withanolides were evaluated for their cytotoxic activity against a panel of tumor cell lines including LNCaP (androgen-sensitive human prostate adenocarcinoma), 22Rv1 (androgen-resistant human prostate adenocarcinoma), ACHN (human renal adenocarcinoma), M14 (human melanoma), SK-MEL-28 (human melanoma), and normal human foreskin fibroblast cells. Of these, the 17β-hydroxywithanolides (17-BHWs) 6, 8, 9, 11-13, 15, and 19-22 showed selective cytotoxic activity against the two prostate cancer cell lines LNCaP and 22Rv1, whereas 13 and 20 exhibited selective toxicity for the ACHN renal carcinoma cell line. These cytotoxicity data provide additional structure-activity relationship information for the 17-BHWs.

  3. Antitumor effect of microbubbles enhanced by low frequency ultrasound cavitation on prostate carcinoma xenografts in nude mice

    PubMed Central

    WANG, YU; HU, BING; DIAO, XUEHONG; ZHANG, JIZHEN

    2012-01-01

    The aim of this study was to investigate the antitumor effect induced by low frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145 prostate tumors were percutaneously implanted in 40 nude mice, which were randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups. The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm2 US radiation and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were only treated with US radiation and injection of Mbs, respectively. Tumors were measured with sonography, and the ratio of antitumor growth was calculated. The mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were observed pathologically using light microscopy and transmission electron microscopy. Microvessel density and the average optical density of vascular endothelial growth factor were compared among groups by immunohistochemistry. The average gross tumor volume of the US+Mbs group was significantly reduced compared with the other groups following treatment (P<0.05). The ratio of the antitumor growth in the US+Mbs group was significantly greater than that of the US and Mbs group (P<0.05). Histological examination showed signs of tumor cell injury in the US+Mbs group. Examination by electron microscopy revealed vessel injury in the endothelium in the tumors treated with US+Mbs. Microvessel density and the average optical density of vascular endothelial growth factor in the US+Mbs group were significantly less than that of other groups (P<0.05). In conclusion, low frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the growth of human prostate carcinoma xenografts in nude mice, and the effect is likely realized through microvessel destruction caused by cavitation. PMID:22969866

  4. Antitumor effect of microbubbles enhanced by low frequency ultrasound cavitation on prostate carcinoma xenografts in nude mice.

    PubMed

    Wang, Yu; Hu, Bing; Diao, Xuehong; Zhang, Jizhen

    2012-02-01

    The aim of this study was to investigate the antitumor effect induced by low frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145 prostate tumors were percutaneously implanted in 40 nude mice, which were randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups. The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm(2) US radiation and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were only treated with US radiation and injection of Mbs, respectively. Tumors were measured with sonography, and the ratio of antitumor growth was calculated. The mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were observed pathologically using light microscopy and transmission electron microscopy. Microvessel density and the average optical density of vascular endothelial growth factor were compared among groups by immunohistochemistry. The average gross tumor volume of the US+Mbs group was significantly reduced compared with the other groups following treatment (P<0.05). The ratio of the antitumor growth in the US+Mbs group was significantly greater than that of the US and Mbs group (P<0.05). Histological examination showed signs of tumor cell injury in the US+Mbs group. Examination by electron microscopy revealed vessel injury in the endothelium in the tumors treated with US+Mbs. Microvessel density and the average optical density of vascular endothelial growth factor in the US+Mbs group were significantly less than that of other groups (P<0.05). In conclusion, low frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the growth of human prostate carcinoma xenografts in nude mice, and the effect is likely realized through microvessel destruction caused by cavitation.

  5. Exploiting Novel Polyamine Regulatory Responses to a Therapeutic Advantage in Human Prostatic Carcinoma: A Preclinical Study (Prostate)

    DTIC Science & Technology

    1999-09-01

    Ph.D. CONTRACTING ORGANIZATION: Roswell Park Cancer Institute. Elm & Carlton Streets Buffalo , New York 14263 REPORT DATE: September 1999 TYPE OF...ORGANIZATION Roswell Park Cancer Institute REPORT NUMBER Elm & Carlton Streets Buffalo , New York 14263 e-mail: Porter@sc3101 .med.buffalo.edu 9. SPONSORING...growth, the gland produces massive quantities for export into semen . It might, therefore, be expected that prostatic tumors could exhibit unique polyamine

  6. Role of canine basal cells in postnatal prostatic development, induction of hyperplasia, and sex hormone-stimulated growth; and the ductal origin of carcinoma.

    PubMed

    Leav, I; Schelling, K H; Adams, J Y; Merk, F B; Alroy, J

    2001-08-01

    The canine prostate has often been proposed as a model for abnormal growth of the human gland. Hyperplasia of the prostate is common in aging men and has been estimated to be present in 100% of old intact dogs. While prostatic carcinoma is common in older men, it appears to be rare in dogs and unlike the disease in humans, it occurs with relatively high frequency in castrated animals. Since basal cells are thought to be key participants in normal and abnormal growth of the human gland, we used immunohistochemistry to investigate the role that they may play in canine prostatic development, the evolution of hyperplasia and carcinoma, and the effects of sex hormones on these cells. Prostate specimens were obtained at autopsy from seven sexually immature dogs, autopsy and biopsy samples from 14 sexually mature intact animals, from four castrates, and from19 dogs with prostatic carcinoma. In addition, we also studied the prostates from two intact dogs treated with 5alpha-dihydrotestosterone (DHT) for 6 months and two castrated dogs that were subsequently treated with 5alpha-androstane-3alpha diol and estradiol-17alpha, as well as specimens from two sexually ablated animals given DHT for 2 weeks. All specimens were immunostained for high molecular weight cytokeratin (HMC), pancytokeratin, androgen receptor (AR), and the proliferative marker KI-67. We find that basal cells are the major proliferative cell type in the neonatal and adult canine prostate and that the expression of HMC staining, which defines these cells, may be regulated by androgens. In the adult gland, ductal basal cells formed a contiguous layer, whereas those lining acini were discontinuous. Populations of both basal cell types were variably AR positive, but while HMC immunostaining was abolished in acinar cells following long-term castration, staining remained in ductal cell counterparts. Paralleling the histological development of hyperplasia, the acinar basal cell population increased with age and

  7. Unique G-Rich Oligonucleotides Which Inhibit the Growth of Prostatic Carcinoma Cells

    DTIC Science & Technology

    2003-07-01

    Prostate Cancer) MDA-MB-231 (Breast Cancer) HeLa ( Cervical Cancer ) HS27 (Normal Skin) Nuclear nucleolin staining. (A) Phase contrast (upper panel) and...stained nucleoli in normal HS27 cells. Surface nucleolin staining. DU145 (Prostate Cancer) MDA-MB-231 (Breast Cancer) HeLa ( Cervical Cancer ) HS27 (Normal

  8. Association of Pb, Cd, and Se concentrations and oxidative damage-related markers in different grades of prostate carcinoma.

    PubMed

    Guzel, Savas; Kiziler, Lebriz; Aydemir, Birsen; Alici, Bulent; Ataus, Suleyman; Aksu, Abdullah; Durak, Haydar

    2012-01-01

    Prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body, yet there are very few studies which look into the way it occurs. The aim of this study was to determine whether blood and tissue lead (Pb), cadmium (Cd), and selenium (Se) levels are associated with oxidative damage in the context of prostate cancer progression and development. Seventy-nine patients comprising 25 patients with benign prostatic hypertrophy (BPH), 23 patients with malignant prostatic carcinoma (malign Ca), 16 patients with low-grade prostatic intraepithelial neoplasia (LGPIN), and 15 patients with high-grade prostatic intraepithelial neoplasia (HGPIN) diagnosed on the basis of their clinical profile, transrectal ultrasonography, and histopathology were included in this study. Cd and Pb levels in whole blood were found to be increased in patients with HGPIN compared with the BPH group; also, the levels of Cd in whole blood and tissue were found to be increasing in patients with malign Ca, unlike BPH patients. Moreover, the levels of malondialdehyde (MDA) in plasma and tissue were significantly increased in malign Ca, LGPIN, and HGPIN than those in BPH. However, the levels of tissue Pb were found to be decreasing in BPH, unlike the malign Ca and HGPIN patients, and the levels of tissue protein carbonyls in malign Ca were significantly lower than those in HGPIN. The levels of tissue reduced glutathione (GSH) in malign Ca were significantly lower than those in BPH. Additionally, the levels of Se in serum and tissue in LGPIN were significantly lower than those in BPH. The serum Se levels in HGPIN were also significantly lower than those in BPH and malign Ca groups. Furthermore, the concentrations of serum Se in LGPIN were significantly lower than those in malign Ca. From the Pearson correlation analysis, there were significant positive correlations between tissue Cd and MDA levels in malign Ca, LGPIN, and HGPIN and between the tissue Pb and tissue MDA and

  9. In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4′-acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma

    PubMed Central

    Osmond, Gregory W.; Masko, Elizabeth M.; Tyler, Douglas S.; Freedland, Stephen J.; Pizzo, Salvatore

    2013-01-01

    Background Resveratrol (RESV) is a naturally occurring compound that may possess anti-cancer capabilities in both prostate carcinoma and melanoma. Methods The in vitro and in vivo cytotoxic activity of RESV and 3,5-dihydroxy-4′-acetoxy-trans-stilbene (4-ACE) was tested using cellular assays and a xenograft model. Five prostate carcinoma cell lines were used for in vitro evaluation. A melanoma cell line (Duke melanoma 738 [DM738]) and the prostate carcinoma line CWR22 were used for in vivo experiments. Mice were randomized to osmotic mini pumps with 200 μL of RESV (250 mg/mL), 4-ACE (335 mg/mL), or vehicle (50% dimethyl sulfoxide, 50% polyethylene glycol). Serum drug and metabolite levels were calculated by high-performance liquid chromatography with diode-array detection. Western blots were performed on treated tumors. Results were analyzed using a student’s t-test, analysis of variance, and the Mann–Whitney rank sum test. Results RESV and 4-ACE were cytotoxic in a time- and dose-dependent manner in all prostate carcinoma cell lines tested. Enhanced growth compared with controls was seen at the 24 h time point in four lines treated with RESV and two lines treated with 4-ACE (Ps < 0.048). In vivo, no difference in either tumor growth or postmortem tumor weight was detected in either DM738 (P = 0.555, P = 0.562) or CWR22 (P = 0.166, P = 0.811) xenografts treated with either drug. Serum drug levels did not correlate with tumor growth rates for any treatment group (all Ps > 0.11). Treated tumors demonstrated protein changes by western blot. Conclusion Although in vitro data were promising, RESV and 4-ACE have limited potential as single agents in the treatment of prostate carcinoma and melanoma. PMID:22482756

  10. Incidental Detection of Thyroid Metastases From Renal Cell Carcinoma Using 68Ga-PSMA PET/CT to Assess Prostate Cancer Recurrence.

    PubMed

    Zacho, Helle D; Nielsen, Julie B; Dettmann, Katja; Haberkorn, Uwe; Petersen, Lars J

    2017-03-01

    Ga-PSMA PET/CT is increasingly used to assess prostate cancer. Avid Ga-PSMA uptake by thyroid cancer and renal cell carcinoma (RCC) has been reported in few cases. A 75-year-old man who received a diagnosis of RCC in 2006 and prostate cancer in 2009 presented with elevated prostate-specific antigen levels (0.7 ng/mL) following prostatectomy. Ga-PSMA PET/CT showed avid Ga-PSMA uptake in 1 pelvic and 1 retroperitoneal lymph node and focal Ga-PSMA accumulation in the thyroid. Excised retroperitoneal lymph node and thyroid tissues showed metastases from RCC, whereas the pelvic lymph node exhibited metastasis from prostate cancer.

  11. Demonstration of synchrotron x-ray phase contrast imaging computed tomography of infiltrative transitional cell carcinoma of the prostatic urethra in a dog

    PubMed Central

    Montgomery, James E.; Wesolowski, Michal J.; Wolkowski, Bailey; Chibbar, Rajni; Snead, Elisabeth C. R.; Singh, Jaswant; Pettitt, Murray; Malhi, Pritpal S.; Barboza, Trinita; Adams, Gregg

    2016-01-01

    Abstract. Prostatic urethral transitional cell carcinoma with prostatic invasion in a dog was imaged with abdominal radiography and abdominal ultrasonography antemortem. Synchrotron in-line x-ray phase contrast imaging computed tomography (XPCI-CT) was performed on the prostate ex vivo at the Canadian Light Source Synchrotron and compared to histology. XPCI-CT imaging provides greater soft tissue contrast than conventional absorption-based x-ray imaging modalities, permitting visualization of regions of inflammatory cell infiltration, differentiation of invasive versus noninvasive tumor regions, and areas of necrosis and mineralization. This represents the first report of XPCI-CT images of an invasive prostatic urothelial neoplasm in a dog. PMID:27014719

  12. Italian survey in postoperative radiation therapy for prostate carcinoma by the AIRO National Working Group on Prostate Radiotherapy: definitive results.

    PubMed

    Malinverni, Giuseppe; Greco, Carlo; Bianchi, Pieromaria; Busutti, Luciano; Cagna, Emanuela; Cozzarini, Cesare; Del Duca, Massimo; Franzone, Paola; Frezza, Giovanni; Gabriele, Pietro; Genovesi, Domenico; Girelli, Giuseppe Franco; Italia, Corrado; Mandoliti, Giovanni; Mauro, Floranna; Nava, Simonetta; Pratissoli, Silvia; Saracino, Maria Bianca; Squillace, Luigi; Signor, Marco; Tagliagambe, Angiolo; Vavassori, Vittorio; Villa, Sergio; Zini, Giampaolo; Valdagni, Riccardo

    2005-01-01

    The National Working Group on Prostate Radiotherapy of AIRO (Associazione Italiana Radioterapia Oncologica, Italian Association of Radiotherapeutic Oncology) was established in March 2001. A retrospective multi-center survey was performed to analyze the patterns of care for prostate cancer patients treated with postoperative radiotherapy following radical prostatectomy in Italy with regard to the year 2000. A structured questionnaire was mailed to 47 Italian radiotherapy centers to assess patient accrual in the postoperative setting in the interval comprised between period January-December 2000. Numbers of patients treated for different stages, specific prognostic factors indicating the need for adjuvant radiotherapy, fractionation schedules and prescription doses were acquired as well as other clinically important factors such as radiotherapy timing and the use of hormone therapy. More technical features of the treatment, such as patient positioning, mode of simulation, typical field setup and dose prescription criteria were also included in the questionnaire. The questionnaire was returned by 24 radiotherapy Institutions (51%) with a total number of 470 patients treated postoperatively in the year 2000. An average of about 20 patients were enrolled by each radiotherapy center. The age range was 45-81 years. Radiotherapy was delivered within 6 months of radical prostatectomy in 297 patients (65.4%) (mean, 3.4 months). In 157 (34.6%), the treatment was delivered as a salvage approach for biochemical or micro-macroscopic recurrence. Most of patients had locally advanced stage disease (pT3-pT4) (76%). Unfavorable prognostic factors, such as positive margins, capsular invasion, Gleason pattern score > 7 were present in about 50% of patients. The study confirmed that important risk factors for recurrences are present in a significant percentage of patients treated by radical prostatectomy. The number of patients that would benefit from adjuvant radiotherapy is

  13. miR-129 predicts prognosis and inhibits cell growth in human prostate carcinoma

    PubMed Central

    Xu, Song; Yi, Xiao-Ming; Zhang, Zheng-Yu; Ge, Jing-Ping; Zhou, Wen-Quan

    2016-01-01

    MicroRNAs (miRNAs) are a class of small, well-conserved, non-coding RNAs that are increasingly identified as diagnostic and prognostic biomarkers in a number of cancers. Deregulated miR-129 is closely associated with tumorigenesis and cancer progression. However, the potential role of miR-129 in prostate cancer remains largely elusive. The present study investigated the role of miR-129 as a prognostic biomarker for tumor progression and clinical prognosis in prostate cancer patients. The examined prostate cancer tissues exhibited a significant reduction in miR-129 expression compared with the normal tissues (P=0.013). The expression levels of miR-129 were negatively correlated with histological grade (P<0.001), high preoperative prostate-specific antigen serum levels (P<0.001), pathological stage (P<0.001), high Gleason score (P<0.001), lymph node metastasis (P=0.002), angiolymphatic invasion (P=0.018), and biochemical recurrence (BCR; P=0.001). Use of the Kaplan-Meier analysis demonstrated that low miR-129 expression was closely associated with poorer BCR-free survival. Multivariate survival analysis indicated that miR-129 expression may be an independent prognostic marker for BCR-free survival in prostate cancer patients (P<0.001). Overexpression of miR-129 markedly attenuated prostate cancer cell growth by rescuing cell cycle-regulated protein expression. The present study suggests that miR-129 is downregulated in the cancerous tissues of prostate cancer patients, which was associated with poor BCR-free survival. Thus, it may be considered as a novel independent prognostic biomarker for prostate cancer. In addition, downregulation of miR-129 may serve a critical role in the proliferation of prostate cancer cells. PMID:27779679

  14. (Biological dosimetry)

    SciTech Connect

    Sega, G.A.

    1990-11-06

    The traveler participated in an International Symposium on Trends in Biological Dosimetry and presented an invited paper entitled, Adducts in sperm protamine and DNA vs mutation frequency.'' The purpose of the Symposium was to examine the applicability of new methods to study quantitatively the effects of xenobiotic agents (radiation and chemicals) on molecular, cellular and organ systems, with special emphasis on human biological dosimetry. The general areas covered at the meeting included studies on parent compounds and metabolites; protein adducts; DNA adducts; gene mutations; cytogenetic end-points and reproductive methods.

  15. Vertebral Myeloma Mimicking Prostatic Carcinoma Metastasis in 68Ga-PSMA PET/CT.

    PubMed

    Merrild, Esben Hoej; Baerentzen, Steen; Bouchelouche, Kirsten; Buus, Simon

    2017-10-01

    Ga-PSMA PET/CT was performed in a 75-year-old man with newly diagnosed prostate cancer because of an equivocal lesion in the spine both on Tc-bone-SPECT/CT and MRI. Because of increased PSMA activity on PET/CT, the bone lesion was interpreted as metastasis from prostate cancer. Later, the patient was diagnosed as having monoclonal gammopathy of unknown significance. A biopsy was performed, and histological examination revealed multiple myeloma with PSMA expression in the neovessels but no metastatic prostate cancer cells. The patient was downstaged, and the treatment was changed accordingly. This case illustrates the importance of biopsies from PSMA PET-positive lesions.

  16. The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically

  17. The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas.

    PubMed

    Waliszewski, Przemyslaw

    2016-01-01

    Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. The global fractal capacity D 0, information D 1 and correlation D 2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D 0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D 1 failed to define the same classes of equivalence. The pairs (D 0, LFD), (D 0, H), (D 0, λ), (D 1, LFD), (D 1, H), (D 1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D 0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D 0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. The cut-off D 0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically relevant information. Two novel

  18. [A case of an asynchronic triple tumorous disorder: a rectal adenocarcinoma, a carcinoma of the kidney and a prostatic adenocarcinoma--case report].

    PubMed

    Prosvic, P; Brod'ák, M; Odrázka, K; Morávek, P

    2005-01-01

    The authors describe occurence asynchronic tumor triplicity. In the year 1980 in 56 years old patient had histologically proven rectal adenocarcinoma and consequently was done radical Miles amputation of rectum. In December 1991 in the same patient was histologically proven well differentiated adenocarcinoma of prostate after transurethral resection of prostate. Prostate cancer was threated bilateral orchiectomy (March 1992) and consequently from April to June 1992 was done small-volume irradiation of pelvic by Betatron X-ray, box technique with dosage 70 Gy. In November 1992 there was done radical transperitoneal nephrectomy on right side for renal carcinoma. Histologically was proven moderately differentiated clear cell renal carcinoma. In August 1994 was found suspected pulmonary metastases, wich was proof on CT in the January 1995. Therapy was Imodin, Wobenzym, Vinblastin. Patient was died of generalisation renal cancer in the February 1998. The carcinoma of prostate and rectum wasn't found in the autopsy. The authors emphasize pertinence radical surgical access incuding multiplex malignant tumors and consider to carry out oncology screening in the all of patients with proven malignant tumor.

  19. (Biological dosimetry)

    SciTech Connect

    Preston, R.J.

    1990-12-17

    The traveler attended the 1st International Conference on Biological Dosimetry in Madrid, Spain. This conference was organized to provide information to a general audience of biologists, physicists, radiotherapists, industrial hygiene personnel and individuals from related fields on the current ability of cytogenetic analysis to provide estimates of radiation dose in cases of occupational or environmental exposure. There is a growing interest in Spain in biological dosimetry because of the increased use of radiation sources for medical and occupational uses, and with this the anticipated and actual increase in numbers of overexposure. The traveler delivered the introductory lecture on Biological Dosimetry: Mechanistic Concepts'' that was intended to provide a framework by which the more applied lectures could be interpreted in a mechanistic way. A second component of the trip was to provide advice with regard to several recent cases of overexposure that had been or were being assessed by the Radiopathology and Radiotherapy Department of the Hospital General Gregorio Maranon'' in Madrid. The traveler had provided information on several of these, and had analyzed cells from some exposed or purportedly exposed individuals. The members of the biological dosimetry group were referred to individuals at REACTS at Oak Ridge Associated Universities for advice on follow-up treatment.

  20. Utility of PTEN and ERG immunostaining for distinguishing high-grade PIN from intraductal carcinoma of the prostate on needle biopsy.

    PubMed

    Morais, Carlos L; Han, Jeong S; Gordetsky, Jennifer; Nagar, Michael S; Anderson, Ann E; Lee, Stephen; Hicks, Jessica L; Zhou, Ming; Magi-Galluzzi, Cristina; Shah, Rajal B; Epstein, Jonathan I; De Marzo, Angelo M; Lotan, Tamara L

    2015-02-01

    Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.

  1. 18F-MK-9470 PET imaging of the type 1 cannabinoid receptor in prostate carcinoma: a pilot study

    PubMed Central

    2013-01-01

    Background Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of 18F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated. Methods Eight patients were included and underwent 18F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUVmean) were determined as well as the corresponding area under the curve to compare 18F-MK-9470 uptake over time. Muscle uptake of 18F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. 18F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUVmean values of metastases with these of the contralateral bone tissue. Results 18F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with 18F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher 18F-MK-9470 uptake as compared to the uptake in contralateral normal bone

  2. Zoledronic acid but not somatostatin analogs exerts anti-tumor effects in a model of murine prostatic neuroendocrine carcinoma of the development of castration-resistant prostate cancer.

    PubMed

    Hashimoto, Kohei; Masumori, Naoya; Tanaka, Toshiaki; Maeda, Toshihiro; Kobayashi, Ko; Kitamura, Hiroshi; Hirata, Koichi; Tsukamoto, Taiji

    2013-04-01

    Since neuroendocrine (NE) cells play an important role in the development of castration-resistant prostate cancer (CRPC), target therapy to NE cells should be considered for treating CRPC. We investigated the effects zoledronic acid (ZOL) and two somatostatin analogs (octreotide: SMS, and pasireotide: SOM) on an NE allograft (NE-10) and its cell line (NE-CS), which were established from the prostate of the LPB-Tag 12T-10 transgenic mouse. We examined the in vivo effects of ZOL, SMS and SOM as single agents and their combinations on subcutaneously inoculated NE-10 allografts and the in vitro effects on NE-CS cells. Apoptosis and cell cycle activity were assessed by immunohistochemistry using TdT-mediated dUTP-biotin nick-end labeling (TUNEL) and a Ki-67 antibody, respectively. In vivo growth of NE-10 tumors treated with ZOL, ZOL plus SMS, or ZOL plus SOM was significantly inhibited compared to the control as a consequence of induction of apoptosis and cell cycle arrest. ZOL induced time- and dose-dependent inhibition of in vitro proliferation of NE-CS cells, but the somatostatin analogs (SMS and SOM) did not. ZOL also inhibited migration of NE-CS cells. These effects were caused by inhibition of Erk1/2 phosphorylation via impairment of prenylation of Ras. ZOL, but not SMS or SOM, induced apoptosis and inhibition of proliferation and migration through impaired prenylation of Ras in NE carcinoma models. Our findings support the possibility that ZOL could be used in the early phase for controlling NE cells, which may trigger progression to CRPC. Copyright © 2012 Wiley Periodicals, Inc.

  3. Non-THC cannabinoids inhibit prostate carcinoma growth in vitro and in vivo: pro-apoptotic effects and underlying mechanisms

    PubMed Central

    De Petrocellis, Luciano; Ligresti, Alessia; Schiano Moriello, Aniello; Iappelli, Mariagrazia; Verde, Roberta; Stott, Colin G; Cristino, Luigia; Orlando, Pierangelo; Di Marzo, Vincenzo

    2013-01-01

    BACKGROUND AND PURPOSE Cannabinoid receptor activation induces prostate carcinoma cell (PCC) apoptosis, but cannabinoids other than Δ9-tetrahydrocannabinol (THC), which lack potency at cannabinoid receptors, have not been investigated. Some of these compounds antagonize transient receptor potential melastatin type-8 (TRPM8) channels, the expression of which is necessary for androgen receptor (AR)-dependent PCC survival. EXPERIMENTAL APPROACH We tested pure cannabinoids and extracts from Cannabis strains enriched in particular cannabinoids (BDS), on AR-positive (LNCaP and 22RV1) and -negative (DU-145 and PC-3) cells, by evaluating cell viability (MTT test), cell cycle arrest and apoptosis induction, by FACS scans, caspase 3/7 assays, DNA fragmentation and TUNEL, and size of xenograft tumours induced by LNCaP and DU-145 cells. KEY RESULTS Cannabidiol (CBD) significantly inhibited cell viability. Other compounds became effective in cells deprived of serum for 24 h. Several BDS were more potent than the pure compounds in the presence of serum. CBD-BDS (i.p.) potentiated the effects of bicalutamide and docetaxel against LNCaP and DU-145 xenograft tumours and, given alone, reduced LNCaP xenograft size. CBD (1–10 µM) induced apoptosis and induced markers of intrinsic apoptotic pathways (PUMA and CHOP expression and intracellular Ca2+). In LNCaP cells, the pro-apoptotic effect of CBD was only partly due to TRPM8 antagonism and was accompanied by down-regulation of AR, p53 activation and elevation of reactive oxygen species. LNCaP cells differentiated to androgen-insensitive neuroendocrine-like cells were more sensitive to CBD-induced apoptosis. CONCLUSIONS AND IMPLICATIONS These data support the clinical testing of CBD against prostate carcinoma. LINKED ARTICLE This article is commented on by Pacher et al., pp. 76–78 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2012.02121.x PMID:22594963

  4. Neutron personnel dosimetry

    SciTech Connect

    Griffith, R.V.

    1981-06-16

    The current state-of-the-art in neutron personnel dosimetry is reviewed. Topics covered include dosimetry needs and alternatives, current dosimetry approaches, personnel monitoring devices, calibration strategies, and future developments. (ACR)

  5. [Impact of International Association of Urological Pathology Gleason scoring system on prostatic carcinoma grading: a preliminary analysis of 185 cases].

    PubMed

    Wang, Gongwei; Shen, Danhua

    2014-10-01

    To explore the impact of the 2005 International Association of Urological Pathology (ISUP) Gleason score (GS) system on prostatic carcinoma grading. Using the 1977 revision and ISUP version of GS system, 112 needle biopsies, 18 transurethral resections of the prostate and 55 radical prostatectomies were scored. The proportion of grading discrepancy was observed and compared between the two versions of GS. Gleason scores of 3+3, 3+4 and 4+3 accounted for 47.0% (87/185), 11.4% (21/185) and 17.3% (32/185) in the modified system, and accounted for 25.9% (48/185), 21.6% (40/185) and 27.6 % (51/185) in ISUP system, respectively. The percentages of primary grade by modified vs. ISUP system were 62.7% (116/185) vs.50.8% (94/185) for grade 3, and 31.4% (58/185) vs. 41.6% (77/185) for grade 4. The percentages of secondary grade by modified vs. ISUP system were 65.9% (122/185) vs. 54.6% (101/185) for grade 3, and 21.1% (39/185) vs. 31.4% (58/185) for grade 4. ISUP system is different from the modified system. Compared with the modified system, the proportion scored by ISUP system tends to decline for GS 3+3 but increase for GS 3+4 and 4+3.

