Hidekazu Kitakata

Adjuvant Immunochemotherapy with Protein-Bound Polysaccharide K for Colon Cancer in Relation to Oncogenic β-Catenin Activation

PurposeProtein-bound polysaccharide K is an immunotherapeutic agent that promotes apoptosis by inhibiting nuclear factor-kappaB activation in cancer cells. We previously showed that oncogenic β-catenin activates nuclear factor-kappaB and inhibits apoptosis by up-regulating β-transducin repeat-containing protein. We investigated whether the activation state of β-catenin in the primary tumor is associated with differences in survival rates of patients with colon cancer undergoing immunochemotherapy with 5-fluorouracil plus polysaccharide K vs. chemotherapy with 5-fluorouracil alone.MethodsWe assessed the activation states of β-catenin and nuclear factor-kappaB in the primary tumors of 202 colon cancer patients, and analyzed the data in terms of the clinicopathologic characteristics and survival of patients undergoing the two forms of adjuvant therapy.ResultsWe found two distinct patterns of nuclear accumulation of activated β-catenin in the tumor cells: diffuse nuclear accumulation in 89 cases (44 percent) and selective nuclear accumulation at the tumor invasion front in 18 cases (9 percent). Nuclear factor-kappaB activation was found in 64 cases (32 percent). In patients with diffuse nuclear accumulation-type β-catenin activation, immunochemotherapy significantly improved recurrence-free survival, cancer death survival, and overall survival rates compared with patients receiving chemotherapy alone. No survival benefit was found in cases with nuclear accumulation at the tumor invasion front-type β-catenin activation or no activation. Similarly, immunochemotherapy favored the survival of patients with nuclear factor-kappaB activation. Multivariate analysis established the TNM stage and administration of polysaccharide K as independent prognostic factors in the patients with diffuse nuclear accumulation-type β-catenin activation.ConclusionsThe presence of diffuse nuclear accumulation-type β-catenin activation identifies patients with colon cancer who respond better to immunotherapy with polysaccharide K.

Pilot Study of Low-Dose, Divided Maximum Tolerated Dose of CPT-11 in 21 Consecutive Patients with Metastatic Colorectal or Gastric Cancer

PurposeWe devised a new treatment regimen, delivering a frequent low dose of CPT-11, calculated by dividing the maximum tolerated dose (MTD) to reduce its toxicity without impairing its efficacy.MethodsCPI-11, 25 mg/m2, determined by dividing the MTD dose per month by 12, was given on days 1, 2, and 3 of every week, to 21 consecutive patients; 12 with metastatic colon cancer and 9 with metastatic gastric cancers.ResultsThe total delivered dose of CPI-11 per patient was more than 1 000 mg in 17 (80.1%) of the 21 patients. Grade 3 marrow depression developed in 3 (14.3%) patients, and although nausea, vomiting, alopecia, and diarrhea developed in some patients, these side effects were all categorized as grade 2 or milder. The antitumor effect was evaluated in 18 patients with measurable lesions, who had received CPI-11 according to our regimen for at least 3 weeks. Of these 18 patients, 10, 7, and 1, respectively, had a found to have partial response, no change, or progression of disease, demonstrating a 55.6% efficacy rate [colon 6/10 (60.0%) and stomach 4/8 (50.0%)]. Moreover, time to progression (TTP) was greater than 90 days in 12 (75.0%) of these 18 patients.ConclusionThese results show that our low-dose, divided MTD of CPI-11 regimen is a promising method of reducing toxicity and strengthening the antitumor effect, justifying further large-scale comparative clinical studies to verify this potential.

Heterotopic pancreas with calcification: A lesion mimicking leiomyosarcoma of the stomach☆

Current affiliations: The Department of Internal Medicine and Department of Surgery, National Ishikawa Hospital, Kanazawa, and the Department of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan. Reprint requests: Rie Oka, MD, The Department of Internal Medicine, National Ishikawa Hospital, 150 Tezuka-machi, Kaga, 922-0405, Japan. Copyright

Erratum: Adjuvant immunochemotherapy with protein-bound polysaccharide K for colon cancer in relation to oncogenic β-catenin activation (Diseases of the Colon and Rectum DOI: 10.1007/s10350-006-0842-5)

Adjuvant Immunochemotherapy with Protein-bound Polysaccharide K for Colon Cancer in Relation to Oncogenic b-Catenin Activation Kaname Yamashita, M.D., Ph.D., Andrei V. Ougolkov, M.D., Ph.D., Hiroaki Nakazato, M.D., Ph.D., Katsuki Ito, M.D., Ph.D., Yasuo Ohashi, Ph.D., Hidekazu Kitakata, M.D., Ph.D., Kazuo Yasumoto, M.D., Ph.D., Kazuhiko Omote, M.D., Ph.D., Masayoshi Mai, M.D., Ph.D., Yutaka Takahashi, M.D., Ph.D., Toshinari Minamoto, M.D., Ph.D. 1 Divisions of Translational and Clinical Oncology and Surgical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan 2 Division of Developmental Oncology Research, Mayo Clinic, Rochester, Minnesota 3 The Study Group of Colon Cancer Immunochemotherapy with PSK and 5-FU (CIP), Aichi Japan