Construction and Characterization of a High-Capacity Replication-Competent Murine Cytomegalovirus Vector for Gene Delivery.

We investigated the basic characteristics of a new murine cytomegalovirus (MCMV) vector platform. Using BAC technology, we engineered replication-competent recombinant MCMVs with deletions of up to 26% of the wild-type genome. To this end, we targeted five gene blocks (m01-m17, m106-m109, m129-m141, m144-m158, and m159-m170).

A Multicenter Analysis of Revision of Aneurysmal Dialysis Access Using Bovine Carotid Artery Conduit.

Background: Dialysis access complications and failure requiring revision are common. Understanding which methods of revision yield the optimal patency rates and lowest complications remain in evolution. Revision of native vessels is preferred, with revision using expanded polytetrafluoroethylene (ePTFE) graft as an alternative.

A Comparative Analysis of Critical Limb Ischemia in the Intensive Care Unit since the COVID-19 Pandemic.

Background: Emerging data and case reports have found coagulation abnormalities and thrombosis as sequelae of infection with SARS-CoV-2 (COVID-19). Case reports have reported thrombotic complications caused by COVID-19-related coagulopathy leading to limb loss. Alarmingly, many of these patients had no underlying vascular disease prior to being infected with COVID-19.

COVID-19-related Peripheral Arterial Thrombosis Treated in a Large Health Maintenance Organization.

Background: COVID-19 was initially identified as an acute respiratory disease, but it was quickly recognized that multiple organ systems could be affected. Venous thrombosis and pulmonary embolism have been well reported. However, there is a paucity of data on COVID-19-related arterial thrombosis.

The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.

Despite advancements in cancer management, tumor relapse and metastasis are associated with poor outcomes in many cancers. Over the past decade, oncogene-driven carcinogenesis, dysregulated cellular signaling networks, dynamic changes in the tissue microenvironment, epithelial-mesenchymal transitions, protein expression within regulatory pathways, and their part in tumor progression are described in several studies. However, the complexity of metabolic enzyme expression is considerably under evaluated.

Inhibition of Metabolic Shift can Decrease Therapy Resistance in Human High-Grade Glioma Cells.

The high-grade brain malignancy, glioblastoma multiforme (GBM), is one of the most aggressive tumours in central nervous system. The developing resistance against recent therapies and the recurrence rate of GBMs are extremely high. In spite several new ongoing trials, GBM therapies could not significantly increase the survival rate of the patients as significantly.

Synchronizing Protein Traffic to the Primary Cilium.

The primary cilium is able to maintain a specific protein composition, which is critical for its function as a signaling organelle. Here we introduce a system to synchronize biosynthetic trafficking of ciliary proteins that is based on conditional aggregation domains (CADs). This approach enables to create a wave of ciliary proteins that are transported together, which opens novel avenues for visualizing and studying ciliary import mechanisms.

Targeting cellular metabolism using rapamycin and/or doxycycline enhances anti-tumour effects in human glioma cells.

Background: Glioma is the most common highly aggressive, primary adult brain tumour. Clinical data show that therapeutic approaches cannot reach the expectations in patients, thus gliomas are mainly incurable diseases. Tumour cells can adapt rapidly to alterations during therapeutic treatments related to their metabolic rewiring and profound heterogeneity in tissue environment.

GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas.

Background: Bioenergetic characterisation of malignant tissues revealed that different tumour cells can catabolise multiple substrates as salvage pathways, in response to metabolic stress. Altered metabolism in gliomas has received a lot of attention, especially in relation to IDH mutations, and the associated oncometabolite D-2-hydroxyglutarate (2-HG) that impact on metabolism, epigenetics and redox status. Astrocytomas and oligodendrogliomas, collectively called diffuse gliomas, are derived from astrocytes and oligodendrocytes that are in metabolic symbiosis with neurons; astrocytes can catabolise neuron-derived glutamate and gamma-aminobutyric acid (GABA) for supporting and regulating neuronal functions.

In situ analysis of mTORC1/2 and cellular metabolism-related proteins in human Lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare progressive cystic lung disease with features of a low-grade neoplasm. It is primarily caused by mutations in TSC1 or TSC2 genes. Sirolimus, an inhibitor of mTOR complex 1 (mTORC1), slows down disease progression in some, but not all patients.

[Anticancer drug research in Hungary, 1950-2000].

The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action.

Rapamycin (mTORC1 inhibitor) reduces the production of lactate and 2-hydroxyglutarate oncometabolites in IDH1 mutant fibrosarcoma cells.

Background: Multiple studies concluded that oncometabolites (e.g. D-2-hydroxyglutarate (2-HG) related to mutant isocitrate dehydrogenase 1/2 (IDH1/2) and lactate) have tumour promoting potential.

Characterisation of bioenergetic pathways and related regulators by multiple assays in human tumour cells.

Background: Alterations in cellular metabolism are considered as hallmarks of cancers, however, to recognize these alterations and understand their mechanisms appropriate techniques are required. Our hypothesis was to determine whether dominant bioenergetic mechanism may be estimated by comparing the substrate utilisation with different methods to detect the labelled carbon incorporation and their application in tumour cells.