  6. The tolerance to multiple daily fractionated radiotherapy for the treatment of prostatic and bladder carcinoma: a feasibility study

    SciTech Connect

    Ang, K.K.; van der Schueren, E.

    1982-10-01

    A modified fractionation schedule was designed with the purpose of reducing the treatment burden. Three fractions of 2 Gy with four hours interval were given during 5 days. The whole scheme was repeated after a rest period of 4 weeks. This makes it possible to deliver a dose of 60 Gy in 10 treatment days and over a total time of 6 weeks. A total of 30 patients, 22 with prostatic cancer and 8 with invasive bladder carcinoma, have been treated. The feasibility has been found to be very good. Forty-seven percent of the patients had acute morbidity, although it was mild in all patients. One patient had a persistent, another had a transient delayed symptom, and one had a severe late complication. The tolerance to this schedule is better than that observed with conventional fractionation schedules. Together with the drastical reduction of the total treatment days, this multiple daily fractionation (MDF) schedule has already been shown to improve the therapeutic ratio by diminishing the burden on the patients. Longer follow-up is necessary for the assessment of the efficacy of this schedule for local tumor control. However, with a follow-up period of 7 to 16 months no recurrence of the prostate cancer in the pelvis has been observed. These results warrant further exploration of the possible benefits of modifications in time-dose-fractionation schedules.

  7. Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.

    PubMed

    Morrissey, Jeremiah J; Mobley, Jonathan; Figenshau, R Sherburne; Vetter, Joel; Bhayani, Sam; Kharasch, Evan D

    2015-01-01

    To evaluate the sensitivity and specificity of urine aquaporin 1 (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary renal cell carcinoma (RCC) by comparing urine concentrations of these unique biomarkers in patients with RCC, noncancer renal masses, bladder cancer, and prostate cancer. From February 1, 2012, through October 31, 2012, preoperative urine samples were obtained from patients with a presumptive diagnosis of RCC based on an imaged renal mass, prostate cancer, or transitional cell bladder cancer. Imaged renal masses were diagnosed postnephrectomy—as malignant or benign—by histology. Urine AQP1 and PLIN2 concentrations were measured by using a sensitive and specific Western blot and normalized to urine creatinine concentration. Median concentrations of urine AQP1 and PLIN2 in patients with clear cell and papillary RCC (n=47) were 29 and 36 relative absorbance units/mg urine creatinine, respectively. In contrast, median concentrations in patients with bladder cancer (n=22) and prostate cancer (n=27), patients with chromophobe tumors (n=7), and patients with benign renal oncocytomas (n=9) and angiomyolipomas (n=7) were all less than 10 relative absorbance units/mg urine creatinine (Kruskal-Wallis test, P<.001 vs RCC for both biomarkers) and comparable with those in healthy controls. The area under the receiver operating characteristic curve ranged from 0.99 to 1.00 for both biomarkers. These results support the specificity and sensitivity of urine AQP1 and PLIN2 concentrations for RCC. These novel tumor-specific proteins have high clinical validity and high potential as specific screening biomarkers for clear cell and papillary RCC as well as in the differential diagnosis of imaged renal masses. clinicaltrials.gov Identifier: NCT00851994. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  8. [Laparoscopic sentinel lymph node (SLN) dissection for clinically localized prostate carcinoma: results obtained in the first 70 patients].

    PubMed

    Rousseau, T; Lacoste, J; Pallardy, A; Campion, L; Bridji, B; Mouaden, A; Testard, A; Aillet, G; Le Coguic, G; Potiron, E; Curtet, C; Kraeber-Bodéré, F; Rousseau, C

    2012-01-01

    The lymph node metastasis is an important prognostic factor in prostatic cancer. The aim of this prospective study was to evaluate the relevance of the sentinel lymph node biopsy by laparoscopy in staging locoregional patients with clinically localized PC. A transrectal ultrasound-guided injection by 0.3 mL/100 MBq (99m)Tc-sulfur rhenium colloid in each prostatic lobe was performed the day before surgery. The detection was realized intraoperatively with a laparoscopic probe (Clerad(®) Gamma Sup) followed by extensive dissection. Counts of SLN were performed in vivo and confirmed ex vivo. The histological analysis was performed by hematoxyline-phloxine-safran staining and followed by immunochemistry if SLN is free. Seventy patients with carcinoma of the prostate at intermediate or high risk of lymph node metastases were included. The intraoperative detection rate was 68/70 (97%). Fourteen patients had lymph node metastases, six only in SLN. The false negative rate was 2/14 (14%). The internal iliac region was the first metastatic site (40.9%). A metastatic sentinel node in common iliac region beyond the ureteral junction was present in 18.2%. A non-negligible sentinel metastatic region was the common iliac area (18.2%). Limited or standard lymph node dissection would have ignored respectively 72.7% and 59% of lymph node metastases. The laparoscopy is adapted to a broad identification of SLN and targeted dissection of these lymph nodes significantly limited the risk of surgical extended dissection while maintaining the accuracy of the information. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Interleukin-13 receptors on human prostate carcinoma cell lines represent a novel target for a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin.

    PubMed

    Maini, A; Hillman, G; Haas, G P; Wang, C Y; Montecillo, E; Hamzavi, F; Pontes, J E; Leland, P; Pastan, I; Debinski, W; Puri, R K

    1997-09-01

    We have discovered a new cell surface protein in the form of interleukin-13 receptor on several solid tumor cells, including human renal cell carcinoma cells (Obiri et al., 1995; Debinski et al., 1995). This study reports that human prostate cancer cell lines also express high affinity IL-13 receptors (Kd = 159 pM). These receptors are functional because IL-13 surprisingly increased proliferation of all three prostate cancer cell lines studied as determined by thymidine uptake and clonogenic assays. IL-13 receptors on prostate cancer cell lines were targeted using a chimeric protein composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE38QQR). This molecule, termed IL13-PE38QQR, has been found cytotoxic to all three prostate cancer cell lines as determined by the inhibition of protein synthesis. The IC50 ranged between 1 nmol/l, to 15 nmol/l. These data were confirmed by clonogenic assays in which IL13-PE38QQR almost completely inhibited colony formation at 10 nmol/l. IL13-PE38QQR was not cytotoxic to cells that express little or no IL-13R. Heat inactivated IL13-PE38QQR was not cytotoxic to prostate cancer cells indicating specificity. IL13-PE38QQR was also cytotoxic to colonies when they were allowed to form first for several days before the addition of toxins. Our data suggest that additional studies should be performed to target IL-13 receptor bearing prostate cancer.

  10. Cisplatin modulates B-cell translocation gene 2 to attenuate cell proliferation of prostate carcinoma cells in both p53-dependent and p53-independent pathways.

    PubMed

    Chiang, Kun-Chun; Tsui, Ke-Hung; Chung, Li-Chuan; Yeh, Chun-Nan; Feng, Tsui-Hsia; Chen, Wen-Tsung; Chang, Phei-Lang; Chiang, Hou-Yu; Juang, Horng-Heng

    2014-07-01

    Cisplatin is a widely used anti-cancer drug. The B-cell translocation gene 2 (BTG2) is involved in the cell cycle transition regulation. We evaluated the cisplatin effects on prostate cancer cell proliferation and the expressions of BTG2, p53, androgen receptor (AR) and prostate specific antigen (PSA) in prostate carcinoma, p53 wild-type LNCaP or p53-null PC-3, cells. Cisplatin treatments attenuated cell prostate cancer cell growth through inducing Go/G1 cell cycle arrest in lower concentration and apoptosis at higher dosage. Cisplatin treatments enhanced p53 and BTG2 expression, repressed AR and PSA expression, and blocked the activation of androgen on the PSA secretion in LNCaP cells. BTG2 knockdown in LNCaP cells attenuated cisplatin-mediated growth inhibition. Cisplatin enhanced BTG2 gene expression dependent on the DNA fragment located within -173 to -82 upstream of BTG2 translation initiation site in prostate cancer cells. Mutation of the p53 response element from GGGCAGAGCCC to GGGCACC or mutation of the NFκB response element from GGAAAGTCC to GGAAAGGAA by site-directed mutagenesis abolished the stimulation of cisplatin on the BTG2 promoter activity in LNCaP or PC-3 cells, respectively. Our results indicated that cisplatin attenuates prostate cancer cell proliferation partly mediated by upregulation of BTG2 through the p53-dependent pathway or p53-independent NFκB pathway.

  11. State-of-the-art radiotherapy in the management of clinically localized prostate carcinoma.

    PubMed

    Bermudez, R Scott; Izaguirre, Alejandra; Roach, Mack

    2007-02-01

    Four Phase III trials demonstrating higher prostate-specific antigen control rates in prostate cancer patients treated with higher doses of radiation have changed the standard of care. Emerging on-line technologies, improved imaging and computer algorithms, combined with an improved understanding of how best to apply them, have allowed radiation oncologists to move ever closer to the optimal application of curative radiation. This technology allows a higher dose to be delivered to tumor-bearing areas while minimizing the dose delivered to surrounding normal tissues. Real-time adaptive techniques have made each step more accurate, and commercialization has increasingly moved these advances further into the community setting. Phase III trials have also helped to define the role of hormonal therapy in combination with radiation and the benefits of prophylactic pelvic nodal radiotherapy in subsets of patients. We have also learnt how to optimize the use of prostate-specific antigen to better determine success and failure following radiotherapy.

  12. A useful treatment for patients with advanced mixed-type small cell neuroendocrine carcinoma of the prostate: A case report.

    PubMed

    Uemura, Kei-Ichiro; Nakagawa, Go; Chikui, Katsuaki; Moriya, Fukuko; Nakiri, Makoto; Hayashi, Tokumasa; Suekane, Shigetaka; Matsuoka, Kei

    2013-03-01

    Treating extended prostatic small cell neuroendocrine carcinoma (PSCNC) is extremely difficult and no standard treatment has yet been established. We experienced a case of advanced mixed-type PSCNC in which the patient achieved long-term survival and local control following combined therapy. Locally advanced PSCNC causing lower urinary obstruction was detected during androgen-ablation therapy for stage D2 mixed adenocarcinoma PSCNC. The patient was treated with intra-arterial infusion chemotherapy using a reservoir system and external-beam radiotherapy (EBRT) to the whole pelvis and local tumor. After chemoradiotherapy, the patient's lower urinary obstruction was reduced and did not return during the remaining 40 months of the patient's life. The patient survived for 70 months following the start of the androgen-ablation therapy. The present study reports a useful treatment for advanced mixed-type PSCNC, androgen-ablation therapy and chemoradiotherapy. The present results also suggest that the prognostic factors for advanced mixed-type PSCNC are the sensitivity of the conventional adenocarcinoma to androgen-ablation therapy, degree of metastasis and extent of the small cell neuroendocrine carcinoma component.

  13. ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells

    PubMed Central

    Höll, Monika; Koziel, Rafal; Schäfer, Georg; Pircher, Haymo; Pauck, Alexander; Hermann, Martin; Klocker, Helmut; Jansen‐Dürr, Pidder

    2015-01-01

    Prostate cancer (PCa) is the most commonly diagnosed cancer and second leading cause of male cancer death in Western nations. Thus, new treatment modalities are urgently needed. Elevated production of reactive oxygen species (ROS) by NADPH oxidase (Nox) enzymes is implicated in tumorigenesis of the prostate and other tissues. However, the identity of the Nox enzyme(s) involved in prostate carcinogenesis remains largely unknown. Analysis of radical prostatectomy tissue samples and benign and malignant prostate epithelial cell lines identified Nox5 as an abundantly expressed Nox isoform. Consistently, immunohistochemical staining of a human PCa tissue microarray revealed distinct Nox5 expression in epithelial cells of benign and malignant prostatic glands. shRNA‐mediated knockdown of Nox5 impaired proliferation of Nox5‐expressing (PC‐3, LNCaP) but not Nox5‐negative (DU145) PCa cell lines. Similar effects were observed upon ROS ablation via the antioxidant N‐acetylcysteine confirming ROS as the mediators. In addition, Nox5 silencing increased apoptosis of PC‐3 cells. Concomitantly, protein kinase C zeta (PKCζ) protein levels and c‐Jun N‐terminal kinase (JNK) phosphorylation were reduced. Moreover, the effect of Nox5 knockdown on PC‐3 cell proliferation could be mimicked by pharmacological inhibition of JNK. Collectively, these data indicate that Nox5 is expressed at functionally relevant levels in the human prostate and clinical PCa. Moreover, findings herein suggest that Nox5‐derived ROS and subsequent depletion of PKCζ and JNK inactivation play a critical role in modulating intracellular signaling cascades involved in the proliferation and survival of PCa cells. © 2014 The Authors. Molecular Carcinogenesis published by Wiley Periodicals, Inc. PMID:25559363

  14. Radiation dosimetry.

    PubMed Central

    Cameron, J

    1991-01-01

    This article summarizes the basic facts about the measurement of ionizing radiation, usually referred to as radiation dosimetry. The article defines the common radiation quantities and units; gives typical levels of natural radiation and medical exposures; and describes the most important biological effects of radiation and the methods used to measure radiation. Finally, a proposal is made for a new radiation risk unit to make radiation risks more understandable to nonspecialists. PMID:2040250

  15. On the relationship between tumor structure and complexity of the spatial distribution of cancer cell nuclei: a fractal geometrical model of prostate carcinoma.

    PubMed

    Waliszewski, Przemyslaw; Wagenlehner, Florian; Gattenlöhner, Stefan; Weidner, Wolfgang

    2015-03-01

    A risk of the prostate cancer patient is defined by both the objective and subjective criteria, that is, PSA concentration, Gleason score, and pTNM-stage. The subjectivity of tumor grading influences the risk assessment owing to a large inter- and intra-observer variability. Pathologists propose a central prostate pathology review as a remedy for this problem; yet, the review cannot eliminate the subjectivity from the diagnostic algorithm. The spatial distribution of cancer cell nuclei changes during tumor progression. It implies changes in complexity measured by the capacity dimension D0, the information dimension D1, and the correlation dimension D2. The cornerstone of the approach is a model of prostate carcinomas composed of the circular fractals CF(4), CF(6 + 0), and CF(6 + 1). This model is both geometrical and analytical, that is, its structure is well-defined, the capacity fractal dimension D0 can be calculated for the infinite circular fractals, and the dimensions D0, D1, D2 can be computed for their finite counterparts representing distribution of cell nuclei. The model enabled both the calibration of the software and the validation of the measurements in 124 prostate carcinomas. The ROC analysis defined the cut-off D0 values for seven classes of complexity. The Gleason classification matched in part with the classification based on the D0 values. The mean ROC sensitivity was 81.3% and the mean ROC specificity 75.2%. Prostate carcinomas were re-stratified into seven classes of complexity according to their D0 values. This increased both the mean ROC sensitivity and the mean ROC specificity to 100%. All homogeneous Gleason patterns were subordinated to the class C1, C4, or C7. D0 = 1.5820 was the cut-off D0 value between the complexity class C2 and C3 representing low-risk cancers and intermediate-risk cancers, respectively. The global fractal dimensions eliminate the subjectivity in the diagnostic algorithm of prostate cancer. Those complexity

  16. A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinoma.

    PubMed

    Potters, Louis; Purrazzella, Rosemary; Brustein, Sheryl; Fearn, Paul; Leibel, Steven A; Kattan, Michael W

    2002-10-01

    The purpose of the current study was to evaluate modeling strategies using sextant core prostate biopsy specimen data that would best predict biochemical control in patients with localized prostate carcinoma treated with permanent prostate brachytherapy (PPB). One thousand four hundred seventy-seven patients underwent PPB between 1992 and 2000. The authors restricted analysis to those patients who had sextant biopsies (n = 1073). A central pathology review was undertaken on all specimens. Treatment consisted of PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two hundred twenty-eight patients (21%) received PPB in combination with external radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen (pretx-PSA), the following detailed biopsy variables were considered: mean percentage of cancer in an involved core; maximum percentage of cancer; mean primary and secondary Gleason grades; maximum Gleason grade (primary or secondary); percentage of cancer in the apex, mid, and base; percent of cores positive; maximum primary and secondary Gleason grades in apex, mid, and base; maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex, mid, and base; maximum primary Gleason grade; and maximum secondary Gleason grade. In all, 23 biopsy variables were considered. Four modeling strategies were compared. As a base model, the authors considered the pretx-PSA, clinical stage, and biopsy Gleason sum as predictors. For the second model, the authors added percent of cores positive. The third modeling strategy was to use stepwise variable selection to select only those variables (from the total pool of 26) that were statistically significant. The fourth strategy was to apply principal components analysis, which has theoretical advantages over the other strategies. Principal components analysis creates component scores that account for

  17. Long non-coding RNA ATB promotes growth and epithelial-mesenchymal transition and predicts poor prognosis in human prostate carcinoma

    PubMed Central

    XU, SONG; YI, XIAO-MING; TANG, CHAO-PENG; GE, JING-PING; ZHANG, ZHENG-YU; ZHOU, WEN-QUAN

    2016-01-01

    Long non-coding RNAs (lncRNAs) have been identified to be critical mediators in various tumors associated with cancer progression. Long non-coding RNA activated by TGF-β (lncRNA-ATB) is a stimulator of epithelial-mesenchymal transition (EMT) and serves as a novel prognostic biomarker for hepatocellular carcinoma. However, the biological role and clinical significance of lncRNA-ATB in human prostate cancer have yet to be fully elucidated. The present study was designed to explore the expression of lncRNA-ATB in human prostate cancer patients and the role of lncRNA-ATB in prostate cancer cells. We showed that lncRNA-ATB expression was significantly upregulated in tumor tissues in patients with prostate cancer in comparison with adjacent non-tumor tissues. Further analysis indicted that high lncRNA-ATB expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival in prostate cancer patients. Overexpression of lncRNA-ATB promoted, and knockdown of lncRNA-ATB inhibited the growth of prostate cancer cells via regulations of cell cycle regulatory protein expression levels. In addition, lncRNA-ATB stimulated epithelial-mesenchymal transition (EMT) associated with ZEB1 and ZNF217 expression levels via ERK and PI3K/AKT signaling pathways. These results indicated that lncRNA-ATB may be considered as a new predictor in the clinical prognosis of patients with prostate cancer. Overexpression of lncRNA-ATB exerts mitogenic and EMT effects of prostate cancer via activation of ERK and PI3K/AKT signaling pathways. PMID:27176634

  18. In Vivo 18 FDG/18 Choline Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging

    DTIC Science & Technology

    2016-10-01

    AWARD NUMBER: W81XWH-13-1-0138 TITLE: In Vivo 18-FDG/18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical...18-Choline-Mediated Cerenkov Radiation Energy Transfer (CRET) Multiplexed Optical Imaging for Human Prostate Carcinoma Detection and Staging 5b...fluorocholine/18F-FDG Cerenkov radiation energy transfer (CRET) coupled with TF- and ErbB2/3- molecularly targeted near- infrared (NIR) QDs can be used

  19. Eupalitin induces apoptosis in prostate carcinoma cells through ROS generation and increase of caspase-3 activity.

    PubMed

    Kaleem, Sarjeel; Siddiqui, Sahabjada; Siddiqui, Hefazat Hussain; Badruddeen; Hussain, Arshad; Arshad, Mohammad; Akhtar, Juber; Rizvi, Aleza

    2016-02-01

    Prostate cancer is the second most common malignancy in the human reproductive system. Eupalitin is one of the O-methylated flavonol-exhibited enhanced cancer chemopreventive agents. The current study highlights the structural determination of eupalitin and aims to explore the antitumor activity of eupalitin in human prostate cancer cell (PC3) and its underlying mechanism. Eupalitin structure was determined by using FTIR, (1)H NMR, and (13)C NMR. PC3 cells were treated with increasing concentrations of eupalitin, followed by analysis of the cell viability with an MTT assay. The results demonstrated that eupalitin markedly inhibited the proliferation of PC3 cells in a concentration-dependent manner. The results from fluorescent microscopic analysis of nuclear condensation and intracellular ROS generation determined that eupalitin significantly induced ROS level lead to nuclear apoptosis. Cell cycle analysis revealed that eupalitin-induced cell cycle progression as a percentage of cells in G0/G1 phase decreased whereas S phase increased. Caspase-3 immunofluorescence analysis confirms the efficacy of eupalitin-inducing apoptotic pathway and cell death. Thus, our study is helpful in understanding the mechanism underlying these effects in prostate cancer and it may provide novel molecular targets for prostate cancer therapy. © 2015 International Federation for Cell Biology.

  20. Cadmium, Zinc, and Selenium Levels in Carcinoma of the Human Prostate

    DTIC Science & Technology

    2008-04-01

    Original contains colored plates: ALL DTIC reproductions will be in black and white. 14. ABSTRACT The purpose of this study is to examine...radicals, and therefore hypnotized at the loci of its high deposition to contribute in prostate cancerogenesis. In these experiments, we used

  1. [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.

  2. Hypofractionated stereotactic body radiotherapy in low- and intermediate-risk prostate carcinoma

    PubMed Central

    Kim, Hun Jung; Phak, Jeong Hoon; Kim, Woo Chul

    2016-01-01

    Purpose Stereotactic body radiotherapy (SBRT) takes advantage of low α/β ratio of prostate cancer to deliver a large dose in few fractions. We examined clinical outcomes of SBRT using CyberKnife for the treatment of low- and intermediate-risk prostate cancer. Materials and Methods This study was based on a retrospective analysis of the 33 patients treated with SBRT using CyberKnife for localized prostate cancer (27.3% in low-risk and 72.7% in intermediate-risk). Total dose of 36.25 Gy in 5 fractions of 7.25 Gy were administered. The acute and late toxicities were recorded using the Radiation Therapy Oncology Group scale. Prostate-specific antigen (PSA) response was monitored. Results Thirty-three patients with a median 51 months (range, 6 to 71 months) follow-up were analyzed. There was no biochemical failure. Median PSA nadir was 0.27 ng/mL at median 33 months and PSA bounce occurred in 30.3% (n = 10) of patients at median at median 10.5 months after SBRT. No grade 3 acute toxicity was noted. The 18.2% of the patients had acute grade 2 genitourinary (GU) toxicities and 21.2% had acute grade 2 gastrointestinal (GI) toxicities. After follow-up of 2 months, most complications had returned to baseline. There was no grade 3 late GU and GI toxicity. Conclusion Our experience with SBRT using CyberKnife in low- and intermediate-risk prostate cancer demonstrates favorable efficacy and toxicity. Further studies with more patients and longer follow-up duration are required. PMID:27306777

  3. Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

    SciTech Connect

    Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo; Rivard, Mark J.

    2013-03-15

    Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using {sup 60}Co or {sup 192}Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes from an adult reference man defined in ICRP Publication 89. Point sources of {sup 60}Co or {sup 192}Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by {sup 60}Co source were smaller (8%-19%) than from {sup 192}Ir. However, as the distance increases, the more penetrating gamma rays produced by {sup 60}Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a {sup 60}Co source (11.1 mSv/Gy) is lower than from a {sup 192}Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials

  4. Sister Mary Joseph nodule as the presenting sign of disseminated prostate carcinoma.

    PubMed

    Deb, Prabal; Rai, Radhey Shyam; Rai, Rahul; Gupta, Ekawali; Chander, Yogesh

    2009-01-01

    Sister Mary Joseph's nodule is referred to as metastasis of visceral malignancy to the umbilicus. Most common primaries are in the gastrointestinal or genital tract, while other locations are rare. We recently encountered a 76-year-old male who was referred to the surgery clinic with an erythematous nodule in the umbilicus measuring 6 cm in diameter with complaints of painless profuse hematuria. History revealed severe obstructive voiding symptoms of 2-year duration, along with significant loss of weight and difficulty in walking. A detailed examination showed hard nodular hepatomegaly, along with grade IV prostatomegaly. Serum prostate-specific antigen was 3069 ng/ml. A pelvic radiograph displayed multiple osteolytic lesions, while ultrasonography showed multiple iso- and hypoechoic lesions in both lobes of the liver, suggestive of metastasis. Histopathology of a Tru-cut biopsy of the prostate confirmed an adenocarcinoma (Gleason score 9) with umbilical metastasis. The patient was on regular follow-up and died 3 months later.

  5. Is the in vivo dosimetry with the OneDosePlusTM system able to detect intra-fraction motion? A retrospective analysis of in vivo data from breast and prostate patients

    PubMed Central

    2012-01-01

    Background The OneDosePlusTM system, based on MOSFET solid-state radiation detectors and a handheld dosimetry reader, has been used to evaluate intra-fraction movements of patients with breast and prostate cancer. Methods An Action Threshold (AT), defined as the maximum acceptable discrepancy between measured dose and dose calculated with the Treatment Planning System (TPS) (for each field) has been determined from phantom data. To investigate the sensitivity of the system to direction of the patient movements, fixed displacements have been simulated in phantom. The AT has been used as an indicator to establish if patients move during a treatment session, after having verified the set-up with 2D and/or 3D images. Phantom tests have been performed matching different linear accelerators and two TPSs (TPS1 and TPS2). Results The ATs have been found to be very similar (5.0% for TPS1 and 4.5% for TPS2). From statistical data analysis, the system has been found not sensitive enough to reveal displacements smaller than 1 cm (within two standard deviations). The ATs applied to in vivo treatments showed that among the twenty five patients treated for breast cancer, only four of them moved during each measurement session. Splitting data into medial and lateral field, two patients have been found to move during all these sessions; the others, instead, moved only in the second part of the treatment. Patients with prostate cancer have behaved better than patients with breast cancer. Only two out of twenty five moved in each measurement session. Conclusions The method described in the paper, easily implemented in the clinical practice, combines all the advantages of in vivo procedures using the OneDosePlusTM system with the possibility of detecting intra-fraction patient movements. PMID:22716260

  6. Sarcomatoid Carcinoma of the Prostate: Retrospective Review of a Case Series from Johns Hopkins Hospital

    PubMed Central

    Markowski, Mark C.; Eisenberger, Mario; Zahurak, Marianna; Epstein, Jonathan I.; Paller, Channing

    2015-01-01

    Objective To identify survival differences in patients with sarcomatoid prostate cancer based on initial staging and treatment regimens. Methods We retrospectively reviewed the clinical outcomes of patients with a pathologically confirmed diagnosis of sarcomatoid prostate cancer. The primary statistical objective was to estimate overall survival and assess the survival of patients at different stages treated with either local and/or systemic approaches. Results We identified 70 transurethral resections, needle biopsies or prostatectomy specimens that were reviewed by the Department of Pathology at Johns Hopkins Hospital from 2002–2012 and given the diagnosis of sarcomatoid prostate cancer. Of the 45 patients with available survival data, complete medical histories were obtained on 27 patients who were stratified based on a modified staging system (local disease, local disease with bladder invasion, and metastatic disease). After a median follow-up of 106 months, the median overall survival (OS) of patients in the local disease group was not reached. Notably, five of the 9 patients diagnosed with local disease survived > 5 years and were treated with surgery and/or external beam radiation therapy. The OS hazard was significantly increased in patients with either clinical evidence of bladder invasion (HR: 20.46 [95% CI: 2.43,172]; p = < 0.0001) or metastatic disease (HR: 43.34 [95% CI: 4.39,427.4]; p = < 0.0001), which both demonstrated poor outcomes (median OS: local with bladder invasion – 9 months; metastatic disease – 7.1 months). Conclusions This retrospective analysis suggests that local sarcomatoid prostate cancer can be effectively treated with definitive therapy leading to favorable outcomes. PMID:26126695

  7. Carcinoma of the prostate: the treatment of bone metastases by radioactive phosphorus (TSP)

    SciTech Connect

    Ariel, I.M.; Hassouna, H.

