Stonikacidin A, an Antimicrobial 4-Bromopyrrole Alkaloid Containing L-Idonic Acid Core from the Northwestern Pacific Marine Sponge .

Stonikacidin A (), the first representative of a new class of 4-bromopyrrole alkaloids containing an aldonic acid core, was isolated from the marine sponge . The compound is named in honor of Prof. Valentin A.

Limited prognostic role of routine serum markers (AP, CEA, LDH and NSE) in oligorecurrent prostate cancer patients undergoing PSMA-radioguided surgery.

Introduction: We evaluated the prognostic role of pre-salvage prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) serum levels of alkaline phosphatase (AP), carcinoembryonic antigen (CEA), lactate dehydrogenase (LDH), and neuron-specific enolase (NSE).

Materials And Methods: Patients who consecutively underwent PSMA-RGS for prostate cancer (PCa) oligorecurrence between January 2019 and January 2022 were selected. Biomarkers were assessed one day before surgery.

Anticancer Activity of the Marine Triterpene Glycoside Cucumarioside A-2 in Human Prostate Cancer Cells.

Despite recent advances in the treatment of metastatic castration-resistant prostate cancer (CRPC), treatment is inevitably hampered by the development of drug resistance. Thus, new drugs are urgently needed. We investigated the efficacy, toxicity, and mechanism of action of the marine triterpene glycoside cucumarioside A-2 (CA-2) using an in vitro CRPC model.

Molecular refinement of pilocytic astrocytoma in adult patients.

Aim: Pilocytic astrocytomas (PA) in adults are rare and may be challenging to identify based only on histomorphology. Compared to their paediatric counterparts, they are reportedly molecularly more diverse and associated with a worse prognosis. We aimed to describe the characteristics of adult PAs more precisely by comprehensively profiling a series of 79 histologically diagnosed adult cases (≥18 years).

Mouse models of pediatric high-grade gliomas with MYCN amplification reveal intratumoral heterogeneity and lineage signatures.

Pediatric high-grade gliomas of the subclass MYCN (HGG-MYCN) are highly aggressive tumors frequently carrying MYCN amplifications, TP53 mutations, or both alterations. Due to their rarity, such tumors have only recently been identified as a distinct entity, and biological as well as clinical characteristics have not been addressed specifically. To gain insights into tumorigenesis and molecular profiles of these tumors, and to ultimately suggest alternative treatment options, we generated a genetically engineered mouse model by breeding hGFAP-cre::Trp53::lsl-MYCN mice.

Rhizochalinin Exhibits Anticancer Activity and Synergizes with EGFR Inhibitors in Glioblastoma In Vitro Models.

Rhizochalinin (Rhiz) is a recently discovered cytotoxic sphingolipid synthesized from the marine natural compound rhizochalin. Previously, Rhiz demonstrated high in vitro and in vivo efficacy in various cancer models. Here, we report Rhiz to be highly active in human glioblastoma cell lines as well as in patient-derived glioma-stem like neurosphere models.

New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus KMM 4685.

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (), β-resoantarctines A-C (, , ) and 8-dehydro-β-resoantarctine A (), together with known 14-hydroxyasperentin (5'-hydroxyasperentin) (), were isolated from the ethyl acetate extract of the fungus KMM 4685 associated with the brown alga . The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher's method, and the biogenetic pathways for compounds - were proposed. For the very first time, the relative configuration of the C-14 center of a known compound was assigned via analyses of magnitudes of the vicinal coupling constants.

Absence of Malaria-Associated Coagulopathy in Asymptomatic Infection: Results From a Cross-sectional Study in the Ashanti Region, Ghana.

Background: Coagulopathy is common in acute symptomatic malaria, and the degree of coagulation abnormality correlates with parasitemia and disease severity. Chronic asymptomatic malaria has been associated with increased morbidity. However, the role of coagulation activation in asymptomatic, semi-immune individuals remains unclear.

New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide.

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide () from the marine-derived fungus KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data.

New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Induce Apoptosis and Autophagy in Prostate Cancer Cells.

Two new guanidine alkaloids, batzelladines O () and P (), were isolated from the deep-water marine sponge The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O () and P () induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage.

Meroantarctines A-C, Meroterpenoids with Rearranged Skeletons from the Alga-Derived Fungus KMM 4685 with Potent p-Glycoprotein Inhibitory Activity.

New meroterpenoids, meroantarctines A-C (-), with unique 6/5/6/6, 6/5/6/5/6, and 6/5/6/5 polycyclic systems were isolated from the alga-derived fungus KMM 4685. Their structures were elucidated by spectroscopic methods, X-ray diffraction, and quantum chemical calculations. A biogenetic pathway for - was proposed.

Cytotoxic N-Methylpretrichodermamide B Reveals Anticancer Activity and Inhibits P-Glycoprotein in Drug-Resistant Prostate Cancer Cells.

