Youko Itoh

Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer

It has not been elucidated whether certain types of M1b prostate cancer (M1b PC) are associated with a poor outcome. The present study retrospectively identified predictive factors related to the outcome of M1b PC. The subjects were 104 patients who attended our hospital and received a diagnosis of M1b PC. The observation period ranged from 4 to 122 months (median, 43 months). The parameters investigated were: T classification, N classification, Gleason score (GS), pretreatment prostate-specific antigen (PSA) level, extent of disease (EOD) grade, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), calcium, and hemoglobin (Hb) levels, platelet count, and the status of HER-2 overexpression as determined with a Hercep Test(TM) Kit using initial needle biopsy specimens for diagnosis. Log-rank test and Cox univariate analysis identified the following factors with statistically significant differences: pretreatment PSA ≥ 192, N1, GS ≥ 8, EOD grade 3+4, high LDH, high ALP, low Hb, and HER-2 overexpression. Multivariate Cox proportional hazard analysis identified the factors GS ≥ 8, high LDH, and HER-2 overexpression with significant differences. The hazard ratio was 5.962, 2.465, and 2.907, respectively, and the probability value was P=0.0218, P=0.0207 and P=0.0090, respectively. When the subjects with GS ≥ 8, high LDH, and HER-2 over-expression were classified as the high-risk group, the 5-year cause-specific survival rate was 51.2, 29.6, and 20.0%, respectively. The present study showed that M1b PC patients with GS ≥ 8, high LDH, and HER-2 overexpression have a very poor outcome and thus, should be treated as a high-risk group requiring close follow-up.

Combining anti-tumor drugs with mild hyperthermia increases the cytotoxic effects of drugs on human leukemia cells in vitro

Although the benefits of using a combination of hyperthermia and chemotherapy or radiotherapy in the treatment of cancer have been theoretically established, the use of such combination therapy is not widespread at the clinical level, as the application of hyperthermia is complex and maintaining a tumor temperature of 43°C or higher is exceedingly difficult. Consequently, in the present study, the effects of chemotherapy combined with mild hyperthermia at 41°C (which is easier to apply than standard hyperthermia) were examined in the NALM-6 leukemia cell line. The results were as follows: i) NALM-6 leukemia cells, like most cells, survived mild hyperthermia at 41°C, but were killed at temperatures over 43°C. ii) Low concentrations of adriamycin (0.1 µg/ml) or mild hyperthermia applied separately did not have a visible effect on the survival rate of NALM-6 cells, whereas combined treatment with these therapies decreased the survival rate of NALM-6 cells in a time-dependent manner. The anti-tumor effect after 5 h of the combination of 0.1 µg/ml adriamycin and mild hyperthermia was the same as that observed with a 10-fold higher concentration (1 µg/ml) of adriamycin alone. iii) Another anti-tumor drug, vincristine, exhibited the same behavior as adriamycin. The anti-tumor effect after 1 h of the combination of 5x10-11 M vincristine and mild hyperthermia was the same as that observed with a 10-fold higher concentration (5x10-10 M) of vincristine alone. The results indicate that it may be possible to reduce the required concentrations of anti-tumor drugs by using them in combination with mild hyperthermia. In this way, the side effects of chemotherapy may be reduced in clinical settings. Mild hyperthermia is a useful and practical heating method, and could result in the increasing clinical application of hyperthermia in the treatment of cancer.

Enhancement of enterohemorrhagic Escherichia coli O157:H7 stress tolerance via pre-heating

Enterohemorrhagic Escherichia coli O157:H7 infection causes several hundred cases of food poisoning every year in Japan. In severe cases, this type of food poisoning can be fatal. In the present study, we examined the induction of HSP70 in E. coli O157:H7 cells at various temperatures and the thermotolerance of E. coli O157:H7 cells alone and in contaminated food following pre-heating. We evaluated the possibility that thermotolerance by E. coli O157:H7 increases the likelihood of food poisoning. E. coli O157:H7 cells were heated at 43-51 °C, and the survival rate was examined. The temperature of highest induction of HSP70 was used as the pre-heating temperature. We measured the thermotolerance of E. coli O157:H7 cells following pre-heating as the survival after heating at 53 °C (lethal temperature). Additionally, we evaluated the thermotolerance of E. coli O157:H7 cells in ground beef following pre-heating. Heating at 47 °C for 30 min caused the highest induction of HSP70 and this temperature was selected as the pre-heating temperature. The survival rate was significantly higher for 0-90 min compared to that in cultures incubated at 53 °C without pre-heating indicating thermotolerance. Additionally, in ground beef, thermotolerance in E. coli O157:H7 cells was induced by pre-heating. We showed that E. coli O157:H7 cells acquired thermotolerance after pre-heating, which significantly increased survival after a lethal temperature, and increased the likelihood of food poisoning.