The clinical significance of hypoalbuminaemia.

Albumin is a relatively small molecule with a radius of 7.5 nm and a molecular weight of 65 kDa. It is the most abundant protein in plasma, accounting for 60-75% of its oncotic pressure.

Investigation of the cytotoxicity induced by cannabinoids on human ovarian carcinoma cells.

Cannabinoids have been shown to induce anti-tumor activity in a variety of carcinoma cells such as breast, prostate, and brain. The aim of the present study is to investigate the anti-tumor activity of cannabinoids, CBD (cannbidiol), and CBG (cannabigerol) in ovarian carcinoma cells sensitive and resistant to chemotherapeutic drugs. Sensitive A2780 cells and resistant A2780/CP70 carcinoma cells and non-carcinoma cells were exposed to varying concentrations of CBD, CBG, carboplatin or CB and CB receptor antagonists, AM251 and AM630, respectively, alone or in combination, at different exposure times and cytotoxicity was measured by MTT assay.

Preclinical Evaluation of Zn(II) Self-Assemblies with Selective Cytotoxic Activity Against Cancer Cells In Vitro and In Ovo.

Dipodal pyridylthiazole amine ligands L and L both form different metallo-supramolecular self-assemblies with Zn and Cu and these are shown to be toxic and selective towards cancer cell lines in vitro. Furthermore, potency and selectivity are highly dependent upon the metal ions, ligand system and bound anion, with significant changes in chemosensitivity and selectivity dependent upon which species are employed. Importantly, significant anti-tumor activity was observed in ovo at doses that are non-toxic.

Novel Anti-Cancer Agents and Cellular Targets and Their Mechanism(s) of Action.

Whilst there have been some significant improvements in treatments and patient outcomes for some cancers, for other cancers there has been little change in survival rates for many years [...

Investigation of the cytotoxicity induced by didocosahexaenoin, an omega 3 derivative, in human prostate carcinoma cell lines.

The aim of the present study was to investigate the cytotoxicity induced by an omega-3 derivative, didocosahexaenoin (Dido) on human prostate carcinoma cells and to compare the cytotoxicity to that of docosahexaenoic acid (DHA). Different carcinoma- and non-carcinoma cells were exposed to various concentrations of omega-3 compounds at varying exposure times and the cytotoxicity was measured by MTT assay. The mechanism of Dido-induced apoptosis was investigated in prostate carcinoma cells.

Postoperative arginine-enriched immune modulating nutrition: Long-term survival results from a randomised clinical trial in patients with oesophagogastric and pancreaticobiliary cancer.

Background & Aims: Immune modulating nutrition (IMN) has been shown to reduce postoperative infectious complications and length of stay in patients with gastrointestinal cancer. Two studies of IMN in patients undergoing surgery for head and neck cancer also suggested that this treatment might improve long-term survival and progression-free survival. In the present study, we analysed follow-up data from our previous randomised controlled trial of IMN, in patients undergoing surgery for oesophagogastric and pancreaticobiliary cancer, in order to evaluate the long-term impact on survival of postoperative IMN versus an isocaloric, isonitrogenous control feed.

The Warburg effect as a therapeutic target for bladder cancers and intratumoral heterogeneity in associated molecular targets.

Bladder cancer is the 10th most common cancer worldwide. For muscle-invasive bladder cancer (MIBC), treatment includes radical cystectomy, radiotherapy, and chemotherapy; however, the outcome is generally poor. For non-muscle-invasive bladder cancer (NMIBC), tumor recurrence is common.

Self-assembly of an anion receptor with metal-dependent kinase inhibition and potent in vitro anti-cancer properties.

One topical area of supramolecular chemistry is the binding of anionic species but despite the importance of anions in diverse cellular processes and for cancer development, anion receptors or 'binders' have received little attention as potential anti-cancer therapeutics. Here we report self-assembling trimetallic cryptands (e.g.

An Efficient Method for the Isolation of Toxins from Pteridium aquilinum and Evaluation of Ptaquiloside Against Cancer and Non-cancer Cells.

The common fern, bracken (), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside ( 1: ), although other toxins are present including the cyanogenic glycoside, prunasin ( 2: ). Here, we report an improved and relatively "green" process for the isolation of 1: and 2: from fresh bracken fronds and the evaluation of 1: for cytotoxicity against several cancer cell lines. The results indicate that 1: displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1: is expected to facilitate further exploration of its pharmacological properties.

Nicotinamide adenine dinucleotide (NAD+): essential redox metabolite, co-substrate and an anti-cancer and anti-ageing therapeutic target.

Nicotinamide adenine dinucleotide (NAD+) and its reduced form NADH are essential coupled redox metabolites that primarily promote cellular oxidative (catabolic) metabolic reactions. This enables energy generation through glycolysis and mitochondrial respiration to support cell growth and survival. In addition, many key enzymes that regulate diverse cell functions ranging from gene expression to proteostasis require NAD+ as a co-substrate for their catalytic activity.

Glycoconjugated Metallohelices have Improved Nuclear Delivery and Suppress Tumour Growth In Vivo.

