Iodinated PSMA Ligands as XFI Tracers for Targeted Cell Imaging and Characterization of Nanoparticles.

Prostate cancer is the second most commonly diagnosed cancer in men worldwide. Despite this, current diagnostic tools are still not satisfactory, lacking sensitivity for early-stage or single-cell diagnosis. This study describes the development of small-molecule tracers for the well-known tumor marker prostate-specific membrane antigen (PSMA).

Golden Gate Cloning of Multigene Constructs Using the Modular Cloning System MoClo.

Modular cloning systems that rely on type IIS enzymes for DNA assembly have many advantages for construct engineering for biological research and synthetic biology. These systems are simple to use, efficient, and allow users to assemble multigene constructs by performing a series of one-pot assembly steps, starting from libraries of cloned and sequenced parts. The efficiency of these systems also facilitates the generation of libraries of construct variants.

Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2.

While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers.

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.

The structure of the rat vitamin B transporter TC and its complex with glutathionylcobalamin.

Vitamin B (cobalamin or Cbl) functions as a cofactor in two important enzymatic processes in human cells, and life is not sustainable without it. B is obtained from food and travels from the stomach, through the intestine, and into the bloodstream by three B-transporting proteins: salivary haptocorrin (HC), gastric intrinsic factor, and transcobalamin (TC), which all bind B with high affinity and require proteolytic degradation to liberate Cbl. After intracellular delivery of dietary B, Cbl in the aquo/hydroxocobalamin form can coordinate various nucleophiles, for example, GSH, giving rise to glutathionylcobalamin (GSCbl), a naturally occurring form of vitamin B.

HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis.

Background: Metastasis is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC) patients. We previously showed that low HERC5 expression predicts early tumor dissemination and a dismal prognosis in NSCLC patients. Here, we performed functional studies to unravel the mechanism underlying the "metastasis-suppressor" effect of HERC5, with a focus on mitochondrial metabolism pathways.

Facile Purification and Use of Tobamoviral Nanocarriers for Antibody-Mediated Display of a Two-Enzyme System.

Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of protein A (PA) on every coat protein (CP) subunit (TVCV) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCV and the wild-type subgroup 3 tobamovirus.

Assessment of transient expression strategies to sialylate recombinant proteins in N. benthamiana.

There is a demand for increasing the current manufacturing capacities for recombinant protein-based drugs. Novel expression systems such as plants are being explored as faster, more flexible, and possibly cheaper platforms. Many of these therapeutic proteins are glycosylated and require terminal sialylation to attain full biological activity.

Structural Analysis and Intrinsic Enzyme Mimicking Activities of Ligand-Free PtAg Nanoalloys.

Nanozymes are nanomaterials with biocatalytic properties under physiological conditions and are one class of artificial enzymes to overcome the high cost and low stability of natural enzymes. However, surface ligands on nanomaterials will decrease the catalytic activity of the nanozymes by blocking the active sites. To address this limitation, ligand-free PtAg nanoclusters (NCs) are synthesized and applied as nanozymes for various enzyme-mimicking reactions.

Liquid biopsy for monitoring of tumor dormancy and early detection of disease recurrence in solid tumors.

Cancer is one of the three leading causes of death worldwide. Even after successful therapy and achieving remission, the risk of relapse often remains. In this context, dormant residual cancer cells in secondary organs such as the bone marrow constitute the cellular reservoir from which late tumor recurrences arise.

Experimental in vitro, ex vivo and in vivo models in prostate cancer research.

Androgen deprivation therapy has a central role in the treatment of advanced prostate cancer, often causing initial tumour remission before increasing independence from signal transduction mechanisms of the androgen receptor and then eventual disease progression. Novel treatment approaches are urgently needed, but only a fraction of promising drug candidates from the laboratory will eventually reach clinical approval, highlighting the demand for critical assessment of current preclinical models. Such models include standard, genetically modified and patient-derived cell lines, spheroid and organoid culture models, scaffold and hydrogel cultures, tissue slices, tumour xenograft models, patient-derived xenograft and circulating tumour cell eXplant models as well as transgenic and knockout mouse models.

Prosodic features in Finnish-speaking adults with Parkinson´s disease.

The aim of this study was to assess prosodic features in Finnish speakers with (n = 16) and without (n = 20) Parkinson's disease (PD), as there are no published studies to date of prosodic features in Finnish speakers with PD. Chosen metrics were articulation rate (syllables/second), pitch (mean F) and pitch variability (standard deviation F), energy proportion below 1 kHz (epb1kHz), normalised pairwise variability index (nPVI), and a novel syllabic prosody index (SPI). Four statistically significant results were found: (1) energy was distributed more to lower frequencies in speakers with PD compared to control speakers, (2) male PD speakers had higher pitch and (3) higher syllabic prosody index compared to control males, and (4) female PD speakers had narrower pitch variability than controls.

Expression Patterns and Corepressor Function of Retinoic Acid-induced 2 in Prostate Cancer.

Background: Revealing molecular mechanisms linked to androgen receptor activity can help to improve diagnosis and treatment of prostate cancer. Retinoic acid-induced 2 (RAI2) protein is thought to act as a transcriptional coregulator involved in hormonal responses and epithelial differentiation. We evaluated the clinical relevance and biological function of the RAI2 protein in prostate cancer.

Immunotherapy in Advanced Prostate Cancer-Light at the End of the Tunnel?

