Breast cancer plasticity is restricted by a LATS1-NCOR1 repressive axis.

Breast cancer, the most frequent cancer in women, is generally classified into several distinct histological and molecular subtypes. However, single-cell technologies have revealed remarkable cellular and functional heterogeneity across subtypes and even within individual breast tumors. Much of this heterogeneity is attributable to dynamic alterations in the epigenetic landscape of the cancer cells, which promote phenotypic plasticity.

Voxel-based comparison of [Ga]Ga-RM2-PET/CT and [Ga]Ga-PSMA-11-PET/CT with histopathology for diagnosis of primary prostate cancer.

Background: Focal therapies or focally escalated therapies of primary prostate cancer are becoming more and more important. This increases the need to identify the exact extension of the intraprostatic tumor and possible dominant intraprostatic lesions by imaging techniques. While the prostate-specific membrane antigen (PSMA) is already a well-established target for imaging of prostate cancer cells, the gastrin-releasing peptide receptor (GRPR) seems to provide interesting additional information.

Results from extended lymphadenectomies with [In]PSMA-617 for intraoperative detection of PSMA-PET/CT-positive nodal metastatic prostate cancer.

Purpose: Identification of suspicious PSMA-PET/CT-positive lymph node (LN) metastases (LNM) from prostate cancer (PCa) during lymphadenectomy (LA) is challenging. We evaluated an In-labelled PSMA ligand (DKFZ-617, referred to as [In]PSMA-617) as a γ-emitting tracer for intraoperative γ-probe application for resected tissue samples in PCa patients. Forty-eight hours prior to LA, [In]PSMA-617 was administered intravenously in 23 patients with suspected LNM on PSMA-PET/CT (n = 21 with biochemical relapse, n = 2 at primary therapy).

Accuracy of [Ga]Ga-RM2-PET/CT for diagnosis of primary prostate cancer compared to histopathology.

Introduction: Prostate cancer (PCa) often shows an overexpression of the gastrin-releasing peptide receptor (GRPr). Therefore, GRPr is a possible theragnostic target. An interesting antagonist GRPr-ligand is RM2 or BAY86-7548.

Detection Rate of F-Choline PET/CT and Ga-PSMA-HBED-CC PET/CT for Prostate Cancer Lymph Node Metastases with Direct Link from PET to Histopathology: Dependence on the Size of Tumor Deposits in Lymph Nodes.

Accurate detection of prostate cancer lymph node metastases (LNM) through PET/CT before lymphadenectomy is crucial for successful therapy. PET/CT with choline derivatives used to be the standard tool for imaging metastases, whereas Ga-PSMA (prostate-specific membrane antigen) PET/CT was introduced recently. Both PET techniques were investigated with respect to what extent the detection rate of LNM depends on the size of tumor deposits (TDs) within LNM.

Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas.

Background: Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5-7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding.

Performance of In-labelled PSMA ligand in patients with nodal metastatic prostate cancer: correlation between tracer uptake and histopathology from lymphadenectomy.

Purpose: Intraoperative identification of lymph node (LN) metastases (LNM) detected on preoperative PSMA PET/CT may be facilitated by PSMA radioguided surgery with the use of a gamma probe. We evaluated the uptake of In-labelled PSMA ligand DKFZ-617 (referred to as In-PSMA-617) in unaffected LN and LNM at the level of single LN.

Methods: Six patients with prostate cancer (PCa) with suspicion of LNM on preoperative PSMA PET/CT underwent In-PSMA-617-guided lymphadenectomy (LA; four salvage LA and two primary LA).

Focal dose escalation for prostate cancer using Ga-HBED-CC PSMA PET/CT and MRI: a planning study based on histology reference.

Background: Focal radiation therapy has gained of interest in treatment of patients with primary prostate cancer (PCa). The question of how to define the intraprostatic boost volume is still open. Previous studies showed that multiparametric MRI (mpMRI) or PSMA PET alone could be used for boost volume definition.

