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Berlin Brandenburg

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  • 1
    Language: English
    In: The Journal of Urology, April 2013, Vol.189(4), pp.e389-e389
    Keywords: Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
    Source: ScienceDirect Journals (Elsevier)
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  • 2
    Language: English
    In: The Journal of Urology, March 2016, Vol.195(3), pp.771-779
    Description: The retinoblastoma signaling network is frequently altered in advanced bladder cancer. We investigated the potential of CDK4/6 as a therapeutic target and determined biomarkers for patient stratification. Genetic alterations were analyzed using public databases, including TCGA (The Cancer Genome Atlas), COSMIC (Catalogue of Somatic Mutations in Cancer) and CCLE (Cancer Cell Line Encyclopedia). Effects of the CDK4/6-inhibitor PD-0332991 or LY2835219 were examined in 10 bladder cancer cell lines by immunoblot, cell viability, apoptosis and cell cycle progression. Efficacy of the PD-0332991 and cisplatin combination was analyzed using the combination index. Gene expression level was determined by quantitative polymerase chain reaction. Cytomegalovirus promoter regulated recombinant retinoblastoma was used for reconstitution. Three-dimensional xenografts were grown on chicken chorioallantoic membrane and analyzed by measuring tumor weight and immunohistochemical expression of total retinoblastoma and Ki-67. PD-0332991 treatment decreased the proliferation of retinoblastoma positive bladder cancer cell lines and was synergistic in combination with cisplatin. PD-0332991 or LY2835219 treatment decreased the phosphorylation, total protein and transcript level of retinoblastoma. Treatment resulted in a decrease in E2F target gene expression ( and and cell cycle progression from G0/G1 to the S-phase but did not affect apoptosis. In retinoblastoma negative cells reconstituted with recombinant retinoblastoma PD-0332991 affected only phosphorylation and not the total retinoblastoma level. These cells remained resistant to treatment. In 3-dimensional retinoblastoma xenografts, treatment resulted in reduced tumor weight and decreased expression of total retinoblastoma and Ki-67. We provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription.
    Keywords: Urinary Bladder Neoplasms ; Retinoblastoma ; Cyclin-Dependent Kinase Inhibitor Proteins ; Palbociclib ; Biological Markers ; Medicine
    ISSN: 0022-5347
    E-ISSN: 1527-3792
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  • 3
    Language: English
    In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, October 2017, Vol.58(10), pp.1545-1552
    Description: Targeting the prostate-specific membrane antigen (PSMA) with Ga-labeled and F-labeled PET agents has become increasingly important in recent years. Imaging of biochemically recurrent prostate cancer has been established as a widely accepted clinical indication for PSMA ligand PET/CT in many parts of the world because of the results of multiple, primarily retrospective, studies that indicate superior detection efficacy compared with standard-of-care imaging. For high-risk primary prostate cancer, evidence is growing that this modality significantly aids in the detection of otherwise occult nodal and bone metastases. For both clinical indications in recurrent as well as in primary prostate cancer, preliminary data demonstrate a substantial impact on clinical management. Emerging data imply that intraprostatic tumor localization, therapy stratification, and treatment monitoring of advanced disease in specific clinical situations might become future indications. Current criteria for image reporting of PSMA ligand PET are evolving given the expanding body of literature on physiologic and pathologic uptake patterns and pitfalls. This article intends to give an educational overview on the current status of PSMA ligand PET imaging, including imaging procedure and interpretation, clinical indications, diagnostic potential, and impact on treatment planning.