N-methylpretrichodermamide B (NB) is a biologically active epidithiodiketopiperazine isolated from several strains of the algae-derived fungus sp. Recently, we reported the first data on its activity in human cancer cells lines in vitro. Here, we investigated the activity, selectivity, and mechanism of action of NB in human prostate cancer cell lines, including drug-resistant subtypes.

Src family kinase targeting in head and neck tumor cells using SU6656, PP2 and dasatinib.

Background: We have recently shown a frequent upregulation of Src-family kinases (SFK) in head and neck squamous cell carcinoma (HNSCC). Here we tested, if SFK targeting is effective especially in HNSCC cells with upregulated SFK signaling.

Methods: The impact of SFK inhibitors SU6656, PP2 and dasatinib on three HNSCC cell lines with different SFK activity levels was analyzed using proliferation and colony formation assays, Western blot and functional kinomics.

1--Alkylglycerol Ethers from the Marine Sponge and Their Cytotoxic Activity.

The cytotoxicity-bioassay-guided fractionation of the ethanol extract from the marine sponge , whose 1--alkyl--glycerol ethers (AGEs) have not been investigated so far, led to the isolation of a complex lipid fraction containing, along with previously known compounds, six new lipids of the AGE type. The composition of the AGE fraction as well as the structures of 6 new and 22 previously known compounds were established using H and C NMR, GC/MS, and chemical conversion methods. The new AGEs were identified as: 1--(Z-docos-15-enyl)--glycerol (), 1--(Z-docos-17-enyl)--glycerol (), 1--(Z-tricos-15-enyl)--glycerol (), 1--(Z-tricos-16-enyl)--glycerol (), 1--(Z-tricos-17-enyl)--glycerol (), and 1--(Z-tetracos-15-enyl)--glycerol ().

Kinomic comparison of snap frozen and ex vivo-cultured head and neck tumors.

Objectives: The use of primary tumor tissue in experimental and pre-clinical cancer research is becoming increasingly important. Especially the use of tissue slice cultures of tumor specimen, so called ex vivo cultures or tumor explants, promises functional analysis under approximate physiological conditions. This includes screening and testing of targeted therapeutics directed against deregulated protein kinases.

Analyzing tyrosine kinase activity in head and neck cancer by functional kinomics: Identification of hyperactivated Src family kinases as prognostic markers and potential targets.

Signal transduction via protein kinases is of central importance in cancer biology and treatment. However, the clinical success of kinase inhibitors is often hampered by a lack of robust predictive biomarkers, which is also caused by the discrepancy between kinase expression and activity. Therefore, there is a need for functional tests to identify aberrantly activated kinases in individual patients.

Integrative public data-mining pipeline for the validation of novel independent prognostic biomarkers for lung adenocarcinoma.

We aimed to develop a candidate-based integrative public data mining strategy for validation of novel prognostic markers in lung adenocarcinoma. An approach integrating meta-analyses of publicly available clinical information linked RNA expression, gene copy number and mutation datasets combined with independent immunohistochemistry and survival datasets. After validation of pipeline integrity utilizing data from the well-characterized prognostic factor Ki-67, prognostic impact of the calcium- and integrin-binding protein, CIB1, was analyzed.

SLAMF receptors negatively regulate B cell receptor signaling in chronic lymphocytic leukemia via recruitment of prohibitin-2.

We identified a subset of Chronic Lymphocytic Leukemia (CLL) patients with high Signaling Lymphocytic Activation Molecule Family (SLAMF) receptor-related signaling that showed an indolent clinical course. Since SLAMF receptors play a role in NK cell biology, we reasoned that these receptors may impact NK cell-mediated CLL immunity. Indeed, our experiments showed significantly decreased degranulation capacity of primary NK cells from CLL patients expressing low levels of SLAMF1 and SLAMF7.

Activation of Epidermal Growth Factor Receptor Sensitizes Glioblastoma Cells to Hypoxia-Induced Cell Death.

Background: The epidermal growth factor receptor (EGFR) signaling pathway is genetically activated in approximately 50% of glioblastomas (GBs). Its inhibition has been explored clinically but produced disappointing results, potentially due to metabolic effects that protect GB cells against nutrient deprivation and hypoxia. Here, we hypothesized that EGFR activation could disable metabolic adaptation and define a GB cell population sensitive to starvation.

A novel workflow for three-dimensional analysis of tumour cell migration.

The limitations of two-dimensional analysis in three-dimensional (3D) cellular imaging impair the accuracy of research findings in biological studies. Here, we report a novel 3D approach to acquisition, analysis and interpretation of tumour spheroid images. Our research interest in mesenchymal-amoeboid transition led to the development of a workflow incorporating the generation and analysis of 3D data with instant structured illumination microscopy and a new ImageJ plugin.