Hyperthyroidism induced by paraneoplastic human chorionic gonadotropin (hCG) production from testicular tumours: a retrospective clinical and histopathological study.

Human chorionic gonadotropin (hCG) has structural similarities with thyroid-stimulating hormone (TSH) and may stimulate TSH receptors at higher concentrations. During pregnancy, placental hCG causes TSH suppression, contributing to hyperemesis. However, in males, clinical manifestations caused by excess hCG are rare.

Establishment of primary prostate epithelial and tumorigenic cell lines using a non-viral immortalization approach.

Background: Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro.

Loss of PDE4D7 expression promotes androgen independence, neuroendocrine differentiation and alterations in DNA repair: implications for therapeutic strategies.

Background: Androgen signalling remains the seminal therapeutic approach for the management of advanced prostate cancer. However, most tumours eventually shift towards an aggressive phenotype, characterised by androgen independence and treatment resistance. The cyclic adenosine monophosphate (cAMP) pathway plays a crucial role in regulating various cellular processes, with the phosphodiesterase PDE4D7 being a vital modulator of cAMP signalling in prostate cancer cells.

Systematic comparison of local approaches for isotopically nonstationary metabolic flux analysis.

Quantification of reaction fluxes of metabolic networks can help us understand how the integration of different metabolic pathways determine cellular functions. Yet, intracellular fluxes cannot be measured directly but are estimated with metabolic flux analysis (MFA) that relies on the patterns of isotope labeling of metabolites in the network. For metabolic systems, typical for plants, where all potentially labeled atoms effectively have only one source atom pool, only isotopically nonstationary MFA can provide information about intracellular fluxes.

The CAPRA&PDE4D5/7/9 Prognostic Model Is Significantly Associated with Adverse Post-Surgical Pathology Outcomes.

Objectives: To investigate the association of the prognostic risk score CAPRA&PDE4D5/7/9 as measured on pre-surgical diagnostic needle biopsy tissue with pathological outcomes after radical prostatectomies in a clinically low−intermediate-risk patient cohort. Patients and Methods: RNA was extracted from biopsy punches of diagnostic needle biopsies. The patient cohort comprises n = 151 patients; of those n = 84 had low−intermediate clinical risk based on the CAPRA score and DRE clinical stage View Article and Find Full Text PDF

An automated workflow that generates atom mappings for large-scale metabolic models and its application to Arabidopsis thaliana.

Quantification of reaction fluxes of metabolic networks can help us understand how the integration of different metabolic pathways determines cellular functions. Yet, intracellular fluxes cannot be measured directly but are estimated with metabolic flux analysis (MFA), which relies on the patterns of isotope labeling of metabolites in the network. The application of MFA also requires a stoichiometric model with atom mappings that are currently not available for the majority of large-scale metabolic network models, particularly of plants.

Prostate-specific membrane antigen and fibroblast activation protein distribution in prostate cancer: preliminary data on immunohistochemistry and PET imaging.

Introduction: Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives.

Diagnostic efficiency of hybrid imaging using PSMA ligands, PET/CT, PET/MRI and MRI in identifying malignant prostate lesions.

Objective: The objective of this study was to assess the accuracy of Ga-PSMA-11 PET/MRI, F-PSMA-1007 PET/CT, Ga-PSMA-11 PET/CT, and multiparametric (mp)MRI for the delineating of dominant intraprostatic lesions (IPL).

Materials And Methods: 35 patients with organ-confined prostate cancer who were assigned to definitive radiotherapy (RT) were divided into three groups based on imaging techniques: Ga-PSMA-PET/MRI (n = 9), F-PSMA-PET/CT (n = 16) and Ga-PSMA-PET/CT (n = 10). All patients without PSMA-PET/MRI received an additional mpMRI.

Roles of CCR2 and CCR5 for Hepatic Macrophage Polarization in Mice With Liver Parenchymal Cell-Specific NEMO Deletion.

Background & Aims: Macrophages are key regulators of inflammation and cancer promotion in the liver, and their recruitment and activation is linked to chemokine receptor signaling. However, the exact roles of the chemokine receptors CCR2 and CCR5 for macrophage functions in the liver is obscure.

Methods: To study CCR2 and CCR5 in inflammatory liver injury, we used mice with a hepatocyte-specific knock-out of the nuclear factor κB (NF-κB) essential modulator (NEMO), termed NEMO mice, and generated NEMOCcr2 and NEMOCcr5 mice.

