COVID-19 Pandemic Impact on Uro-Oncological Disease Outcomes at a German Referral Center.

Introduction: To assess differences in referral and pathologic outcomes for uro-oncology cases prior to, during, and after the COVID-19 pandemic, comparing clinical and pathological data from cancer surgeries performed at a university medical center between 2018 and 2023.

Methods: We collected data of 212 patients with radical prostatectomy (RP) for prostate cancer, 157 patients with radical cystectomies (RCs) for bladder cancer, 36 patients with radical nephroureterectomies (RNUs) for upper tract urothelial carcinoma, 133 patients with partial nephrectomies (PNs), and 160 patients with radical nephrectomies (RNs) for renal cancer, 93 patients with orchifunicolectomy for testicular cancer, 39 patients with newly diagnosed penile cancer. Data from patients treated between 2018 and February 2020 (before the COVID-19 pandemic) were compared with data from patients treated between March 2020 and March 2022 (during the COVID-19 pandemic) and between April 2022 and February 2023 (after the COVID-19 pandemic).

Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinomas (UTUCs) occur in about 5-10% of all urothelial carcinomas and are frequently discovered in high-stage disease. We aimed to evaluate human epidermal growth factor receptor 2 (ERBB2) protein expression immunohistochemically and amplification in UTUCs by fluorescence in situ hybridization, applying a tissue microarray technique. ERBB2 overexpression and amplification were defined according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for breast cancer and gastric carcinoma (GC), revealing scores of 2+ and 3+ in 10.

Loss of Mismatch-repair Protein Expression and Microsatellite Instability in Upper Tract Urothelial Carcinoma and Clinicopathologic Implications.

Background: Upper tract urothelial carcinoma (UTUC) may arise in the setting of hereditary non-polyposis colorectal cancer (Lynch syndrome [LS]) or sporadically. Variable frequencies of microsatellite instability (MSI) were found in UTUC. For advanced solid MSI tumors, targeted therapy with programmed death-ligand 1 inhibitors is available.

[Renal cell carcinoma diagnosis and prognosis within the context of the WHO classification 2016].

Background: Histological classification of renal cell carcinoma (RCC) has become more and more important for clinical management, but relatively few is known regarding the swiftness with which the 2016 World Health Organization (WHO) classification of RCC was adopted in the daily routine diagnostics.

Aim: To retrospectively review the histological diagnosis of RCC within the context of 2016 WHO classification followed by survival analysis.

Material And Methods: Retrospective register based analysis of RCC diagnosis between 1998 and 2017 and survival analysis.

Frequent and Yet Unreported GNAQ and GNA11 Mutations are Found in Uveal Melanomas.

Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing.

Frameshift mutational target gene analysis identifies similarities and differences in constitutional mismatch repair-deficiency and Lynch syndrome.

Mismatch-repair deficient (MMR-D) malignancies include Lynch Syndrome (LS), which is secondary to germline mutations in one of the MMR genes, and the rare childhood-form of constitutional mismatch repair-deficiency (CMMR-D); caused by bi-allelic MMR gene mutations. A hallmark of LS-associated cancers is microsatellite instability (MSI), characterized by coding frameshift mutations (cFSM) in target genes. By contrast, tumors arising in CMMR-D patients are thought to display a somatic mutation pattern differing from LS.

Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011.

Background: Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients.

[Diagnostic Workup and Treatment of Antibody-Related Encephalomyelitis].

The results of laboratory tests for antineuronal antibodies in immune-mediated encephalitis nowadays are not only relevant for diagnostic purposes but are instead closely connected to outcome measures and treatment response. Besides the mere detection of antibodies, investigating the cerebrospinal fluid is indispensible to rule out an infectious etiology of encephalitis prior to the initiation of immunosuppressive treatment, whereas imaging studies are relevant to gain information on the temporal course of disease and for ruling out other etiologies, e. g.

[Autoimmune-Mediated Encephalomyelitis: a Heterogeneous Entity in Between Neurology and Psychiatry].

Within the last decade, autoantibody-associated encephalitis and encephalomyelitis have stepped into the focus of clinical research and practice. Besides the "classic" autoantibodies against intracellular neuronal antigenes, a growing number of antibodies directed against pre- and postsynaptic surface proteins of neurons have been described since the millennium change. Whereas the "classic" are closely linked to paraneoplastic syndromes, this association is loose for most of the yet known surface antigen-antibodies.

Expression and clinicopathological correlations of retinoid acid receptor responder protein 1 in renal cell carcinomas.

Aim: To evaluate the expression and prognostic value of RARRES1 at protein level in renal cell carcinoma (RCC).

Materials & Methods: Expression profile of RARRES1 was analyzed in 903 documented RCC followed by clinicopathological correlations and survival analysis.

Results: RARRES1 expression was seen in 72.

Substrate-specific effects of pirinixic acid derivatives on ABCB1-mediated drug transport.

Pirinixic acid derivatives, a new class of drug candidates for a range of diseases, interfere with targets including PPARα, PPARγ, 5-lipoxygenase (5-LO), and microsomal prostaglandin and E2 synthase-1 (mPGES1). Since 5-LO, mPGES1, PPARα, and PPARγ represent potential anti-cancer drug targets, we here investigated the effects of 39 pirinixic acid derivatives on prostate cancer (PC-3) and neuroblastoma (UKF-NB-3) cell viability and, subsequently, the effects of selected compounds on drug-resistant neuroblastoma cells. Few compounds affected cancer cell viability in low micromolar concentrations but there was no correlation between the anti-cancer effects and the effects on 5-LO, mPGES1, PPARα, or PPARγ.

