Changes in plasma alpha and gamma tocopherol levels before and after long-term local hyperthermia in cancer patients.

Local hyperthermia is one of the heat therapies for cancer patients. The effect of this therapy is recognized to affect the immune function. On the other hand, researchers have recently suggested that vitamin E has not only antioxidant but also other functions including the immune function. However, the association between local hyperthermia therapy and vitamin E level is not yet well understood. Comparing plasma alpha and gamma tocopherol levels before and after the therapy, the basal levels of both tocopherols in the cancer patients did not significantly differ from those in healthy subjects. However, the interindividual difference in the basal levels was very wide in the cancer patients. After long-term local hyperthermia (more than 70 days), the levels of both tocopherols were significantly higher than the basal levels. This result suggests that long-term local hyperthermia therapy influences plasma tocopherol level in cancer patients; thus, an increase in vitamin E level may play an important role in the therapy of cancer patients.

Increased liver temperature efficiently augments human cellular immune response: T-cell activation and possible monocyte translocation.

Hyperthermia (HT), in combination with other conventional therapeutic modalities, has become a promising approach in cancer therapy. In addition to heat-induced apoptosis, an augmented immunological effect is considered to be a benefit of hyperthermic treatment over chemo- or radiotherapy. Here, we investigated the effect of regional HT targeting the liver on immune cells, especially T cells and antigen-presenting cells, which are important in recognizing and eliminating tumor cells and pathogens such as viruses. In healthy volunteers exposed to such regional HT, both CD4(+) and CD8(+) T cells that express an activation marker CD69 increased transiently at 1 h post-treatment, with a subsequent decrease to base levels at 6 h after the treatment. At 24 h post-treatment, the percentage of CD69-positive cells significantly increased again but only among CD8(+) T cells. IFN-gamma production from PHA-stimulated peripheral blood mononuclear cells was gradually and significantly increased in the 2 days following the heating procedure, peaking at 36 h post-treatment. Furthermore, we found marked increases in plasma levels of IL-1beta and IL-6 starting at 24 h post-treatment. With regard to the number of each leukocyte subpopulation, a transient and dramatic decrease in the number of a subset of monocytes, CD14(+) CD16(-) cells, was observed at 1 h after the hyperthermic treatment, suggesting that the regional HT aimed at the liver may have influenced the extravasation of blood monocytes. No significant changes in T-cell activities or monocyte counts were observed in the volunteers exposed to heating of the lungs or the legs. These results suggest that heating of the liver may efficiently induce cellular immune responses to liver cancers.

Immune-related effects of local hyperthermia in patients with primary liver cancer.

BACKGROUND/AIMS: To investigate immune-related effects of local hyperthermia (HT) with hepatocellular carcinoma (HCC). METHODOLOGY: Immune status after 7 HT was studied in 11 patients (M/F - 9/2; 1st group). The effects were also evaluated during one HT session in 4 of those pts (M/F - 4/0; 2nd group). The HT treatment was performed by means of an 8-MHz capacitive heating device, Thermotron RF8 (Japan). The mean time of one HT session was 60 min, HT was performed 1-2 times a week. In both groups the percentage of T and B cells, CD4+, CD8+ subsets of T cells, the CD4/CD8 ratio and activation of NK cells were evaluated. RESULTS: In the 1st group, CD4/CD8 ratio was decreased significantly (p < 0.05), whereas the relative amount of CD4+ T cells showed a tendency to decrease (p=0.063), and CD8--to increase (p=0.088). An activation of NK cells was observed in patients who had a low or normal pretreatment level of activation. In the 2nd group, there was a significant decrease in the CD4/CD8 ratio by the end of the treatment (p < 0.05) and increased activity of NK cells as early as 20 min after the onset of HT (p < 0.05). CONCLUSIONS: Our results suggest that HT stimulates the immunity of cancer patients by several means and therefore may exhibit indirect anticancer effect. In addition, activation of NK cells by HT may be associated with improved quality of life.

Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B.

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV. METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV. RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA I/II restricted recognition epitopes reported by some investigators. CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia.

The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.