Neoadjuvant cisplatin for head and neck cancer: Simulation of a novel schedule for improved therapeutic ratio

Current clinical studies support the role of neoadjuvant cisplatin administration prior to curative radiotherapy or radio-chemotherapy for advanced head and neck cancer. Nevertheless, based on locoregional control rates the studies indicate that there is need to redesign cisplatin-based schedules for induction chemotherapy, thus the ideal treatment regimen is yet to be established. While the pharmacokinetics/dynamics of daily cisplatin regimens correspond better with the cell cycle properties of head and neck cancers, weekly regimens are more commonly employed in clinics due to lower complications. Yet, the high rates of adverse events induced by current cisplatin schedules often represent a limiting factor in the overall success of the treatment.The aim of the present paper was to model the pharmacodynamic properties of cisplatin and to simulate and compare various neoadjuvant treatment regimens in regards to their effect on tumour control. Treatment simulation was undertaken on a virtual squamous cell carcinoma of the head and neck, previously grown by computer-based probabilistic methods.The model suggests that a novel cisplatin treatment, given every three days is comparable, in regards to tumour control, with the daily administration and more effective than the weekly regimen in neoadjuvant settings. Endpoints were assessed in terms of cell population regrowth after treatment cessation followed by two weeks of unperturbed growth. Simulation of two weeks low-dose daily cisplatin followed by two weeks ‘free growth’ lead to 15% population regrowth, while weekly high-dose cisplatin over three weeks, followed by two weeks unperturbed growth resulted in 52% tumour cell regrowth. The proposed novel schedule of low-dose third-daily cisplatin gives closer tumour regrowth to daily administration (27% versus 15%) than to the weekly regimen (52%) and also similar cell distribution along the cell cycle as the daily one, suggesting therefore comparable response to subsequent treatment.The advantage of using a third-daily drug regimen would be a decrease in normal tissue complication rates compared to daily administration and possibly an increase in tumour control when compared to the ‘conventional’ weekly cisplatin delivery.     

Two‐photon excited fluorescence lifetime measurements through a double‐clad photonic crystal fiber for tissue micro‐endoscopy

This paper presents an endoscopic configuration for measurements of tissue autofluorescence using two–photon excitation and time‐correlated single photon counting detection through a double‐clad photonic crystal fiber (DC‐PCF) without pre‐chirping of laser pulses. The instrument performance was evaluated by measurements of fluorescent standard dyes, biological fluorophores (collagen and elastin), and tissue specimens (muscle, cartilage, tendon). Current results demonstrate the ability of this system to accurately retrieve the fluorescence decay profile and lifetime of these samples. This simple setup, which offers larger penetration depth than one‐photon‐based techniques, may be combined with morphology‐yielding techniques such as photoacoustic and ultrasound imaging. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

A fluorescence lifetime spectroscopy study of matrix metalloproteinases‐2 and ‐9 in human atherosclerotic plaque

Matrix metalloproteinase (MMP)‐2 and ‐9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP‐2 and ‐9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time‐resolved laser‐induced fluorescence spectroscopy (TR‐LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP‐2 and ‐9 content in the atherosclerotic plaque cap using a label‐free imaging technique implemented with a fiberoptic TR‐LIFS system. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Gamma radiation effects on seed germination, growth and pigment content, and ESR study of induced free radicals in maize (Zea mays)

The effects of gamma radiation are investigated by studying plant germination, growth and development, and biochemical characteristics of maize. Maize dry seeds are exposed to a gamma source at doses ranging from 0.1 to 1 kGy. Our results show that the germination potential, expressed through the final germination percentage and the germination index, as well as the physiological parameters of maize seedlings (root and shoot lengths) decreased by increasing the irradiation dose. Moreover, plants derived from seeds exposed at higher doses (≤0.5 kGy) did not survive more than 10 days. Biochemical differences based on photosynthetic pigment (chlorophyll a, chlorophyll b, carotenoids) content revealed an inversely proportional relationship to doses of exposure. Furthermore, the concentration of chlorophyll a was higher than chlorophyll b in both irradiated and non-irradiated seedlings. Electron spin resonance spectroscopy used to evaluate the amount of free radicals induced by gamma ray treatment demonstrates that the relative concentration of radiation-induced free radicals depends linearly on the absorbed doses.