    1985-01-01

    The administration of radioactive phosphorus and testosterone benefitted two-thirds of thirty patients with prostate cancer treated. Subjective relief of bone pain occurred in 73% of cases and measurable objective improvement occurred in 50%. Hematopoietic depression occurred in 30% of the patients necessitating readmission to hospital for transfusion. This method of treatment is advocated for patients with widespread osseous metastasis, especially those with severe pain.

  8. Sarcomatoid Carcinoma of the Prostate: Retrospective Review of a Case Series From the Johns Hopkins Hospital.

    PubMed

    Markowski, Mark C; Eisenberger, Mario A; Zahurak, Marianna; Epstein, Jonathan I; Paller, Channing J

    2015-09-01

    To identify survival differences in patients with sarcomatoid prostate cancer based on initial staging and treatment regimens. We retrospectively reviewed the clinical outcomes of patients with a pathologically confirmed diagnosis of sarcomatoid prostate cancer. The primary statistical objective was to estimate overall survival (OS) and to assess the survival of patients at different stages treated with local and/or systemic approaches. We identified 70 transurethral resections, needle biopsies, or prostatectomy specimens that were reviewed by the Department of Pathology at the Johns Hopkins Hospital from 2002-2012 and given the diagnosis of sarcomatoid prostate cancer. Of the 45 patients with available survival data, complete medical histories were obtained for 27 patients who were stratified based on a modified staging system (local disease, local disease with bladder invasion, and metastatic disease). After a median follow-up of 106 months, the median OS of patients in the local disease group was not reached. Notably, 5 of the 9 patients diagnosed with local disease survived >5 years and were treated with surgery and/or external beam radiation therapy. The OS hazard was significantly increased in patients with either clinical evidence of bladder invasion (HR: 20.46 [95% CI: 2.43,172]; P = 0.005) or metastatic disease (HR: 43.34 [95% CI: 4.39,427.4]; P = 0.001), which both demonstrated poor outcomes (median OS: local disease with bladder invasion-9 months; metastatic disease-7.1 months). This retrospective analysis suggests that local sarcomatoid prostate cancer can be effectively treated with definitive therapy leading to favorable outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Phyto-, endo- and synthetic cannabinoids: promising chemotherapeutic agents in the treatment of breast and prostate carcinomas.

    PubMed

    Fraguas-Sánchez, A I; Fernández-Carballido, A; Torres-Suárez, A I

    2016-11-01

    The term 'cannabinoids' designates a family of compounds with activity upon cannabinoid receptors. Cannabinoids are classified in three groups: phytocannabinoids, endocannabinoids, and the synthetic analogues of both groups. They have become a promising tool in the treatment of cancer disease, not only as palliative agents, but also as antitumor drugs, due to their ability to inhibit the proliferation, adhesion, migration, invasion, and angiogenesis of tumour cells. Two of the cancers where they have shown high anticancer activity are breast and prostate tumours. Despite this potential clinical interest, several studies have also reported that cannabinoids can stimulate the proliferation of cancer cells at very low concentrations. Areas covered: The aim of this review is to evaluate the promising chemotherapeutic utility of phytocannabinoids, endocannabinoids, and synthetic cannabinoids in breast and prostate cancer. Expert opinion: Cannabinoids, in particular the non-psychoactive CBD, may be promising tools in combination therapy for breast and prostate cancer, due to their direct antitumor effects, their ability to improve the efficacy of conventional antitumor drugs and their usefulness as palliative treatment. Nevertheless, deeper studies to fully establish the mechanisms responsible for their antitumour and pro-tumour properties and their formulation in efficient delivery systems remain to be established.

  10. 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

  11. Oldest known case of metastasizing prostate carcinoma diagnosed in the skeleton of a 2,700-year-old Scythian king from Arzhan (Siberia, Russia).

    PubMed

    Schultz, Michael; Parzinger, Hermann; Posdnjakov, Dmitrij V; Chikisheva, Tatjana A; Schmidt-Schultz, Tyede H

    2007-12-15

    To determine whether a 2,700-year-old tumor can be reliably diagnosed using microscopic and proteomic techniques and whether such prostate carcinomas show the same morphological pattern at the micro-level as modern-day carcinomas, this case was investigated. A 40-50-year-old Scythian king who lived during the Iron Age in the steppe of Southern Siberia (Russia) suffered from macroscopically visible osteoblastic and osteoclastic lesions throughout his entire skeleton. Macro-morphological (macroscopy, endoscopy, radiology) and micro-morphological techniques (histology, scanning-electron microscopy) as well as proteomic techniques (1-D- and 2-D-electrophoresis, Western blot) were applied. The results of the morphological and biochemical investigation proved that this mature male suffered for many years from and probably died of a carcinoma of the prostate. The diagnosis mainly rests on the results of the microscopic examination of the lesions and the positive evidence of PSA, which is an important marker for the diagnosis of prostate cancer. It is remarkable that, in this ancient case, the morphological pattern at the microlevel is the same as in recent cases. The loss of the spongy bone substance (red bone marrow) provoked chronic anemia during the final months of the life of this king. The proteomic techniques applied are new for the investigation of recent and ancient macerated bones. Sensitive and reliable biochemical markers (PSA) are an important precondition to detect such tumors in recent and ancient materials. Currently, this is the oldest known case of prostate cancer diagnosed reliably by morphological and biochemical techniques. (c) 2007 Wiley-Liss, Inc.

  12. 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

  13. Cyclic AMP induces transforming growth factor beta 2 gene expression and growth arrest in the human androgen-independent prostate carcinoma cell line PC-3.

    PubMed Central

    Bang, Y J; Kim, S J; Danielpour, D; O'Reilly, M A; Kim, K Y; Myers, C E; Trepel, J B

    1992-01-01

    The standard therapy for advanced prostate cancer is androgen ablation. Despite transitory responses, hormonally treated patients ultimately relapse with androgen-independent disease that is resistant to further hormonal manipulation and cytotoxic chemotherapy. To develop an additional approach to the treatment of advanced prostate cancer, we have been studying the signal transductions controlling the growth of human androgen-independent prostate carcinoma cell lines. We report here that elevation of intracellular cAMP markedly inhibits the growth of the hormone-refractory cell line PC-3. To examine the mechanism of cAMP action in PC-3 cells, we tested the effect of the cAMP analog dibutyryl cAMP (Bt2-cAMP) on the regulation of the potent negative growth factor transforming growth factor beta (TGF-beta). Bt2-cAMP selectively induced the secretion of TGF-beta 2 and not TGF-beta 1 by PC-3 cells. This TGF-beta 2 was shown to be bioactive by using the CCL-64 mink lung cell assay. TGF-beta 1 was not activated despite being present at 3-fold higher concentrations than TGF-beta 2. Northern analysis showed that Bt2-cAMP induced an increase in the five characteristic TGF-beta 2 transcripts and had no effect on the level of TGF-beta 1 or TGF-beta 3 transcripts. TGF-beta 2 induction was only weakly enhanced by cycloheximide and was completely inhibited by actinomycin D. These data show that Bt2-cAMP induces the expression of active TGF-beta 2 by PC-3 prostate carcinoma cells, suggesting a new approach to the treatment of prostate cancer and a new molecular mechanism of cAMP action. Images PMID:1373503

  14. T2 Star-weighted Angiography (SWAN) Allows to Concomitantly Assess the Prostate Contour While Detecting Fiducials Before MR-based Intensity-modulated Radiation Therapy in Prostate Carcinoma.

    PubMed

    Dirajlal, Pierre-Antoine; Jambon, Eva; Albat-Esquirou, Agnes; Galmiche, Chloe; Bernhard, Jean-Christophe; Grenier, Nicolas; Haaser, Thibaud; Cornelis, François H

    2017-08-22

    To evaluate the performance of T2 star-weighted angiography (SWAN) to concomitantly assess the prostate contour while detecting fiducials before magnetic resonance (MR)-based intensity-modulated radiation therapy (IMRT) in prostate carcinoma. Forty patients (mean age: 73.1 ± 7.5 years; average Gleason score: 7 ± 1; average prostate-specific antigen: 14.7 ± 11.6 ng/mL) underwent MR and computed tomography imaging before fiducial-based IMRT. MR protocol included SWAN, T2-weighted (T2w) and diffusion-weighted imaging in a first group (n = 20) and SWAN, T2w and T2-star weighted imaging in a second group (n = 20). In group 1, the depiction of fiducials, image sharpness and visibility of prostate boundaries were independently evaluated by 2 readers on SWAN, T2w or diffusion-weighted images. In group 2, a similar evaluation was performed by 2 other readers on SWAN and T2-star images only. Depiction of fiducials was compared to computed tomography findings. The median scores of visibility of prostate boundaries, image sharpness and depiction of fiducials by SWAN were above average to excellent for all readers. In group 1, readers correctly located 56 of 57 (98.2%) and 47 of 57 (82.5%) fiducials, respectively; and 50 of 51 (98%), and 48 of 51 (88.2%) fiducials in group 2, respectively. By allowing adequate visualization of the prostate boundaries and high depiction of fiducial markers concomitantly, SWAN might be used for treatment planning of IMRT. The use of this sequence might simplify the registration process and limit any errors associated with image fusion. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  15. Studying the efficacy of escalated dose conformal radiation therapy in prostate carcinoma - Pakistan experience.

    PubMed

    Zamir, Asad; Farooq, Ahmad; Nisar, Hasan; Fatima, Ismat; Khan, Irfan Ullah; Masood, Misbah; Shahid, Abubaker

    2017-09-14

    Our objective in this study was to evaluate the role and benefits in terms of local toxicity and biochemical disease-free survival (bDFS) following escalated-dose conformal radiation therapy in prostate adenocarcinoma. The study population was composed of 53 patients with histologically proven T1b-T4, NO, MO prostate adenocarcinoma, having any Gleason score with prostate-specific antigen (PSA) of less than 50 ng/mL at diagnosis, given escalated dose EBRT (74 Gy) during the period between January 2011 and December 2013, retrospectively and evaluated for a period of 2 years post-radiation. Patients were followed up for a period of 2 years, beginning after completion of escalated dose external beam radiotherapy (EBRT) for biochemical failure as defined in ASTRO consensus committee guidelines 1996 and investigated for gastrointestinal, genitourinary skin toxicity. Out of 53 patients, 35 showed no biochemical failure at the end of 2 years following the completion of definitive escalated dose conformal radiotherapy while 18 were observed to have biochemical relapse. Acute gastrointestinal grade 1 toxicity was found in 26 patients, grade 2 in 24, and grade 3 only in 3 patients. Late gastrointestinal grade 0 toxicity was found in 16 patients, grade 1 in 28, grade 2 in 7 and grade 3 only in 2 patients. Grade 1 acute genitourinary toxicity was the highest in frequency observed in 28 of the total population followed by grade 2 in 21, grade 0 and grade 3 each, only in 2 patients. Late genitourinary Grade 0 toxicity was observed in 32 patients, grade 1 in 19, grade 2 and 3 only in 1 patient of the total population, respectively. Our data were comparable to international studies of dose escalation using 3D and beneficial as compared to conventional radiation therapy delivered by 2D in terms of biochemical failure rate and treatment related toxicity. Copyright © 2017. Published by Elsevier Taiwan LLC.

  16. [Exclusive irradiation of clinically localized prostatic carcinoma: comparison with various techniques].

    PubMed

    Scandolaro, L; Bossi, A; Ostinelli, A; Marinoni, M A; Isella, E

    1997-01-01

    The frequency of prostate cancer is on the increase and many intracapsular tumors are diagnosed in asymptomatic and relatively young patients. Radiotherapy is an effective alternative to surgery when the technique which reduces the rate of acute reactions and late side-effects is chosen. On the other hand, dose distribution on the target volume and dose delivered to surrounding tissues (rectum and femoral heads) depend on several variables, namely irradiation technique, treatment planning simulation procedures and study and patient positioning. 5 by 5 mm CT studies of the prostate and/or seminal vesicles and the execution of retrograde urethrography to define the prostatic apex plan are essential steps of the simulation procedure. To compare the adequacy of various techniques, we analyzed several isodose distribution maps of nonconformational treatments, calculated by our radiotherapy planning system on the central slice. Arc and multiportal (3 or 4 fields) techniques were considered. The statistical analysis of our results demonstrated that the 4-field perpendicular technique permits better dose distribution to the target volume than the 3-field perpendicular technique; it also reduces the dose to the femoral heads. However, a combination of anterior irradiation with two oblique posterior fields is preferred in hip prosthesis patients. The comparison between arc and static multiportal techniques shows that the former gives a markedly lower dose (up to 50%) to posterior rectal wall. The bilateral arc appears to be the best technique, especially when the patient restraining device is good, because it permits homogeneous irradiation of the target volume, even at high doses, and marked reduction of the dose to the posterior rectal wall and femoral heads; consequently, treatment morbidity is lower.

  17. Complications associated with preoperative radiation therapy and Iodine-125 brachytherapy for localized prostatic carcinoma

    SciTech Connect

    Flanigan, R.C.; Patterson, J.; Mendiondo, O.A.; Gee, W.F.; Lucas, B.A.; McRoberts, J.W.

    1983-08-01

    Twenty-five consecutive patients with localized adenocarcinoma of the prostate treated with 1,050 rad preoperative radiation therapy and Iodine-125 seed brachytherapy are reviewed. Significant long-term postoperative complications included radiation cystitis (12%), radiation proctitis (4%), genital and leg edema (12%), stress incontinence (8%), total incontinence (4%), and impotence (26%). Complications occurred in 75 per cent of patients who received additional postoperative radiation. Improved staging with CT scan, lymphangiography, and Chiba needle biopsy of any possibly abnormal lymph nodes provided excellent preoperative staging with only 1 patient (6%) upstaged at surgery to Stage D1.

  18. Post-operative infection by pathogenic micro-organisms in the oral cavity of patients with prostatic carcinoma.

    PubMed

    Senpuku, H; Tada, A; Uehara, S; Kariyama, R; Kumon, H

    2006-01-01

    The aim of this study was to analyse the change in the oral cavity microflora of 14 patients who had undergone a radical prostatectomy for prostatic carcinoma. The detection of micro-organisms in the oral cavity was compared before and after the surgical procedure. Post-operative infection, defined as those patients who had increased Candida species counts and/or pathogenic bacteria only at the post-operative examination, was observed in 10 patients. Six patients showed increased Candida species counts at the post-operative examination compared with the pre-operative examination. In five patients, pathogenic bacterial species were detected at the post-operative examination but not at the pre-operative examination. One patient had detectable pathogenic bacterial species only at the post-operative examination along with increased Candida species counts. Our findings suggest that pre-operative oral hygiene to remove bacterial and Candida species from patients who are scheduled for surgical procedures is important for satisfactory clinical outcomes.

  19. Interpersonal sensitivity, partner support, patient-physician communication, and sexual functioning in men recovering from prostate carcinoma.

    PubMed

    Siegel, Scott D; Molton, Ivan; Penedo, Frank J; Llabre, Maria M; Kinsinger, David P; Traeger, Lara; Schneiderman, Neil; Antoni, Michael H

    2007-12-01

    Prostate carcinoma (PC) is the most commonly diagnosed cancer in men. Treatments for localized PC are associated with side effects including sexual dysfunction, which has been linked to decrements in health-related quality of life and elevated distress levels. In this study, we examined the relationship between 2 personality traits, interpersonal sensitivity and lack of sociability, assessed by the Inventory of Interpersonal Problems (IIP; Pilkonis, Kim, Proietti, & Barkham, 1996) and recovery of sexual functioning in 121 men (M age = 60.6 years) recently treated with radical prostatectomy. Interpersonal sensitivity refers to the predisposition to perceive and elicit criticism and rejection from others; lack of sociability refers to chronic difficulties taking the initiative in interpersonal situations. After adjusting for relevant covariates, interpersonal sensitivity, but not sociability, was significantly associated with lower levels of sexual functioning. Patient-physician communication and partner perceived social support were explored as mediators of this relationship. Although interpersonal sensitivity was significantly associated with both poorer patient-physician communication and lower levels of partner support, the results did not support mediation. This study provides preliminary evidence that certain IIP-assessed interpersonal styles may complicate the recovery of sexual functioning after surgical treatment for PC.

  20. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    PubMed Central

    Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

    2013-01-01

    Introduction This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Methods Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. Results The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. Conclusions This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT. PMID:26229621

  1. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    SciTech Connect

    Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

    2013-12-15

    This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

  2. Presumptive Late-Onset Ankylosing Spondylitis Simulating Osteoblastic Skeletal Metastasis in a Patient With a History of Prostate Carcinoma: A Diagnostic Challenge

    PubMed Central

    Fischer, Charles P.; Emary, Peter C.; Taylor, John A.

    2015-01-01

    Objective The purpose of this report is to present a presumptive case of ankylosing spondylitis with late stage progression that simulated osteoblastic metastasis in a patient with a history of prostate carcinoma. Clinical Features A 67-year-old white man presented to a chiropractic clinic complaining of severe and worsening acute low back pain and right foot “numbness.” Further questioning also revealed a history of prostate carcinoma. Intervention and Outcome Imaging examination revealed a sclerotic pedicle and increased uptake of radiopharmaceutical on a nuclear medicine bone scan highly suggestive of osteoblastic skeletal metastasis. Further evaluation, however, revealed that the bone sclerosis was not the result of skeletal metastasis, but more consistent with a seronegative spondyloarthritis such as ankylosing spondylitis. Conclusion This report describes a presumptive case of ankylosing spondylitis simulating skeletal metastasis in a patient with a past medical history of prostate cancer. This atypical presentation illustrates the inherent uncertainty of diagnosis and how that uncertainty can be challenging in clinical practice. It also reinforces that it is critical for healthcare providers to consider a wide spectrum of differential diagnoses to avoid misdiagnoses and inappropriate interventions. PMID:26793037

  3. Inhibition of NF-kappaB pathway in grape seed extract-induced apoptotic death of human prostate carcinoma DU145 cells.

    PubMed

    Dhanalakshmi, Sivanandhan; Agarwal, Rajesh; Agarwal, Chapla

    2003-09-01

    The alarmingly high rate of prostate cancer (PCA) mortality as well as the limited success in the treatment of advanced PCA suggest that additional approaches are needed to control PCA growth and its metastatic potential. A constitutive activation of NF-kappaB family of transcription factors is known to play a major role in chemotherapy resistance in advanced PCA. In recent studies we showed that grape seed extract (GSE) inhibits advanced human PCA growth and induces apoptosis in cell culture and in nude mice. Accordingly, here we assessed the effect of GSE on constitutive and TNFalpha-induced NF-kappaB DNA binding activity and apoptotic death in advanced human prostate carcinoma DU145 cells. Constitutive and TNFalpha-induced NF-kappaB DNA binding activity was inhibited by GSE at doses > or =50 microg/ml and treatments for > or =12 h. This was accompanied by inhibition of IkappaBalpha phosphorylation and IKKalpha kinase activity. A strong induction of apoptosis (P<0.01) was also observed following GSE treatment, while a combination with TNFalpha strongly potentiated apoptosis induction. Our results indicate the potential of developing GSE as an effective cancer therapeutic agent, both alone and in combination with TNFalpha-based chemotherapy of advanced human prostate carcinoma that might prove to be a more effective and less toxic alternative in clinical therapy of PCA.

  4. Laparoscopic sentinel lymph node (SLN) versus extensive pelvic dissection for clinically localized prostate carcinoma.

    PubMed

    Rousseau, Caroline; Rousseau, Thierry; Bridji, Boumédiène; Pallardy, Amandine; Lacoste, Jacques; Campion, Loïc; Testard, Aude; Aillet, Geneviève; Mouaden, Ayat; Curtet, Chantal; Kraeber-Bodéré, Françoise

    2012-02-01

    Lymph node metastasis is an important prognostic factor in prostate cancer (PC). The aim of this prospective study was to evaluate the accuracy of sentinel lymph node (SLN) biopsy by laparoscopy in staging locoregional patients with clinically localized PC. A transrectal ultrasound-guided injection of 0.3 ml/100 MBq (99m)Tc-sulphur rhenium colloid in each prostatic lobe was performed the day before surgery. Detection was performed intraoperatively with a laparoscopic probe (Gamma Sup CLERAD) followed by extensive resection. SLN counts were performed in vivo and confirmed ex vivo. Histological analysis was performed by haematoxylin-phloxine-saffron staining, followed by immunohistochemistry (IHC) if the SLN was free of metastasis. The study included 93 patients with PC at intermediate or high risk of lymph node metastases. The intraoperative detection rate was 93.5% (87/93). Nineteen patients had lymph node metastases, nine only in SLN. The false-negative rate was 10.5% (2/19). The internal iliac region was the primary metastatic site (43.3%). Metastatic sentinel nodes in the common iliac region beyond the ureteral junction were present in 13.3%. Limited or standard lymph node resection would have ignored 73.2 and 56.6% of lymph node metastases, respectively. Laparoscopy is suitable for broad identification of SLN metastasis, and targeted resection of these lymph nodes significantly limits the risk of extended surgical resection whilst maintaining the accuracy of the information.

  5. Complete remission of metastatic carcinoma of the prostate with bicalutamide withdrawal.

    PubMed

    Kundranda, Madappa N; Muslimani, Alaa; Daw, Hamed A; Spiro, Timothy P

    2007-09-01

    An 83-year-old man was diagnosed with stage 4 prostate cancer with a Gleason score of 7 (3+4). His initial prostate-specific antigen (PSA) level was 965 ng/dL, and he demonstrated extensive metastatic disease of the thoracic spine. After an initial response to monthly leuprolide injections, his PSA level began to increase and bicalutamide was added. An initial decrease in his PSA level was observed; however, the level gradually rose to 212 ng/dL and bicalutamide was discontinued. Three months later, his PSA level was <0.05 ng/dL and has remained <1 ng/dL for the past 27 months. Bicalutamide withdrawal usually leads to transient remission, with PSA level dropping to approximately 50% of the initial level. The duration of the remission is usually limited to approximately 6 months. However, the sustained response that was observed in our patient suggests that a trial of androgen withdrawal, even in the setting of rising PSA levels, might be reasonable before initiating more toxic therapies.

  6. Intensified Adjuvant Treatment of Prostate Carcinoma: Feasibility Analysis of a Phase I/II Trial

    PubMed Central

    Mantini, Giovanna; Fersino, Sergio; Frascino, Vincenzo; Massaccesi, Mariangela; Fionda, Bruno; Luzi, Stefano; Balducci, Mario; De Belvis, Antonio; Morganti, Alessio Giuseppe; Valentini, Vincenzo

    2014-01-01

    Purpose. To perform a preliminary feasibility acute and late toxicity evaluation of an intensified and modulated adjuvant treatment in prostate cancer (PCa) patients after radical prostatectomy. Material and Methods. A phase I/II has been designed. Eligible patients were 79 years old or younger, with an ECOG of 0–2, previously untreated, histologically proven prostate adenocarcinoma with no distant metastases, pT2–4 N0-1, and with at least one of the following risk factors: capsular perforation, positive surgical margins, and seminal vesicle invasion. All patients received a minimum dose on tumor bed of 64.8 Gy, or higher dose (70.2 Gy; 85.4%), according to the pathological stage, pelvic lymph nodes irradiation (57.7%), and/or hormonal therapy (69.1%). Results. 123 patients were enrolled and completed the planned treatment, with good tolerance. Median follow-up was 50.6 months. Grade 3 acute toxicity was only 2.4% and 3.3% for genitourinary (GU) and gastrointestinal (GI) tract, respectively. No patient had late grade 3 GI toxicity, and the GU grade 3 toxicity incidence was 5.8% at 5 years. 5-year BDSF was 90.2%. Conclusions. A modulated and intensified adjuvant treatment in PCa was feasible in this trial. A further period of observation can provide a complete assessment of late toxicity and confirm the BDSF positive results. PMID:25093169

  7. 68Ga-PSMA Uptake in an Incidentally Detected Gastrointestinal Stromal Tumor in a Case of Suspected Carcinoma Prostate.

    PubMed

    Sasikumar, Arun; Joy, Ajith; Pillai, Mra; S, Bindu; Sr, Sudin

    2017-10-01

    A 74-year-old man with suspected prostate cancer and a previously negative transrectal ultrasound-guided prostate biopsy underwent Ga-PSMA PET/CT. Scan showed no abnormal tracer concentration in enlarged prostate gland to suggest prostate cancer. Note was made of an incidentally detected well defined soft tissue lesion in the greater curvature of the stomach with moderate tracer concentration in its intraluminal portion. Biopsy of the lesion revealed gastrointestinal stromal tumor.

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

    PubMed

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

    2007-08-01

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

  9. Amiodarone Induced Hyponatremia Masquerading as Syndrome of Inappropriate Antidiuretic Hormone Secretion by Anaplastic Carcinoma of Prostate

    PubMed Central

    Dutta, Pinaki; Kumar, Santosh; Kakkar, Nandita; Bhansali, Anil; Rotondo, Fabio; Kovacs, Kalman

    2014-01-01

    Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the most common causes of hyponatremia. The usual causes are malignancies, central nervous system, pulmonary disorders, and drugs. Amiodarone is a broad spectrum antiarrhythmic agent widely used in the management of arrhythmias. The different side effects include thyroid dysfunction, visual disturbances, pulmonary infiltrates, ataxia, cardiac conduction abnormalities, drug interactions, corneal microdeposits, skin rashes, and gastrointestinal disturbances. SIADH is a rare but lethal side effect of amiodarone. We describe a 62-year-old male who was suffering from advanced prostatic malignancy, taking amiodarone for underlying heart disease. He developed SIADH which was initially thought to be paraneoplastic in etiology, but later histopathology refuted that. This case emphasizes the importance of detailed drug history and the role of immunohistochemistry in establishing the diagnosis and management of hyponatremia due to SIADH. PMID:24818037

  10. 125I implantation for carcinoma of prostate. Further follow-up of first 100 cases.

    PubMed

    Grossman, H B; Batata, M; Hilaris, B; Whitmore, W F

    1982-12-01

    Analysis of the first 100 patients at the Memorial Sloan-Kettering Cancer Center with Stage B or C prostatic cancer treated by pelvic lymph node dissection and Iodine-125 implantation and endocrine therapy when specifically indicated revealed five-year survival rates of 87 and 77 per cent, respectively. Tumor stage, tumor grade, and lymph node metastasis each correlated with survival, but the latter was the most significant factor. Although routine follow-up biopsies were not performed, local tumor control as judged by serial digital rectal examination defined a prognostically favored group of patients. In the absence of controls, however, whether the latter response indicates a salutary effect of the treatment which produces an improved survival or merely identifies a group of patients who were predetermined to have a more favorable survival is undetermined.

