Comparison of molecular subtype composition between independent sets of primary and brain metastatic small cell lung carcinoma and matched samples.

Introduction: Recent advances in the subclassification of small cell lung carcinomas (SCLCs) may help to overcome the unmet need for targeted therapies and improve survival. However, limited information is available on how the expression of the subtype markers changes during tumour progression. Our study aimed to compare the expression of these markers in primary and brain metastatic SCLCs.

Acute type A aortic syndromes and ski: management in an emergency care network.

Background: Skiing can cause aortic syndromes. The pre-hospital management of these patients may be compromised by the mountainous terrain. A regional emergency care network helps to optimize time frames, especially in a challenging geography.

Increased mTOR activity and RICTOR copy number in small cell lung carcinoma progression.

Small cell lung carcinoma (SCLC) is a highly malignant cancer with early metastatic dissemination and poor clinical outcomes. Mutations in the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway, including the frequently occurring rapamycin-insensitive protein (RICTOR) amplification, have been described in these tumours. Moreover, the associated mTOR hyperactivity could be exploited for personalised treatment.

Digital PCR-based quantification of miR-181a in the cerebrospinal fluid aids patient stratification in pediatric acute lymphoblastic leukemia.

Despite remarkable improvements in the survival of pediatric acute lymphoblastic leukemia (ALL), sensitive detection and clinical management of central nervous system leukemia (CNSL) are still immensely challenging. Blast cells residing in the CNS but not circulating in the cerebrospinal fluid (CSF) remain undetected by current diagnostic methods, preventing a truly risk-adapted anti-leukemic treatment in this compartment. We examined the clinical applicability of the molecular marker microRNA (miR)-181a quantified in the cell-free CSF to evaluate the level of CNS involvement and to optimize patient stratification based on CNS status.

Case Report: Benefits of LSVT LOUD in a multilingual patient with hypokinetic-hyperkinetic dysarthria and suspected progressive supranuclear palsy.

Purpose: This case study measured how well the Lee Silverman Voice Treatment (LSVT) improved vocal features, intelligibility, and communicative effectiveness for a multilingual participant with hypokinetic-hyperkinetic dysarthria secondary to suspected progressive supranuclear palsy. LSVT treatment was chosen for the participant due to the strengths and deficits he presented with prior to treatment, and for the anticipated challenges in treatment that may arise from the presence of multilingualism and impaired cognitive functioning.

Methods: A multilingual patient in their 60's (English, Spanish, and French) with hypokinetic-hyperkinetic dysarthria secondary to suspected progressive supranuclear palsy completed the standard treatment sessions for LSVT.

amplification is associated with Rictor membrane staining and does not correlate with PD-L1 expression in lung squamous cell carcinoma.

gene, which encodes the scaffold protein of mTORC2, can be amplified in various tumor types, including squamous cell carcinoma (SCC) of the lung. amplification can lead to hyperactivation of mTORC2 and may serve as a targetable genetic alteration, including in lung SCC patients with no PD-L1 expression who are not expected to benefit from immune checkpoint inhibitor therapy. This study aimed to compare amplification detected by fluorescence hybridization (FISH) with Rictor and PD-L1 protein expression detected by immunohistochemistry (IHC) in SCC of the lung.

Cyclodextrin encapsulation enabling the anticancer repositioning of disulfiram: Preparation, analytical and in vitro biological characterization of the inclusion complexes.

Drug repositioning is a high-priority and feasible strategy in the field of oncology research, where the unmet medical needs are continuously unbalanced. Disulfiram is a potential non-chemotherapeutic, adjuvant anticancer agent. However, the clinical translation is limited by the drug's poor bioavailability.

mTOR hyperactivity and amplification as targets for personalized treatments in malignancies.

The increasing knowledge of molecular alterations in malignancies, including mutations and regulatory failures in the mTOR (mechanistic target of rapamycin) signaling pathway, highlights the importance of mTOR hyperactivity as a validated target in common and rare malignancies. This review summarises recent findings on the characterization and prognostic role of mTOR kinase complexes (mTORC1 and mTORC2) activity regarding differences in their function, structure, regulatory mechanisms, and inhibitor sensitivity. We have recently identified new tumor types with (rapamycin-insensitive companion of mTOR) amplification and associated mTORC2 hyperactivity as useful potential targets for developing targeted therapies in lung cancer and other newly described malignancies.

Pre-emptive veno-arterial ECMO in a giant compressive goiter-related difficult airway: A case report.

A 64-year-old patient required emergency surgery with high risk of intubation failure, without any possibility to perform neither a direct transtracheal access nor VV-ECMO canulation. The patient was managed thanks to a VA-ECMO despite the absence of cardiac function impairment. This report describes perioperative challenges and management of this unconventional case with favorable outcome.

Tumorigenic role of tacrolimus through mTORC1/C2 activation in post-transplant renal cell carcinomas.

Background: Kidney transplant recipients (KTRs) face an increased risk of renal cell carcinoma (RCC), in which the immunosuppressive regimen plays an important role. This study aimed to identify intracellular signalling alterations associated with post-transplant (post-tx) tumour formation.