Proteomic Characterization of Prostate Cancer to Distinguish Nonmetastasizing and Metastasizing Primary Tumors and Lymph Node Metastases.

Patients with metastatic prostate cancer (PCa) have a poorer prognosis than patients with organ-confined tumors. We strove to uncover the proteome signature of primary PCa and associated lymph node metastases (LNMs) in order to identify proteins that may indicate or potentially promote metastases formation. We performed a proteomic comparative profiling of PCa tissue from radical prostatectomy (RPE) of patients without nodal metastases or relapse at the time of surgical resection (n=5) to PCa tissue from RPE of patients who suffered from nodal relapse (n=5).

Proteome profiling of clear cell renal cell carcinoma in von Hippel-Lindau patients highlights upregulation of Xaa-Pro aminopeptidase-1, an anti-proliferative and anti-migratory exoprotease.

Patients of the von Hippel-Lindau (VHL) disease frequently develop clear cell renal cell carcinoma (ccRCC). Using archived, formalin-fixed, paraffin-embedded (FFPE) samples, we sought to determine global proteome alterations that distinguish ccRCC tissue from adjacent, non-malignant kidney tissue in VHL-patients. Our quantitative proteomic analysis clearly discriminated tumor and non-malignant tissue.

Diagnostic Accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before Salvage Lymph Node Dissection for Recurrent Prostate Cancer.

By targeting the prostate-specific membrane antigen (PSMA) on prostate cancer (PCa) cells PSMA-PET/CT shows great potential in locating the site of biochemical recurrence even at low PSA (Prostate-specific antigen)-levels. Accurate imaging of PCa recurrent lymph node metastases (LNM) is crucial for metastases directed therapies such as salvage-lymph node dissection (salvage-LND). To evaluate the diagnostic accuracy of PSMA-PET/CT for detection of affected lymph-node regions at salvage-LND for nodal recurrence of PCa.

Evaluation of intensity modulated radiation therapy dose painting for localized prostate cancer using Ga-HBED-CC PSMA-PET/CT: A planning study based on histopathology reference.

Purpose: To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa).

Methods And Materials: 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%.

IgG4-related disease in autoimmune lymphoproliferative syndrome.

A patient with autoimmune lymphoproliferative disorder (ALPS) developed IgG4-related disease. In retrospect, he had high levels of serum IgG4 for several years prior to presenting with IgG4-related pancreatitis. These high IgG4 levels were masked by hypergammaglobulinemia, a common feature of ALPS.

Diagnosis of recurrent prostate cancer with PET/CT imaging using the gastrin-releasing peptide receptor antagonist Ga-RM2: Preliminary results in patients with negative or inconclusive [F]Fluoroethylcholine-PET/CT.

Purpose/background: [F]fluoroethylcholine (FECH) has been shown to be a valuable PET-tracer in recurrent prostate cancer (PCa), but still has limited accuracy. RM2 is a gastrin-releasing peptide receptor (GRPr) antagonist that binds to GRPr on PCa cells. Recent studies suggest that GRPr imaging with PET/CT is a promising technique for staging and restaging of PCa.

Diabetes and beta-adrenergic blockage are risk factors for metastatic prostate cancer.

Background: We evaluated the influence of comorbidity inferred risks for lymph node metastasis (pN1) and positive surgical margins (R1) after radical prostatectomy in order to optimize pretherapeutic risk classification. We analyzed 454 patients after radical prostatectomy (RP) between 2009 and 2014. Comorbidities were defined by patients' medication from our electronic patient chart and stratified according to the ATC WHO code.

Comparison of Ga-HBED-CC PSMA-PET/CT and multiparametric MRI for gross tumour volume detection in patients with primary prostate cancer based on slice by slice comparison with histopathology.

Purpose: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material.

Methodology: Seven patients with histopathologically proven primary PCa underwent Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy.