Methods: To define the bioenergetic pathways different metabolic tests were applied: (a) measuring CO2 production from [1-(14)C]-glucose and [1-(14)C]-acetate; (b) studying the effect of glucose and acetate on adenylate energy charge; (c) analysing glycolytic and TCA cycle metabolites and the number of incorporated (13)C atoms after [U-(13)C]-glucose/[2-(13)C]-acetate labelling.

[Measuring 14C-glucose and 14C-acetate oxidation in tumour cells and tumorous host organism].

Tumour cell metabolism can be influenced by alterations of the extracellular microenvironment and the tumour-promoting genetically changed mechanisms. There is increasing interest to introduce appropriate bioenergetic assays to describe the therapeutic effect and metabolic subtypes of tumours in clinical oncology. The analysis of 14C-glucose and 14C-acetate oxidation could be a suitable method to examine the metabolic/bioenergetic profiles of tumour cells and tumorous host organisms.

Extracellular matrix as target for antitumor therapy.

The aim of the present review is to survey the accumulated knowledge on the extracellular matrix (ECM) of tumors referring to its putative utility as therapeutic target. Following the traditional observation on the extensive morphological alteration in the tumor-affected tissue, the well-documented aberrant cellular regulation indicated that ECM components have an active role in tumor progression. However, due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components.

Determination of energy metabolites in cancer cells by porous graphitic carbon liquid chromatography electrospray ionization mass spectrometry for the assessment of energy metabolism.

A high performance liquid chromatography (HPLC) tandem mass spectrometric (MS/MS) method has been developed for the simultaneous determination of fifteen glucose, or acetate derived metabolites isolated from tumor cells. Glycolytic and tricarboxylic acid (TCA) cycle metabolites as well as acidic amino acids were separated on a HPLC porous graphitic carbon (PGC) column and simultaneously determined by means of triple quadrupole MS/MS using multiple reaction monitoring (MRM). Target compounds were eluted within 10 min with 8% v/v formic acid as an electronic modifier added to a 4:1 v/v methanol water mobile phase.

DNA fragmentation and caspase-independent programmed cell death by modulated electrohyperthermia.

Background And Purpose: The electric field and the concomitant heat (electrohyperthermia) can synergistically induce cell death in tumor tissue, due to elevated glycolysis, ion concentration, and permittivity in malignant compared with nonmalignant tissues. Here we studied the mechanism and time course of tumor destruction caused by electrohyperthermia.

Material And Methods: Bilateral implants of HT29 colorectal cancer in the femoral regions of Balb/c (nu/nu) mice were treated with a single 30-min shot of modulated, 13.

[History of the therapy of pernicious anemia].

Increased blood cell regeneration in exsanguinated experimental animals treated either with liver or with aqueous liver extracts was reported by Whipple and by Jeney and Jobling, respectively. These findings stimulated Minot and Murphy to provide evidence for the efficacy of liver against anaemia in clinical studies. After oral administration of liver (45-50 g per day) for 45 patients with anaemia perniciosa improvement of the hematological status was demonstrated.

Syndecan-1 enhances proliferation, migration and metastasis of HT-1080 cells in cooperation with syndecan-2.

Syndecans are transmembrane heparan sulphate proteoglycans. Their role in the development of the malignant phenotype is ambiguous and depends upon the particular type of cancer. Nevertheless, syndecans are promising targets in cancer therapy, and it is important to elucidate the mechanisms controlling their various cellular effects.

Enhanced 5-fluorouracil cytotoxicity in high cyclooxygenase-2 expressing colorectal cancer cells and xenografts induced by non-steroidal anti-inflammatory drugs via downregulation of dihydropyrimidine dehydrogenase.

Purpose: To prove that 5-FU cytotoxicity could be increased by combination with low-dose non-steroidal anti-inflammatory drugs (NSAIDs) (indomethacin or NS-398) in high cyclooxygenase-2- (COX-2) expressing cells and xenografts through the modulation of dihydropyrimidine dehydrogenase (DPD) mRNA expression and/or enzyme activity.

Methods: HT-29 cells were grown on collagen IV coated plates (HT-29-C). The antiproliferative effect of 5-fluorouracil (5-FU) +/- NSAIDs was examined on non-COX-2 expressing HT-29 and COX-2-expressing HT-29-C cells by sulphorhodamine B assay.

Co-inhibition of cyclooxygenase-2 and dihydropyrimidine dehydrogenase by non-steroidal anti-inflammatory drugs in tumor cells and xenografts.

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) may be able to enhance the antitumor effect of cancer drugs. Cyclooxygenase-2 (COX-2) is the best characterized target of NSAIDs. It was demonstrated that elevated dihydropyrimidine dehydrogenase (DPD) and COX-2 activities influence the response to 5-fluorouracil (5-FU).

Differential inhibition of single and cluster type tumor cell migration.

For the control of tumor metastasis it is important to identify chemical compounds with antimigratory potency. Agents acting against single cell and cluster type migration are necessary for successful antimetastatic therapy. In the present study, the migration of HT-1080 fibrosarcoma cells and OSCORT osteosarcoma cells was compared in a Boyden chamber and in an extracellular matrix (ECM)-based three-dimensional cell culture (3-DCC) model system.