Randomized Double-Blind Placebo-Controlled Trial of Bestatin in Patients With Resected Stage I Squamous-Cell Lung Carcinoma

Ichinose, Yukito; Genka, Keiichiro; Koike, Teruaki; Kato, Harubumi; Watanabe, Yoh; Mori, Takashi; Iioka, S; Sakuma, Atsushi; Ohta, Mitsuo

doi:10.1093/jnci/95.8.605

Cited by 97 publications

(72 citation statements)

References 35 publications

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“…All of these mechanisms are postulated to result in myeloma cell death, particularly as malignant cells are often more dependent on the availability of amino acids such as arginine. There is a precedent for taking such an approach in hematologic cancers, as bestatin, a broad-spectrum inhibitor of the aminopeptidases, has been shown to be effective in Japan in solid tumors and leukemia and is well tolerated in clinical trials (13,14).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, many tumor cells are dependent on specific amino acids and previous studies have shown that depletion of these amino acids has a greater effect on cancer cells than normal cells (11,12). Evidence for the clinical value of such an approach is seen from the use of bestatin, a broad-range inhibitor of aminopeptidases, which has been used for over a decade in Japan for the treatment of acute and chronic acute myeloid leukemia (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Aminopeptidase inhibition as a targeted treatment strategy in myeloma

Moore

Davenport

Smith

et al. 2009

Molecular Cancer Therapeutics

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Aminopeptidase inhibition as a targeted treatment strategy in myeloma

Moore

Davenport

Smith

et al. 2009

Molecular Cancer Therapeutics

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“…Ichinose et al showed that bestatin had a therapeutic effect of prolonging survival when used as a postoperative adjuvant treatment for patients whose stage I squamous-cell carcinoma was completely resected. 38 Likewise, APN/CD13-targeting treatment such as bestatin combined with paclitaxel-based chemotherapy may lead to better prognosis of OVCA patients. Although further clarification of the mechanism and function of APN/CD13 in tumor biology is essential, APN/CD13 may become a novel therapeutic target for OVCA.…”

Section: Discussionmentioning

confidence: 99%

Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo

Yamashita

Kajiyama

Terauchi

et al. 2007

Intl Journal of Cancer

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Aminopeptidase N (APN/CD13), a 150-kDa metalloproteinase, is a multifunctional cell surface aminopeptidase with ubiquitous expression. Recent studies have suggested that APN/CD13 plays an important role in tumor progression in several human malignancies. In the current study, we investigated the role of APN/CD13 in paclitaxel (PAC)-resistance of ovarian carcinoma (OVCA) cells. We first examined the correlation between APN/CD13 expression and IC50 values of PAC in a variety of OVCA cell lines. Next we investigated whether suppression of APN/CD13 using bestatin, an inhibitor of APN/CD13 activity or the siRNA technique influenced PAC-sensitivity in ES-2 cells, which highly express APN/CD13. Moreover, we investigated the effect of bestatin on peritoneal metastasis using nude mice. We found a negative correlation between APN/CD13 expression and chemosensitivity to PAC in various carcinoma cell lines. Subsequently, we found a significant increase in PAC-sensitivity of APN/CD13 expressing OVCA cells by suppression of this enzyme, using the addition of bestatin or the siRNA technique. Furthermore, in a peritoneal metastasis model using nude mice, combination treatment with PAC and bestatin caused a synergistic increase of survival time compared with PAC alone treatment. (mean survival time: 37.7 6 7.0 s and 27.1 6 6.6 days, respectively). The present findings showed that APN/CD13 may be involved in decreased sensitivity to PAC in OVCA cells and that the mechanism of this effect involves its enzyme activity at least in part. APN/CD13 may be a therapeutic target for the treatment of OVCA in combination with chemotherapy. ' 2007 Wiley-Liss, Inc.

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“…Apart from antioxidant activity, this compound showed selective cytotoxicity in cancer cells. 20 and 24 lg/mL phenazine brought abount IC 50 in HeLa and MCF-7 cell lines respectively (Fig. 3).…”

Section: Assay Of Free Radical Scavenging and Cytotoxicitymentioning

confidence: 91%

“…Clinical trials of cancer therapies in combination with aminopeptidase inhibitors are in progress. Bestatin is an example of aminopeptidase inhibitor used to treat acute and chronic acute myeloid leukemia under the trademark Ubenimex in Japan [20]. It is possible that a bioactive that is inhibitory to Streptomyces aminopeptidase can be inhibitory to eukaryotic aminopeptidases too.…”

Section: Aminopeptidase Inhibitory Activitymentioning

confidence: 99%

Antifungal, Anticancer and Aminopeptidase Inhibitory Potential of a Phenazine Compound Produced by Lactococcus BSN307

et al. 2016

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A bioactive compound was purified from the culture medium of a new strain of Lactococcus BSN307 by solvent extraction followed by chromatographic techniques. This bioactive compound was identified to belong to phenazine class of compounds by MS, NMR and FTIR. The phenazine compound showed antifungal activity against Aspergillus niger, Penicillium chrysogenum as well as Fusarium oxysporum by disc diffusion assay in addition to antioxidant potential as demonstrated by DPPH scavenging assay. The compound demonstrated selective cytotoxicity against cancer cell lines HeLa and MCF-7 where IC 50 was achieved with 20 and 24 lg/mL respectively. At the same time no cytotoxicity was occurred in normal H9c2 cells. The bioactive found to be inhibitory to both leucine and proline aminopeptidases and thus revealed its potential as metalloenzyme inhibitor. This study, for the first time reports the production of phenazine class of compounds by lactic acid bacteria.

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Randomized Double-Blind Placebo-Controlled Trial of Bestatin in Patients With Resected Stage I Squamous-Cell Lung Carcinoma

Abstract: Survival was statistically significantly better for patients with completely resected stage I squamous-cell lung carcinoma who were treated with bestatin as a postoperative adjuvant therapy than for those who received a placebo. This result requires confirmation in other phase III trials.

Cited by 97 publications

References 35 publications

Aminopeptidase inhibition as a targeted treatment strategy in myeloma

Aminopeptidase inhibition as a targeted treatment strategy in myeloma

Involvement of aminopeptidase N in enhanced chemosensitivity to paclitaxel in ovarian carcinoma in vitro and in vivo

Antifungal, Anticancer and Aminopeptidase Inhibitory Potential of a Phenazine Compound Produced by Lactococcus BSN307

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