    Keywords: Pet/CT ; Psma ; Prostate Cancer ; Antigens, Surface -- Metabolism ; Glutamate Carboxypeptidase II -- Metabolism ; Positron Emission Tomography Computed Tomography -- Methods ; Prostatic Neoplasms -- Diagnostic Imaging
    E-ISSN: 1535-5667
    Source: MEDLINE/PubMed (U.S. National Library of Medicine)
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  • 4
    Language: English
    In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, October 2016, Vol.57(Suppl 3), pp.38S-42S
    Description: Early diagnosis and adequate staging are crucial for the choice of adequate treatment in prostate cancer (PC). Morphologic and functional imaging modalities, such as CT and MRI, have had limited accuracy in the diagnosis and nodal staging of PC. Molecular PET/CT imaging with C- or F-choline-labeled derivatives is increasingly being used, but its role in the diagnosis and initial staging of PC is controversial because of limitations in sensitivity and specificity for the detection of primary PC. For T staging, functional MRI is superior to C- or F-choline PET/CT. For N staging, C- or F-choline PET/CT can provide potentially useful information that may influence treatment planning. For the detection of bone metastases, C- or F-choline PET/CT has had promising results; however, in terms of cost-effectiveness, the routine use of C- or F-choline PET/CT is still debatable. C- or F-choline PET/CT might be used in high-risk PC before radiation treatment planning, potentially affecting this planning (e.g., regarding dose escalation). This review provides an overview of the diagnostic accuracy and limitations of C- or F-choline PET/CT in the diagnosis and staging of PC.
    Keywords: Pet/CT ; Choline ; Diagnosis ; Prostate Cancer ; Staging ; Choline -- Analogs & Derivatives ; Positron Emission Tomography Computed Tomography -- Methods ; Prostatic Neoplasms -- Diagnostic Imaging
    ISSN: 01615505
    E-ISSN: 1535-5667
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  • 5
    In: Nuclear Medicine Communications, 2018, Vol.39(3), pp.236-246
    Description: OBJECTIVES: Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival. METHODS: A total of 30 (14 female and 16 male) patients with inoperable/metastatic NEN were treated with 7.4 GBq of Lu-DOTATATE. Occurrence of renal and hematological toxicity wasretrospectively studied. Morever, we examined the effects of hematological toxicity on survival after Lu-DOTATATE-PRRT. RESULTS: In 49 treatment cycles, the mean absorbed dose to the kidneys was 5.13±2.12, 4.49±2.49 Gy to the liver, and 14.44±8.97 Gy to the spleen, whereas tumor lesions absorbed a mean dose of 31.43±36.86 Gy. Comparing different localizations of metastases, no significant differences in absorbed dose were observed. Clinical response status revealed regressive disease in 47.6%, stable disease in 38.1%, and progressive disease in 14.3% of cases (n=21). Biochemically, 81.3% of patients showed reduced serotonin values (n=16; P〈0.05) following Lu-DOTATATE-PRRT. No severe subacute renal or hematological toxicity occurred (one Common Terminology Criteria for Adverse Events-grade 3 for thrombocytopenia and another one for leukocytopenia). No statistically significant relation between baseline kidney function and post-therapeutic hematological changes was identified. CONCLUSION: The findings indicate that Lu-DOTATATE-PRRT is a safe and effective treatment method for patients with NEN. Moreover, these data strongly suggest that hematological parameters may affect survival so a further re-evaluation in prospective studies is warranted.
    Keywords: Lutetium Lu 177 Dotatate – Health Aspects ; Neuroendocrine Tumors – Care and Treatment ; Peptide Receptor Radionuclide Therapy – Usage ; Peptide Receptor Radionuclide Therapy – Health Aspects;
    ISSN: 0143-3636
    E-ISSN: 14735628
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  • 6
    Language: English
    In: Nuklearmedizin. Nuclear medicine, February 2018, Vol.57(1), pp.26-30
    Description: Accurate staging of penile cancer requires invasive methods such as sentinel node biopsy or lymphadenectomy (LAD). We assessed the value of [F]FDG PET/CT for non-invasive nodal staging in penile cancer (PC) patients before inguinal LAD. 41 consecutive patients with PC (stage pT1 or higher, cN0) received [F]FDG PET/CT before undergoing bilateral modified or radical inguinal staging LAD. Lymph nodes with a visually increased [F]FDG uptake were classified as suspicious of lymph node metastases (LNM). Standardized uptake value (SUV) of suspicious inguinal lymph nodes was determined. Results of [F]FDG PET/CT were correlated with histopathology. In total 623 lymph nodes were resected, in 10 patients LNM were histologically confirmed (14/623 lymph nodes). In patient-based analysis [F]FDG PET/CT showed a sensitivity and specificity of 80% and 68 %, respectively, a positive predictive value (PPV) of 44 % and a negative predictive value (NPV) of 91 %. In the groin-based analysis, [F]FDG PET/CT had a sensitivity of 69 %, a specificity of 77 %, a PPV of 36 % and a NPV of 93 %. There was no significant difference in SUV and SUV between true positive and false positive lymph nodes (p = 0.093 and 0.069, respectively). [F]FDG PET/ CT shows a high NPV in penile cancer patients without clinically evident LNM. However, due to its limited sensitivity (especially with respect to LNM of small size) and specificity (i. e. in the differentiation between (post)inflammatory and metastatic lymph nodes) [F]FDG PET/CT cannot replace invasive nodal staging.