Immunotherapeutic treatment approaches are now an integral part of the treatment of many solid tumors. However, attempts to integrate immunotherapy into the treatment of prostate cancer have been disappointing so far. This is due to a highly immunosuppressive, "cold" tumor microenvironment, which is characterized, for example, by the absence of cytotoxic T cells, an increased number of myeloid-derived suppressor cells or regulatory T cells, a decreased number of tumor antigens, or a defect in antigen presentation.

Metastatic Breast Cancer Recurrence after Bone Fractures.

Experimental studies suggest that bone fractures result in the release of cytokines and cells that might promote metastasis. Obtaining observational data on bone fractures after breast cancer diagnoses related to distant breast cancer recurrence could help to provide first epidemiological evidence for a metastasis-promoting effect of bone fractures. We used data from the largest German statutory health insurance fund (Techniker Krankenkasse, Hamburg, Germany) in a population-based cohort study of breast cancer patients with ICD-10 C50 codes documented between January 2015 and November 2019.

Spine Metastases in Immunocompromised Mice after Intracardiac Injection of MDA-MB-231-SCP2 Breast Cancer Cells.

Breast cancer cells frequently metastasize to bone, where their interaction with bone remodeling cell types enhances osteolytic bone destruction. Importantly, however, whereas skeletal analyses of xenograft models are usually restricted to hindlimb bones, human skeletal metastases are far more frequent in the spine, where trabecular bone mass is higher compared to femur or tibia. Here, we addressed whether breast cancer cells injected into immunocompromised mice metastasize to the spine and if this process is influenced by the amount of trabecular bone.

Aggressive variants of prostate cancer: underlying mechanisms of neuroendocrine transdifferentiation.

Prostate cancer is a hormone-driven disease and its tumor cell growth highly relies on increased androgen receptor (AR) signaling. Therefore, targeted therapy directed against androgen synthesis or AR activation is broadly used and continually improved. However, a subset of patients eventually progresses to castration-resistant disease.

Possible Role of Circulating Tumour Cells for Prediction of Salvage Lymph Node Dissection Outcome in Patients with Early Prostate Cancer Recurrence.

Unlabelled: Promising oncological results have been reported for salvage lymph node dissection (SLND) with prostate-specific membrane antigen-radioguided surgery (PSMA-RGS) in patients with prostate cancer (PCa) recurrence. We performed a proof-of-principle study assessing circulating tumour cells (CTCs) as a prognostic marker in patients undergoing SLND. Twenty consecutive patients with recurrent PCa treated with PSMA-RGS during April-July 2019 for PSMA-positive LNs were evaluated.

Emerging Insights into Keratin 16 Expression during Metastatic Progression of Breast Cancer.

Keratins are the main identification markers of circulating tumor cells (CTCs); however, whether their deregulation is associated with the metastatic process is largely unknown. Previously we have shown by in silico analysis that keratin 16 () mRNA upregulation might be associated with more aggressive cancer. Therefore, in this study, we investigated the biological role and the clinical relevance of K16 in metastatic breast cancer.

DNA Damage Response during Replication Correlates with CIN70 Score and Determines Survival in HNSCC Patients.

Aneuploidy is a consequence of chromosomal instability (CIN) that affects prognosis. Gene expression levels associated with aneuploidy provide insight into the molecular mechanisms underlying CIN. Based on the gene signature whose expression was consistent with functional aneuploidy, the CIN70 score was established.

Transient reprogramming of crop plants for agronomic performance.

The development of a new crop variety is a time-consuming and costly process due to the reliance of plant breeding on gene shuffling to introduce desired genes into elite germplasm, followed by backcrossing. Here, we propose alternative technology that transiently targets various regulatory circuits within a plant, leading to operator-specified alterations of agronomic traits, such as time of flowering, vernalization requirement, plant height or drought tolerance. We redesigned techniques of gene delivery, amplification and expression around RNA viral transfection methods that can be implemented on an industrial scale and with many crop plants.

Clinical management and biology of tumor dormancy in breast cancer.

Clinical tumor dormancy is specified as an extended latency period between removal of the primary tumor and subsequent relapse in a cancer patient who has been clinically disease-free. In particular, patients with estrogen receptor-positive breast cancer can undergo extended periods of more than five years before they relapse with overt metastatic disease. Recent studies have shown that minimal residual disease in breast cancer patients can be monitored by different liquid biopsy approaches like analysis of circulating tumor cells or cell-free tumor DNA.

Assembly of Multigene Constructs Using the Modular Cloning System MoClo.

Modular cloning systems that rely on type IIS enzymes for DNA assembly have many advantages for complex pathway engineering. These systems are simple to use, efficient, and allow users to assemble multigene constructs by performing a series of one-pot assembly steps, starting from libraries of cloned and sequenced parts. The efficiency of these systems also facilitates the generation of libraries of construct variants.

Characterization of circulating breast cancer cells with tumorigenic and metastatic capacity.

Functional studies giving insight into the biology of circulating tumor cells (CTCs) remain scarce due to the low frequency of CTCs and lack of appropriate models. Here, we describe the characterization of a novel CTC-derived breast cancer cell line, designated CTC-ITB-01, established from a patient with metastatic estrogen receptor-positive (ER ) breast cancer, resistant to endocrine therapy. CTC-ITB-01 remained ER in culture, and copy number alteration (CNA) profiling showed high concordance between CTC-ITB-01 and CTCs originally present in the patient with cancer at the time point of blood draw.