De-escalating radiotherapy in HPV-positive oropharyngeal squamous cell carcinoma: how much is too little?

Oropharyngeal squamous cell carcinoma (OPSCC) had a rapidly increasing incidence rate in high-income countries, with a significant increase in cases related to human papilloma virus (HPV). HPV-positive (HPV+) OPSCC has shown better survival rates compared with HPV-negative (HPV-) cases, prompting investigations into de-escalation strategies to reduce or change chemoradiotherapy protocols. We present a case of a patient with HPV+ OPSCC who discontinued chemoradiotherapy after 2 weeks, effectively receiving a de-escalated dose of 18 Gy over nine fractions and only one cycle of cisplatin, subsequently undergoing curative surgical resection with no residual disease in the radiotherapy field 14 years later.

A new standardized electrochemical array for drug metabolic profiling with human cytochromes P450.

Over the past two decades, a wealth of information on the human cytochrome P450 enzymes and their role in drug metabolism both in vitro and in vivo has been gathered. Our understanding of this area has progressed greatly, but our confidence in the development of quantitative projections of drug interactions, made from in vitro data, is somehow still shaky. There are therefore no doubts in the necessity for reliable and fast methodologies for P450 drug metabolism analysis, capable of providing accurate and precise in vitro data.

Enzyme-based amperometric platform to determine the polymorphic response in drug metabolism by cytochromes P450.

"Personalized medicine" is a new concept in health care, one aspect of which defines the specificity and dosage of drugs according to effectiveness and safety for each patient. Dosage strongly depends from the rate of metabolism which is primarily regulated by the activity of cytochrome P450. In addition to the need for a genetic characterization of the patients, there is also the necessity to determine the drug-clearance properties of the polymorphic P450 enzyme.

An electrochemical microfluidic platform for human P450 drug metabolism profiling.

This paper is the first report of a P450-electrode in a microfluidic format. A 30 μL microfluidic cell was made in poly(methyl methacrylate) containing the inlet, outlet, and reaction chamber with two electrode strips, one of which contains the human cytochrome P450 3A4 covalently bound to gold via a 6-hexanethiol and 7-mercaptoheptanoic acid (1:1) self-assembled monolayer. The electrochemical response of the P450-electrode in the microfluidic cell was tested using four drugs that are known substrates of P450 3A4: quinidine, nifedipine, alosetron and ondansetron.

Direct electrochemistry of drug metabolizing human flavin-containing monooxygenase: electrochemical turnover of benzydamine and tamoxifen.

This communication reports on the first electrochemical study of the human flavin-containing monooxygenase 3 (hFMO3) either absorbed or covalently linked to different electrode surfaces. Glassy carbon and gold electrodes gave reversible electrochemical signals of an active hFMO3. The midpoint potential measured for the immobilized enzyme on a glassy carbon electrode was -445 +/- 8 mV (versus Ag/AgCl).

Engineering human cytochrome P450 enzymes into catalytically self-sufficient chimeras using molecular Lego.

The membrane-bound human cytochrome P450s have essential roles in the metabolism of endogenous compounds and drugs. Presented here are the results on the construction and characterization of three fusion proteins containing the N-terminally modified human cytochrome P450s CYP2C9, CY2C19 and CYP3A4 fused to the soluble NADPH-dependent oxidoreductase domain of CYP102A1 from Bacillus megaterium. The constructs, CYP2C9/BMR, CYP2C19/BMR and CYP3A4/BMR are well expressed in Escherichia coli as holo proteins.