  11. Antiandrogenic mechanisms of pesticides in human LNCaP prostate and H295R adrenocortical carcinoma cells.

    PubMed

    Robitaille, Christina N; Rivest, Patricia; Sanderson, J Thomas

    2015-01-01

    Several pesticides suspected or known to have endocrine disrupting effects were screened for pro- or antiandrogenic properties by determining their effects on proliferation, prostatic-specific antigen (PSA) secretion and androgen receptor (AR) expression, and AR phosphorylation in androgen-dependent LNCaP human prostate cancer cells, as well as on the expression and catalytic activity of the enzyme CYP17 in H295R human adrenocortical carcinoma cells, an in vitro model of steroidogenesis. Effects on SRD5A gene expression were determined in both cell lines. Benomyl, vinclozolin, and prochloraz, but not atrazine, concentration dependently (1-30 μM) decreased dihydrotestosterone (DHT)-stimulated proliferation of LNCaP cells. All pesticides except atrazine decreased DHT-stimulated PSA secretion, AR nuclear accumulation, and AR phosphorylation on serines 81 and 213 in LNCaP cells. Benomyl and prochloraz, but not vinclozolin or atrazine, decreased levels of CYP17 gene and protein expression, as well as catalytic activity in H295R cells. In the case of prochloraz, some of these effects corresponded with cytotoxicity. H295R cells expressed AR protein and SRD5A1, but not SRD5A2 transcripts. SRD5A1 gene expression in H295R cells was increased by 10 nM DHT, whereas in LNCaP cells significant induction was observed by 0.1 nM DHT. AR protein expression in H295R cells was not increased by DHT. Vinclozolin decreased DHT-induced SRD5A1 gene expression in LNCaP, but not H295R cells, indicating a functional difference of AR between the cell lines. In conclusion, pesticides may exert antiandrogenic effects through several mechanisms that are cell type-specific, including AR antagonism and down-regulation or catalytic inhibition of androgen biosynthetic enzymes, such as CYP17 and SRD5A1. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and toxicity studies required for regulatory approval of a phase I clinical trial with 111In-CP04 in medullary thyroid carcinoma patients

    PubMed Central

    Maina, Theodosia; Konijnenberg, Mark W.; KolencPeitl, Petra; Garnuszek, Piotr; Nock, Berthold A.; Kaloudi, Aikaterini; Kroselj, Marko; Zaletel, Katja; Maecke, Helmut; Mansi, Rosalba; Erba, Paola; von Guggenberg, Elisabeth; Hubalewska-Dydejczyk, Alicja; Mikolajczak, Renata; Decristoforo, Clemens

    2016-01-01

    Introduction From a series of radiolabelled cholecystokinin (CCK) and gastrin analogues, 111In-CP04 (111In-DOTA-(DGlu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) was selected for further translation as a diagnostic radiopharmaceutical towards a first-in-man study in patients with medullary thyroid carcinoma (MTC). A freeze-dried kit formulation for multicentre application has been developed. We herein report on biosafety, in vivo stability, biodistribution and dosimetry aspects of 111In-CP04 in animal models, essential for the regulatory approval of the clinical trial. Materials and methods Acute and extended single dose toxicity of CP04 was tested in rodents, while the in vivo stability of 111In-CP04 was assessed by HPLC analysis of mouse blood samples. The biodistribution of 111In-CP04 prepared from a freeze-dried kit was studied in SCID mice bearing double A431-CCK2R(±) xenografts at 1, 4 and 24 h pi. Further 4-h animal groups were either additionally treated with the plasma expander gelofusine or injected with 111In-CP04 prepared by wet-labelling. Pharmacokinetics in healthy mice included the 30 min, 1, 4, 24, 48 and 72 h time points pi. Dosimetric calculations were based on extrapolation of mice data to humans adopting two scaling models. Results CP04 was well-tolerated by both mice and rats, with an LD50 > 178.5 μg/kg body weight for mice and a NOAEL (no-observed-adverse-effect-level) of 89 μg/kg body weight for rats. After labelling, 111In-CP04 remained >70% intact in peripheral mouse blood at 5 min pi. The uptake of 111In-CP04 prepared from the freeze-dried kit and by wet-labelling were comparable in the A431-CCK2R(+)-xenografts (9.24 ± 1.35%ID/g and 8.49 ± 0.39%ID/g, respectively; P > 0.05). Gelofusine-treated mice exhibited significantly reduced kidneys values (1.69 ± 0.15%ID/g vs. 5.55 ± 0.94%ID/g in controls, P < 0.001). Dosimetry data revealed very comparable effective tumour doses for the two scaling models applied, of 0.045 and 0.044 m

  13. Contemporary Gleason Grading of Prostatic Carcinoma: An Update With Discussion on Practical Issues to Implement the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

    PubMed

    Epstein, Jonathan I; Amin, Mahul B; Reuter, Victor E; Humphrey, Peter A

    2017-02-07

    The primary proceedings of the 2014 International Society of Urological Pathology Grading Conference were published promptly in 2015 and dealt with: (1) definition of various grading patterns of usual acinar carcinoma, (2) grading of intraductal carcinoma; and (3) support for the previously proposed new Grade Groups. The current manuscript in addition to highlighting practical issues to implement the 2014 recommendations, provides an updated perspective based on numerous studies published after the 2014 meeting. A major new recommendation that came from the 2014 Consensus Conference was to report percent pattern 4 with Gleason score 7 in both needle biopsies and radical prostatectomy (RP) specimens. This manuscript gives the options how to record percentage pattern 4 and under which situations recording this information may not be necessary. Another consensus from the 2014 meeting was to replace the term tertiary-grade pattern with minor high-grade pattern. Minor high-grade indicates that the term tertiary should not merely be just the third most common pattern but that it should be minor or limited in extent. Although a specific cutoff of 5% was not voted on in the 2014 Consensus meeting, the only quantification of minor high-grade pattern that has been used in the literature with evidence-based data correlating with outcome has been the 5% cutoff. At the 2014 Consensus Conference, there was agreement that the grading rule proposed in the 2005 Consensus Conference on needle biopsies be followed, that tertiary be not used, and that the most common and highest grade patterns be summed together as the Gleason score. Therefore, the term tertiary or minor high-grade pattern should only be used in RP specimens when there are 3 grade patterns, such as with 3+4=7 or 4+3=7 with <5% Gleason pattern 5. It was recommended at the 2014 Conference that for the foreseeable future, the new Grade Groups would be reported along with the Gleason system. The minor high-grade patterns

  14. Role of Early Proctoscopy in Predicting Late Symptomatic Proctitis After External Radiation Therapy for Prostate Carcinoma

    SciTech Connect

    Campostrini, Franco; Musola, Renato; Marchiaro, Giuseppe; Lonardi, Federico; Verlato, Giuseppe

    2013-03-15

    Purpose: To determine whether acute radiation-proctitis, diagnosed by proctoscopy after radiation therapy for prostate cancer, can predict late clinical proctitis. Methods and Materials: A prospective study of 130 patients who underwent external radiation therapy (RT) for stage T1 to T4 prostate cancer between 1997 and 2008 was performed. Treatments were conventional (2-dimensional [2D]) in 61 patients and 3D conformal in 69, with a median target dose of 72 Gy (70-74 Gy). Within 1 week after RT, proctoscopy was performed to detect possible acute endoscopic proctitis (AEP). Acute clinical proctitis (ACP) and late clinical proctitis (LCP) were also evaluated. The median follow-up was 84 months (20-180 months). The influence of AEP and ACP on LCP occurrence was studied using the Cox model controlling for age, dose, prostatectomy, RT technique (2D vs 3D), and hormone therapy. Results: AEP was detected in 15 patients (11.5%) and ACP in 67 (51.5%); in 13 cases (10%) AEP and ACP occurred simultaneously. Thirty-five cases of LCP were recorded. The 5-year probability of developing LCP was highest in patients with AEP and ACP (77%, 95% confidence interval [CI] 53%-94%) and lowest in asymptomatic patients (14%, 95% CI 7%-26%; P<.001). Compared to asymptomatic patients, the 5-year probability also was slightly increased in patients with ACP only (26%, 95% CI 16%-40%; P=.052). In multivariable analysis, the combination of AEP and ACP was the main predictor of LCP: compared to asymptomatic patients, the hazard ratio was 5.6 (2.1-15.2) in patients with AEP plus ACP (P=.001) and 2.1 (0.9-4.9) in those with ACP only (P=.103). Conclusions: In patients with AEP and ACP, the risk of LCP was more than 5-fold increased compared to those who were asymptomatic, while a much smaller increase in risk occurred in patients with ACP only. Early proctoscopy can provide valuable information regarding the likelihood of late proctitis.

  15. Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells

    NASA Technical Reports Server (NTRS)

    Tjandrawinata, R. R.; Dahiya, R.; Hughes-Fulford, M.

    1997-01-01

    Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclooxygenases: COX-1 (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E2 (dmPGE2) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE2 concentration. DmPGE2 also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE2 regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE2 concentration, with maximum stimulation seen at 5 microg ml(-1). The non-steroidal anti-inflammatory drug flurbiprofen (5 microM), in the presence of exogenous dmPGE2, inhibited the up-regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE2 has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE2, perhaps resulting from changes in local cellular PGE2 concentrations.

  16. Argon Plasma Coagulation Therapy Versus Topical Formalin for Intractable Rectal Bleeding and Anorectal Dysfunction After Radiation Therapy for Prostate Carcinoma

    SciTech Connect

    Yeoh, Eric; Tam, William; Schoeman, Mark; Moore, James; Thomas, Michelle; Botten, Rochelle; Di Matteo, Addolorata

    2013-12-01

    Purpose: To evaluate and compare the effect of argon plasma coagulation (APC) and topical formalin for intractable rectal bleeding and anorectal dysfunction associated with chronic radiation proctitis. Methods and Materials: Thirty men (median age, 72 years; range, 49-87 years) with intractable rectal bleeding (defined as ≥1× per week and/or requiring blood transfusions) after radiation therapy for prostate carcinoma were randomized to treatment with APC (n=17) or topical formalin (n=13). Each patient underwent evaluations of (1) anorectal symptoms (validated questionnaires, including modified Late Effects in Normal Tissues–Subjective, Objective, Management, and Analytic and visual analogue scales for rectal bleeding); (2) anorectal motor and sensory function (manometry and graded rectal balloon distension); and (3) anal sphincteric morphology (endoanal ultrasound) before and after the treatment endpoint (defined as reduction in rectal bleeding to 1× per month or better, reduction in visual analogue scales to ≤25 mm, and no longer needing blood transfusions). Results: The treatment endpoint was achieved in 94% of the APC group and 100% of the topical formalin group after a median (range) of 2 (1-5) sessions of either treatment. After a follow-up duration of 111 (29-170) months, only 1 patient in each group needed further treatment. Reductions in rectal compliance and volumes of sensory perception occurred after APC, but no effect on anorectal symptoms other than rectal bleeding was observed. There were no differences between APC and topical formalin for anorectal symptoms and function, nor for anal sphincteric morphology. Conclusions: Argon plasma coagulation and topical formalin had comparable efficacy in the durable control of rectal bleeding associated with chronic radiation proctitis but had no beneficial effect on anorectal dysfunction.

  17. Induction of cyclo-oxygenase-2 mRNA by prostaglandin E2 in human prostatic carcinoma cells

    NASA Technical Reports Server (NTRS)

    Tjandrawinata, R. R.; Dahiya, R.; Hughes-Fulford, M.

    1997-01-01

    Prostaglandins are synthesized from arachidonic acid by the enzyme cyclo-oxygenase. There are two isoforms of cyclooxygenases: COX-1 (a constitutive form) and COX-2 (an inducible form). COX-2 has recently been categorized as an immediate-early gene and is associated with cellular growth and differentiation. The purpose of this study was to investigate the effects of exogenous dimethylprostaglandin E2 (dmPGE2) on prostate cancer cell growth. Results of these experiments demonstrate that administration of dmPGE2 to growing PC-3 cells significantly increased cellular proliferation (as measured by the cell number), total DNA content and endogenous PGE2 concentration. DmPGE2 also increased the steady-state mRNA levels of its own inducible synthesizing enzyme, COX-2, as well as cellular growth to levels similar to those seen with fetal calf serum and phorbol ester. The same results were observed in other human cancer cell types, such as the androgen-dependent LNCaP cells, breast cancer MDA-MB-134 cells and human colorectal carcinoma DiFi cells. In PC-3 cells, the dmPGE2 regulation of the COX-2 mRNA levels was both time dependent, with maximum stimulation seen 2 h after addition, and dose dependent on dmPGE2 concentration, with maximum stimulation seen at 5 microg ml(-1). The non-steroidal anti-inflammatory drug flurbiprofen (5 microM), in the presence of exogenous dmPGE2, inhibited the up-regulation of COX-2 mRNA and PC-3 cell growth. Taken together, these data suggest that PGE2 has a specific role in the maintenance of human cancer cell growth and that the activation of COX-2 expression depends primarily upon newly synthesized PGE2, perhaps resulting from changes in local cellular PGE2 concentrations.

  18. Origin and Properties of Prostatic Stem Cells

    DTIC Science & Technology

    2006-02-01

    treating prostate cancer and benign prostatic hyperplasia . prostate 6 integrin Bcl-2 S tem cell biology and tumorigenesis may be closely linked...In addition to being a source of carcinomas, stem cells may also give rise to benign prostatic hyperplasia (7). The isolation and characterization of...expression may contribute to the etiology of prostatic diseases such as benign prostatic hyperplasia (48), proliferative inflam- matory atrophy, which

  19. Red marrow and blood dosimetry in (131)I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results.

    PubMed

    Giostra, A; Richetta, E; Pasquino, M; Miranti, A; Cutaia, C; Brusasco, G; Pellerito, R E; Stasi, M

    2016-06-07

    Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher (131)I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from (131)I activity in the blood and the dose from (131)I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher (131)I

  20. Red marrow and blood dosimetry in 131I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results

    NASA Astrophysics Data System (ADS)

    Giostra, A.; Richetta, E.; Pasquino, M.; Miranti, A.; Cutaia, C.; Brusasco, G.; Pellerito, R. E.; Stasi, M.

    2016-06-01

    Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be

  1. A universal gene carrier platform for treatment of human prostatic carcinoma by p53 transfection.

    PubMed

    Han, Lu; Zhao, Jing; Liu, Juan; Duan, Xiang-Lin; Li, Lu-Hai; Wei, Xian-Fu; Wei, Yen; Liang, Xing-Jie

    2014-03-01

    Our previous work showed that a charge-reversal layer-by-layer nanosystem, PEI/PAH-Cit/AuNP-CS, effectively facilitates cellular uptake of siRNA and enhances the silencing efficacy of MDR1 siRNA. Here, the plasmid loading capacity of this vehicle was examined using EGFP-N1, and the plasmid release profile was determined in response to pH changes. The cytotoxicity of the EGFP-N1/PEI/PAH-Cit/AuNP-CS complex against HeLa and 293T cells was almost negligible. PEI/PAH-Cit/AuNP-CS efficaciously delivered the plasmids EGFP-N1 (encoding green fluorescent protein) and pGL3.0 (encoding luciferase) into 293T and HeLa cells, thus verifying the universality of PEI/PAH-Cit/AuNP-CS as a gene carrier. The results of an inverted fluorescence microscopy, flow cytometry (FCM) and western blotting methods demonstrated that PC-3 prostate cancer cells treated with EGFP-p53/PEI/PAH-Cit/AuNP-CS expressed higher levels of GFP than cells treated with EGFP-p53/PEI. Furthermore, PC-3 cells treated with EGFP-p53/PEI/PAH-Cit/AuNP-CS showed reduced cellular viability and increased nuclear fragmentation, consistent with elevated p53 expression. Propidium iodide (PI) flow cytometric assays were conducted to demonstrate that EGFP-p53/PEI/PAH-Cit/AuNP-CS elevated the level of apoptosis in PC-3 cells. Western blotting and caspase activation studies revealed that EGFP-p53/PEI/PAH-Cit/AuNP-CS complexes may induce PC-3 apoptosis via the mitochondria-mediated signaling pathway by up-regulation of Bax, down-regulation of Bcl-2, and activation of caspase-3. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Acrylonitrile Butadiene Styrene (ABS) plastic based low cost tissue equivalent phantom for verification dosimetry in IMRT.

    PubMed

    Kumar, Rajesh; Sharma, S D; Deshpande, Sudesh; Ghadi, Yogesh; Shaiju, V S; Amols, H I; Mayya, Y S

    2009-12-17

    A novel IMRT phantom was designed and fabricated using Acrylonitrile Butadiene Styrene (ABS) plastic. Physical properties of ABS plastic related to radiation interaction and dosimetry were compared with commonly available phantom materials for dose measurements in radiotherapy. The ABS IMRT phantom has provisions to hold various types of detectors such as ion chambers, radiographic/radiochromic films, TLDs, MOSFETs, and gel dosimeters. The measurements related to pre-treatment dose verification in IMRT of carcinoma prostate were carried out using ABS and Scanditronics-Wellhoffer RW3 IMRT phantoms for five different cases. Point dose data were acquired using ionization chamber and TLD discs while Gafchromic EBT and radiographic EDR2 films were used for generating 2-D dose distributions. Treatment planning system (TPS) calculated and measured doses in ABS plastic and RW3 IMRT phantom were in agreement within +/-2%. The dose values at a point in a given patient acquired using ABS and RW3 phantoms were found comparable within 1%. Fluence maps and dose distributions of these patients generated by TPS and measured in ABS IMRT phantom were also found comparable both numerically and spatially. This study indicates that ABS plastic IMRT phantom is a tissue equivalent phantom and dosimetrically it is similar to solid/plastic water IMRT phantoms. Though this material is demonstrated for IMRT dose verification but it can be used as a tissue equivalent phantom material for other dosimetry purposes in radiotherapy.

  3. Cytotoxicity of PP(Arg)(2)- and Hp(Arg)(2)-mediated photodynamic therapy and early stage of apoptosis induction in prostate carcinoma in vitro.

    PubMed

    Nowak-Stępniowska, Agata; Wiktorska, Katarzyna; Małecki, Maciej; Romiszewska, Anna; Padzik-Graczyk, Alfreda

    2011-01-01

    Porphyrin photosensitizers tend to localize in mitochondria. The depolarization of mitochondrial membrane is one of the early stages of apoptosis and Laser Scanning Fluorescence Microscopy allows to determine changes in transmembrane mitochondrial potential under influence of PDT depending on the kind of photosensitizer (PP(Arg)(2), Hp(Arg)(2)), the energy dose (5, 10, 30 and 50 J/cm(2)) and time periods (24 and 48 hours after irradiation) in the LNCaP (lymphonodal metastasis of prostate carcinoma, the androgen dependent cell line). Cyototoxicity induced by PP(Arg)(2)- and Hp(Arg)(2)-based PDT depending on energy dose and time after irradiation in prostate carcinoma is determined with MTT. Generally, it was shown that lower energy doses induce greater changes in transmembrane mitochondrial potential. Hp(Arg)(2)-based PDT was more effective causing greater mitochondrial membrane depolarization and cell viability decrease in comparison to PP(Arg)(2)-mediated PDT (in the case of maximal nontoxic photosensitizer doses used).

  4. Urethral dose sparing in squamous cell carcinoma of anal canal using proton therapy matching electrons with prior brachytherapy for prostate cancer: A case study.

    PubMed

    Apinorasethkul, Ontida; Lenards, Nishele; Hunzeker, Ashley

    2016-01-01

    The purpose of this case study is to communicate a technique on treating the re-irradiation of squamous cell carcinoma (SCC) of anal canal with proton fields matched with electron fields to spare prostatic urethra. A 76-year old male presented with a secondary radiation-induced malignancy as a result of prostate brachytherapy seeds irradiation 10 years prior. A rectal examination revealed a bulky tumor at the top of the anal canal involving the left superior-most aspect of the anal canal extending superiorly into the rectum. The inferior extent was palpable approximately 3cm from the anal verge and the superior extent of the mass measured greater than 5cm in the superior-inferior dimension. Chemoradiation was suggested since the patient was opposed to abdominoperineal resection (APR) and colostomy. The use of proton therapy matching with electron fields in the re-irradiation setting could help reduce the complications. A 2 lateral proton beams were designed to treat the bulky tumor volume with 2 electron beams treating the nodal volumes. This complication of treatment fields helped spare the prostatic urethra and reduced the risk of urinary obstruction in the future. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  5. Smoking increased the risk of prostate cancer with grade group ≥ 4 and intraductal carcinoma in a prospective biopsy cohort.

    PubMed

    Tang, Bo; Han, Cheng-Tao; Gan, Hua-Lei; Zhang, Gui-Ming; Zhang, Cui-Zhu; Yang, Wei-Yi; Shen, Ying; Zhu, Yao; Ye, Ding-Wei

    2017-06-01

    To investigate the association between smoking and different prostate cancer (PCa) pathological subtypes incidence in Chinese men. We prospectively included 1795 patients who underwent prostate biopsies in one tertiary center between March 2013 and April 2016. Clinical data and biopsy outcomes were collected. Logistic regression was used to evaluate the association between cigarette smoking and PCa incidence. A total of 737 men, 480 men and 58 men were diagnosed with PCa, high-grade PCa (HGPCa, grade group ≥ 4 as accepted by the 2014 ISUP) and intraductal carcinoma of the prostate (IDC-P), respectively. Current smokers had a significantly higher risk of HGPCa than never smokers (OR = 1.89, 95%CI: 1.44-2.48). No such association was observed for low-grade disease and cigarette smoking (OR = 0.84, 95%CI: 0.61-1.16). In a sub-analysis, men who had smoked longer than 30 years had a higher risk of HGPCa, compared with men who had smoked fewer than 30 years (OR = 1.50, 95%CI: 1.09-2.06). Current smokers were more likely to develop IDC-P than never smokers (OR = 2.29, 95%CI: 1.14-4.59). Among men in this Chinese biopsy cohort, current smoking was associated with highly malignant PCa incidence, such as HGPCa and IDC-P. The duration of smoking may be associated with HGPCa. © 2017 Wiley Periodicals, Inc.

  6. Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison

    SciTech Connect

    Duttenhaver, J.R.; Shipley, W.U.; Perrone, T.; Verhey, L.J.; Goitein, M.; Munzenrider, J.E.; Prout, G.R.; Parkhurst, E.C.; Suit, H.D.

    1983-05-01

    A total of 180 patients with carcinoma of the prostate limited to the pelvis were treated with one of two external beam irradiation techniques between 1972 and 1979. One hundred and sixteen patients were treated with conventional pelvic megavoltage x-ray therapy. Sixty-four patients were treated with combined pelvic x-ray therapy plus a perineal proton beam boost to a carefully defined prostatic tumor volume. A 160 MeV proton beam has been modified to irradiate patients with localized tumors by using conventional treatment schedules. This proton beam has the physical advantage over megavoltage x-rays of reducing the dose to normal tissues adjacent to the tumor volume. By using the proton beam boost we have delivered an increased prostatic tumor dose of 500 to 700 cGy without increasing treatment morbidity at all. The two groups are actuarially analyzed for patient survival, disease-free survival and local recurrence-free survival, and thus far, no significant differences have been noted. Because of the minimal complications observed in the proton group despite a 10% increase in dose, a randomized clinical trial comparing these two treatment techniques is studied.

  7. Prospective validation of an algorithm with systematic sextant biopsy to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma.

    PubMed

    Conrad, Stefan; Graefen, Markus; Pichlmeier, Uwe; Henke, Rolf-Peter; Erbersdobler, Andreas; Hammerer, Peter G; Huland, Hartwig

    2002-02-01

    We prospectively validate an algorithm to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma. A total of 293 patients with prostatic cancer were identified before pelvic lymph node dissection according to an algorithm developed with the classification and regression tree analysis as high-greater than 3 sextant biopsies containing any Gleason grade 4 or 5 cancer, intermediate-at least 1 biopsy dominated by Gleason grade 4 or 5 cancer but not high risk and low risk-all other patients. Observed and predicted frequencies of pelvic lymph node metastasis were compared. The observed frequencies of lymph node metastasis were remarkably similar to the predicted frequencies, including 2.8% versus 2.2% in 85.7% of patients in the low risk group, 16.7% versus 19.4% in 10.2% intermediate and 41.7% versus 45.5% in 4.1% high, respectively. If patients in the low risk group were considered to have node negative disease the specificity and negative predictive value of the algorithm were 88.4% and 97.2%, respectively. Our algorithm is valid as a simple and accurate tool for the prediction of pelvic lymph node metastasis in patients with clinically localized prostatic cancer. Those 85.7% of patients classified by the algorithm to have a low risk of lymphatic spread should not undergo pelvic lymph node dissection before definitive local treatment.

  8. Refining prostate seed brachytherapy: Comparing high-, intermediate-, and low-activity seeds for I-125 permanent seed prostate brachytherapy.

    PubMed

    Delouya, Guila; Bahary, Pascal; Carrier, Jean-François; Larouche, Renée-Xavière; Hervieux, Yannick; Béliveau-Nadeau, Dominic; Donath, David; Taussky, Daniel

    2015-01-01

    To analyze the difference in prostate coverage and dose to the rectum in men with prostate carcinoma treated with permanent seed brachytherapy with different seed activities. Forty-nine patients treated with iodine-125 permanent seed prostate brachytherapy with low-activity seeds of 0.30-0.37 mCi were identified. For each of these patients, 2 patients with similar prostate volume (±2 cc) were paired: one treated with intermediate seed activity (0.44-0.46 mCi) and one with high seed activity (0.60-0.66 mCi). The doses to prostate and rectum were compared using CT on Day 30. A total of 147 patients divided into the three seed activity groups were analyzed. Mean prostate volume was 35.7 cc (standard deviation [SD], 11.70). Compared with low-activity seeds, implants with high-activity seeds consisted of an average of 22 seeds and 4.7 needles less. The dose to the prostate (prostate volume receiving 100% of the prescribed dose [V100], prostate volume receiving 150% of the prescribed dose, and minimal dose covering 90% of the prostate volume expressed in Gy) was not higher on Day 30 (p = 0.58-0.97). The mean volume (in cubic centimeters) of rectal wall receiving 100% of the prescribed dose (V100) increased with activity: low activity, 0.34 cc (SD, 0.49), intermediate activity, 0.47 cc (SD, 0.48), and high activity, 0.72 cc (SD, 0.79) (p = 0.009). There was a trend (p = 0.073) toward a higher frequency of clinically unfavorable rectal dosimetry (V100 > 1.3 cc) in patients with high-activity seeds (16.7%) compared with low-activity (6.3%) or intermediate-activity (4.2%) seeds. High-activity seeds do not result in a higher dose to the prostate but in a higher dose to the rectum. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  9. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions.

    PubMed

    Afshar-Oromieh, Ali; Hetzheim, Henrik; Kratochwil, Clemens; Benesova, Martina; Eder, Matthias; Neels, Oliver C; Eisenhut, Michael; Kübler, Wolfgang; Holland-Letz, Tim; Giesel, Frederik L; Mier, Walter; Kopka, Klaus; Haberkorn, Uwe

    2015-11-01

    PET imaging with the prostate-specific membrane antigen (PSMA)-targeted radioligand (68)Ga-PSMA-11 is regarded as a significant step forward in the diagnosis of prostate cancer (PCa). More recently, a PSMA ligand was developed that can be labeled with (68)Ga, (111)In, (177)Lu, and (90)Y. This ligand, named PSMA-617, therefore enables both diagnosis and therapy of PCa. The aims of this evaluation were to clinically investigate the distribution of (68)Ga-PSMA-617 in normal tissues and in PCa lesions as well as to evaluate the radiation exposure by the radioligand in PET imaging. Nineteen patients, most of them with recurrent PCa, were referred for (68)Ga-PSMA-617 PET/CT. The quantitative assessment of tracer uptake of several organs and of 53 representative tumor lesions was performed in 15 patients at 1 and 3 h after injection. In 4 additional patients, the same procedure was conducted at 5 min, 1 h, 2 h, 3 h, 4 h, and 5 h after injection. On the basis of the data for these 4 patients (mean injected dose, 231 MBq), the radiation exposure of a (68)Ga-PSMA-617 PET/CT was identified. Intense tracer uptake was observed in the kidneys and salivary glands. In 14 of 19 patients (73.7%), at least 1 lesion suspected of being a tumor was detected at 3 h after injection. Of 53 representative tumor lesions selected at 3 h after injection, 47 lesions were visible at 1 h after injection. The mean tumor-to-background ratio for maximum standardized uptake value was 20.4 ± 17.3 (range, 2.3-84.0) at 1 h after injection and 38.2 ± 38.6 (range, 3.6-154.3) at 3 h after injection. The average radiation exposure (effective dose) was approximately 0.021 mSv/MBq. Within healthy organs, the kidneys and salivary glands showed the highest (68)Ga-PSMA-617 uptake. The radiation exposure was relatively low. (68)Ga-PSMA-617 shows PCa lesions with high contrast. Images obtained between 2 and 3 h after injection seem to be the best option with regard to radiotracer uptake and tumor contrast. Later

  10. Prostate Diseases

    MedlinePlus

    ... The Most Common Types of Prostate Diseases Benign prostatic hyperplasia (BPH) Prostatitis Prostate cancer For men over the ... the prostate disease most often encountered is benign prostatic hyperplasia (BPH). If you have BPH, your prostate has ...

