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Establishment of a cell line from Japanese patient useful for generating an in vivo model for malignant pleural mesothelioma

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Page 648–55

Malignant pleural mesothelioma (MPM) is an aggressive tumor that arises from mesothelial cells on the serosal surfaces of the thoracic cavity and is associated with asbestos exposure. Once a rare disease, the incidence of MPM has been increasing worldwide. With poor early detection and limited efficacy of conventional treatments, MPM patients have a median survival rate of 9–17 months. Improved understanding of MPM’s behavior is necessary to increase early diagnosis and treatment efficacy. In an effort to develop a better in vivo model of MPM, Sato and colleagues investigated six MPM cell lines from pleural effusion fluids or surgically resected tumors. Following subcutaneous inoculation in BALB/c-nude mice, one cell line, MM56, rapidly generated tumors that maintained the expression of mesothelioma-related markers. Furthermore, orthotopic implantation of MM56 into BALB/c-nude mice resulted in diffuse growth of thoracic tumors; orthotopic implantation models are considered to provide the most useful models for in vivo MPM study. The authors conclude that MM56 cells behave in a manner characteristic of human MPM and may provide a useful in vivo model with which to study the behavior of this disease.

doi: 10.1111/j.1349-7006.2010.01827.x

Broad spectrum and potent anti-tumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models

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Page 614–21

Survivin, a member of the inhibitor of apoptosis protein family, is a novel target for anticancer therapy. Highly expressed in a range of solid tumors and hematological malignancies, survivin is associated with negative prognostic factors in a variety of tumor types. Inhibition of survivin has been found to disturb cell proliferation and induce apoptosis in various tumor types. A novel small-molecule survivin suppressant, YM155, has anti-tumor activity in a number of human cancer models. To better characterize YM155’s therapeutic potential, Nakahara and colleagues investigated the molecule’s anti-tumor activity in a broad range of human cancer cell lines and xenograft models. YM155 inhibited tumor growth in 155 human cancer cell lines; tumor regression was associated with decreased intratumoral survivin expression, increased apoptosis, and decreased mitotic indices. The authors identify YM155 as a potent anticancer agent and call for further investigation of YM155’s therapeutic potential both alone and in conjunction with conventional chemotherapeutic agents and with molecular targeted agents.

doi: 10.1111/j.1349-7006.2010.01834.x

The in vitro and in vivo anti-tumor effect of KO-202125, a sauristolactam derivative, as a novel epidermal growth factor receptor inhibitor in human breast cancer

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Page 597–604

Epidermal growth factor receptor (EGFR) plays an important role in regulating various biological processes, such as cell proliferation, apoptosis, angiogenesis, and differentiation. Overexpression of EGFR is a marker of poor prognosis in many cancer types including breast cancer. As one of the most promising targets for cancer therapy, EGFR is the target of many anti-tumor drugs. However, current EGFR inhibitors have limited efficacy on the more aggressive breast cancers. In this issue, Oh and colleagues report the anticancer effects of a novel EGFR inhibitor, KO-202125, in EGFR-overexpressing cancer cell lines. KO-202125 is one of the synthesized aristolactam analogs and has previously been shown to induce apoptosis in KB human oral squamous carcinoma cells. The authors now report anti-proliferative and apoptotic activity of KO-202125 in EGFR-overexpressing breast cancers both in vitro and in vivo. Downregulation of EGFR activity and the Akt pathway were identified as possible molecular mechanisms of KO-202125’s therapeutic effects. The researchers suggest that KO-202125 is a potential anticancer drug for EGFR-overexpressing breast cancers.

doi: 10.1111/j.1349-7006.2010.01817.x