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