  11. Cannabinoid Receptor Type 1 (CB1) Activation Inhibits Small GTPase RhoA Activity and Regulates Motility of Prostate Carcinoma Cells

    PubMed Central

    Gomez-Granados, Ana Doris; Tang, Alan T.; Pfeiffer, Adam W.; Williams, Carol L.; Campbell, William B.

    2012-01-01

    The cannabinoid receptor type 1 (CB1) is a G protein-coupled receptor that is activated in an autocrine fashion by the endocannabinoids (EC), N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG). The CB1 and its endogenous and synthetic agonists are emerging as therapeutic targets in several cancers due to their ability to suppress carcinoma cell invasion and migration. However, the mechanisms that the CB1 regulates cell motility are not well understood. In this study, we examined the molecular mechanisms that diminish cell migration upon the CB1 activation in prostate carcinoma cells. The CB1 activation with the agonist WIN55212 significantly diminishes the small GTPase RhoA activity but modestly increases the Rac1 and Cdc42 activity. The diminished RhoA activity is accompanied by the loss of actin/myosin microfilaments, cell spreading, and cell migration. Interestingly, the CB1 inactivation with the selective CB1 antagonist AM251 significantly increases RhoA activity, enhances microfilament formation and cell spreading, and promotes cell migration. This finding suggests that endogenously produced EC activate the CB1, resulting in chronic repression of RhoA activity and cell migration. Consistent with this possibility, RhoA activity is significantly diminished by the exogenous application of AEA but not by 2-AG in PC-3 cells (cells with very low AEA hydrolysis). Pretreatment of cells with a monoacylglycerol lipase inhibitor, JZL184, which blocks 2-AG hydrolysis, decreases the RhoA activity. These results indicate the unique CB1 signaling and support the model that EC, through their autocrine activation of CB1 and subsequent repression of RhoA activity, suppress migration in prostate carcinoma cells. PMID:22087025

  12. 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.

  13. [Pudendal block or combined spinal-epidural anaesthesia in high-dose-rate brachytherapy for prostate carcinoma?].

    PubMed

    Schenck, M; Kliner, S J; Achilles, M; Schenck, C; Berkovic, K; Ruebben, H; Stuschke, M

    2010-01-01

    In male patients the pudendal block has been applied only in rare cases as a therapy for neuralgia of the pudendal nerve. Up to now there is no comparison of pudendal block with an anaesthesia form close to the spinal cord. In this pilot study the bilateral perineal infiltration of the pudendal nerve was compared to combined spinal-epidural anaesthesia in high-dose-rate (HDR) brachytherapy. In 30 patients (68.8 +/- 5.4 years) who underwent a core needle biopsy for high-risk prostate carcinoma, an HDR brachytherapy in CSE or NPB was carried out. Both anaesthesia forms were examined concerning the perioperative compatibility, the subjective feeling (German school marks principle 1-6), the pain feeling (VAS, 1-10) and the early postoperative course (mobility, complications). Both anaesthesia procedures were offered to all patients. For 2 patients the NPB was favoured primarily, because they had undergone surgery of the lumbal spine, so that the CSE was not applicable. There was no change of anaesthesia form necessary. The expense of time for NPB was 10.5 +/- 2.5 min, for CSE 30.5 +/- 5.5 min (p < 0.005). The hollow needles remained in place on average for 79 +/- 11.7 min (p = 0.23). Inter- and postoperative pain feelings were in both groups between 1.3 +/- 1.1 and 1.1 +/- 1.0 (p = 0.61 and p = 0.29). The difference is not significant. The NPB group considered postoperative mobility as an advantage. All patients felt the bladder catheter as annoying, but the NPB group considered postoperative mobility as more important than complete lack of pain. The subjective feeling in the NPB group was described as 2.06 +/- 0.59 and in the CSE group 2.73 +/- 0.79. This is a significant difference (p < 0.005). No side effects or complications in both anaesthesia forms appeared. The perineal pudendal block is equivalent to epidural anaesthesia in HDR brachytherapy. Concerning the objectifiable pain score measurement and the subjective feeling there are no essential significant

  14. Radiation Dosimetry for (177)Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions.

    PubMed

    Okamoto, Shozo; Thieme, Anne; Allmann, Jakob; D'Alessandria, Calogero; Maurer, Tobias; Retz, Margitta; Tauber, Robert; Heck, Matthias M; Wester, Hans-Juergen; Tamaki, Nagara; Fendler, Wolfgang P; Herrmann, Ken; Pfob, Christian H; Scheidhauer, Klemens; Schwaiger, Markus; Ziegler, Sibylle; Eiber, Matthias

    2017-03-01

    Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using (177)Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBEDCC)] ((68)Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic (68)Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 ± 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 ± 0.21 Gy/GBq for the kidneys; 0.12 ± 0.06 Gy/GBq for the liver; and 0.55 ± 0.14 Gy/GBq for the parotid, 0.64 ± 0.40 Gy/GBq for the submandibular, and 3.8 ± 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 ± 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 ± 2.9 Gy/GBq for the first, 3.3 ± 2.5 Gy/GBq for the second, 2.7 ± 2.3 Gy/GBq for the third, and 2.4 ± 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r = 0.44, P < 0.001 for SUVmax; r = 0.43, P < 0.001 for SUVmean) and moderately correlated with the change of SUV (r = 0.478, P < 0.001 for SUVmax, and r = 0.50, P < 0

  15. The 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System.

    PubMed

    Epstein, Jonathan I; Egevad, Lars; Amin, Mahul B; Delahunt, Brett; Srigley, John R; Humphrey, Peter A

    2016-02-01

    In November, 2014, 65 prostate cancer pathology experts, along with 17 clinicians including urologists, radiation oncologists, and medical oncologists from 19 different countries gathered in a consensus conference to update the grading of prostate cancer, last revised in 2005. The major conclusions were: (1) Cribriform glands should be assigned a Gleason pattern 4, regardless of morphology; (2) Glomeruloid glands should be assigned a Gleason pattern 4, regardless of morphology; (3) Grading of mucinous carcinoma of the prostate should be based on its underlying growth pattern rather than grading them all as pattern 4; and (4) Intraductal carcinoma of the prostate without invasive carcinoma should not be assigned a Gleason grade and a comment as to its invariable association with aggressive prostate cancer should be made. Regarding morphologies of Gleason patterns, there was clear consensus on: (1) Gleason pattern 4 includes cribriform, fused, and poorly formed glands; (2) The term hypernephromatoid cancer should not be used; (3) For a diagnosis of Gleason pattern 4, it needs to be seen at 10x lens magnification; (4) Occasional/seemingly poorly formed or fused glands between well-formed glands is insufficient for a diagnosis of pattern 4; (5) In cases with borderline morphology between Gleason pattern 3 and pattern 4 and crush artifacts, the lower grade should be favored; (6) Branched glands are allowed in Gleason pattern 3; (7) Small solid cylinders represent Gleason pattern 5; (8) Solid medium to large nests with rosette-like spaces should be considered to represent Gleason pattern 5; and (9) Presence of unequivocal comedonecrosis, even if focal is indicative of Gleason pattern 5. It was recognized by both pathologists and clinicians that despite the above changes, there were deficiencies with the Gleason system. The Gleason grading system ranges from 2 to 10, yet 6 is the lowest score currently assigned. When patients are told that they have a Gleason score 6 out

  16. Thin film tritium dosimetry

    DOEpatents

    Moran, Paul R.

    1976-01-01

    The present invention provides a method for tritium dosimetry. A dosimeter comprising a thin film of a material having relatively sensitive RITAC-RITAP dosimetry properties is exposed to radiation from tritium, and after the dosimeter has been removed from the source of the radiation, the low energy electron dose deposited in the thin film is determined by radiation-induced, thermally-activated polarization dosimetry techniques.

  17. Hypericum perforatum methanolic extract inhibits growth of human prostatic carcinoma cell line orthotopically implanted in nude mice.

    PubMed

    Martarelli, D; Martarelli, B; Pediconi, D; Nabissi, M I; Perfumi, M; Pompei, P

    2004-07-08

    The antiproliferative effect of serotonin-reuptake inhibitors (SSRI) and serotonin antagonists has been demonstrated in prostate tumors. Since Hypericum perforatum components act as serotonin-reuptake inhibitors and exert cytotoxic effects on several human cancer cell lines, in this work we analyzed the effect of a treatment with Hypericum perforatum extract (HPE) on the growth of human prostate cancer cells in vitro and in vivo. This study highlighted a significant reduction of tumor growth and number of metastasis suggesting that this natural compound may be useful in the treatment of prostate cancer. Copyright 2004 Elsevier Ireland Ltd.

  18. A Phase 1, Open-Label Study of the Biodistribution, Pharmacokinetics, and Dosimetry of 223Ra-Dichloride in Patients with Hormone-Refractory Prostate Cancer and Skeletal Metastases.

    PubMed

    Chittenden, Sarah J; Hindorf, Cecilia; Parker, Christopher C; Lewington, Valerie J; Pratt, Brenda E; Johnson, Bernadette; Flux, Glenn D

    2015-09-01

    The aim of this single-site, open-label clinical trial was to determine the biodistribution, pharmacokinetics, absorbed doses, and safety from 2 sequential weight-based administrations of (223)Ra-dichloride in patients with bone metastases due to castration-refractory prostate cancer. Six patients received 2 intravenous injections of (223)Ra-dichloride, 6 wk apart, at 100 kBq/kg of whole-body weight. The pharmacokinetics and biodistribution as a function of time were determined, and dosimetry was performed for a range of organs including bone surfaces, red marrow, kidneys, gut, and whole body using scintigraphic imaging; external counting; and blood, fecal, and urine collection. Safety was assessed from adverse events. The injected activity cleared rapidly from blood, with 1.1% remaining at 24 h. The main route of excretion was via the gut, although no significant toxicity was reported. Most of the administered activity was taken up rapidly into bone (61% at 4 h). The range of absorbed doses delivered to the bone surfaces from α emissions was 2,331-13,118 mGy/MBq. The ranges of absorbed doses delivered to the red marrow were 177-994 and 1-5 mGy/MBq from activity on the bone surfaces and from activity in the blood, respectively. No activity-limiting toxicity was observed at these levels of administration. The absorbed doses from the second treatment were correlated significantly with the first for a combination of the whole body, bone surfaces, kidneys, and liver. A wide range of interpatient absorbed doses was delivered to normal organs. Intrapatient absorbed doses were significantly correlated between the 2 administrations for any given patient. The lack of gastrointestinal toxicity is likely due to the low absorbed doses delivered to the gut wall from the gut contents. The lack of adverse myelotoxicity implies that the absorbed dose delivered from the circulating activity may be a more relevant guide to the potential for marrow toxicity than that due to activity

  19. In vivo monitoring of sorafenib therapy effects on experimental prostate carcinomas using dynamic contrast-enhanced MRI and macromolecular contrast media

    PubMed Central

    Schwarz, Bettina; Paprottka, Philipp M.; Sourbron, Steven; von Einem, Jobst C.; Dietrich, Olaf; Hinkel, Rabea; Clevert, Dirk A.; Bruns, Christiane J.; Reiser, Maximilian F.; Nikolaou, Konstantin; Wintersperger, Bernd J.

    2013-01-01

    Abstract Purpose: To investigate dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with macromolecular contrast media (MMCM) to monitor the effects of the multikinase inhibitor sorafenib on subcutaneous prostate carcinomas in rats with immunohistochemical validation. Materials and methods: Copenhagen rats, implanted with prostate carcinoma allografts, were randomized to the treatment group (n = 8) or the control group (n = 8). DCE-MRI with albumin-(Gd-DTPA)35 was performed at baseline and after 1 week using a clinical 3-Tesla system. The treatment group received sorafenib, 10 mg/kg body weight daily. Kinetic analysis yielded quantitative parameters of tumor endothelial permeability–surface area product (PS; ml/100 ml/min) and fractional blood volume (Vb, %). Tumors were harvested on day 7 for immunohistochemical analysis. Results: In sorafenib-treated tumors, PS (0.62 ± 0.20 vs 0.08 ± 0.09 ml/100 ml/min; P < 0.01) and Vb (5.1 ± 1.0 vs 0.56 ± 0.48%; P < 0.01) decreased significantly from day 0 to day 7. PS showed a highly significant inverse correlation with tumor cell apoptosis (TUNEL; r = −0.85, P < 0.001). Good, significant correlations of PS were also observed with tumor cell proliferation (Ki-67; r = 0.67, P < 0.01) and tumor vascularity (RECA-1; r = 0.72, P < 0.01). MRI-assayed fractional blood volume Vb showed a highly significant correlation with tumor vascularity (RECA-1; r = 0.87, P < 0.001) and tumor cell proliferation (Ki-67; r = 0.82, P < 0.01). Conclusion: Results of DCE-MRI with MMCM demonstrated good, significant correlations with the immunohistochemically assessed antiangiogenic, antiproliferative, and proapoptotic effects of a 1-week, daily treatment course of sorafenib on experimental prostate carcinoma allografts. PMID:24380871

  20. Modulation of endogenous β-tubulin isotype expression as a result of human βIII cDNA transfection into prostate carcinoma cells

    PubMed Central

    Ranganathan, S; McCauley, R A; Dexter, D W; Hudes, G R

    2001-01-01

    Increases of individual β tubulin isotypes in antimicrotubule drug resistant cell lines have been reported by several laboratories. We have previously described elevations in βIII and βIVa isotypes in estramustine and paclitaxel resistant human prostate carcinoma cells. To investigate further the function of β tubulin isotypes in antimicrotubule drug response, human prostate carcinoma cells that normally have very low to undetectable levels of βIII were stably transfected with βIII cDNA in pZeoSV system. An 18 bp haemagglutinin (HA) epitope tag was added at the 3′ end prior to cloning into the vector. Cells were transfected with pZeoSV or pZeoSV-βIII plasmids and selected in the presence of Zeocin. Immunofluorescent staining of the transfectant cells have shown significant expression and incorporation of HA-tagged βIII tubulin into cellular microtubules. Quantitation of Western blots revealed the HA-tagged βIII levels to be approximately 7-fold higher than the vector control cells. RT-PCR analysis confirmed the increase at the transcript level and also revealed a collateral increase of βII and βIVb transcripts. Cell viability assays indicated that sensitivity of βIII transfected cells to various antimicrotubule agents was similar to vector transfected cells: IC50 values for estramustine, paclitaxel, colchicine and vinblastine were 4 μM, 4 nM, 22 nM and 2 nM, respectively for both cell lines. Thus, overexpression of βIII isotype in human prostate carcinoma cells by stable transfection failed to confer antimicrotubule drug resistance to these cells. Counterregulatory increases of endogenous βII and βIVb tubulin isotypes in these βIII transfected cells may be a compensatory mechanism used by the cells to overcome the effects of elevated βIII levels on the cellular microtubules. These results highlight the difficulty in isolating the contribution of single tubulin isotypes in drug response studies. © 2001 Cancer Research Campaign http

  1. Dual-Nuclide Radiopharmaceuticals for Positron Emission Tomography Based Dosimetry in Radiotherapy.

    PubMed

    Wurzer, Alexander; Seidl, Christof; Morgenstern, Alfred; Bruchertseifer, Frank; Schwaiger, Markus; Wester, Hans-Jürgen; Notni, Johannes

    2017-08-21

    Improvement of the accuracy of dosimetry in radionuclide therapy has the potential to increase patient safety and therapeutic outcomes. Although positron emission tomography (PET) is ideally suited for acquisition of dosimetric data because PET is inherently quantitative and offers high sensitivity and spatial resolution, it is not directly applicable for this purpose because common therapeutic radionuclides lack the necessary positron emission. This work reports on the synthesis of dual-nuclide labeled radiopharmaceuticals with therapeutic and PET functionality, which are based on common and widely available metal radionuclides. Dual-chelator conjugates, featuring interlinked cyclen- and triazacyclononane-based polyphosphinates DOTPI and TRAP, allow for strictly regioselective complexation of therapeutic (e.g., (177) Lu, (90) Y, or (213) Bi) and PET (e.g., (68) Ga) radiometals in the same molecular framework by exploiting the orthogonal metal ion selectivity of these chelators (DOTPI: large cations, such as lanthanide(III) ions; TRAP: small trivalent ions, such as Ga(III) ). Such DOTPI-TRAP conjugates were decorated with 3 Gly-urea-Lys (KuE) motifs for targeting prostate-specific membrane antigen (PSMA), employing Cu-catalyzed (CuAAC) as well as strain-promoted (SPAAC) click chemistry. These were labeled with (177) Lu or (213) Bi and (68) Ga and used for in vivo imaging of LNCaP (human prostate carcinoma) tumor xenografts in SCID mice by PET, thus proving practical applicability of the concept. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    ClinicalTrials.gov

    2017-06-02

    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

  3. Collecting and Studying Blood and Tissue Samples From Patients With Locally Recurrent or Metastatic Prostate or Bladder/Urothelial Cancer

    ClinicalTrials.gov

    2016-12-06

    Healthy Control; Localized Urothelial Carcinoma of the Renal Pelvis and Ureter; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Urothelial Carcinoma of the Renal Pelvis and Ureter; Recurrent Bladder Carcinoma; Recurrent Prostate Carcinoma; Recurrent Urothelial Carcinoma of the Renal Pelvis and Ureter; Stage IV Bladder Cancer; Stage IV Bladder Urothelial Carcinoma; Stage IV Prostate Cancer

  4. Scanned ion beam therapy for prostate carcinoma: Comparison of single plan treatment and daily plan-adapted treatment.

    PubMed

    Hild, Sebastian; Graeff, Christian; Rucinski, Antoni; Zink, Klemens; Habl, Gregor; Durante, Marco; Herfarth, Klaus; Bert, Christoph

    2016-02-01

    Intensity-modulated particle therapy (IMPT) for tumors showing interfraction motion is a topic of current research. The purpose of this work is to compare three treatment strategies for IMPT to determine potential advantages and disadvantages of ion prostate cancer therapy. Simulations for three treatment strategies, conventional one-plan radiotherapy (ConvRT), image-guided radiotherapy (IGRT), and online adaptive radiotherapy (ART) were performed employing a dataset of 10 prostate cancer patients with six CT scans taken at one week intervals. The simulation results, using a geometric margin concept (7-2 mm) as well as patient-specific internal target volume definitions for IMPT were analyzed by target coverage and exposure of critical structures on single fraction dose distributions. All strategies led to clinically acceptable target coverage in patients exhibiting small prostate motion (mean displacement <4 mm), but IGRT and especially ART led to significant sparing of the rectum. In 20% of the patients, prostate motion exceeded 4 mm causing insufficient target coverage for ConvRT (V95mean = 0.86, range 0.63-0.99) and IGRT (V95mean = 0.91, range 0.68-1.00), while ART maintained acceptable target coverage. IMPT of prostate cancer demands consideration of rectal sparing and adaptive treatment replanning for patients exhibiting large prostate motion.

  5. Prophylactic tamsulosin (Flomax) in patients undergoing prostate {sup 125}I brachytherapy for prostate carcinoma: Final report of a double-blind placebo-controlled randomized study

    SciTech Connect

    Elshaikh, Mohamed A.; Ulchaker, James C.; Reddy, Chandana A.; Angermeier, Kenneth W.; Klein, Eric A.; Chehade, Nabil; Altman, Andrew; Ciezki, Jay P. . E-mail: ciezkj@ccf.org

    2005-05-01

    Purpose: To evaluate the effectiveness of prophylactic tamsulosin (Flomax) in reducing the urinary symptoms in patients undergoing {sup 125}I prostate implantation (PI) for prostate adenocarcinoma. Methods and materials: This is a single-institution, double-blind, placebo-controlled, randomized trial for patients undergoing PI for prostate adenocarcinoma comparing prophylactic tamsulosin versus placebo. Eligibility criteria included patients not taking tamsulosin or other {alpha}-blockers treated with PI. The patients were randomly assigned to either tamsulosin (0.8 mg, orally once a day) or matched placebo. All patients started the medication 4 days before PI and continued for 60 days. The American Urologic Association (AUA) symptom index questionnaire was used to assess urinary symptoms. The AUA questionnaire was administered before PI for a baseline score and weekly for 8 weeks after PI. Patients were taken off the study if they developed urinary retention, had intolerable urinary symptoms, or wished to discontinue with the trial. Results: One hundred twenty-six patients were enrolled in this study from November 2001 to January 2003 (118 were evaluable: 58 in the tamsulosin arm and 60 in the placebo group). Pretreatment and treatment characteristics were comparably matched between the two groups. The urinary retention rate was 17% (10 patients) in the placebo group compared with 10% (6 patients) in the tamsulosin group (p = 0.3161). Eighty-eight percent (14 patients) of those who developed urinary retention experienced it within 2 weeks after the PI. Intolerable urinary symptoms were reported equally (10 patients in each group) with 70% occurring in the first 2 weeks after PI. There was a significant difference in mean AUA score in favor of tamsulosin at Week 5 after PI (p = 0.03). Conclusions: Prophylactic tamsulosin (0.8 mg/day) before prostate brachytherapy did not significantly affect urinary retention rates, but had a positive effect on urinary morbidity at

  6. REVIEW OF DOSIMETRY FIELD

    DTIC Science & Technology

    three, oxalic acid , polyisobutylene, and Mylar film, seem sufficiently promising to warrant further development. Their current states of development...ceric sulfate dosimeters be included in the dosimetry handbook, but that additional work should be done on oxalic acid , polyisobutylene, and Mylar as dosimetry materials. (Author)

  7. Changes of the transverse diameter and volume and dosimetry before the 25th fraction during the course of intensity-modulated radiation therapy (IMRT) for patients with nasopharyngeal carcinoma

    SciTech Connect

    Yang Haihua; Hu Wei; Ding Weijun; Shan Guoping; Wang Wei; Yu Changhui; Wang Biyun; Shao Minghai; Wang Jianhua; Yang Weifang

    2012-07-01

    To quantify changes of the transverse diameter and volume and dosimetry, and to illustrate the inferiority of non-replanning during intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) patients. Fifty-three NPC patients who received IMRT in 33 fractions were enrolled in this prospective trial. Before the 25th fraction, a new simulation computed tomography (CT) scan was acquired for all patients. The dose-volume histograms of the phantom plan were compared with the initial plan. Significant reduction of the transverse diameter of the nasopharyngeal, the neck, and 2 parotid glands volume was observed on second CT compared with the first CT (mean reduction 7.48 {+-} 4.45 mm, 6.80 {+-} 15.14 mm, 5.70 {+-} 6.26 mL, and 5.04 {+-} 5.85 mL, respectively; p < 0.01). The maximum dose and V-40 of the spinal cord, mean dose, and V30 of the left and right parotid, and V-50 of the brain stem were increased significantly in the phantom plan compared with the initial plan (mean increase 4.75 {+-} 5.55 Gy, 7.18 {+-} 10.07%, 4.51 {+-} 8.55 Gy, 6.59 {+-} 17.82%, 5.33 {+-} 8.55 Gy, 11.68 {+-} 17.11% and 1.48 {+-} 3.67%, respectively; p < 0.01). On the basis of dose constraint criterion in the RTOG0225 protocol, the dose of the normal critical structures for 52.83% (28/53) of the phantom plans were out of limit compared with 1.89% (1/53) of the initial plans (p < 0.0001). Because of the significant change in anatomy and dose before the 25th fraction during IMRT, replanning should be necessary during IMRT with NPC.

  8. Role of imaging and biopsy to assess local recurrence after definitive treatment for prostate carcinoma (surgery, radiotherapy, cryotherapy, HIFU).

    PubMed

    Martino, Pasquale; Scattoni, Vincenzo; Galosi, Andrea B; Consonni, Paolo; Trombetta, Carlo; Palazzo, Silvano; Maccagnano, Carmen; Liguori, Giovanni; Valentino, Massimo; Battaglia, Michele; Barozzi, Libero

    2011-10-01

    Defining the site of recurrent disease early after definitive treatment for a localized prostate cancer is a critical issue as it may greatly influence the subsequent therapeutic strategy or patient management. A systematic review of the literature was performed by searching Medline from January 1995 up to January 2011. Electronic searches were limited to the English language, and the keywords prostate cancer, radiotherapy [RT], high intensity focused ultrasound [HIFU], cryotherapy [CRIO], transrectal ultrasound [TRUS], magnetic resonance [MRI], PET/TC, and prostate biopsy were used. Despite the fact that diagnosis of a local recurrence is based on PSA values and kinetics, imaging by means of different techniques may be a prerequisite for effective disease management. Unfortunately, prostate cancer local recurrences are very difficult to detect by TRUS and conventional imaging that have shown limited accuracy at least at early stages. On the contrary, functional and molecular imaging such as dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), offers the possibility of imaging molecular or cellular processes of individual tumors. Recently, PET/CT, using 11C-choline, 18F-fluorocholine or 11C-acetate has been successfully proposed in detecting local recurrences as well as distant metastases. Nevertheless, in controversial cases, it is necessary to perform a biopsy of the prostatic fossa or a biopsy of the prostate to assess the presence of a local recurrence under guidance of MRI or TRUS findings. It is likely that imaging will be extensively used in the future to detect and localize prostate cancer local recurrences before salvage treatment.

  9. Magnolol suppresses metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in PC-3 human prostate carcinoma cells.

    PubMed

    Hwang, Eun-Sun; Park, Kwang-Kyun

    2010-01-01

    Magnolol, a hydroxylated biphenyl compound isolated from the root and stem bark of Magnolia officinalis, has been reported to have anticancer activity, but little is known about its molecular mechanisms of action. Increased expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, has been identified in many cancer types. Matrix metalloproteinases (MMPs) are enzymes involved in various steps of metastasis development. The objective of this study was to study the effects of magnolol on cancer invasion and metastasis using PC-3 human prostate carcinoma cells. Cellular proliferation was determined by MTT colorimetric assay. Magnolol inhibited cell growth in a dose-dependent manner. In an invasion assay conducted in Transwell chambers, magnolol showed 33 and 98% inhibition of cancer cell at 10 microM and 20 microM concentrations, respectively, compared to the control. The expression of MMP-2/-9 and COX-1/-2 was assessed by gelatin zymography and Western blot respectively. The protein and mRNA levels of both MMP-2 and MMP-9 were down-regulated by magnolol treatment in a dose-dependent manner. These results demonstrate the antimetastatic properties of magnolol in inhibiting the adhesion, invasion, and migration of PC-3 human prostate cancer cells.

  10. Autoregulated expression of p53 from an adenoviral vector confers superior tumor inhibition in a model of prostate carcinoma gene therapy.

    PubMed

    Tamura, Rodrigo Esaki; da Silva Soares, Rafael Bento; Costanzi-Strauss, Eugenia; Strauss, Bryan E

    2016-12-01

    Alternative treatments for cancer using gene therapy approaches have shown promising results and some have even reached the marketplace. Even so, additional improvements are needed, such as employing a strategically chosen promoter to drive expression of the transgene in the target cell. Previously, we described viral vectors where high-level transgene expression was achieved using a p53-responsive promoter. Here we present an adenoviral vector (AdPGp53) where p53 is employed to regulate its own expression and which outperforms a traditional vector when tested in a model of gene therapy for prostate cancer. The functionality of AdPGp53 and AdCMVp53 were compared in human prostate carcinoma cell lines. AdPGp53 conferred greatly enhanced levels of p53 protein and induction of the p53 target gene, p21, as well as superior cell killing by a mechanism consistent with apoptosis. DU145 cells were susceptible to induction of death with AdPGp53, yet PC3 cells were quite resistant. Though AdCMVp53 was shown to be reliable, extremely high-level expression of p53 offered by AdPGp53 was necessary for tumor suppressor activity in PC3 and DU145. In situ gene therapy experiments revealed tumor inhibition and increased overall survival in response to AdPGp53, but not AdCMVp53. Upon histologic examination, only AdPGp53 treatment was correlated with the detection of both p53 and TUNEL-positive cells. This study points to the importance of improved vector performance for gene therapy of prostate cancer.

