Acute leukemia is classified broadly as either acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL). The main treatments remain remission induction therapy and postremission chemotherapy. The advances in chemotherapy for pediatric patients with ALL have been dramatic, with some 95% achieving complete remission, and long-term survival is 60-80%. Among adults, high long-term survival rates due to improvements in chemotherapy for B-cell type ALL and core binding factor leukemias have been reported. For adult leukemias overall, however, long-term survival rates have stalled at 15-40% despite the high remission rate attained. In most cases this is due to a recurrence. Among the prognostic factors reported for acute leukemia, chromosome type may be cited as the currently most reliable. Acute leukemia patients are classified based on chromosome type, and the postremission therapeutic strategy is considered in terms of an appropriate combination of chemotherapy and hematopoietic stem cell transplant. This accounts for an important part of the treatment given today. Target-based therapies such as all-trans-retinoic acid (ATRA) for AML have brought dramatic improvements in treatment results. The effect of imanitib against Philadelphia chromosome positive ALL, for which the prognosis is poor, is also attracting attention. Moreover, promising new treatment strategies that have been developed, including cord blood transplant, mini-transplant, antibody therapy, and immunotherapy, Clinical studies of PCR and other means to reveal small residual lesions and estimate prognosis are also making progress. In the future it will be possible to identify prognostic factors in genetic tests such as DNA microarrays and single nucleotide polymorphisms, so that the optimum treatment can be selected for individual patients.

A 20-year-old Japanese woman was diagnosed as having acute myeloid leukemia with inv(16)(p13 q22). She achieved complete remission (CR) after treatment with a standard dose of cytarabine(ara-C) and idarubicin. She received high dose ara-C and etoposide for the 2nd consolidation chemotherapy. On the 5th fraction of high dose ara-C, her heart rate dropped to 52/minute and returned to 72/minute after the cessation of ara-C. After achieving informed consent, we gave her another course of high dose ara-C, which once again resulted in a decreased heart rate. This suggests that the administration of high dose ara-C could cause bradycardia.

A 29-year-old man was referred to our hospital with leukocytosis on March 7th, 2002. The white blood cell count was 132.9 x 10(3)/microliter with 42.0% blast cells. We diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia (CML) in a blast crisis and started imatinib mesylate therapy at a dose of 800 mg/day on March 9th, 2002. The patient's peripheral blood blasts had disappeared by March 22nd, 2002, and the percentage of blasts in the bone marrow was 0.6% on May 2nd, 2002. The patient achieved a complete cytogenetic response on May 13th, 2002, and underwent allogeneic peripheral blood stem cell transplantation from his HLA-identical sibling donor on May 30th, 2002. Although adverse reactions such as grade 3/4 of hematological events (leukopenia, anemia, thrombocytopenia and neutropenia) and grade 1/2 of non-hematological events (hyperbilirubinemia, dermatitis and edema) were observed, these adverse reactions were clinically managed. This case suggested the usefulness of imatinib mesylate in the management of the CML-associated blast crisis.

Diffuse astrocytomas are slowly growing tumors with a relatively long overall survival. Considerable controversy exists as to the best therapeutic management for patients with such tumors. In the present study, we retrospectively analyzed a series of 64 patients with WHO grade II astrocytomas of the cerebral hemispheres. Gross total resection and interferon-beta therapy were significantly associated with both longer progression free survival (PFS) and overall survival (OS). Immediate postoperative radiation therapy did not prolong either the PFS or OS. The presence of promoter hypermethylation of the O6-methylguanine-DNA methyltransferase (MGMT) gene was an independent predictor of a shorter PFS. Our data suggest that radical surgery plus interferon-beta therapy may offer the best chance for long survival. Since the presence of MGMT methylation is a probable indication of an increased sensitivity to alkylating chemotherapeutic agents, determining the methylation status of MGMT could provide a potential basis for logical therapeutic intervention in identifying a subgroup of patients who could be candidates for early chemotherapy.

Many molecular factors related to the carcinogenesis and malignant behavior of pancreatic cancer were identified by investigation of intraductal papillary mucinous tumors (IPMTs). Molecules controlling the G1/S phase, such as p53, p21, p61, and cyclin D1, tumor suppressors including DPC-4, and many other factors such as MUC-1/2 contribute to the promotion of the malignant behavior of IPMTs. They will be important molecular targets for the radical treatment of pancreatic cancer.

Many intraductal papillary-mucinous tumors (IPMTs) have been diagnosed with improvements in diagnostic imaging techniques. The histology of IPMT is various, including hyperplasia to invasive carcinoma. IPMTs are thought to occur multicentrically through the hyperplasia-adenoma-carcinoma sequence. IPMTs are characterized by genetic heterogeneity associated with histologic heterogeneity that may be due to slow growth and favorable prognosis. However, some IPMTs progress to invasive pancreatic cancer through malignant transformation with aggressive clonal progression. Thus some conventional pancreatic cancers may be derived from IPMTs. Although IPMTs and conventional pancreatic cancer initially occur in the ductal epithelium, they are thought to be totally different entities in terms of large or peripheral pancreatic duct origin, developmental style, genetic alterations, and prognosis. In future, differences and/or similarities will be discussed on the basis of molecular analyses of the carcinogensis of both tumors.

Based on the results of ecological studies of intestinal microflora, we have been studying from various perspectives, the relationship between health and intestinal microflora. Concerning intestinal microflora and cancer, we reported in Cancer Research (61: 2395-2398, 2001) that spontaneous colon cancers that developed in Tcr beta/p53-double knockout mice did not develop in germfree conditions. This study, catching the attention of researchers, was reviewed in the 'News Feature' column of Nature (415: 8-9, 2002), which introduces recent studies attracting significant attention. Cancers are diseases of genes. However, in this study, which Nature found to be an as intriguing transformation (development of colon cancer in this case), did not occur only by genetic changes, unless accompanied by environmental factors (intestinal flora in this case). The fact that intestinal microflora are involved in the development of colon cancer suggests, on the other hand, that cancers can be prevented by controlling intestinal microflora. Here, data will be presented to show the relationship between intestinal microflora and colon cancers, mainly from our studies, and the mechanism involved will be further discussed.

The patient was a 68-year-old woman who was diagnosed as having Ph-positive acute lymphoblastic leukemia (ALL). Complete remission (CR) was not obtained with the induction therapy of the Japan Adult Leukemia Study Group Protocol. We then considered administration of imatinib (ST1571). The institutional review board of our hospital approved this therapy, and we initiated the administration of imatinib 400 mg/day after obtaining written informed consent from the patient. At day 10 of the regimen, CR was achieved, treatment had to be discontinued RT-PCR showed no induction of detectable minor bcr-abl mRNA after three courses of consolidation chemotherapy combined with imatinib. We changed the administration protocol of Imatinib to two weeks out of every in four, weeks, and conducted 9 courses of consolidation chemotherapy. The negative result of RT-PCR has been maintained 10 months after diagnosis. The adverse effects were body weight gain and retaining pleural effusion, and these were controlled by the diuretics. The negative result of RT-PCR in Ph positive ALL after chemotherapy has rarely been reported, so the combination of imatinib and chemotherapy may be considered to be effective for Ph positive ALL.