Characterization of osteoblastic properties of 7F2 and UMR-106 cultures after acclimation to reduced levels of fetal bovine serum.

Estrogen plays an important role in skeletal physiology by maintaining a remodeling balance between the activity of osteoblasts and osteoclasts. In an attempt to decipher the mechanism through which estrogen elicits its action on osteoblasts, experimentation necessitated the development of a culturing environment reduced in estrogenic compounds. The selected medium (OPTI-MEM) is enriched to sustain cultures under reduced fetal bovine serum (FBS) conditions and is devoid of the pH indicator phenol red, a suspected estrogenic agent. This protocol reduced the concentration of FBS supplementation to 0% through successive 24 h incubations with diminishing amounts of total FBS (1%, 0.1%, and 0%). The protocol does not appear to alter the viability, cell morphology, or osteoblast-like phenotype of 7F2 and UMR-106 cell lines when compared with control cells grown in various concentrations of FBS. Although the rate of mitotic divisions declined, the 7F2 and UMR-106 cultures continued to express osteoblast-specific markers and exhibited estrogen responsiveness. These experimental findings demonstrate that the culture protocol developed did not alter the osteoblast nature of the cell lines and provides a model system to study estrogen's antiresorptive role on skeletal turnover.

Has hyperthermia a place in cancer treatment?

Long before ionising radiations were discovered, attempts were made to exploit elevated temperatures to control malignant tumours. At irregular intervals over the last 100 years, hyperthermia has been suggested for use in cancer therapy but has never become established. There is little doubt that heat alone can destroy tumours; and it can enhance the anti-cancer effects of radiation and chemotherapeutic agents. Laboratory and in vivo animal data provide hyperthermia with a strong biological rationale, which gives the more recent revival of interest a sounder base than previously. The exact science of hyperthermia, however, is still in its infancy, and how it should be employed to its best advantage in human cancer therapy remains illusive. We review the current position of hyperthermia in clinical cancer management and look to see what achievements are likely in the near future.

The effect of hyperthermia and radiation on small bowel permeability using 51Cr EDTA and 14C mannitol in man.

A prospective study was conducted to study the effect of radiotherapy (RT) and regional pelvic hyperthermia (HT) on intestinal permeability in three groups of patients. Fifteen acted as cancer controls, receiving RT away from the peritoneal cavity, 21 patients received radical pelvic or abdominopelvic RT and 13 patients pelvic RT followed by pelvic HT using a BSD 1000 phased array applicator. Small bowel permeability was measured by oral administration of a mixture of [51Cr]EDTA, [14C]mannitol and lactulose before and after a course of treatment. The absorption of each marker was calculated by measuring the urinary excretion over 0-6 and 0-12 hours. The 6 hour collection gave results similar to the 12 hour collection, but had logistical advantages. The EDTA absorption rose and the mannitol absorption fell during a course of treatment, but the best index of permeability change was the EDTA/mannitol ratio (E/M). The E/M ratio rose by a factor of 2.4 (P less than 0.001) and 1.82 (P = 0.05) following RT and RT/HT respectively. There was no significant difference between the RT and RT/HT groups but the thermal dose to the RT/HT group was low (23 min./equiv 43 degrees C over three or four fractions in 4 weeks). There was no correlation between small bowel permeability and bowel frequency. The E/M permeability test is a useful simple functional assay for assessing small bowel damage after RT and RT/HT.

Regional hyperthermia for extensive pelvic tumours using an annular phased array applicator: a feasibility study.

Twenty patients with extensive pelvic tumours have been treated with radiotherapy and regional hyperthermia using an annular phased array applicator (APA). The majority of patients had bulky disease with a mean tumour volume of 206 cm3. In 63 of 67 attempted treatments heating was achieved, temperatures in excess of 42 degrees C being reached in the pelvis in 78%. Heat doses, however, were low, only 41% of treatments exceeding 5 min equivalent at 43 degrees C. Treatment was usually limited by acute toxicity and, although this was marked, it was of short duration and no long-term sequelae have been noted. With gain in operator experience, later treatments have achieved improved thermal doses. Response was difficult to assess but we have documented responses in six of 12 assessable patients. Palliation has been achieved in all patients with symptoms. Preliminary attempts to shift the region of maximum heating by phase variations in the APA output are promising, and this technique should improve the quality of treatments and reduce toxicity. The APA is thus capable of inducing pelvic regional hyperthermia, and a randomised controlled study is now planned to assess the value of pelvic hyperthermia as a treatment modality.

A clinical microwave hyperthermia system with multipoint real-time thermal dosimetry.

A clinical hyperthermia system using a 915 MHz microwave generator and incorporating multipoint thermocouple thermometry is described. Temperatures can be monitored simultaneously at 16 points and measurements displayed on a visual display unit and a plotter. The power output of the generator is adjusted under computer control to maintain a constant predetermined temperature in a chosen control channel. A clinically useful feature of the system is the ability to determine the effective cumulative thermal dose delivered to the tissue at points monitored in real time. The basis for the thermal dose calculation is discussed in detail. The calculated dose parameter is displayed for each of the 16 channels during the treatment and updated every 30 s. This real-time display of a thermal dose parameter has made possible a more homogeneous heating of tumours.