    Keywords: Fluorodeoxyglucose F18 ; Positron Emission Tomography Computed Tomography ; Radiopharmaceuticals ; Carcinoma, Squamous Cell -- Diagnostic Imaging ; Lymphatic Metastasis -- Diagnostic Imaging ; Penile Neoplasms -- Diagnostic Imaging
    ISSN: 00295566
    E-ISSN: 2567-6407
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  • 7
    Language: English
    In: Urologic Oncology: Seminars and Original Investigations, September 2017, Vol.35(9), pp.544.e1-544.e10
    Description: To analyze the contribution of Wnt signaling pathway to bladder cancer growth in order to identify suitable target molecules for therapy. Expression of Wnt 2/4/7, LRP5/6, TCF1/2/4, LEF-1, and β-actin was detected by reverse transcription polymerase chain reaction in a panel of 9 and for Wntless (WLS) in 17 bladder cancer cell lines. Protein expression of WLS was detected in 6 cell lines. Wnt/β-catenin activity was analyzed using the TOPflash/FOPflash luciferase reporter assay. Expression level of β-catenin, WIF1, Dickkopf proteins (DKK), HSulf-2, sFRP4, and WLS was modulated by transfecting or infecting cells transiently or stably with respective shRNAs, siRNAs, or cDNAs. For protein detection, whole cell lysates were applied to sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by immunoblots. Effects on cell growth were determined by cell viability assays and BrdU/APC incorporation/staining. For 3-dimensional tumor growth, the chicken chorioallantoic membrane model was used. Tumor growth was characterized by weight. Expression of molecular components and activation of the Wnt signaling pathway could be detected in all cell lines. Expression level of β-catenin, WIF1, DKK, WLS, and HSulf-2 influenced Wnt activity. Expression of WLS was confirmed in 17 cell lines by reverse transcription polymerase chain reaction and in 6 cell lines by immunoblotting. WLS positively regulates Wnt signaling, cell proliferation, and tumor growth in vitro and in vivo. These effects could be reversed by the expression of the Wnt antagonist WIF1 and DKK. Synergistic activity of cisplatin and WLS inactivation by genetic silencing could be observed on cell viability. The Wnt signaling pathway is ubiquitously activated in bladder cancer and regulates tumor growth. WLS might be a target protein for novel therapies in combination with established chemotherapy regimens.
    Keywords: Bladder Cancer ; Cell Signaling ; Wnt ; Wls ; Chorioallantoic Membrane Model ; Medicine
    ISSN: 1078-1439
    E-ISSN: 1873-2496
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  • 8
    Language: English
    In: Oncotarget, 27 September 2016, Vol.7(39), pp.63747-63757
    Description: Recent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients. In [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively). 11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS. The results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.
