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High expression of KIBRA in gastric cancer with low expression of atypical protein kinase C correlates with lymphatic invasion and poor prognosis


Page 259–65

Low levels of atypical protein kinase C (aPKC) in gastric cancer has been shown to confer a better prognosis. However, the role of aPKC's regulators has not been explored. In this study, Yoshihama and colleagues investigated the effect of upstream regulator KIBRA on aPKC expression in gastric cancer. KIBRA seems to work through competitive inhibition of aPKC during epithelial polarity development, leading to decreased polarity, a hallmark of malignancy. This relationship between KIBRA and aPKC is further confirmed by the relationship between the two, specifically, that high KIBRA in a low aPKC setting is predictive of a poor prognosis and lymphatic invasion in gastric cancer. This novel finding offers increased predictive value for patients with low levels of aPKC, as those with low aPKC in a high KIBRA environment are likely to suffer a poor prognosis, whereas those with a low level of aPKC alone have a more favorable prognosis.doi: 10.1111/cas.12066

Tailored immunoconjugate therapy depending on a quantity of tumor stroma


Page 231–7

Hypovascular tumors with thick stroma, such as gastric and pancreatic tumors, currently provide a challenge to treatment with mAbs, as the active agent is unable to penetrate the structure and is thus ineffective. In contrast, stroma-poor tumors such as lymphomas are readily targeted by the standard immunoconjugate therapy in which the mAb is paired to a carbamate bond. Yasunaga and colleagues hypothesized that the treatment effect could be maximized by attaching a conjugate to the mAb that is specific to the type of tumor (stroma-rich versus stroma-poor). To this end, Yasunaga et al. synthesized a novel immunoconjugate that binds to collagen 4 or the fibrin network in a stroma-rich tumor and allows a slow release of the mAb, leading to tumor growth arrest and damage. Indeed, this group successfully showed that the effectiveness of mAb treatment was dependent on both the selection of conjugate design and the actual mAb.doi: 10.1111/cas.12062

Intraperitoneal delivery of siRNA targeting NEDD1 prolongs the survival of scirrhous gastric cancer model mice


Page 214–22

Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. A major factor contributing to the poor prognosis of this disease is the development of peritoneal metastases, and many therapeutic strategies have targeted this feature. In the study presented here, Fujita and coworkers developed a mouse model expressing human GC cells in the peritoneal cavity. They also showed the ability of siRNA to inhibit growth of cancer cells in vivo and in vitro. The in vitro mouse model using siRNA to target the metaphase-related gene NEDD1 led to significantly reduced peritoneal spread of disease as well as improved overall survival. This work not only provides a model for studying peritoneal spread of GC, but also identifies a potential method for treating this complication of the disease.doi: 10.1111/cas.12054