Methods: Expression of mTOR-related proteins were analysed in kidneys obtained from end-stage renal disease (ESRD) patients and RCCs developed in KTRs or non-transplant patients.

Rictor-A Mediator of Progression and Metastasis in Lung Cancer.

Lung carcinoma is one of the most common cancer types for both men and women. Despite recent breakthroughs in targeted therapy and immunotherapy, it is characterized by a high metastatic rate, which can significantly affect quality of life and prognosis. Rictor (encoded by the gene) is known as a scaffold protein for the multiprotein complex mTORC2.

Cell-free ascites from ovarian cancer patients induces Warburg metabolism and cell proliferation through TGFβ-ERK signaling.

Ascites plays a key role in supporting the metastatic potential of ovarian cancer cells. Shear stress and carry-over of cancer cells by ascites flow support carcinogenesis and metastasis formation. In addition, soluble factors may participate in the procarcinogenic effects of ascites in ovarian cancer.

Cangrelor for cardiopulmonary bypass in delayed-onset heparin-induced thrombocytopenia: a case report.

Background: Anticoagulation for cardiopulmonary bypass (CPB) in cases of heparin-induced thrombocytopenia (HIT) is challenging as no convenient and proven alternative, such as heparin alone, exists. A "platelet anesthesia" concept using antiplatelet agent cangrelor with heparin has been successfully reported in this setting.

Key Clinical Question: In cases of acute HIT, is CPB with cangrelor plus heparin effective and safe?.

Dual system of water safety plan auditing in Hungary: benefits and lessons learnt.

A risk-based approach is recognised worldwide as the most reliable means for the provision of safe drinking water. Efficient implementation of the water safety plan (WSP) approach, recommended by the World Health Organization (WHO), is facilitated by an auditing framework. In Hungary, development of WSPs is a legal obligation for water suppliers.

Novel Metabolic Approaches Targeting Cancer Cells.

Metabolic reprogramming is one of the main hallmarks of cancer [...

[Management of Stent-graft migration with obstruction of supra-aortic vessel during an endovascular procedure for aortic isthmus rupture].

The endovascular approach is widely used in the management of aortic isthmic rupture. Even if it remains less invasive than conventional surgery, a life-threatening complications are possible. We report the case of a young female patient presenting a stent-graft migration during the deployment with total obstruction of the supra-aortic vessels.

Novel RICTOR amplification harbouring entities: FISH validation of RICTOR amplification in tumour tissue after next-generation sequencing.

Alterations in mTOR signalling molecules, including RICTOR amplification, have been previously described in many cancers, particularly associated with poor prognosis. In this study, RICTOR copy number variation (CNV) results of diagnostic next-generation sequencing (NGS) were analysed in 420 various human malignant tissues. RICTOR amplification was tested by Droplet Digital PCR (ddPCR) and validated using the "gold standard" fluorescence in situ hybridisation (FISH).

[Effects of 3D tissue structure on drug sensitivity - 3D bioprinted tissue mimetic structures in cancer research].

The issues surrounding the cost effectiveness of drug development and the ethical concerns associated with animal testing, emphasise the necessity for innovative in vitro models that allow enhanced pre-selection. Therefore, we aim to create 3D bioprinted tissue mimetic structures (TMS) utilizing various human cancer cell lines. We have generated TMSs from human tumour cell lines (breast, kidney, glioma), with detailed characterisation of the ZR75.

[he importance of mTOR hyperactivity and RICTOR amplification, and the associated targeted therapy possibilities in malignant tumours].

Failures of anti-tumour therapies and drug resistance initiate difficulties in cancer treatments often caused by alterations in signalling network activity, including PI3K/Akt/mTOR hyperactivity due to oncogenic mutations. In this review, we summarise the relevance of mTOR (mechanistic target of rapamycin) dysregulation identified decades ago, which is now known to be characteristic of many tumours. In this context, we present differences in activity, function and testability of mTOR kinase complexes (mTORC1 and mTORC2) differing in structure, regulatory mechanisms and inhibitor sensitivity.

Dynamic Interplay in Tumor Ecosystems: Communication between Hepatoma Cells and Fibroblasts.

Tumors are intricate ecosystems where cancer cells and non-malignant stromal cells, including cancer-associated fibroblasts (CAFs), engage in complex communication. In this study, we investigated the interaction between poorly (HLE) and well-differentiated (HuH7) hepatoma cells and LX2 fibroblasts. We explored various communication channels, including soluble factors, metabolites, extracellular vesicles (EVs), and miRNAs.

Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of and Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including and Species.

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic-nematode species, release a series of non-ribosomal templated anti-microbial peptides.

BMP-induced non-canonical signaling is upregulated during autophagy-mediated regeneration in inflamed mesothelial cells.

Previously, we showed that after Freund's adjuvant-induced peritonitis, rat mesothelial cells regain their epithelial phenotype through mesenchymal-epithelial transition (MET) accompanied by autophagy. Since bone morphogenetic proteins (BMPs) are well-known MET-inducers, we were interested in the potential expression of BMPs and BMP-induced pathways. Although mesothelial cells expressed lower amounts of BMP7, its level in the peritoneal cavity and mesothelial synthesis of BMP4 were significantly increased during inflammation.