[The parameter "relative survival": Analysis of regional cancer registry data for prostate cancer].

Background: There is a lack of comparability of relative survival rates due to differences in regional mortality.

Objective: How should relative survival be calculated to be able to compare regional cancer mortality?

Materials And Methods: Calculation of relative survival rates of prostate cancer patients from a regional cancer registry using diagnosis year and stage, based on differential mortality tables.

Results: Calculation of relative survival for all prostate cancer patients shows a very slight excess mortality after 5 years compared to a matched general population.

Older patients with inoperable non-small cell lung cancer: long-term survival after concurrent chemoradiotherapy.

Purpose: Considering the various comorbidities associated with aging, the feasibility and usefulness of concurrent chemoradiotherapy (CRT) in older patients with inoperable non-small cell lung cancer (NSCLC) is a controversial issue. Here, we compared the feasibility of CRT and the effects of various comorbidities on the prognosis of a minimally selected population of inoperable NSCLC patients aged 60-77 years.

Patients And Methods: The study comprised 161 patients with inoperable NSCLC who received CRT with a target radiation dose greater than  60 Gy and platinum-based chemotherapy from 1998 to 2007.

C-kit overexpression is not associated with KIT gene mutations in chromophobe renal cell carcinoma or renal oncocytoma.

Introduction: C-kit overexpression has previously been described in chromophobe renal cell carcinoma (cpRCC) and renal oncocytoma (RO). However, so far no KIT mutations have been found. The objective of our study was to analyse c-kit in a large cohort of renal tumors and to perform KIT mutation analysis in a subset cpRCC and RO cases with overexpression of c-kit.

Prognostic and diagnostic implications of epithelial cell adhesion/activating molecule (EpCAM) expression in renal tumours: a retrospective clinicopathological study of 948 cases using tissue microarrays.

Objective: To evaluate the expression and prognostic value of epithelial cell adhesion/activating molecule (EpCAM) in a large set of renal cell carcinomas (RCCs) using a tissue microarray (TMA) approach.

Material And Methods: We studied the immunohistochemical expression and overexpression of EpCAM on TMAs containing formalin-fixed, paraffin-embedded samples of 948 patients with documented renal tumours. EpCAM expression was defined as the presence of a specific membranous staining in >5% of the tumour cells.

Structural basis for the regulation of the mitogen-activated protein (MAP) kinase p38α by the dual specificity phosphatase 16 MAP kinase binding domain in solution.

Mitogen-activated protein kinases (MAPKs) fulfill essential biological functions and are key pharmaceutical targets. Regulation of MAPKs is achieved via a plethora of regulatory proteins including activating MAPKKs and an abundance of deactivating phosphatases. Although all regulatory proteins use an identical interaction site on MAPKs, the common docking and hydrophobic pocket, they use distinct kinase interaction motif (KIM or D-motif) sequences that are present in linear, peptide-like, or well folded protein domains.

Drugs by numbers: reaction-driven de novo design of potent and selective anticancer leads.

A potent and selective inhibitor of the anticancer target Polo-like kinase 1 was found by computer-based molecular design. This type II kinase inhibitor was synthesized as suggested by the design software DOGS and exhibited significant antiproliferative effects against HeLa cells without affecting nontransformed cells. The study provides a proof-of-concept for reaction-based de novo design as a leading tool for drug discovery.

Discovery of γ-secretase modulators with a novel activity profile by text-based virtual screening.

We present an integrated approach to identify and optimize a novel class of γ-secretase modulators (GSMs) with a unique pharmacological profile. Our strategy included (i) virtual screening through application of a recently developed protocol (PhAST), (ii) synthetic chemistry to discover structure-activity relationships, and (iii) detailed in vitro pharmacological characterization. GSMs are promising agents for treatment or prevention of Alzheimer's disease.

DOGS: reaction-driven de novo design of bioactive compounds.

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated 'in silico' assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features.

Identification of 2-mercaptohexanoic acids as dual inhibitors of 5-lipoxygenase and microsomal prostaglandin E₂ synthase-1.

5-Lipoxygenase (5-LO) and microsomal prostaglandin E₂ synthase (mPGES)-1 are key enzymes in the biosynthesis of leukotrienes and prostaglandin (PG)E₂, respectively, and are considered as valuable targets for the treatment of inflammatory diseases. Here, we present the identification of 2-mercaptohexanoic acid derivatives as dual inhibitors of 5-LO and mPGES-1. The lead compound 2(4-(3-biphenyloxypropoxy)phenylthio)hexanoic acid (21) inhibits human 5-LO and mPGES-1 in cell-free assays with an IC₅₀ = 3.

Reaction-driven de novo design, synthesis and testing of potential type II kinase inhibitors.

Background: De novo design of drug-like compounds with a desired pharmacological activity profile has become feasible through innovative computer algorithms. Fragment-based design and simulated chemical reactions allow for the rapid generation of candidate compounds as blueprints for organic synthesis.

Methods: We used a combination of complementary virtual-screening tools for the analysis of de novo designed compounds that were generated with the aim to inhibit inactive polo-like kinase 1 (Plk1), a target for the development of cancer therapeutics.