    Keywords: Pet/CT ; Choline ; Neoadjuvant Therapy ; Prostate Cancer ; Therapy Response Assessment ; Positron Emission Tomography Computed Tomography ; Choline -- Chemistry ; Prostatectomy -- Methods ; Prostatic Neoplasms -- Diagnostic Imaging
    E-ISSN: 1949-2553
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  • 9
    Language: English
    In: Oncotarget, 10 May 2016, Vol.7(19), pp.28151-9
    Description: Due to the high expression of the integrin αvβ3 not only on endothelial cells, but also on mature osteoclasts and prostate cancer cells, imaging of osseous metastases with αvβ3-targeted tracers seems promising. However, little is known about the patterns of αvβ3-expression in metastasized prostate cancer lesions in-vivo. Thus we evaluated the uptake of the αvβ3-specific PET tracer [18F]Galacto-RGD for assessment of bone metastases in prostate cancer patients. [18F]Galacto-RGD PET identified 58/74 bone-lesions (detection rate of 78.4%) and lymph node metastases in 2/5 patients. The SUVmean was 2.12+/-0.94 (range 0.70-4.38; tumor/blood 1.36+/-0.53; tumor/muscle 2.82+/-1.31) in bone-lesions and 2.21+/-1.18 (range 0.75-3.56) in lymph node metastases. Good visualization and detection of bone metastases was feasible due to a low background activity of the surrounding normal bone tissue. 12 patients with known metastasized prostate cancer according to conventional staging (including bone-scintigraphy and contrast-enhanced CT; median PSA 68.63 ng/ml, range 3.72-1935) were examined with PET after i.v.-injection of [18F]Galacto-RGD. Two blinded nuclear-medicine physicians evaluated the PET-scans in consensus concerning lesion detectability. Volumes-of-interest were drawn in the PET-scans over all metastases defined by conventional staging (maximum of 11 lesions/patient), over the left ventricle, liver and muscle and standardized-uptake-values (SUVs) were calculated. Our data show generally elevated uptake of [18F]Galacto-RGD in bone metastases from prostate cancer with a marked inter- and intrapatient variability. While [18F]Galacto-RGD PET is inferior to bone scintigraphy for detection of osseous metastases, it might be valuable in patient screening and monitoring of αvβ3-targeted therapies due to the high variability of αvβ3-expression.
    Keywords: Pet ; Angiogenesis ; Integrins ; Prostate Cancer ; Αvβ3 ; Bone Neoplasms -- Diagnostic Imaging ; Integrin Alphavbeta3 -- Analysis ; Positron-Emission Tomography -- Methods ; Prostatic Neoplasms -- Pathology
    E-ISSN: 1949-2553
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  • 10
    Language: English
    In: Journal of nuclear medicine : official publication, Society of Nuclear Medicine, September 2017, Vol.58(Suppl 2), pp.67S-76S
    Description: The prostate-specific membrane antigen (PSMA) is highly expressed on most prostate cancer (PC) cells. Therefore, the targeting of PSMA has become increasingly important over the last decade. Glu-urea-based PSMA ligands used for both imaging and radioligand therapy are the mainstays of the current success. For PET imaging, both Ga- and F-labeled agents have been successfully translated to clinical applications. Mainly retrospective cohort studies have shown a high value in the setting of biochemical recurrence, with high detection rates even in the presence of low prostate-specific antigen levels. Preliminary data indicated that radioguided surgery with PSMA ligands may help to further improve patient outcomes because it facilitates the removal of small tumor deposits that are otherwise difficult to detect. For primary PC, PSMA ligand PET imaging has been shown to be superior to cross-sectional imaging for the detection of metastatic lymph nodes. In addition, it promises to also provide intraprostatic tumor localization, especially when used in combination with multiparametric MRI. Increasing numbers of studies have reported considerable changes in management resulting from PSMA ligand PET imaging for both biochemical recurrence and primary disease. The use of Lu-PSMA-based radioligand therapy has demonstrated a reasonable response, mainly as defined by a prostate-specific antigen response of more than 50%, comparable to other recently introduced agents. Especially given the high level of safety of Lu-PSMA radioligand therapy, with only minimal grade 3 and 4 toxicities reported so far, it has the potential to expand options for metastatic castration-resistant PC. This review is intended to provide a comprehensive overview of the current literature on low-molecular-weight PSMA ligands for both PET imaging and therapeutic approaches, with a focus on agents that have been clinically adopted.
    Keywords: Imaging ; Prostate Cancer ; Prostate-Specific Membrane Antigen ; Therapy ; Antigens, Surface -- Metabolism ; Diagnostic Imaging -- Methods ; Glutamate Carboxypeptidase II -- Metabolism ; Molecular Targeted Therapy -- Methods
    ISSN: 01615505
    E-ISSN: 1535-5667
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