  11. Molecular dosimetry of aflatoxin exposure: contribution to understanding the multifactorial etiopathogenesis of primary hepatocellular carcinoma with particular reference to hepatitis B virus.

    PubMed Central

    Wild, C P; Jansen, L A; Cova, L; Montesano, R

    1993-01-01

    Aflatoxin exposure and hepatitis B virus infection have been implicated as major risk factors for primary hepatocellular carcinoma (PHC) in high-incidence regions of the world. Investigations using the assay of aflatoxin bound to peripheral blood albumin have shown that exposure can occur throughout the life span of the individual, including during the perinatal period, in high-incidence areas such as The Gambia, Senegal, Kenya, and The People's Republic of China. The possibility of measuring aflatoxin exposure at the individual level permits an investigation of the putative mechanisms of interaction of this carcinogen with HBV in the etiopathogenesis of PHC. Animal models, e.g., Pekin duck and HBV-transgenic mice, have also been used to study these questions, and the available data are reviewed. PMID:8391433

  12. Nucleolar organizer regions: preliminary results of the clinical use of a new marker for prostatic carcinoma (40 cases).

    PubMed

    Marandola, P; Lardennois, B; Ploton, D; Derenzini, M; Treré, D; Campo, B; Corrada, P; Valentino, V; Roggia, A; Broggini, P

    1992-01-01

    It is a widely diffused opinion that moving backwards in time the moment of the diagnosis of cancer of prostate, so that the tumor is detected earlier than normal, means that the treatment would be more effective than the one adopted in the usual times of diagnosis. For this reason the earlier diagnosis of prostate cancer has become more and more a compulsory target of the modern urologist, at a time of booming of the third age, of increased lifetime expectancy, of significant elevation of prostate cancer rate and of the persistent uncertainty of the efficacy of available treatments. Theoretically the mortality rate of prostate cancer can be reduced by the prevention programs and by the improvements of treatment methods, but the 'earlier' diagnosis is certainly an easier and less expensive strategy to achieve the same objective. The authors have evaluated the argyrophilic-nucleolar organizer region (Ag-NOR) proteins on 40 cases of adenocarcinoma of prostate collected through a multicentric program in France and in Italy. The Ag-NOR have been stained with silver technique set up by Ploton and Derenzini while the quantitative index has been evaluated by a semiautomatic system partially commercially available, partially modified by the authors. The conclusions: (a) the Ag-NOR index is a simple and reproducible method; (b) the Ag-NOR staging system corresponds to Gleason's grading; (c) the Ag-NOR elevation is a reliable marker of increased cell proliferation and is detectable much earlier than the morphologic changes of Gleason's classification.

  13. Cadmium Levels in Tissue and Plasma as a Risk Factor for Prostate Carcinoma: a Meta-Analysis.

    PubMed

    Zhang, Liang; Zhu, Yi; Hao, Rui; Shao, Mengmeng; Luo, Yunbo

    2016-07-01

    Cadmium is a heavy metal that has been suggested to be a carcinogen by evidence. A number of published studies have investigated the association between cadmium levels and prostate cancer, but the results were inconsistent. Thus, we conducted a meta-analysis to get a precise estimate of this subject. After a careful searching and screening, a total of 11 publications containing 14 separated studies were included. Based on a random-effect model, the pooled data showed that cadmium levels of prostate tissues (standard mean difference (SMD) = 3.17, 95 % confidence interval (CI) = 0.60-5.74, P < 0.05) and plasma (SMD = 4.07, 95 % CI = 2.01-6.13, P < 0.05) were significantly higher in prostate cancer patients than those in the healthy controls. No difference of hair and nail cadmium levels between the prostate cancer cases and the controls was found. The data suggested that cadmium exposure might exert an influence on the tumorigenesis of prostate tissues. Future investigations with large sample sizes are needed to verify the results.

  14. Inositol Hexaphosphate Inhibits Growth and Induces G1 Arrest and Apoptotic Death of Androgen-Dependent Human Prostate Carcinoma LNCaP Cells1

    PubMed Central

    Agarwal, Chapla; Dhanalakshmi, Sivanandhan; Singh, Rana P; Agarwal, Rajesh

    2004-01-01

    Abstract Prostate cancer (PCA) is the most common invasive malignancy and the second leading cause of cancer-related deaths in the US male population. One approach to control this malignancy is its preventive intervention by dietary agents. Inositol hexaphosphate (IP6), a dietary constituent, has shown promising efficacy against various cancers; however, limited studies have been performed with IP6 against PCA. Here, we investigated the growth-inhibitory effect and associated mechanisms of IP6 in androgen-dependent human prostate carcinoma LNCaP cells. IP6 treatment of cells resulted in a strong growth inhibition and an increase in G1 cell population. In mechanistic studies, IP6 resulted in an increase in cyclin-dependent kinase inhibitors (CDKIs) Cip1/p21 and Kip1/p27 levels, together with a decrease in cyclin-dependent kinase (CDK) 4 and cyclin D1 protein levels. An increase in CDKI levels by IP6 also led to a concomitant increase in their interactions with CDK2 and CDK4, together with a strong decrease in the kinase activity of both CDKs. Downstream in CDKI-CDK-cyclin cascade, consistent with its inhibitory effect on CDK kinase activity, IP6 treatment of cells increased hypophosphorylated levels of retinoblastoma (Rb) with a decrease in Rb phosphorylation at serine 780, 807, and 811 sites, and caused a moderate to strong decrease in the levels of transcription factors E2F1, E2F4, and E2F5. In other studies, IP6 caused a dose- and a time-dependent apoptotic death of LNCaP cells, and a decrease in Bcl2 levels, causing a strong increase in Bax versus Bcl2 ratio, as well as an inhibition of constitutively active AKT phosphorylation. Taken together, these molecular alterations provide an insight into IP6-caused growth inhibition, G1 arrest, and apoptotic death of human prostate carcinoma LNCaP cells. Because early clinical PCA growth is an androgen-dependent response, the results of the present study employing androgen-dependent LNCaP cells suggest that IP6 has

  15. The Influence of Prostate Volume on Outcome After High-Dose-Rate Brachytherapy Alone for Localized Prostate Cancer

    SciTech Connect

    Le, Hien Rojas, Ana; Alonzi, Roberto; Hughes, Robert; Ostler, Peter; Lowe, Gerry; Bryant, Linda; Hoskin, Peter

    2013-10-01

    Objective: To determine whether late genitourinary toxicity, biochemical control of prostate cancer, and dosimetric parameters in patients with large prostate glands is different from those variables in men with smaller glands after treatment with high-dose-rate brachytherapy alone (HDR-BT). Methods: From November 2003 to July 2009, 164 patients with locally advanced prostate carcinoma were sequentially enrolled and treated with 34 or 36 Gy in 4 fractions and 31.5 Gy in 3 fractions of {sup 192}Ir HDR-BT alone. The median follow-up time was 71 months. Gland size was not considered in the selection criteria for this study. Estimates of freedom from biochemical relapse (FFbR) and late morbidity, stratified by median clinical target volume (CTV), were obtained, and differences were compared. Results: The median CTV volume was 60 cc (range, 15-208 cc). Dose–volume parameters D90 and V100 (ie, minimum dose to 90% of the prostate volume and volume receiving 100% of the prescribed isodose) achieved in patients with glands ≥60 cc were not significantly different from those with glands <60 cc (P≥.2). Nonetheless, biochemical control in patients with larger CTV was significantly higher (91% vs 78% at 6 years; P=.004). In univariate and multivariate analysis, CTV was a significant predictor for risk of biochemical relapse. This was not at the expense of an increase in either moderate (P=.6) or severe (P=.3) late genitourinary toxicity. The use of hormonal therapy was 17% lower in the large gland group (P=.01). Conclusions: Prostate gland size does not affect dosimetric parameters in HDR-BT assessed by D90 and V100. In patients with larger glands, a significantly higher biochemical control of disease was observed, with no difference in late toxicity. This improvement cannot be attributed to differences in dosimetry. Gland size should not be considered in the selection of patients for HDR-BT.

  16. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    SciTech Connect

    Luna, J. A.; Rojas, J. I.

    2016-07-07

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  17. Evaluation of volume change in rectum and bladder during application of image-guided radiotherapy for prostate carcinoma

    NASA Astrophysics Data System (ADS)

    Luna, J. A.; Rojas, J. I.

    2016-07-01

    All prostate cancer patients from Centro Médico Radioterapia Siglo XXI receive Volumetric Modulated Arc Therapy (VMAT). This therapy uses image-guided radiotherapy (IGRT) with the Cone Beam Computed Tomography (CBCT). This study compares the planned dose in the reference CT image against the delivered dose recalculate in the CBCT image. The purpose of this study is to evaluate the anatomic changes and related dosimetric effect based on weekly CBCT directly for patients with prostate cancer undergoing volumetric modulated arc therapy (VMAT) treatment. The collected data were analyzed using one-way ANOVA.

  18. Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

    PubMed Central

    Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

    2016-01-01

    Summary Introduction Osteoporosis is a complication of androgen deprivation therapy (ADT) in men with prostate carcinoma. The best defense against osteoporosis in prostate cancer is to identify patients with a high risk for fracture during the first clinical visit, select an effective anti-osteoporosis agent, and advise the patient to change his lifestyle and diet to prevent further bone loss. New agents include denosumab, a human monoclonal antibody that inhibits the RANK ligand (RANKL). RANKL promotes the formation, activity, and survival of osteoclasts and, thus, supports the breakdown of bone. Purpose This is a multicenter, randomized, double-blind prospective study on use of denosumab versus alendronate in the therapy of secondary osteoporosis related to ADT in prostate cancer patients in three European countries (Italy, France, Switzerland). Patients and methods In this 24-month observation study we enrolled 234 patients with diagnosis of osteoporosis underwent ADT for prostate cancer. All patients aged ≥55 years and had a dual-energy X-ray absorptiometry (DEXA) T-score <−1.0 (hip or spine, measured within last 2 years) and ≥ 1 fragility fracture. Patients were randomly assigned 1:1 to receive denosumab 60 mg subcutaneously every 6 months or alendronate (70 mg weekly) for 2 years. All patient received supplemental vitamin D (600 IU per day) and supplemental calcium to maintain a calcium intake of 1200 mg per day. Effectiveness of therapy in both groups (denosumab group and alendronate group) was assessed by changes in bone turnover markers (BTMs), Bone Mineral Density (BMD), fracture incidence, Visual Analogue Scale (VAS) score for back pain, and Short Form-8 (SF-8TM) health survey score for health-related quality of life (HRQoL). Percent changes from baseline in BTMs and BMD were assessed using the paired t test; a P-value 0.05). Mean changes in BMD at final follow-up differed significantly between two groups. BMD changes at the lumbar spine at 24

  19. Internal dosimetry - a review.

    SciTech Connect

    Potter, Charles Augustus

    2004-06-01

    The field history and current status of internal dosimetry is reviewed in this article. Elements of the field that are reviewed include standards and models, derivation of dose coefficients and intake retention fractions, bioassay measurements, and intake and dose calculations. In addition, guidance is developed and provided as to the necessity of internal dosimetry for a particular facility or operation and methodology for implementing a program. A discussion of the purposes of internal dosimetry is included as well as recommendations for future development and direction.

  20. Internal dosimetry: a review.

    PubMed

    Potter, Charles A

    2005-06-01

    The field history and current status of internal dosimetry is reviewed in this article. Elements of the field that are reviewed include standards and models, derivation of dose coefficients and intake retention fractions, bioassay measurements, and intake and dose calculations. In addition, guidance is developed and provided as to the necessity of internal dosimetry for a particular facility or operation and methodology for implementing a program. A discussion of the purposes of internal dosimetry is included as well as recommendations for future development and direction.

  1. Robotic brachytherapy of the prostate.

    PubMed

    Wilson, Kyle J

    2009-01-01

    Recent applications of robotics in the field of prostate brachytherapy are seeding the future and could potentially lead to a fully automated prostate brachytherapy surgery. Currently, a typical prostate brachytherapy surgery involves the implantation of upwards of 100 radioactive I-125 seeds by a surgeon. This review supplies background information on prostate biology, brachytherapy of the prostate, robotic brachytherapy, and transrectal ultrasound. Subsequently, it examines the physics involved in ultrasound, radiation from an I-125 source, dosimetry, and robotics. A current semi-automated robotic brachytherapy system is examined in detail and a discussion on future improvements is outlined. Finally, future work to improve prostate brachytherapy is postulated, most notably, phantom optimization using polyvinyl alcohol cryogel. The future of robotic brachytherapy lies in the advent of more sophisticated robotics. This review will give the reader a superior understanding of brachytherapy and its recent robotic advancements. Hopefully, this review will generate new ideas needed to advance prostate brachytherapy procedures leading to more accurate dosimetry, faster procedure time, less ionizing radiation received by surgery staff, more rapid patient recovery, and an overall safer procedure.

  2. Chemotherapy-Induced Monoamine Oxidase Expression in Prostate Carcinoma Functions as a Cytoprotective Resistance Enzyme and Associates with Clinical Outcomes

    PubMed Central

    Huang, Chung-Ying; Harris, William P.; Sim, Hong Gee; Lucas, Jared M.; Coleman, Ilsa; Higano, Celestia S.; Gulati, Roman; True, Lawrence D.; Vessella, Robert; Lange, Paul H.; Garzotto, Mark; Beer, Tomasz M.; Nelson, Peter S.

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes. PMID:25198178

  3. Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes.

    PubMed

    Gordon, Ryan R; Wu, Mengchu; Huang, Chung-Ying; Harris, William P; Sim, Hong Gee; Lucas, Jared M; Coleman, Ilsa; Higano, Celestia S; Gulati, Roman; True, Lawrence D; Vessella, Robert; Lange, Paul H; Garzotto, Mark; Beer, Tomasz M; Nelson, Peter S

    2014-01-01

    To identify molecular alterations in prostate cancers associating with relapse following neoadjuvant chemotherapy and radical prostatectomy patients with high-risk localized prostate cancer were enrolled into a phase I-II clinical trial of neoadjuvant chemotherapy with docetaxel and mitoxantrone followed by prostatectomy. Pre-treatment prostate tissue was acquired by needle biopsy and post-treatment tissue was acquired by prostatectomy. Prostate cancer gene expression measurements were determined in 31 patients who completed 4 cycles of neoadjuvant chemotherapy. We identified 141 genes with significant transcript level alterations following chemotherapy that associated with subsequent biochemical relapse. This group included the transcript encoding monoamine oxidase A (MAOA). In vitro, cytotoxic chemotherapy induced the expression of MAOA and elevated MAOA levels enhanced cell survival following docetaxel exposure. MAOA activity increased the levels of reactive oxygen species and increased the expression and nuclear translocation of HIF1α. The suppression of MAOA activity using the irreversible inhibitor clorgyline augmented the apoptotic responses induced by docetaxel. In summary, we determined that the expression of MAOA is induced by exposure to cytotoxic chemotherapy, increases HIF1α, and contributes to docetaxel resistance. As MAOA inhibitors have been approved for human use, regimens combining MAOA inhibitors with docetaxel may improve clinical outcomes.

  4. Clinicopathological Overview of Granulomatous Prostatitis: An Appraisal

    PubMed Central

    Dravid, Nandkumar; Nikumbh, Dhiraj; Patil, Ashish; Nagappa, Karibasappa Gundabaktha

    2016-01-01

    Introduction Granulomatous prostatitis is a rare inflammatory condition of the prostate. Granulomatous prostatitis is important because, it mimics prostatic carcinoma clinically and hence the diagnosis can be made only by histopathological examination. Aim To study the histomorphological features and to know the prevalence of granulomatous prostatitis. Materials and Methods Histopathological records of 1,203 prostatic specimens received in the Department of the Pathology over a period of five years (June 2009 – June 2014). Seventeen cases of histopathologically, diagnosed granulomatous prostatitis were retrieved and reterospective data was collected from the patient’s records. Results Out of 17 cases of granulomatous prostatitis, we encountered 9 cases of non-specific granulomatous prostatitis, 5 cases of xanthogranulomatous prostatitis and 3 cases of specific tubercular prostatitis. The common age ranged from 51-75 years (mean 63 years) with mean PSA level of 15.8ng/ml. Six patients showed focal hypoechoic areas on TRUS and 11 cases revealed hard and fixed nodule on DRE. Conclusion Non-specific granulomatous prostatitis is the most common type of granulomatous prostatitis. There is no specific pattern of clinical, biochemical and ultrasound findings that allows the diagnosis of granulomatous prostatitis or differentiates it from prostatic carcinoma. Hence, histomorphological diagnosis is the gold standard in differentiating various prostatic lesions. PMID:27014642

  5. Complimentary role of FDG-PET imaging and skeletal scintigraphy in the evaluation of patients of prostate carcinoma.

    PubMed

    Tiwari, B P; Jangra, S; Nair, N; Tongaonkar, H B; Basu, S

    2010-01-01

    Prostate cancer is one of the most common malignancies of elderly males. Management depends on the accurate estimation of disease both at initial diagnosis and in its subsequent course. In the present study, we evaluated the diagnostic utility of positron emission tomography with 18 F-fluorodeoxyglucose (FDG-PET) in patients having prostate cancer. The findings were compared with the results of bone scan (BS) for the detection of bone metastases. Sixteen patients (age range, 55-83 years) with confirmed diagnosis of prostate cancer were included in the prospective study. Three patients had undergone bilateral orchidectomy, 1 had hormonal therapy, 9 had undergone both, and 3 had no therapy. All the patients underwent wholebody BS and FDG-PET within 1 week. Interpretation of BS and FDG-PET were performed qualitatively. Osseous abnormalities detected by both methods were compared. Involvement of the disease in other sites as seen on FDG-PET was also noted. BS detected 197 osseous lesions, whereas FDG-PET could detect 97 (49%) bone lesions. However, in 3 patients without any prior therapeutic intervention, FDG-PET results were superior or equivalent to that of BS. FDG-PET also detected extensive involvement of the disease in the bone marrow in 4 patients, lymph node metastases at various sites in 8, liver metastases in 2, and lung metastases in 1 patient. FDG-PET could demonstrate less number of osseous metastases in comparison with BSs, but the results have to be interpreted in the background of prior treatment administered and the tumor biology of the lesion. It is evident that FDG-PET could detect the unknown soft tissue involvement of the disease with good sensitivity, which might play an important role in the management of prostate cancer. Overall, in the absence of novel PET tracers, both skeletal scintigraphy and FDG-PET imaging can play a complimentary role in the management of prostate cancer.

  6. SU-E-T-112: Dose Distribution of Praseodymium-142 Microspheres in Microcapillary Using Radiochromic Film Dosimetry and Applications in Hepatocellular Carcinoma Microsphere Brachytherapy

    SciTech Connect

    Ferreira, M; Rasmussen, K; Jung, J

    2014-06-01

    Purpose: This work verified simulations of beta-minus emitter Praseodymium-142 (Pr-142) for microsphere brachytherapy by performing absolute dose measurements for Pr 142 microspheres in a microcapillary as a simplified model for a single blood vessel for the treatment of Hepatocellular Carcinoma (HCC). Methods: Pr-142 microspheres (mass: 0.169g, average diameter: 29.7±3.9μm) were activated by thermal neutron activation at the University of Missouri Research Reactor. Experimental setup consisted of a microsphere solution (initial activity 36.6mCi in 0.1ml of sterile water) within a glass microcapillary (internal and external diameter: 305μm and 453μm, respectively) placed for 51h in a custom made Gammex Solid Water™ phantom. GAFCHROMIC™ EBT2 film calibrated with a 6MeV electron beam was used to access the dose fall-off of microspheres. The microcapillary was modeled in MCNPX2.6 in order to compare with experiments. Results: The radial dose fall-off on the transverse plane due to scatter and attenuation in the solid water phantom was analyzed using ImageJ for both film and MCNPX2.6 simulations. Isodose analysis showed close agreement among the methods used, i.e. measurements and simulations agree within 3.9% for doses below 1600cGy. Experimental and simulated doses obtained at 0.5 cm radially from the source were 1547cGy and 1610cGy respectively. Discrepancies for points close to the microcapillary surface were observed between MCNPX2.6 and measurements due to film saturation for high doses. Dose due to Pr-142 3.7% gamma emission was below the threshold of detection for the film. Conclusion: A detailed dosimetric study was performed for Pr-142 glass microspheres within a single microcapillary. MCNPX2.6 simulations were verified by means of direct measurement. Based on these results, Pr-142 appears to be a viable choice of radionuclide for treating HCC.

  7. Intra-Operative Dosimetry in Prostate Brachytherapy

    DTIC Science & Technology

    2006-11-01

    instrumentation and does not interfere with the workspace. 1 Introduction C-arm fluoroscopy is ubiquitous in general surgery , interventional radiology...toward computational fluoroscopy guidance in general surgery , developing various tools for distortion correction and calibration23,24. However, C-arms...additional error on the reconstruction of small objects. 1 Introduction C-arm fluoroscopy is ubiquitous in general surgery , due to its real-time nature

  8. Intra-Operative Dosimetry in Prostate Brachytherapy

    DTIC Science & Technology

    2007-11-01

    additional cost to the existing clinical installation. 1 Introduction With an approximate annual incidence of 220,000 new cases and 33,000 deaths...isocentric C-arm, at negligible additional cost to the existing clinical installation. Furthermore, the proposed system is the first of its kind that...PC050042, DoD PC050170 and NIH 2R44CA099374. optimal solution has a near-zero cost when the pose error is low , and is actu- ally zero without pose error

  9. Characterization of primary prostate carcinoma by anti-1-amino-2-[18F] -fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) uptake

    PubMed Central

    Schuster, David M; Taleghani, Pooneh A; Nieh, Peter T; Master, Viraj A; Amzat, Rianot; Savir-Baruch, Bital; Halkar, Raghuveer K; Fox, Tim; Osunkoya, Adeboye O; Moreno, Carlos S; Nye, Jonathon A; Yu, Weiping; Fei, Baowei; Wang, Zhibo; Chen, Zhengjia; Goodman, Mark M

    2013-01-01

    Anti-1-amino-3-[18F] fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) is a synthetic amino acid positron emission tomography (PET) radiotracer with utility in the detection of recurrent prostate carcinoma. The aim of this study is to correlate uptake of anti-3-[18F] FACBC with histology of prostatectomy specimens in patients undergoing radical prostatectomy and to determine if uptake correlates to markers of tumor aggressiveness such as Gleason score. Ten patients with prostate carcinoma pre-radical prostatectomy underwent 45 minute dynamic PET-CT of the pelvis after IV injection of 347.8 ± 81.4 MBq anti-3-[18F] FACBC. Each prostate was co-registered to a separately acquired MR, divided into 12 sextants, and analyzed visually for abnormal focal uptake at 4, 16, 28, and 40 min post-injection by a single reader blinded to histology. SUVmax per sextant and total sextant activity (TSA) was also calculated. Histology and Gleason scores were similarly recorded by a urologic pathologist blinded to imaging. Imaging and histologic analysis were then compared. In addition, 3 representative sextants from each prostate were chosen based on highest, lowest and median SUVmax for immunohistochemical (IHC) analysis of Ki67, synaptophysin, P504s, chromogranin A, P53, androgen receptor, and prostein. 79 sextants had malignancy and 41 were benign. Highest combined sensitivity and specificity was at 28 min by visual analysis; 81.3% and 50.0% respectively. SUVmax was significantly higher (p<0.05) for malignant sextants (5.1±2.6 at 4 min; 4.5±1.6 at 16 min; 4.0±1.3 at 28 min; 3.8±1.0 at 40 min) compared to non-malignant sextants (4.0±1.9 at 4 min; 3.5±0.8 at 16 min; 3.4±0.9 at 28 min; 3.3±0.9 at 40 min), though there was overlap of activity between malignant and non-malignant sextants. SUVmax also significantly correlated (p<0.05) with Gleason score at all time points (r=0.28 at 4 min; r=0.42 at 16 min; r=0.46 at 28 min; r=0.48 at 40 min). There was no significant

  10. Prostate biopsy

    MedlinePlus

    ... prostate biopsy; Fine needle biopsy of the prostate; Core biopsy of the prostate; Targeted prostate biopsy; Prostate ... to the principles of the Health on the Net Foundation (www.hon.ch). The information provided herein ...

  11. Sequential evaluation of prostate edema after permanent seed prostate brachytherapy using CT-MRI fusion

    SciTech Connect

    Taussky, Daniel; Austen, Lyn; Toi, Ants; Yeung, Ivan; Williams, Theresa; Pearson, Shannon; McLean, Michael; Pond, Gregory; Crook, Juanita . E-mail: juanita.crook@rmp.uhn.on.ca

    2005-07-15

    Purpose: To analyze the extent and time course of prostate edema and its effect on dosimetry after permanent seed prostate brachytherapy. Methods and Materials: Twenty patients scheduled for permanent seed {sup 125}I prostate brachytherapy agreed to a prospective study on postimplant edema. Implants were preplanned using transrectal ultrasonography. Postimplant dosimetry was calculated using computed tomography-magnetic resonance imaging (CT-MRI) fusion on the day of the implant (Day 1) and Days 8 and 30. The prostate was contoured on MRI, and the seeds were located on CT. Factors investigated for an influence on edema were the number of seeds and needles, preimplant prostate volume, transitional zone index (transition zone volume divided by prostate volume), age, and prostate-specific antigen level. Prostate dosimetry was evaluated by the percentage of the prostate volume receiving 100% of the prescribed dose (V{sub 100}) and percentage of prescribed dose received by 90% of the prostate volume (D{sub 90}). Results: Prostate edema was maximal on Day 1, with the median prostate volume 31% greater than preimplant transrectal ultrasound volume (range, 0.93-1.72; p < 0.001) and decreased with time. It was 21% greater than baseline at Day 8 (p = 0.013) and 5% greater on Day 30 (p < 0.001). Three patients still had a prostate volume greater than baseline by Day 30. The extent of edema depended on the transition zone volume (p = 0.016) and the preplan prostate volume (p 0.003). The median V{sub 100} on Day 1 was 93.6% (range, 86.0-98.2%) and was 96.3% (range, 85.7-99.5%) on Day 30 (p = 0.079). Patients with a Day 1 V{sub 100} >93% were less affected by edema resolution, showing a median increase in V{sub 100} of 0.67% on Day 30 compared with 2.77% for patients with a V{sub 100} <93 % on Day 1. Conclusion: Despite the extreme range of postimplant edema, the effect on dosimetry was less than expected. Dose coverage of the prostate was good for all patients during Days 1

  12. Combinatorial Targeting of Prostate Carcinoma Cells and Tumor Associated Pericytes with Antibody-Based Immunotherapy and Metronomic Chemotherapy

    DTIC Science & Technology

    2011-03-01

    4 ( CSPG4 ). This antigen has a restricted distribution in normal tissues, but has high expression in malignant lesions with limited inter-and intra...mesothelioma, melanoma and sarcoma. Relevant to this proposal AN-2 and CSPG4 are expressed in mouse and human prostate cancer cell lines, respectively...Fig. 1). Furthermore AN-2 and CSPG4 expression is upregulated on activated pericytes in the tumor microenvironment (Fig.2). As to the function of

  13. Analysis of Argonaute Complex Bound mRNAs in DU145 Prostate Carcinoma Cells Reveals New miRNA Target Genes

    PubMed Central

    Jung, Volker; Beitzinger, Michaela; Nolte, Elke; Wach, Sven; Hart, Martin; Sapich, Sandra; Wiesehöfer, Marc; Wennemuth, Gunther; Eichner, Norbert; Stempfl, Thomas; Wullich, Bernd; Meister, Gunter

    2017-01-01

    Posttranscriptional gene regulation by microRNAs (miRNAs) contributes to the induction and maintenance of prostate carcinoma (PCa). To identify mRNAs enriched or removed from Ago2-containing RISC complexes, these complexes were immunoprecipitated from normal prostate fibroblasts (PNFs) and the PCa line DU145 and the bound mRNAs were quantified by microarray. The analysis of Ago complexes derived from PNFs or DU145 confirmed the enrichment or depletion of a variety of mRNAs already known from the literature to be deregulated. Novel potential targets were analyzed by luciferase assays with miRNAs known to be deregulated in PCa. We demonstrate that the mRNAs of the death effector domain-containing protein (DEDD), the tumor necrosis factor receptor superfamily, member 10b protein (TNFRSF10B), the tumor protein p53 inducible nuclear protein 1 (TP53INP1), and the secreted protein, acidic, cysteine-rich (SPARC; osteonectin) are regulated by miRNAs miR-148a, miR-20a, miR-24, and miR-29a/b, respectively. Therefore, these miRNAs represent potential targets for therapy. Surprisingly, overexpression of miR-24 induced focus formation and proliferation of DU145 cells, while miR-29b reduced proliferation. The study confirms genes deregulated in PCa by virtue of their presence/absence in the Ago2-complex. In conjunction with the already published miRNA profiles of PCa, the data can be used to identify miRNA-regulated mRNAs. PMID:28163933

  14. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations

    PubMed Central

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution. Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years. Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported

  15. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations.