Monosaccharides are added to the hydrophilic face of a self-assembled asymmetric Fe metallohelix, using CuAAC chemistry. The sixteen resulting architectures are water-stable and optically pure, and exhibit improved antiproliferative selectivity against colon cancer cells (HCT116 p53 ) with respect to the non-cancerous ARPE-19 cell line. While the most selective compound is a glucose-appended enantiomer, its cellular entry is not mainly glucose transporter-mediated.

Discovery of selective, antimetastatic and anti-cancer stem cell metallohelices post-assembly modification.

Helicates and related metallofoldamers, synthesised by dynamic self-assembly, represent an area of chemical space inaccessible by traditional organic synthesis, and yet with potential for discovery of new classes of drug. Here we report that water-soluble, optically pure Fe(ii)- and even Zn(ii)-based triplex metallohelices are an excellent platform for post-assembly click reactions. By these means, the anticancer activity and most importantly the selectivity of a triplex metallohelix Fe(ii) system are dramatically improved.

Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy.

Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure-activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia.

Chemically induced neurite-like outgrowth reveals a multicellular network function in patient-derived glioblastoma cells.

Tumor stem cells and malignant multicellular networks have been separately implicated in the therapeutic resistance of glioblastoma multiforme (GBM), the most aggressive type of brain cancer in adults. Here, we show that small-molecule inhibition of RHO-associated serine/threonine kinase proteins (ROCKi) significantly promoted the outgrowth of neurite-like cell projections in cultures of heterogeneous patient-derived GBM stem-like cells. These projections formed -induced cellular network (iNet) 'webs', which regressed after withdrawal of ROCKi.

Selective anti-cancer activity of non-alkylating minor groove binders.

Traditional cytotoxic agents which act through a DNA-alkylating mechanism are relatively non-specific, resulting in a small therapeutic window and thus limiting their effectiveness. In this study, we evaluate a panel of 24 non-alkylating Strathclyde Minor Groove Binders (S-MGBs), including 14 novel compounds, for anti-cancer activity against a human colon carcinoma cell line, a cisplatin-sensitive ovarian cancer cell line and a cisplatin-resistant ovarian cancer cell line. A human non-cancerous retinal epithelial cell line was used to measure selectivity of any response.

The death of Charlotte Brontë from hyperemesis gravidarum and refeeding syndrome: A new perspective.

Many theories have been advanced concerning the cause of Charlotte Brontë's death, none of which fully explain all the symptoms she experienced in the course of her final illness. Her death certificate records the cause of death as phthisis (tuberculosis), but there is no evidence, other than circumstantial, to support this diagnosis. A diagnosis of Addison's disease, caused by tuberculosis of the adrenals, has been proposed, but this is unlikely, since it does not fit well with two and a half months of severe anorexia, nausea and vomiting, followed by remission of these symptoms and eventual death.

KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice.

Pharmacological inhibition of uncontrolled cell growth with small-molecule inhibitors is a potential strategy for treating glioblastoma multiforme (GBM), the most malignant primary brain cancer. We showed that the synthetic small-molecule KHS101 promoted tumor cell death in diverse GBM cell models, independent of their tumor subtype, and without affecting the viability of noncancerous brain cell lines. KHS101 exerted cytotoxic effects by disrupting the mitochondrial chaperone heat shock protein family D member 1 (HSPD1).

Ruthenium-Containing Linear Helicates and Mesocates with Tuneable p53-Selective Cytotoxicity in Colorectal Cancer Cells.

The ligands L and L both form separable dinuclear double-stranded helicate and mesocate complexes with Ru . In contrast to clinically approved platinates, the helicate isomer of [Ru (L ) ] was preferentially cytotoxic to isogenic cells (HCT116 p53 ), which lack the critical tumour suppressor gene. The mesocate isomer shows the reverse selectivity, with the achiral isomer being preferentially cytotoxic towards HCT116 p53 .

Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands.

Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including topoisomerase I/II and thioredoxin reductase inhibition and induction of reactive oxygen species.

Bis-picolinamide Ruthenium(III) Dihalide Complexes: Dichloride-to-Diiodide Exchange Generates Single trans Isomers with High Potency and Cancer Cell Selectivity.

A library of new bis-picolinamide ruthenium(III) dihalide complexes of the type [RuX L ] (X=Cl or I, L=picolinamide) have been synthesised and characterised. The complexes exhibit different picolinamide ligand binding modes, whereby one ligand is bound (N,N) and the other bound (N,O). Structural studies revealed a mixture of cis and trans isomers for the [RuCl L ] complexes but upon a halide exchange reaction to yield [RuI L ], only single trans isomers were detected.

Development and characterization of a microfluidic model of the tumour microenvironment.

The physical microenvironment of tumours is characterized by heterotypic cell interactions and physiological gradients of nutrients, waste products and oxygen. This tumour microenvironment has a major impact on the biology of cancer cells and their response to chemotherapeutic agents. Despite this, most in vitro cancer research still relies primarily on cells grown in 2D and in isolation in nutrient- and oxygen-rich conditions.