Hirokazu Tanino

Bisphosphonate therapy for bone metastases from Breast Cancer: Clinical results and a new therapeutic approach

BackgroundWe evaluated the usefulness of bisphosphonate (BIS) monotherapy, the safety of rapid infusion of BIS and the efficacy of BIS-sequential therapy for bone metastases from breast cancer.Patients and MethodsTwenty-nine patients with bone metastasis or invasion were treated with BIS monotherapy. Each BIS (pamidronate 30 mg, alendronate 10 mg, or incadronate 10 mg) was infused over 30 minutes every two weeks a median of 12 times.ResultsWith BIS therapy, five patients (17%) showed partial response of the bone lesions, and eighteen patients (64%) had pain relief. Of the nine patients treated with BIS-sequential therapy, one (11%) showed a partial response of the bone metastases, three (33%) had pain relief, and one (11%) showed a decrease in the serum tumor marker level.ConclusionBIS therapy is effective against bone metastases from breast cancer, and rapid infusion of BIS is both safe and convenient for patients. BIS-sequential therapy can be a unique therapeutic option in some cases.

Analysis of the early postoperative serum carcinoembryonic antigen time-course as a prognostic tool for bronchogenic carcinoma.

The serum kinetics of carcinoembryonic antigen (CEA) after resection of lung carcinoma are not well characterized. Its prognostic implications remain unclear. This study was designed to clarify the correlation between postoperative CEA time‐course and patient prognosis.

A metastatic model of human colon cancer constructed using cecal implantation of cancer tissue in nude mice

COL-2-JCK, a human colon cancer xenograft line able to be transplanted into nude mice, was implanted in the subserosal layer of the cecum, either as cancer tissue or as a single cell suspension. When cancer tissue was used for the cecal implantation, 100% extensive local tumor growth and a high incidence of metastases to the regional lymph nodes, peritoneum, liver, and lung was observed. In contrast, when the cell suspension of this line was injected into the cecal wall, no metastases were observed, with significantly reduced local tumor growth. The use of cancer tissue maintaining the original cancer tissue structure is therefore considered imperative for allowing full expression of the biological characteristics of cancer cells. This nude mouse model using the cecal implantation of cancer tissue should thus prompt further study on the biology of human colon cancer.

In Vitro and In Vivo Modulation of Growth Regulation in the Human Breast Cancer Cell Line MCF-7 by Estradiol Metabolites.

BackgroundThe natural estrogen 17β-estradiol (E2) functions as a potent tumor promoter during tumorigenic transformation of the mammary gland. From amongst the various pathways of E2 metabolism upregulation of C16α-hydroxylation of E2 has been associated with carcinogenesis. In the present studyin vitro andin vivo experiments were performed on estrogen receptor positive human breast cancer MCF-7 cells to examine whether the natural estrogen E2 and its metabolites 16α-hydroxyestrone (16α-OHEi) and 2-hydroxyestrone (2-OHE1) function as modulators of tumor cell growth.MethodsAn anchorage-independent growth assay was used forin vitro study by counting the number of tri-dimensional colonies formed by MCF-7 cells suspended in 0.33% agar.In vivo experiments examined the effect of implanting metabolite material pellets into female nude mice.ResultsIn the anchorage-independent growth assay (AIG), continuous 14-day exposure to E2 and to 16α-OHE1 at 200 ng/ml induced a 59.4% and a 105.9% increase (P=0.001) respectively in the number of colonies of MCF-7 cells. Identical treatment with 2-OHE1, however, failed to increase AIG relative to that seen in the solvent treated control cultures. In thein vivo tumorigenicity assay, treatment of nude mice with 1.5 mg E2 or 16α-OHE1 resulted in a 335.4% and a 384.1% increase (P<0.0002) in tumor growth, while identical treatment with 2-OHE1 failed to exhibit any increase relative to the control group.ConclusionsThese results suggest that the 16α- and 2-hydroxylated metabolites of E2 may directly affectin vitro growth of MCF-7 cells via an autocrine mechanism andin vivo growth via paracrine mechanisms. Thus, E2-mediated growth regulation in MCF-7 cells may in part be due to distinct effects of specific E2 metabolites on the breast cancer cells.

Enhancement of antitumor activity of cisplatin on human gastric cancer cells in vitro and in vivo by buthionine sulfoximine.

An attempt was made to evaluate the enhancement of the antitumor activity of cisplatin (DDP) by buthionine sulfoximine (BSO) in vitro and in vivo. In the in vitro study, pre‐treatment with BSO (5, 10 and 25 mM) increased the antitumor activity of DDP against the gastric cancer cell lines MKN‐28 and MKN‐45, whereas BSO alone exhibited only slight antitumor activity (inhibition rate, 20–30%). In the in vivo study, the antitumor effects of DDP against human gastric cancer xenografts St‐15 and SC‐l‐NU in BALB/c nu/nu mice were enhanced pretreatment with BSO, which was administered intraperitoneally at a dose of 500 mg/kg according to a schedule of qd × 3. BSO alone showed no antitumor effects against these tumors in nude mice. The side effects (assessed in terms of death rate and body weight loss) associated with the maximum tolerated dose of DDP (9 mg/kg) were not increased by BSO pretreatment. As BSO increased the antitumor activity of DDP without a corresponding increment of its toxicity, BSO appears to be a promising agent for further study.