    PubMed

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered "Virtual HDR" treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create "HDR-like" PTV dose distribution. Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient's potent pre-SBRT, 65% remained so at 5 years. Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported post-HDR brachytherapy.

  16. Proanthocyanidins from grape seeds inhibit expression of matrix metalloproteinases in human prostate carcinoma cells, which is associated with the inhibition of activation of MAPK and NF kappa B.

    PubMed

    Vayalil, Praveen K; Mittal, Anshu; Katiyar, Santosh K

    2004-06-01

    Prostate cancer (PCA) is the second most frequently diagnosed and leading cause of cancer-related deaths in men in the USA. The recognition that matrix metalloproteinases (MMPs) facilitate tumor cell invasion and metastasis of PCA has led to the development of MMP inhibitors as cancer therapeutic agents. As part of our efforts to develop newer and effective chemopreventive agents for PCA, we evaluated the effect of proanthocyanidins from grape seeds (GSP) on metastasis-specific MMP-2 and -9 in human prostate carcinoma DU145 cells by employing western blot and gelatinolytic zymography. Treatment of GSP dose-dependently inhibited cell proliferation (15-100% by 5-80 microg/ml of GSP), viability (30-80% by 20-80 microg/ml of GSP) and fibroblast conditioned medium (FCM)-induced expression of MMP-2 and -9 in DU145 cells. Since the signaling cascade of mitogen-activated protein kinases (MAPK) have been shown to regulate the expression of MMPs in tumor cells, we found that the treatment of DU145 cells with GSP (20-80 microg/ml) resulted in marked inhibition of FCM-induced phosphorylation of extracellular signal regulated kinase (ERK)1/2 and p38 but had little effect on c-Jun N-terminal kinase under similar experimental conditions. GSP treatment (20-80 microg/ml) to DU145 cells also dose-dependently inhibited FCM-induced activation of NF kappa B concomitantly with inhibition of MMP-2 and -9 expression in the same system. Additionally, the treatment of inhibitors of MEK (PD98059) and p38 (SB203580) to DU145 cells resulted in the reduction of FCM-induced phosphorylation of ERK1/2 and p38 concomitantly marked reduction in MMP-2 and -9 expressions. In further studies, treatment of androgen-sensitive LNCaP cells with a synthetic androgen R1881, resulted in an increase of MMP-2 and -9, which were completely abrogated in the presence of GSP (20-60 microg/ml). These data suggest that inhibition of metastasis-specific MMPs in tumor cells by GSP is associated with the inhibition of

  17. Cerebellar Metastases From Prostate Cancer on 68Ga-PSMA PET/CT.

    PubMed

    Chan, Mico; Hsiao, Edward; Turner, Jennifer

    2017-03-01

    Ga prostate-specific membrane antigen PET/CT is increasingly used to evaluate extent of disease in prostate carcinoma. Parenchymal brain metastases originating from prostate cancer have highly variable imaging appearance. We present a 77-year-old man with cerebellar metastasis from prostate cancer showing focal uptake on prostate-specific membrane antigen PET/CT.

  18. Renal-cell carcinoma risk estimates based on participants in the prostate, lung, colorectal, and ovarian cancer screening trial and national lung screening trial.

    PubMed

    Lotan, Yair; Karam, Jose A; Shariat, Shahrokh F; Gupta, Amit; Roupret, Morgan; Bensalah, Karim; Margulis, Vitaly

    2016-04-01

    Current knowledge regarding risk of renal-cell carcinoma (RCC) is based on meta-analyses of case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and National Lung Screening Trial (NLST) provide robust prospective databases with clinical information and rates of cancer development. PLCO and NLST were used to identify risk factors for RCC. Data were extracted from PLCO and NLST to stratify risk of RCC by sex, race, age at inclusion, obesity, and smoking status. Incidence rates between groups were compared using the chi-square test. We excluded urothelial carcinomas. Overall, 701/154,118 and 190/53,242 RCCs were detected in PLCO and NLST, respectively. Incidence rates were higher in men (PLCO: 0.56 vs. 0.28/1000 person y, NLST: 0.73 vs. 0.35/1000 person y; both with P<0.0001). In the PLCO, male sex, age>60 years, obesity, and intensity of smoking were associated with higher risk of developing RCC. In the NLST, sex and morbid obesity increased the risk for RCC but age, ethnicity, and smoking intensity were not predictors. There was no effect of screening for other cancers on detection of RCC. High-grade (grades ≥3) RCCs were diagnosed in 145 (20.7%) and 60 (31.6%) in the PLCO and NLST. In PLCO, age (60-64y), male sex, obesity, and current smokers with>50 pack years were at increased risk for high-grade RCC. In NLST, only male sex was an independent predictor of high-grade RCC. Age over 60 years, male sex, smoking intensity, and obesity affect the risk of RCC. Identification of a high-risk population may allow a pilot study of rational screening for RCC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Cytotoxicity of herbal extracts used for treatment of prostatic disease on head and neck carcinoma cell lines and non-malignant primary mucosal cells.

    PubMed

    Schmidt, Marianne; Polednik, Christine; Roller, Jeanette; Hagen, Rudolf

    2013-02-01

    Previously, a growth inhibiting effect of PC-Spes on head and neck carcinoma cell lines had been demonstrated. In order to determine the toxic impact of particular herbs in the mixture, we exposed the head and neck cancer cell lines FADU, HLaC79 and its Paclitaxel-resistant subline HLaC79-Clone1 as well as primary mucosal keratinocytes to increasing concentrations of the herbal mixture Prostaprotect, which has a similar formulation as PC-Spes, as well as its single herbal components Dendranthema morifolium, Ganoderma lucidium, Glycyrrhiza glabra, Isatis indigotica, Panax pseudo-ginseng, Rabdosia rubescens, Scutellaria baicalensis and Pygeum africanum. Growth inhibition was measured using the MTT assay. Expression of P-glycoprotein (P-GP), multidrug resistance protein-1 (MRP-1), multidrug resistance protein-2 (MRP-2), breast cancer resistance protein (BCRP) and androgen receptor (AR) were examined by western blot analysis. Pygeum africanum extract clearly turned out as the main cytotoxic component of the Prostaprotect prescription mixture, and initated apoptosis in sensitive cell lines. All other extracts had only minor toxic effects. Western blot analysis revealed increased expression of P-GP in HLaC79-Clone1 cells, while HLaC79 and FADU cells were negative. All three cell lines were negative for MRP-1 and BCRP but positive for MRP-2. HLaC79 and its descendant HLaC79-Clone1 both expressed AR, as verified by western blotting and immunofluorescence staining. Primary mucosal keratinocytes were negative for all multidrug resistance markers as well as for AR. Growth inhibition rates of the single herbal extracts were compared with previously published results in prostate carcinoma cell lines. The relationship between expression levels of AR and multidrug resistance markers in relation to the measured toxicity of herbal extracts in our head and neck cancer cell system is critically discussed.

  20. 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.

  1. 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

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

    PubMed Central

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

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

  3. Long term results of HDR brachytherapy in men older than 75 with localized carcinoma of the prostate.

    PubMed

    Soumarová, Renata; Homola, Luboš; Perková, Hana

    2012-01-01

    Prostate cancer is an illness with a high incidence, especially among older men. The choice of a treatment option among men above 75 years is, however, not clear. Radical prostatectomy in this age group is connected with a relatively high morbidity. A further possibility of curative treatment is radiotherapy which can be administered in the form of external beam or in combination with high dose rate (HDR) brachytherapy. The aim of our work was to evaluate how HDR brachytherapy is tolerated among men older than 75 and how associated diseases can influence the tolerance to this treatment. Of interest to us were the treatment results and mortality from other diseases. We analyzed a sample of 20 men above 75 years old (median 77 years) who were undergoing treatment by a combination of external radiotherapy and brachytherapy. Sixteen (80%) of them had prostate cancer with an intermediate and high risk of recurrence, four had low risk prostate cancer. Most patients, 14 (70%), had less than two comorbidities. The median observation period was 57 months. No perioperative complications were recorded. Acute genitourinary toxicity (GU) to a maximum grade of 1-2 manifested in 60% of cases. Acute gastrointestinal toxicity (GIT) was observed only at grade 1 and in 25% of cases. Late GU toxicity occurred in 35% of patients, with only one showing grade 3; late GIT toxicity was recorded at grade 1 only in 3 patients (15%). 70% of the men lived longer than 3 years after treatment, at present, 50% lived more than 5 years. Long-term biochemical remission was achieved in 18 patients (90%). HDR BRT is possible and well-tolerated in older men above 75 years in good condition and without serious intercurrence. Well-selected older patients with higher-risk tumours and without serious comorbidities undoubtedly benefit from radical treatment when compared with watchful waiting.

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

    PubMed

    Bonetta, Alberto; Di Pierro, Francesco

    2012-01-01

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

  5. Anti-3-[18F]FACBC Positron Emission Tomography-Computerized Tomography and 111In-Capromab Pendetide Single Photon Emission Computerized Tomography-Computerized Tomography for Recurrent Prostate Carcinoma: Results of a Prospective Clinical Trial

    PubMed Central

    Schuster, David M.; Nieh, Peter T.; Jani, Ashesh B.; Amzat, Rianot; Bowman, F. DuBois; Halkar, Raghuveer K.; Master, Viraj A.; Nye, Jonathon A.; Odewole, Oluwaseun A.; Osunkoya, Adeboye O.; Savir-Baruch, Bital; Alaei-Taleghani, Pooneh; Goodman, Mark M.

    2014-01-01

    Purpose We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[18F]FACBC compared to ProstaScint® (111In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. Materials and Methods A total of 93 patients met study inclusion criteria who underwent anti-3-[18F]FACBC positron emission tomography-computerized tomography plus 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. Results In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[18F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to 111In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[18F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to 111In-capromabpendetide with10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[18F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[18F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. Conclusions Better diagnostic performance was noted for anti-3-[18F]FACBC positron emission tomography-computerized tomography than for 111In

  6. Apium graveolens Extract Inhibits Cell Proliferation and Expression of Vascular Endothelial Growth Factor and Induces Apoptosis in the Human Prostatic Carcinoma Cell Line LNCaP.

    PubMed

    Köken, Tülay; Koca, Buğra; Özkurt, Mete; Erkasap, Nilüfer; Kuş, Gökhan; Karalar, Mustafa

    2016-12-01

    Apium graveolens has been shown to inhibit the growth of a variety of cancer tissues. In this study, we investigated the anticancer effect of A. graveolens on the human prostatic carcinoma cell line LNCaP. LNCaP cells were treated with increasing concentrations of an ethanolic extract of A. graveolens ranging from 1000 to 3000 μg/mL, and viability was determined after 24 and 48 h using the XTT cell proliferation assay. The levels of cleaved poly (ADP-ribose) polymerase (PARP), one of the best biomarkers of apoptosis, were analyzed. Finally, quantitative gene expression analysis of vascular endothelial growth factor (VEGF), a critical mediator of angiogenesis, was performed using real-time reverse transcription-polymerase chain reaction. A. graveolens extract inhibited cell viability in both a time- and dose-dependent manner. Data from cleaved PARP assays suggested that A. graveolens caused induction of apoptosis in these cells. Treatment of cells with A. graveolens also resulted in downregulation of VEGF expression. This study showed that the antiproliferative effect exerted by an ethanolic extract of A. graveolens is triggered by induction of apoptosis. We also demonstrated that VEGF expression was downregulated by treatment with A. graveolens extract.

  7. [The role of mitogen-activated protein kinase cascades in inhibition of proliferation in human prostate carcinoma cells by raloxifene: an in vitro experiment].

    PubMed

    Zhang, Yu-Xi; Kong, Chui-Ze

    2008-01-22

    To investigate the role of mitogen-activated protein kinase (MAPK) in the apoptosis and cell cycle arrest of human prostate carcinoma cells induced by raloxifene (RAL). Human prostate carcinoma cells of the line PC3 were cultured. RAL of the concentrations of 10(-4), 10(-5), 10(-6), and 10(-7) mol/L were added into the culture fluid. MTT method was used to detect the inhibitory rate of the PC3 proliferation. RAL of the concentrations of 10(-6) mol/L or 10(-6) mol/L +10 micromol/L PD98059, a MEK1/2 inhibitor, and 10(-6) mol/L RAL +10 micromol/L SB203580, JNK inhibitor, and RAL + SB203580, a p38 inhibitor were added respectively for 48 h, and the flow cytometry (FCM) was used to detect the cell cycle. The cell apoptosis percentage was measured by TUNEL staining. The activation of extra cellular regulated protein kinases (ERK1/2), c-Jun N-terminal protein kinase (JNK), and p38 mitogen-activated protein kinase (p38), and the expressions of Bcl-2, Bax, phospho-Bcl-2 (p-Bcl-2), and caspase-3 were determined by Western blotting. The expressions of estrogen receptor (ER) alpha, ERbeta, cyclin dependent kinase inhibitor (P21(WAF1)), and cyclinD1 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR). A dose-dependent proliferation inhibition of RAL was demonstrated in the PC3 cells. A G(1) cell cycle arrest and apoptosis were induced in the PC3 cells exposed to 10(-6) mol/L RAL. 10(-6) mol/L RAL induced the activation of ERK1/2 and p38 with different time courses, but it did not induce the activation of JNK. Suppression ERK1/2 activation by treatment with PD98059 or p38 activation by treatment with SB203580 attenuated the cell-cycle arrest at the G(1) phase respectively. 48 h after the treatment of 10(-6) mol/L RAL the PC3 cells was arrested at G(1) stage, however, 48 h after the treatment of 10(-6) mol/L RAL +10 micromol/L PD98059 and 10(-6) mol/L RAL +10 micromol/L SB203580 the degree of PC3 cell arrest at the G(1) stage was lower. 18 h after the

  8. Polypeptide Expression in Prostate Hyperplasia and Prostate Adenocarcinoma

    PubMed Central

    Alaiya, Ayodele; Roblick, Uwe; Egevad, Lars; Carlsson, Adelaide; Franzén, Bo; Volz, Daniela; Huwendiek, Sören; Linder, Stig; Auer, Gert

    2000-01-01

    Cells were collected from prostate hyperplasias (n=6) and prostate carcinomas (n=6) and subjected to two‐dimensional gel electrophoresis (2‐DE). The resulting polypeptide patterns were analysed with the PDQUEST computer software. Malignant tumors showed significant increases in the level of expression of proliferating cell nuclear antigen (PCNA), calreticulin, HSP 90 and pHSP 60, oncoprotein 18(v), elongation factor 2, glutathione‐S‐transferase π (GST‐π), superoxide dismutase and triose phosphate isomerase. In addition, decreases in the levels of tropomyosin‐1 and 2 and cytokeratin 18 were observed in prostate carcinomas compared to prostate hyperplasias. This pattern of alterations is similar to that observed in other carcinomas in our previous studies. All malignant tumors showed simultaneous alterations in 5 or more of 9 markers studied, whereas only one case of benign hyperplasia showed alterations in 5 markers. The EST‐data base for prostate tumors available from NCI (CGAP) was searched for the expression of the mRNAs corresponding to proteins identified in our gels. Large differences in the relative expression of mRNAs and proteins were observed. Our data show alterations in the pattern of polypeptide expression in prostate carcinomas which are similar to those observed in other carcinomas. PMID:11254220

  9. Evaluation of multiple image-based modalities for image-guided radiation therapy (IGRT) of prostate carcinoma: A prospective study

    SciTech Connect

    Mayyas, Essa; Chetty, Indrin J.; Chetvertkov, Mikhail; Wen, Ning; Neicu, Toni; Nurushev, Teamor; Ren Lei; Pradhan, Deepak; Movsas, Benjamin; Elshaikh, Mohamed A.; Lu Mei; Stricker, Hans

    2013-04-15

    Purpose: Setup errors and prostate intrafraction motion are main sources of localization uncertainty in prostate cancer radiation therapy. This study evaluates four different imaging modalities 3D ultrasound (US), kV planar images, cone-beam computed tomography (CBCT), and implanted electromagnetic transponders (Calypso/Varian) to assess inter- and intrafraction localization errors during intensity-modulated radiation therapy based treatment of prostate cancer. Methods: Twenty-seven prostate cancer patients were enrolled in a prospective IRB-approved study and treated to a total dose of 75.6 Gy (1.8 Gy/fraction). Overall, 1100 fractions were evaluated. For each fraction, treatment targets were localized using US, kV planar images, and CBCT in a sequence defined to determine setup offsets relative to the patient skin tattoos, intermodality differences, and residual errors for each patient and patient cohort. Planning margins, following van Herk's formalism, were estimated based on error distributions. Calypso-based localization was not available for the first eight patients, therefore centroid positions of implanted gold-seed markers imaged prior to and immediately following treatment were used as a motion surrogate during treatment. For the remaining 19 patients, Calypso transponders were used to assess prostate intrafraction motion. Results: The means ({mu}), and standard deviations (SD) of the systematic ({Sigma}) and random errors ({sigma}) of interfraction prostate shifts (relative to initial skin tattoo positioning), as evaluated using CBCT, kV, and US, averaged over all patients and fractions, were: [{mu}{sub CBCT}= (-1.2, 0.2, 1.1) mm, {Sigma}{sub CBCT}= (3.0, 1.4, 2.4) mm, {sigma}{sub CBCT}= (3.2, 2.2, 2.5) mm], [{mu}{sub kV}= (-2.9, -0.4, 0.5) mm, {Sigma}{sub kV}= (3.4, 3.1, 2.6) mm, {sigma}{sub kV}= (2.9, 2.0, 2.4) mm], and [{mu}{sub US}= (-3.6, -1.4, 0.0) mm, {Sigma}{sub US}= (3.3, 3.5, 2.8) mm, {sigma}{sub US}= (4.1, 3.8, 3.6) mm], in the anterior

  10. Dosimetry with diamond detectors

    NASA Astrophysics Data System (ADS)

    Gervino, G.; Marino, C.; Silvestri, F.; Lavagno, A.; Truc, F.

    2010-05-01

    In this paper we present the dosimetry analysis in terms of stability and repeatability of the signal and dose rate dependence of a synthetic single crystal diamond grown by Chemical Vapor Deposition (CVD) technique. The measurements carried out by 5 MeV X-ray photons beam show very promising results, even if the dose rate detector response points out that the charge trapping centers distribution is not uniform inside the crystal volume. This handicap that affects the detectors performances, must be ascribed to the growing process. Synthetic single crystal diamonds could be a valuable alternative to air ionization chambers for quality beam control and for intensity modulated radiation therapy beams dosimetry.

  11. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity.

    PubMed

    Haffner, Michael C; Laimer, Johannes; Chaux, Alcides; Schäfer, Georg; Obrist, Peter; Brunner, Andrea; Kronberger, Irmgard E; Laimer, Klaus; Gurel, Bora; Koller, Johann-Benedikt; Seifarth, Christof; Zelger, Bettina; Klocker, Helmut; Rasse, Michael; Doppler, Wolfgang; Bander, Neil H

    2012-08-01

    Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n=96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P=0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio=2.19, P=0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

  12. Endocavitary in vivo Dosimetry for IMRT Treatments of Gynecologic Tumors

    SciTech Connect

    Cilla, Savino; Macchia, Gabriella; Digesu, Cinzia; Deodato, Francesco; Sabatino, Domenico; Morganti, Alessio G.; Piermattei, Angelo

    2011-01-01

    The accuracy and reproducibility of endometrial carcinoma treatment with intensity-modulated radiotherapy (IMRT) was assessed by means of in vivo dosimetry. Six patients who had previously undergone radical hysterectomy for endometrial carcinoma were treated with IMRT using a vaginal applicator with radio-opaque fiducial markers. An ion-chamber inserted into the applicator supplied an endocavitary in vivo dosimetry for quality assurance purposes. The ratio R = D/D{sub TPS} between the in vivo measured dose D and the predicted dose by the treatment planning system D{sub TPS} was determined for every fraction of the treatment. Results showed that 90% and 100% of the ratios resulted equal to 1 within 5% and 10%, respectively. The mean value of the ratios distribution for the 6 patients was R = 0.995 and the SD = 0.034. The ratio R* between the measured and predicted total doses for each patient was near to 1, within 2%. The dosimetric results suggest that the use of a vaginal applicator in an image-guided approach could make the interfractions target position stable and reproducible, allowing a safe use of the IMRT technique in the treatment of postoperative vaginal vault. In vivo dosimetry may supply useful information about the discrimination of random vs. systematic errors. The workload is minimum and this in vivo dosimetry can be applied also in the clinical routine.

  13. Ion-kill dosimetry

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Fromm, M.; Chambaudet, A.

    2001-01-01

    Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'.

  14. Dosimetry in diagnostic radiology.

    PubMed

    Meghzifene, Ahmed; Dance, David R; McLean, Donald; Kramer, Hans-Michael

    2010-10-01

    Dosimetry is an area of increasing importance in diagnostic radiology. There is a realisation amongst health professionals that the radiation dose received by patients from modern X-ray examinations and procedures can be at a level of significance for the induction of cancer across a population, and in some unfortunate instances, in the acute damage to particular body organs such as skin and eyes. The formulation and measurement procedures for diagnostic radiology dosimetry have recently been standardised through an international code of practice which describes the methodologies necessary to address the diverging imaging modalities used in diagnostic radiology. Common to all dosimetry methodologies is the measurement of the air kerma from the X-ray device under defined conditions. To ensure the accuracy of the dosimetric determination, such measurements need to be made with appropriate instrumentation that has a calibration that is traceable to a standards laboratory. Dosimetric methods are used in radiology departments for a variety of purposes including the determination of patient dose levels to allow examinations to be optimized and to assist in decisions on the justification of examination choices. Patient dosimetry is important for special cases such as for X-ray examinations of children and pregnant patients. It is also a key component of the quality control of X-ray equipment and procedures. Copyright © 2010. Published by Elsevier Ireland Ltd.

  15. Ion storage dosimetry

    NASA Astrophysics Data System (ADS)

    Mathur, V. K.

    2001-09-01

    The availability of a reliable, accurate and cost-effective real-time personnel dosimetry system is fascinating to radiation workers. Electronic dosimeters are contemplated to meet this demand of active dosimetry. The development of direct ion storage (DIS) dosimeters, a member of the electronic dosimeter family, for personnel dosimetry is also an attempt in this direction. DIS dosimeter is a hybrid of the well-established technology of ion chambers and the latest advances in data storage using metal oxide semiconductor field effect transistor (MOSFET) analog memory device. This dosimeter is capable of monitoring legal occupational radiation doses of gamma, X-rays, beta and neutron radiation. Similar to an ion chamber, the performance of the dosimeter for a particular application can be optimized through the selection of appropriate wall materials. The use of the floating gate of a MOSFET as one of the electrodes of the ion chamber allows the miniaturization of the device to the size of a dosimetry badge and avoids the use of power supplies during dose accumulation. The concept of the device, underlying physics and the design of the DIS dosimeter are discussed. The results of preliminary testing of the device are also provided.

  16. Ion-kill dosimetry

    NASA Technical Reports Server (NTRS)

    Katz, R.; Cucinotta, F. A.; Fromm, M.; Chambaudet, A.

    2001-01-01

    Unanticipated late effects in neutron and heavy ion therapy, not attributable to overdose, imply a qualitative difference between low and high LET therapy. We identify that difference as 'ion kill', associated with the spectrum of z/beta in the radiation field, whose measurement we label 'ion-kill dosimetry'.

  17. Proposed morphologic classification of prostate cancer with neuroendocrine differentiation.

    PubMed

    Epstein, Jonathan I; Amin, Mahul B; Beltran, Himisha; Lotan, Tamara L; Mosquera, Juan-Miguel; Reuter, Victor E; Robinson, Brian D; Troncoso, Patricia; Rubin, Mark A

    2014-06-01

    On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.

  18. 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 ...

  19. A randomized, double-blind, placebo-controlled, cross-over study to assess the efficacy of tadalafil (Cialis[reg]) in the treatment of erectile dysfunction following three-dimensional conformal external-beam radiotherapy for prostatic carcinoma

    SciTech Connect

    Incrocci, Luca . E-mail: l.incrocci@erasmusmc.nl; Slagter, Cleo; Slob, A. Koos; Hop, Wim C.J.

    2006-10-01

    Purpose: Erectile dysfunction after three-dimensional conformal external-beam radiotherapy (3DCRT) for prostatic carcinoma is reported in as many as 64% of those patients. The purpose of this study was to determine the efficacy of the oral drug tadalafil (Cialis (registered) ) in patients with erectile dysfunction after radiotherapy for prostatic carcinoma. Methods and Materials: Patients (N = 358) who completed radiotherapy at least 12 months before the study were approached by mail. All patients had been treated by 3DCRT; 60 patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received 20 mg of tadalafil or placebo for 6 weeks. Drug or placebo was taken on demand at patient's discretion, with no restrictions regarding the consumption of alcohol or food, at least once a week and no more than once daily. At 6 weeks patients crossed over to the alternative treatment. Data were collected using the Sexual Encounter Profile (SEP) and the International Index of Erectile Function (IIEF) questionnaires. Side effects were also recorded. Results: Mean age at study entry was 69 years. All patients completed the study. For almost all questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with tadalafil, but not with placebo. Sixty-seven percent of the patients reported an improvement of erectile function with tadalafil (placebo: 20%), and 48% reported successful intercourse with tadalafil (placebo: 9%) (p < 0.0001). Side effects were mild or moderate. Conclusions: Tadalafil is an effective treatment for erectile dysfunction after 3DCRT for prostatic carcinoma with successful intercourse reported in almost 50% of the patients, and it is well tolerated.

  20. Testosterone-mediated increase in 5 alpha-dihydrotestosterone content, nuclear androgen receptor levels, and cell division in an androgen-independent prostate carcinoma of Noble rats.