Response of Different Treatment Protocols to Treat Chronic Non-Bacterial Osteomyelitis (CNO) of the Mandible in Adult Patients: A Systematic Review.

(1) Background: Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of finally unknown etiology, which can occur alone or related with syndromes (chronic recurrent multifocal osteomyelitis-CRMO; synovitis, acne, pustulosis, hyperostosis and osteitis syndrome-SAPHO). The involvement of the mandible is rather rare. (2) Methods: We carried out a systematic literature search on CNO with mandibular involvement, according to the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines, considering the different synonyms for CNO, with a special focus on therapy.

Novel pathogenic alterations in pediatric and adult desmoid-type fibromatosis - A systematic analysis of 204 cases.

Desmoid-type fibromatosis (DTF, aggressive fibromatosis) is a non-metastasizing mesenchymal neoplasm of deep soft tissue with a tendency towards local recurrence. Genetic alterations affecting canonical Wnt/β-catenin signaling are reported in the majority of DTF. While most sporadic DTF harbor somatic mutations in CTNNB1, germline mutations in adenomatous polyposis coli (APC) are known to occur in hereditary DTF types (FAP, Gardner-Syndrome).

Prevalence of the Hippo Effectors YAP1/TAZ in Tumors of Soft Tissue and Bone.

Tumors of soft tissue and bone represent a heterogeneous group of neoplasias characterized by a wide variety of genetic aberrations. Albeit knowledge on tumorigenesis in mesenchymal tumors is continuously increasing, specific insights on altered signaling pathways as a basis for molecularly targeted therapeutic strategies are still sparse. The aim of this study was to determine the involvement of YAP1/TAZ-mediated signals in tumors of soft tissue and bone.

Prognostic impact of CD34 and SMA in cancer-associated fibroblasts in stage I-III NSCLC.

Background: Epithelial-to-mesenchymal transition (EMT) is a crucial step in lung cancer pathogenesis. Among others, cancer-associated fibroblasts (CAFs) are reported to regulate this process.

Objectives: To investigate the prognostic and clinical impact, we analyzed CD34+ and SMA+ CAFs in non-small cell lung cancer (NSCLC).

FDG-PET proves to be reliable in the diagnostic workup of a rare cardiac hemangioma.

The noninvasive characterization of cardiac tumors is of clinical importance for surgical resection planning. Conventional radiological examinations like cardiac computed tomography (CT) or magnetic resonance imaging (MRI) may be misleading as benign cardiac lesions can present features suspicious for malignancy. Moreover, the low prevalence of cardiac tumors may additionally hamper a sound diagnosis.

Using Image-guided Intensity-modulated Radiotherapy on Patients With Head and Neck Soft-tissue Sarcoma.

Background: Image-guided intensity-modulated radiotherapy (IG-IMRT) is increasingly being used to treat patients with soft-tissue sarcoma (STS) of the head and neck. Although there is no comparison between IMRT and conventional radiation therapy (CRT) concerning their efficacy. In this analysis, we compared CRT and IMRT outcomes for head and neck STS.

The Association of the Long Prostate Cancer Expressed PDE4D Transcripts to Poor Patient Outcome Depends on the Tumour's TMPRSS2-ERG Fusion Status.

Objectives: To investigate the added value of assessing transcripts for the long cAMP phosphodiesterase-4D (PDE4D) isoforms, PDE4D5 and PDE4D9, regarding the prognostic power of the 'CAPRA & PDE4D7' combination risk model to predict longitudinal postsurgical biological outcomes in prostate cancer.

Patients And Methods: RNA was extracted from both biopsy punches of resected tumours (606 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). RT-qPCR was performed in order to determine PDE4D5, PDE4D7, and PDE4D9 transcript scores in both study cohorts.

Noncaseating granulomatous diseases in germ cell cancer patients-A single-center experience.

Objectives: In patients with testicular Germ Cell Tumors (GCT) noncaseating granulomatous diseases such as Sarcoid Like Lesions (SLL) or Sarcoidosis can mimic metastasis due to hilar or mediastinal lymphadenopathy. Due to the clinical and prognostic impact, exclusion of malignant diseases is mandatory.

