Cancer therapy combining the modalities of hyperthermia and chemotherapy: In vitro cellular response after rapid heat accumulation in the cancer cell

Hyperthermia is usually used at a sub-lethal level in cancer treatment to potentiate the effects of chemotherapy. The purpose of this study is to investigate the role of heating rate in achieving synergistic cell killing by chemotherapy and hyperthermia. For this purpose, in vitro cell culture experiments with a uterine cancer cell line (MES-SA) and its multidrug resistant (MDR) variant MES-SA/Dx5 were conducted. The cytotoxicity, mode of cell death, induction of thermal tolerance and P-gp mediated MDR following the two different modes of heating were studied. Doxorubicin (DOX) was used as the chemotherapy drug. Indocyanine green (ICG), which absorbs near infrared light at 808nm (ideal for tissue penetration), was chosen for achieving rapid rate hyperthermia. A slow rate hyperthermia was provided by a cell culture incubator. The results show that the potentiating effect of hyperthermia to chemotherapy can be maximized by increasing the rate of heating as evident by the results from the cytotoxicity assay. When delivered at the same thermal dose, a rapid increase in temperature from 37°C to 43°C caused more cell membrane damage than gradually heating the cells from 37°C to 43°C and thus allowed for more intracellular accumulation of the chemotherapeutic agents. Different modes of cell death are observed by the two hyperthermia delivery methods. The rapid rate laser-ICG hyperthermia @ 43°C caused cell necrosis whereas the slow rate incubator hyperthermia @ 43°C induced very mild apoptosis. At 43°C a positive correlation between thermal tolerance and the length of hyperthermia exposure is identified. This study shows that by increasing the rate of heating, less thermal dose is needed in order to overcome P-gp mediated MDR.

Stated versus observed performance levels in patients with chronic low back pain

This study examined the relationship between chronic low back pain (CLBP) patients' perceived (stated) levels of function and their measured (observed) performance in squatting and stair climbing activities as compared to healthy volunteers. Twenty patients with CLBP and 20 healthy subjects were asked through an interview to self-assess their ability to comfortably perform stair climbing and squatting as well as other tolerances. The subjects were then asked to perform the activities and their performance levels were recorded. Results of the t-tests and Analysis of Variance (ANOVA) procedures revealed that patients' estimate of squatting and stair climbing abilities as well as their demonstrated levels were significantly lower (p < 0.001) than those of the healthy subjects. There was a significant difference between groups in terms of the time required to perform squatting but not stair climbing. Both healthy subjects and patients with CLBP underestimated their physical capabilities. Findings indicate that the use of actual performance measurement combined with self-report of functional abilities is needed when assessing performance levels of both healthy as well as patients with CLBP.