    PubMed

    Ho, S M; Leav, I; Damassa, D; Kwan, P W; Merk, F B; Seto, H S

    1988-02-01

    An androgen-independent, transplantable prostate carcinoma line (AIT), originally derived from the dorsolateral prostate (DLP) of Noble rat, was implanted into orchiectomized Noble rats and its response to androgen stimulation was studied and compared to that of the regenerating DLP tissue in sexually ablated rats. AIT tumors carried in castrated hosts displayed a high basal level of proliferative activity (mitotic index (MI), 15.0 +/- 0.5) while DLP tissue in untreated castrates exhibited no proliferative activity. Following androgen stimulation by testosterone capsule implantation into host rats, the AIT responded with a marked increase in cell proliferation; MI values doubled to 30.0 +/- 2.9 on Day 5 following androgen stimulation. This androgen-induced increase in MI values was coincident with elevations in nuclear androgen receptor (20-fold increase) and 5 alpha-dihydrotestosterone content (3-fold increase) in the tumor. However, by Day 10 following androgen treatment, indices of cell proliferation in the AIT declined to pre-androgen-stimulated levels (MI, 14.8 +/- 1.9) despite the continued elevations in nuclear androgen receptor and tissue 5 alpha-dihydrotestosterone contents. Parallel changes in MI were also observed in the normal regenerating DLP following androgen stimulation. MI values in this tissue increased from nondetectable levels to 38.1 +/- 4.7 on Day 5 but declined to relatively low levels (4.5 +/- 0.9) by Day 10 following androgen replacement. Taken together these findings led us to conclude that the AIT carried in castrates is capable of responding to testosterone in a manner similar to that observed for androgen-stimulated DLP of sexually ablated rats. Thus, in both the neoplastic and regenerating tissues, the initial response to androgen is characterized by a marked enhancement of cell proliferation which was correlated with an increase in androgen receptor and 5 alpha-dihydrotestosterone content. However, like its tissue of origin, the AIT

  1. ALGEBRA: ALgorithm for the heterogeneous dosimetry based on GEANT4 for BRAchytherapy.

    PubMed

    Afsharpour, H; Landry, G; D'Amours, M; Enger, S; Reniers, B; Poon, E; Carrier, J-F; Verhaegen, F; Beaulieu, L

    2012-06-07

    Task group 43 (TG43)-based dosimetry algorithms are efficient for brachytherapy dose calculation in water. However, human tissues have chemical compositions and densities different than water. Moreover, the mutual shielding effect of seeds on each other (interseed attenuation) is neglected in the TG43-based dosimetry platforms. The scientific community has expressed the need for an accurate dosimetry platform in brachytherapy. The purpose of this paper is to present ALGEBRA, a Monte Carlo platform for dosimetry in brachytherapy which is sufficiently fast and accurate for clinical and research purposes. ALGEBRA is based on the GEANT4 Monte Carlo code and is capable of handling the DICOM RT standard to recreate a virtual model of the treated site. Here, the performance of ALGEBRA is presented for the special case of LDR brachytherapy in permanent prostate and breast seed implants. However, the algorithm is also capable of handling other treatments such as HDR brachytherapy.

  2. ALGEBRA: ALgorithm for the heterogeneous dosimetry based on GEANT4 for BRAchytherapy

    NASA Astrophysics Data System (ADS)

    Afsharpour, H.; Landry, G.; D'Amours, M.; Enger, S.; Reniers, B.; Poon, E.; Carrier, J.-F.; Verhaegen, F.; Beaulieu, L.

    2012-06-01

    Task group 43 (TG43)-based dosimetry algorithms are efficient for brachytherapy dose calculation in water. However, human tissues have chemical compositions and densities different than water. Moreover, the mutual shielding effect of seeds on each other (interseed attenuation) is neglected in the TG43-based dosimetry platforms. The scientific community has expressed the need for an accurate dosimetry platform in brachytherapy. The purpose of this paper is to present ALGEBRA, a Monte Carlo platform for dosimetry in brachytherapy which is sufficiently fast and accurate for clinical and research purposes. ALGEBRA is based on the GEANT4 Monte Carlo code and is capable of handling the DICOM RT standard to recreate a virtual model of the treated site. Here, the performance of ALGEBRA is presented for the special case of LDR brachytherapy in permanent prostate and breast seed implants. However, the algorithm is also capable of handling other treatments such as HDR brachytherapy.

  3. Biphasic ⁶⁸Ga-PSMA-HBED-CC-PET/CT in patients with recurrent and high-risk prostate carcinoma.

    PubMed

    Sahlmann, Carsten-Oliver; Meller, Birgit; Bouter, Caroline; Ritter, Christian Oliver; Ströbel, Philipp; Lotz, Joachim; Trojan, Lutz; Meller, Johannes; Hijazi, Sameh

    2016-05-01

    Binding of (68)Ga-PSMA-HBED-CC ((68)Ga-PSMA) at prostate cancer (PC) cells increases over time. A biphasic protocol may help separating benign from tumor lesions. The aim of this study was the retrospective evaluation of a diagnostic incremental value of a dual-time point (biphasic) (68)Ga-PSMA-PET/CT in patients with prostate cancer. Retrospective analysis of 35 consecutive patients (49-78 years, median 71) with newly diagnosed PC (12/35) or recurrence of PC (23/35). PET/CT (Gemini TF16, Philips) was acquired 1 h and 3 h p. i. of 140-392 MBq (300 MBq median) (68)Ga-PSMA, followed by a diagnostic contrast CT. PET findings were correlated with histology or unequivocal CT findings. Semiquantitative PET data (SUVmax, SUV mean) were acquired and target-to-background-ratios (T/B-ratio) were calculated for benign and malign lesions for both time points. Size of lymph nodes (LN) on diagnostic CT was recorded. Statistical analysis was performed for assessment of significant changes of semiquantitative PET-parameters over time and for correlation of size and uptake of lymph nodes. One hundred and four lesions were evaluated. Sixty lesions were referenced by histology or unequivocal CT findings, including eight (13.3 %) histopathologically benign lymph nodes, 12 (20 %) histopathologically lymph node metastases, 12 (20 %) primary tumors, three (5 %) local recurrences, and 25 (41.7 %) bone metastases. Forty-four lesions were axillary LN with normal CT-appearance. Benign lesions had significantly lower SUVmax and T/B-ratios compared with malignant findings. Malign lesions showed a significant increase of both parameters over time compared to benign findings. There was no correlation between LN size and SUVmax. The sensitivity, specificity, the positive predictive value and negative predictive value of PET/CT regarding pelvic LN was 94 %, 99 %, 89 %, and 99.5 %, respectively. In contrast to benign tissues, the uptake of proven tumor lesions increases on (68)Ga-PSMA-PET/CT over

  4. Detection and quantification of (223)Ra uptake in bone metastases of patients with castration resistant prostate carcinoma, with the aim of determining the absorbed dose in the metastases.

    PubMed

    Mínguez, P; Gómez de Iturriaga, A; Fernández, I L; Rodeño, E

    2017-06-20

    To obtain the necessary acquisition and calibration parameters in order to evaluate the possibility of detecting and quantifying (223)Ra uptake in bone metastases of patients treated for castration resistant prostate carcinoma. Furthermore, in the cases in which the activity can be quantified, to determine the absorbed dose. Acquisitions from a Petri dish filled with (223)Ra were performed in the gamma camera. Monte Carlo simulations were also performed to study the partial volume effect. Formulae to obtain the detection and quantification limits of (223)Ra uptake were applied to planar images of two patients 7 days post-administration of 55kBq/kg of (223)Ra. In order to locate the lesions in advance, whole-body scans and SPECT/CT images were acquired after injecting (99m)Tc-HDP. The optimal energy window was found to be at 82keV with a medium-energy collimator MEGP. Of the lesions found in the patients, only those that had been detected in both the AP and PA projections could be quantified. These lesions were those which had shown a higher (99m)Tc-HDP uptake. The estimated values of absorbed doses ranged between 0.7Gy and 7.8Gy. Of the lesions that can be detected, it is not possible to quantify the activity uptake in some of them, which means that the absorbed dose cannot be determined either. This does not mean that the absorbed dose in these lesions can be regarded as negligible. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  5. Apoptosis Induction of Human Prostate Carcinoma DU145 Cells by Diallyl Disulfide via Modulation of JNK and PI3K/AKT Signaling Pathways

    PubMed Central

    Shin, Dong Yeok; Kim, Gi-Young; Lee, Jun Hyuk; Choi, Byung Tae; Yoo, Young Hyun; Choi, Yung Hyun

    2012-01-01

    Diallyl disulfide (DADS), a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound’s anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells. Our results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis. Apoptosis was accompanied by modulation of Bcl-2 and inhibitor of apoptosis protein (IAP) family proteins, depolarization of the mitochondrial membrane potential (MMP, ΔΨm) and proteolytic activation of caspases. We also found that the expression of death-receptor 4 (DR4) and Fas ligand (FasL) proteins was increased and that the level of intact Bid proteins was down-regulated by DADS. Moreover, treatment with DADS induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular-signal regulating kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). A specific JNK inhibitor, SP600125, significantly blocked DADS-induced-apoptosis, whereas inhibitors of the ERK (PD98059) and p38 MAPK (SB203580) had no effect. The induction of apoptosis was also accompanied by inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt and the PI3K inhibitor LY29004 significantly increased DADS-induced cell death. These findings provide evidence demonstrating that the proapoptotic effect of DADS is mediated through the activation of JNK and the inhibition of the PI3K/Akt signaling pathway in DU145 cells. PMID:23203057

  6. Apoptosis induction of human prostate carcinoma DU145 cells by diallyl disulfide via modulation of JNK and PI3K/AKT signaling pathways.

    PubMed

    Shin, Dong Yeok; Kim, Gi-Young; Lee, Jun Hyuk; Choi, Byung Tae; Yoo, Young Hyun; Choi, Yung Hyun

    2012-11-02

    Diallyl disulfide (DADS), a sulfur compound derived from garlic, has various biological properties, such as anticancer, antiangiogenic and anti-inflammatory effects. However, the mechanisms of action underlying the compound's anticancer activity have not been fully elucidated. In this study, the apoptotic effects of DADS were investigated in DU145 human prostate carcinoma cells. Our results showed that DADS markedly inhibited the growth of the DU145 cells by induction of apoptosis. Apoptosis was accompanied by modulation of Bcl-2 and inhibitor of apoptosis protein (IAP) family proteins, depolarization of the mitochondrial membrane potential (MMP, ΔΨm) and proteolytic activation of caspases. We also found that the expression of death-receptor 4 (DR4) and Fas ligand (FasL) proteins was increased and that the level of intact Bid proteins was down-regulated by DADS. Moreover, treatment with DADS induced phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular-signal regulating kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). A specific JNK inhibitor, SP600125, significantly blocked DADS-induced-apoptosis, whereas inhibitors of the ERK (PD98059) and p38 MAPK (SB203580) had no effect. The induction of apoptosis was also accompanied by inactivation of phosphatidylinositol 3-kinase (PI3K)/Akt and the PI3K inhibitor LY29004 significantly increased DADS-induced cell death. These findings provide evidence demonstrating that the proapoptotic effect of DADS is mediated through the activation of JNK and the inhibition of the PI3K/Akt signaling pathway in DU145 cells.

  7. In aqua vivo EPID dosimetry

    SciTech Connect

    Wendling, Markus; McDermott, Leah N.; Mans, Anton; Olaciregui-Ruiz, Igor; Pecharroman-Gallego, Raul; Sonke, Jan-Jakob; Stroom, Joep; Herk, Marcel J.; Mijnheer, Ben van

    2012-01-15

    applying the in aqua vivo approach are considerable. The percentage of {gamma} values {<=}1 increased on average from 66.2% to 93.1% and from 43.6% to 97.5% for the IMRT and VMAT cases, respectively. The corresponding mean {gamma} value decreased from 0.99 to 0.43 for the IMRT cases and from 1.71 to 0.40 for the VMAT cases, which is similar to the accepted clinical values for the verification of IMRT treatments of prostate, rectum, and head-and-neck cancers. The deviation between the reconstructed and planned dose at the isocenter diminished on average from 5.3% to 0.5% for the VMAT patients and was almost the same, within 1%, for the IMRT cases. The in aqua vivo verification results for IMRT and VMAT treatments of a large group of patients had a mean {gamma} of approximately 0.5, a percentage of {gamma} values {<=}1 larger than 89%, and a difference of the isocenter dose value less than 1%. Conclusions: With the in aqua vivo approach for the verification of lung cancer treatments (IMRT and VMAT), we can achieve results with the same accuracy as obtained during in vivo EPID dosimetry of sites without large inhomogeneities.

  8. In vivo dosimetry for IMRT

    SciTech Connect

    Vial, Philip

    2011-05-05

    In vivo dosimetry has a well established role in the quality assurance of 2D radiotherapy and 3D conformal radiotherapy. The role of in vivo dosimetry for IMRT is not as well established. IMRT introduces a range of technical issues that complicate in vivo dosimetry. The first decade or so of IMRT implementation has largely relied upon pre-treatment phantom based dose verification. During that time, several new devices and techniques for in vivo dosimetry have emerged with the promise of providing the ultimate form of IMRT dose verification. Solid state dosimeters continue to dominate the field of in vivo dosimetry in the IMRT era. In this report we review the literature on in vivo dosimetry for IMRT, with an emphasis on clinical evidence for different detector types. We describe the pros and cons of different detectors and techniques in the IMRT setting and the roles that they are likely to play in the future.

  9. Three dimensional conformal photon radiotherapy at a moderate dose level of 66 Gy for prostate carcinoma: early results.

    PubMed

    Wachter, S; Gerstner, N; Goldner, G; Dieckmann, K; Colotto, A; Pötter, R

    1999-06-01

    The therapeutic outcome and toxicity of 3-D conformal photon external beam therapy of prostate cancer is well documented in the literature. Progress is still in work for optimization of treatment strategies by risk-adapted dose escalation studies to improve local tumor control without increase of radiation side effects. We present our experience of 291 patients treated between January 1994 and August 1997 with a 3-D planned four-field box technique and a central dose of 66 Gy. Biochemical response of patients with radiotherapy alone (group 1, n = 72 pts.) has been analyzed in detail. Acute radiation side effects are given for all patients (n = 291), late radiation side effects are given for patients treated between Jan 1994 and Jan 1996 with a median follow-up of 22 months (n = 115 pts.). We have observed a biochemical response (nadir PSA < 1 after 12 months, < 2 after 6 months) for patients treated with radiotherapy alone without hormone manipulation in 67%. Incidence of late rectal and bladder morbidity (grade 2 and 3) was 9.4% and 4%, respectively. Compared to other reports our results indicate a high rate of local tumor control (early biochemical response) and a low rate of late morbidity. Nevertheless, we will start a risk-adapted dose escalation study up to 74 Gy for unfavorable subgroups (G2-3, Gleason Score > 7, PSA > 10) to improve treatment outcome.

  10. Relative Biological Effectiveness of Carbon Ions for Local Tumor Control of a Radioresistant Prostate Carcinoma in the Rat

    SciTech Connect

    Peschke, Peter; Karger, Christian P.; Scholz, Michael; Debus, Juergen; Huber, Peter E.

    2011-01-01

    Purpose: To study the relative biological effectiveness (RBE) of carbon ion beams relative to X-rays for local tumor control in a syngeneic rat prostate tumor (Dunning subline R3327-AT1). Methods and Materials: A total of 198 animals with tumors in the distal thigh were treated with increasing single and split doses of either {sup 12}C ions or photons using a 20-mm spread-out Bragg peak. Endpoints of the study were local control (no tumor recurrence within 300 days) and volumetric changes after irradiation. The resulting values for D{sub 50} (dose at 50% tumor control probability) were used to determine RBE values. Results: The D{sub 50} values for single doses were 32.9 {+-} 0.9 Gy for {sup 12}C ions and 75.7 {+-} 1.6 Gy for photons. The respective values for split doses were 38.0 {+-} 2.3 Gy and 90.6 {+-} 2.3 Gy. The corresponding RBE values were 2.30 {+-} 0.08 for single and 2.38 {+-} 0.16 for split doses. The most prominent side effects were dry and moist desquamation of the skin, which disappeared within weeks. Conclusion: The study confirmed the effectiveness of carbon ion therapy for severely radioresistant tumors. For 1- and 2-fraction photon and {sup 12}C ion radiation, we have established individual D{sub 50} values for local tumor control as well as related RBE values.

  11. Dosimetry for Radiopharmaceutical Therapy

    PubMed Central

    Sgouros, George; Hobbs, Robert F.

    2014-01-01

    Radiopharmaceutical therapy (RPT) involves the use of radionuclides that are either conjugated to tumor-targeting agents (eg, nanoscale constructs, antibodies, peptides, and small molecules) or concentrated in tissue through natural physiological mechanisms that occur predominantly in neoplastic or otherwise targeted cells (eg, Graves disease). The ability to collect pharmacokinetic data by imaging and use this to perform dosimetry calculations for treatment planning distinguishes RPT from other systemic treatment modalities. Treatment planning has not been widely adopted, in part, because early attempts to relate dosimetry to outcome were not successful. This was partially because a dosimetry methodology appropriate to risk evaluation rather than efficacy and toxicity was being applied to RPT. The weakest links in both diagnostic and therapeutic dosimetry are the accuracy of the input and the reliability of the radiobiological models used to convert dosimetric data to the relevant biologic end points. Dosimetry for RPT places a greater demand on both of these weak links. To date, most dosimetric studies have been retrospective, with a focus on tumor dose-response correlations rather than prospective treatment planning. In this regard, transarterial radioembolization also known as intra-arterial radiation therapy, which uses radiolabeled (90Y) microspheres of glass or resin to treat lesions in the liver holds much promise for more widespread dosimetric treatment planning. The recent interest in RPT with alpha-particle emitters has highlighted the need to adopt a dosimetry methodology that specifically accounts for the unique aspects of alpha particles. The short range of alpha-particle emitters means that in cases in which the distribution of activity is localized to specific functional components or cell types of an organ, the absorbed dose will be equally localized and dosimetric calculations on the scale of organs or even voxels (~5 mm) are no longer sufficient

  12. Dosimetry of two new interstitial brachytherapy sources

    NASA Astrophysics Data System (ADS)

    Saidi, Pooneh; Sadeghi, Mahdi

    2011-01-01

    With increased demand for low 103Pd (palladium) seed sources, to treat prostate and eye cancers, new sources have been designed and introduced. This article presents the two new palladium brachytherapy sources, IR03-103Pd and IR04-103Pd that have been developed at Nuclear Science and Technology Research Institute. The dosimetry parameters such as the dose rate constant Λ, the radial dose function g(r), and the anisotropy function F(r,θ), around the sources have been characterized using Version 5 Monte Carlo radiation transport code in accordance with the update AAPM Task Group No. 43 report (TG-43U1). The results indicated the dose rate constant of 0.689±0.02 and 0.667±0.02 cGy h-1 U-1 for the IR03-103Pd and IR04-103Pd sources respectively, which are in acceptable agreement with other commercial seeds. The calculated results were compared with published results for those of other source manufacturers. However, they show an acceptable dose distribution, using for clinical applications is pending experimental dosimetry.

  13. Electron Paramagnetic Resonance Retrospective Dosimetry

    SciTech Connect

    Romanyukha, Alex; Trompier, Francois

    2011-05-05

    Necessity for, principles of, and general concepts of the electron paramagnetic resonance (EPR) retrospective dosimetry are presented. Also presented and given in details are examples of EPR retrospective dosimetry applications in tooth enamel, bone, and fingernails with focus on general approaches for solving technical and methodological problems. Advantages, drawbacks, and possible future developments are discussed and an extensive bibliography on EPR retrospective dosimetry is provided.

  14. Hanford External Dosimetry Program

    SciTech Connect

    Fix, J.J.

    1990-10-01

    This document describes the Hanford External Dosimetry Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy (DOE) and its Hanford contractors. Program services include administrating the Hanford personnel dosimeter processing program and ensuring that the related dosimeter data accurately reflect occupational dose received by Hanford personnel or visitors. Specific chapters of this report deal with the following subjects: personnel dosimetry organizations at Hanford and the associated DOE and contractor exposure guidelines; types, characteristics, and procurement of personnel dosimeters used at Hanford; personnel dosimeter identification, acceptance testing, accountability, and exchange; dosimeter processing and data recording practices; standard sources, calibration factors, and calibration processes (including algorithms) used for calibrating Hanford personnel dosimeters; system operating parameters required for assurance of dosimeter processing quality control; special dose evaluation methods applied for individuals under abnormal circumstances (i.e., lost results, etc.); and methods for evaluating personnel doses from nuclear accidents. 1 ref., 14 figs., 5 tabs.

  15. Neutron beam measurement dosimetry

    SciTech Connect

    Amaro, C.R.

    1995-11-01

    This report describes animal dosimetry studies and phantom measurements. During 1994, 12 dogs were irradiated at BMRR as part of a 4 fraction dose tolerance study. The animals were first infused with BSH and irradiated daily for 4 consecutive days. BNL irradiated 2 beagles as part of their dose tolerance study using BPA fructose. In addition, a dog at WSU was irradiated at BMRR after an infusion of BPA fructose. During 1994, the INEL BNCT dosimetry team measured neutron flux and gamma dose profiles in two phantoms exposed to the epithermal neutron beam at the BMRR. These measurements were performed as a preparatory step to the commencement of human clinical trials in progress at the BMRR.

  16. Image-guided adaptive radiation therapy (IGART): Radiobiological and dose escalation considerations for localized carcinoma of the prostate

    SciTech Connect

    Song, William; Schaly, Bryan; Bauman, Glenn; Battista, Jerry; Van Dyk, Jake

    2005-07-15

    The goal of this work was to evaluate the efficacy of various image-guided adaptive radiation therapy (IGART) techniques to deliver and escalate dose to the prostate in the presence of geometric uncertainties. Five prostate patients with 15-16 treatment CT studies each were retrospectively analyzed. All patients were planned with an 18 MV, six-field conformal technique with a 10 mm margin size and an initial prescription of 70 Gy in 35 fractions. The adaptive strategy employed in this work for patient-specific dose escalation was to increase the prescription dose in 2 Gy-per-fraction increments until the rectum normal tissue complication probability (NTCP) reached a level equal to that of the nominal plan NTCP (i.e., iso-NTCP dose escalation). The various target localization techniques simulated were: (1) daily laser-guided alignment to skin tattoo marks that represents treatment without image-guidance, (2) alignment to bony landmarks with daily portal images, and (3) alignment to the clinical target volume (CTV) with daily CT images. Techniques (1) and (3) were resimulated with a reduced margin size of 5 mm to investigate further dose escalation. When delivering the original clinical prescription dose of 70 Gy in 35 fractions, the 'CTV registration' technique yielded the highest tumor control probability (TCP) most frequently, followed by the 'bone registration' and 'tattoo registration' techniques. However, the differences in TCP among the three techniques were minor when the margin size was 10 mm ({<=}1.1%). Reducing the margin size to 5 mm significantly degraded the TCP values of the 'tattoo registration' technique in two of the five patients, where a large difference was found compared to the other techniques ({<=}11.8%). The 'CTV registration' technique, however, did maintain similar TCP values compared to their 10 mm margin counterpart. In terms of normal tissue sparing, the technique producing the lowest NTCP varied from patient to patient. Reducing the

  17. Cosmic Ray Dosimetry

    NASA Astrophysics Data System (ADS)

    Si Belkhir, F.; Attallah, R.

    2010-10-01

    Radiation levels at aircraft cruising altitudes are twenty times higher than at sea level. Thus, on average, a typical airline pilot receives a larger annual radiation dose than some one working in nuclear industry. The main source of this radiation is from galactic cosmic radiation, high energy particles generated by exploding stars within our own galaxy. In this work we study cosmic rays dosimetry at various aviation altitudes using the PARMA model.

  18. Thorium metabolism and dosimetry

    SciTech Connect

    Johnson, J.R.; Hill, R.L.; Birchall, A.; Jarvis, N.S.

    1994-07-01

    Thorium occurs widely in nature, and has been used in medicine, industry, and advanced nuclear fuel cycles. Despite many studies, there still remains uncertainty in the dosimetry of Th, particularly that associated with the Th-232 decay chain. This presentation reviews past and current uses of thorium, and describes the residual difficulties involved with monitoring methods and calculations used in both environmental and occupational exposure evaluations.

  19. Prognostic Value of Ki67 in Localized Prostate Carcinoma: A Multi-Institutional Study of >1,000 Prostatectomies

    PubMed Central

    Tretiakova, Maria S.; Wei, Wei; Boyer, Hilary D.; Newcomb, Lisa F.; Hawley, Sarah; Auman, Heidi; Vakar-Lopez, Funda; McKenney, Jesse K.; Fazli, Ladan; Simko, Jeffry; Troyer, Dean A.; Hurtado-Coll, Antonio; Thompson, Ian M.; Carroll, Peter R.; Ellis, William J.; Gleave, Martin E.; Nelson, Peter S.; Lin, Daniel W.; True, Lawrence D.; Feng, Ziding; Brooks, James D.

    2017-01-01

    Background Expanding interest in and use of active surveillance for early state prostate cancer has increased need for prognostic biomarkers. Using a multi-institutional tissue microarray resource including over 1000 radical prostatectomy samples, we sought to correlate Ki67 expression captured by an automated image analysis system with clinico-pathologic features and validate its utility as a clinical grade test in predicting cancer-specific outcomes. Methods After immunostaining, the Ki67 proliferation index (PI) of tumor areas of each core (3 cancer cores/case) was analyzed using a nuclear quantification algorithm (Aperio). We assessed whether Ki67 PI was associated with clinico-pathologic factors and recurrence free survival including biochemical recurrence, metastasis or PC death (7-year median follow-up). Results In 1004 PCs (~4,000 tissue cores) Ki67 PI showed significantly higher inter-tumor (0.68) than intra-tumor variation (0.39). Ki67 PI was associated with stage (p<0.0001), seminal vesicle invasion (SVI, p=0.02), extracapsular extension (ECE, p<0.0001) and Gleason Score (GS, p<0.0001). Ki67 PI as a continuous variable significantly correlated with recurrence free, overall and disease-specific survival by multivariable Cox proportional hazard model (HR=1.04–1.1, p=0.02–0.0008). High Ki67 score (defined as ≥5%) was significantly associated with worse recurrence free survival (HR=1.47, p=0.0007) and worse overall survival (HR=2.03, p=0.03). Conclusion In localized PC treated by radical prostatectomy, higher Ki67 PI assessed using a clinical grade automated algorithm is strongly associated with a higher GS, stage, SVI and ECE, and greater probability of recurrence. PMID:27136741

  20. Feasibility of salvage interstitial microwave thermal therapy for prostate carcinoma following failed brachytherapy: studies in a tissue equivalent phantom

    NASA Astrophysics Data System (ADS)

    McCann, Claire; Kumaradas, J. Carl; Gertner, Mark R.; Davidson, Sean R. H.; Dolan, Alfred M.; Sherar, Michael D.

    2003-04-01

    Thermal therapy is an experimental treatment to destroy solid tumours by heating them to temperatures ranging from 55 °C to 90 °C, inducing thermal coagulation and necrosis of the tumour. We are investigating the feasibility of interstitial microwave thermal therapy as a salvage treatment for prostate cancer patients with local recurrence following failed brachytherapy. Due to the electrical and thermal conductivity of the brachytherapy seeds, we hypothesized that the seeds could scatter the microwave energy and cause unpredictable heating. To investigate this, a 915 MHz helical antenna was inserted into a muscle-equivalent phantom with and without brachytherapy seeds. Following a 10 W, 5 s input to the antenna, the temperature rise was used to calculate absorbed power, also referred to as specific absorption rate (SAR). Plane wave models based on Maxwell's equations were also used to characterize the electromagnetic scattering effect of the seeds. In addition, the phantom was heated with 8 W for 5 min to quantify the effect of the seeds on the temperature distribution during extended heating. SAR measurements indicated that the seeds had no significant effect on the shape and size of the SAR pattern of the antenna. However, the plane wave simulations indicated that the seeds could scatter the microwave energy resulting in hot spots at the seed edges. Lack of experimental evidence of these hot spots was probably due to the complex polarization of the microwaves emitted by the helical antenna. Extended heating experiments also demonstrated that the seeds had no significant effect on the temperature distributions and rates of temperature rise measured in the phantom. The results indicate that brachytherapy seeds are not a technical impediment to interstitial microwave thermal therapy as a salvage treatment following failed brachytherapy.