Material And Methods: Retrospectively, data from 636 GCT patients, who were seen in the course of tumor surveillance/follow-up were collected.

Requirement for YAP1 signaling in myxoid liposarcoma.

Myxoid liposarcomas (MLS), malignant tumors of adipocyte origin, are driven by the fusion gene encoding an aberrant transcription factor. The mechanisms whereby FUS-DDIT3 mediates sarcomagenesis are incompletely understood, and strategies to selectively target MLS cells remain elusive. Here we show, using an unbiased functional genomic approach, that FUS-DDIT3-expressing mesenchymal stem cells and MLS cell lines are dependent on YAP1, a transcriptional co-activator and central effector of the Hippo pathway involved in tissue growth and tumorigenesis, and that increased YAP1 activity is a hallmark of human MLS Mechanistically, FUS-DDIT3 promotes YAP1 expression, nuclear localization, and transcriptional activity and physically associates with YAP1 in the nucleus of MLS cells.

SS18-SSX-Dependent YAP/TAZ Signaling in Synovial Sarcoma.

Purpose: Synovial sarcoma is a soft tissue malignancy characterized by a reciprocal t(X;18) translocation. The chimeric SS18-SSX fusion protein acts as a transcriptional dysregulator representing the major driver of the disease; however, the signaling pathways activated by SS18-SSX remain to be elucidated to define innovative therapeutic strategies.

Experimental Design: Immunohistochemical evaluation of the Hippo signaling pathway effectors YAP/TAZ was performed in a large cohort of synovial sarcoma tissue specimens.

Phosphatidylinositol-3-kinase (PI3K)/Akt Signaling is Functionally Essential in Myxoid Liposarcoma.

Myxoid liposarcoma (MLS) is an aggressive soft-tissue tumor characterized by a specific reciprocal t(12;16) translocation resulting in expression of the chimeric FUS-DDIT3 fusion protein, an oncogenic transcription factor. Similar to other translocation-associated sarcomas, MLS is characterized by a low frequency of somatic mutations, albeit a subset of MLS has previously been shown to be associated with activating mutations. This study was performed to assess the prevalence of PI3K/Akt signaling alterations in MLS and the potential of PI3K-directed therapeutic concepts.

A Cardiac Metastasis of Follicular Thyroid Carcinoma With Partly Squamous Cell Differentiation: Detection in FDG-PET Preceded Visibility on Echocardiography and MRI by More Than a Year.

PET using the radiotracer F-fluorodeoxyglucose (FDG) was performed in a patient who presented with elevated thyroglobulin (Tg) levels several years after initial therapy of follicular thyroid carcinoma (oncocytic variant) and in whom high-dose radioiodine (I) failed to locate recurrent tumor or to decrease Tg levels. A focal fluorodeoxyglucose uptake in the apical septum of the heart did not have a discernible correlate in echocardiography or MRI for more than 12 months. Finally, a metastasis of the follicular thyroid carcinoma with partly squamous cell differentiation was confirmed and treated by resection and stereotactic body radiotherapy.

Expression levels of hnRNP K and p21WAF1/CIP1 are associated with resistance to radiochemotherapy independent of p53 pathway activation in rectal adenocarcinoma.

Ionizing radiation (IR) is frequently applied in the treatment of rectal adenocarcinoma, however, there is marked variance in the response to radiochemotherapy between individual tumors. In our previous investigations, it was shown that the overexpression of heterogeneous nuclear ribonucleoprotein K (hnRNP K) confers radioresistance to malignant melanoma and colorectal carcinoma (CRC) in vitro, however, the underlying mechanism remains to be elucidated. As hnRNP K, a p53 binding partner and cofactor for the transcriptional activation of p53 target genes, is overexpressed in CRC, the present study investigated the possible radioprotective effect of the hnRNP K/p53‑induced upregulation of p21 (also known as WAF1/CIP1) in rectal adenocarcinoma.

Somatic aberrations of BRCA1 gene are associated with ALDH1, EGFR, and tumor progression in prostate cancer.

BRCA1 is a pivotal tumor suppressor. Its dysfunction is known to play a role in different tumors. Among others, BRCA1 germline mutations account for higher risk and more aggressive course of prostate cancer (PCa).

The Prognostic PDE4D7 Score in a Diagnostic Biopsy Prostate Cancer Patient Cohort with Longitudinal Biological Outcomes.

To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes.