Selective activation of prodrugs in breast cancer using metabolic glycoengineering and the tetrazine ligation bioorthogonal reaction.

Increasing the selectivity of chemotherapies by converting them into prodrugs that can be activated at the tumour site decreases their side effects and allows discrimination between cancerous and non-cancerous cells. Herein, the use of metabolic glycoengineering (MGE) to selectively label MCF-7 breast cancer cells with tetrazine (Tz) activators for subsequent activation of prodrugs containing the trans-cyclooctene (TCO) moiety by a bioorthogonal reaction is demonstrated. Three novel Tz-modified monosaccharides, AcManNTz 7, AcGalNTz 8, and AcSiaTz 16, were used for expression of the Tz activator within sialic-acid rich breast cancer cells' surface glycans through MGE.

Bioorthogonal activation of prodrugs, for the potential treatment of breast cancer, using the Staudinger reaction.

Selective prodrug activation at a tumor site is crucial to maximise the efficiency of chemotherapy approaches and minimise side effects due to off-site activation. In this paper, a new prodrug activation strategy is reported based on the bioorthogonal Staudinger reaction. The feasibility of this prodrug activation strategy was initially demonstrated using 9-azido sialic acid 4 as a trigger and two novel triphenylphosphine-modified N-mustard-PRO 10 and doxorubicin-PRO 12 prodrugs in an HPLC-monitored release study.

In Vivo Applications of Bioorthogonal Reactions: Chemistry and Targeting Mechanisms.

Bioorthogonal chemistry involves selective biocompatible reactions between functional groups that are not normally present in biology. It has been used to probe biomolecules in living systems, and has advanced biomedical strategies such as diagnostics and therapeutics. In this review, the challenges and opportunities encountered when translating in vitro bioorthogonal approaches to in vivo settings are presented, with a focus on methods to deliver the bioorthogonal reaction components.

Systematic Reviews and Meta-Analyses of Portal Vein Embolization, Associated Liver Partition and Portal Vein Ligation, and Radiation Lobectomy Outcomes in Hepatocellular Carcinoma Patients.

Purpose Of Review: To understand portal vein embolization (PVE), associated liver partition and portal vein ligation (ALPPS) and radiation lobectomy (RL) outcomes in hepatocellular carcinoma (HCC) patients. Systematic reviews of future liver remnant (FLR) percent hypertrophy, proportion undergoing hepatectomy and proportion with major complications following PVE, ALPPS, and RL were performed by searching Ovid MEDLINE, Ovid EMBASE, The Cochrane Library, and Web of Science. Separate meta-analyses using random-effects models with assessment of study heterogeneity and publication bias were performed whenever allowable by available data.

Hashimoto's Encephalopathy: A Rare Cause of Seizure-like Activity.

Hashimoto's encephalopathy is an uncommon disorder that may present with a wide variety of different neurological signs and symptoms that can include acute altered level of consciousness, psychosis, seizures, ataxia, dementia, myoclonus, and stupor. We present a case of a 60-year-old female patient who was admitted to the internal medicine floor for workup for seizures of unknown etiology. Investigations, including a complete blood count, basic metabolic panel, magnetic resonance imaging (MRI) of the brain, cerebrospinal fluid analysis, and NMDA (N-methyl-D-aspartate) receptor encephalitis screen, were all unremarkable.