Clinical relevance of survivin as a biomarker in neoplasms, especially in adult T-cell leukemias and acute leukemias.

Survivin has been identified as one of the top 4 transcripts among 3.5 million human transcriptomes uniformly up-regulated in cancer tissues but not in normal tissues. Therefore, we quantitatively determined the messenger RNA (mRNA) expression profile for survivin by a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) technique in 113 patients with leukemias, such as adult T-cell leukemia (ATL), acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia in crisis, and chronic lymphocytic leukemia (CLL), and in 25 cell lines, including 7 ATL cell lines and 15 solid-tumor cell lines. Furthermore, we examined whether the plasma level of survivin protein as measured by enzyme-linked immunosorbent assay (ELISA) substituted for mRNA expression by PCR quantification. Gene expression was quantitatively confirmed to be up-regulated in approximately 90% of ATL and acute leukemia cases and in all of the cell lines tested, whereas it was down-regulated in almost all cases of CLL. Furthermore, with respect to the interpretation of the gene expression findings, attention was paid to standardization with a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in the real-time PCR quantification, because the variability in GAPDH expression among the different cell types was significant. GAPDH expression was relatively low in ATL cells and high in ALL and AML cells. The rates of increase in the levels of survivin protein in the plasma of ATL patients and in the supernatants from in vitro cultures of solid-tumor cell lines were low compared with rates of increase of the mRNA and protein level in the cells, suggesting that the protein levels in plasma do not always reflect survivin expression in tumor cells. Our findings indicate the potential clinical relevance of survivin quantified by real-time PCR but not for the protein level in plasma as determined by ELISA, especially in cases of ATL and acute leukemias.

Expression of heat shock protein (Hsp) 70 and Hsp 40 in colorectal cancer.

Heat shock protein (Hsp) 70 and Hsp 40 are stress proteins that cooperate as chaperones in mammalian cells. The present study was designed to determine the expression levels of Hsp 70 and Hsp 40 in colorectal cancer by immunohistochemistry and Western blot analysis. Among 50 colorectal cancer tissues studied, 80% and 14% of tumors showed specific immunoreactivity to Hsp 70 and Hsp 40, respectively. Hsp 70 and Hsp 40 were overexpressed in cancer tissue samples compared with normal tissues, on both analytic sets. However, there were no significant correlations between their expression and various clinicopathological parameters of colorectal cancer. Hsp 70 and Hsp 40 may be tumor markers for colorectal cancer.

[CPT-11 hepatic arterial injection plus oral UFT administration for liver metastasis of rectal cancer--report of two cases].

The first patient was a 51-year-old male who had 5-fluorouracil-resistant recurrent rectal cancer with multiple liver metastases. He was given our new combination chemotherapy consisting of hepatic arterial injection of CPT-11 (20 mg/body) on day 1 and day 2 and oral administration of UFT (300 mg/day) on days 3 to 6 of a 7 day cycle starting in January 2001. Six weeks after the beginning of chemotherapy, the liver metastatic lesions were reduced. He is now living with outpatient treatment. The second patient was a 76-year-old male who had initial recurrent rectal cancer with multiple liver metastases. Thirty-two weeks after the same chemotherapy, the metastatic lesions had completely disappeared. Twelve months have passed since this chemotherapy, and we have not found any recurrent tumor. While significant antitumor effects were observed, there were few adverse events in either patient. These results suggest that combined chemotherapy of CPT-11 by hepatic arterial injection and oral administration of UFT is an effective treatment for liver metastases of rectal cancer.