Diagnostic Accuracy of Robot-Guided, Software Based Transperineal MRI/TRUS Fusion Biopsy of the Prostate in a High Risk Population of Previously Biopsy Negative Men.

. In this study, we compared prostate cancer detection rates between MRI-TRUS fusion targeted and systematic biopsies using a robot-guided, software based transperineal approach. .

Single punch, double biopsy.

Objective: In lethal primary metastatic prostate cancer, biopsy material is often the only accessible cancer tissue. Lack of tissue quantity limited the use of biopsy cores for analyzing higher numbers of molecular markers and standard histopathologic evaluation for clinical diagnosis simultaneously. Recent advances in single cell analytics have paved the way to characterize a tumor in more depth from minute input material such as biopsies.

Gastrin-releasing Peptide Receptor Imaging in Breast Cancer Using the Receptor Antagonist (68)Ga-RM2 And PET.

Introduction: The gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer. The present study evaluates GRPR imaging as a novel imaging modality in breast cancer by employing positron emission tomography (PET) and the GRPR antagonist (68)Ga-RM2.

Methods: Fifteen female patients with biopsy confirmed primary breast carcinoma (3 bilateral tumors; median clinical stage IIB) underwent (68)Ga-RM2-PET/CT for pretreatment staging.

(68)Ga-HBED-CC-PSMA PET/CT Versus Histopathology in Primary Localized Prostate Cancer: A Voxel-Wise Comparison.

Purpose: We performed a voxel-wise comparison of (68)Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of (68)Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa).

Methodology: Nine patients with histopathological proven primary PCa underwent (68)Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared.

A novel miRNA-based predictive model for biochemical failure following post-prostatectomy salvage radiation therapy.

Purpose: To develop a microRNA (miRNA)-based predictive model for prostate cancer patients of 1) time to biochemical recurrence after radical prostatectomy and 2) biochemical recurrence after salvage radiation therapy following documented biochemical disease progression post-radical prostatectomy.

Methods: Forty three patients who had undergone salvage radiation therapy following biochemical failure after radical prostatectomy with greater than 4 years of follow-up data were identified. Formalin-fixed, paraffin-embedded tissue blocks were collected for all patients and total RNA was isolated from 1mm cores enriched for tumor (>70%).

Cell type specific gene expression analysis of prostate needle biopsies resolves tumor tissue heterogeneity.

A lack of cell surface markers for the specific identification, isolation and subsequent analysis of living prostate tumor cells hampers progress in the field. Specific characterization of tumor cells and their microenvironment in a multi-parameter molecular assay could significantly improve prognostic accuracy for the heterogeneous prostate tumor tissue. Novel functionalized gold-nano particles allow fluorescence-based detection of absolute mRNA expression levels in living cells by fluorescent activated flow cytometry (FACS).

PRK1/PKN1 controls migration and metastasis of androgen-independent prostate cancer cells.

The major threat in prostate cancer is the occurrence of metastases in androgen-independent tumor stage, for which no causative cure is available. Here we show that metastatic behavior of androgen-independent prostate tumor cells requires the protein-kinase-C-related kinase (PRK1/PKN1) in vitro and in vivo. PRK1 regulates cell migration and gene expression through its kinase activity, but does not affect cell proliferation.

Adjuvant radiotherapy after salvage lymph node dissection because of nodal relapse of prostate cancer versus salvage lymph node dissection only.

Background: Nodal pelvic/retroperitoneal recurrent prostate cancer (PCa) after primary therapy can be treated with salvage lymph node dissection (salvage-LND) in order to delay disease progression and offer cure for a subset of patients. Whether adjuvant radiotherapy (ART) in affected regions improves the outcome by elimination of residual tumour burden remains unclear.

Methods: A total of 93 patients with exclusively nodal PCa relapse underwent choline-positron-emission tomography-computed-tomography-directed pelvic/retroperitoneal salvage-LND; 46 patients had surgery only and 47 patients received ART in regions with proven lymph node metastases.