Novel HER2 selective tyrosine kinase inhibitor, TAK-165, inhibits bladder, kidney and androgen-independent prostate cancer in vitro and in vivo

金沢大学医学部附属病院泌尿器科Purpose: TAK-165 is a new potent inhibitor of human epidermal growth factor receptor 2 (HER2) tyrosine kinase. Several reports suggest HER2 expression in bladder cancer, renal cell carcinoma (RCC) and androgen-independent prostate cancer. We therefore investigated the antitumor effect of TAK-165 on these urological cancer cells. Materials and methods: Western blot analysis was performed to confirm HER2 expression in cell lines. To study in vitro efficacy, cells were treated with TAK-165 at various concentrations for 72 h and then counted using a hemocytometer. Then the IC50 value was calculated. In the xenograft model, after the tumor reached 200-300 mm3 in volume, mice were orally administered TAK-165 10 mg/kg per day or 20 mg/kg per day or saline for 14 consecutive days (n = 6-8). Results: HER2 expression was observed in HT1376, UMUC3, T24 (bladder), ACHN (kidney), DU145, LNCaP, LN-REC4 (prostate), although the expression level in these cells was weak compared with BT474 (a breast cancer cell line which expresses HER2 strongly). IC50 was varied from 0.09 to greater than 25 μmol/L in the bladder cancer cell line. ACHN cells were less sensitive in vitro. The prostate cancer cell lines studied were all sensitive (IC50 0.053-4.62 μmol/L). In the xenograft model, treatment with TAK-165 significantly inhibited growth of UMUC-3, ACHN, and LN-REC4. The antitumor effect (T/C [%] = growth of TAK-165 treated tumor/average growth of control tumor × 100) after 14 days treatment were 22.9%, 26.0%, and 26.5% in UMUC3, ACHN and LN-REC4, respectively. Conclusions: TAK-165 may be a hopeful new agent for bladder, kidney and androgen-independent prostate cancer

Psychological and weight-related characteristics of patients with anorexia nervosa-restricting type who later develop bulimia nervosa

<p>Abstract</p> <p>Background</p> <p>Patients with anorexia nervosa-restricting type (AN-R) sometimes develop accompanying bulimic symptoms or the full syndrome of bulimia nervosa (BN). If clinicians could predict who might change into the bulimic sub-type or BN, preventative steps could be taken. Therefore, we investigated anthropometric and psychological factors possibly associated with such changes.</p> <p>Method</p> <p>All participants were from a study by the Japanese Genetic Research Group for Eating Disorders. Of 80 patients initially diagnosed with AN-R, 22 changed to the AN-Binge Eating/Purging Type (AN-BP) and 14 to BN for some period of time. The remaining 44 patients remained AN-R only from the onset to the investigation period. Variables compared by ANOVA included anthropometric measures, personality traits such as Multiple Perfectionism Scale scores and Temperament and Character Inventory scores, and Beck Depression Inventory-II scores.</p> <p>Results</p> <p>In comparison with AN-R only patients, those who developed BN had significantly higher current BMI (p < 0.05) and maximum BMI in the past (p < 0.05). They also scored significantly higher for the psychological characteristic of parental criticism (p < 0.05) and lower in self-directedness (p < 0.05), which confirms previous reports, but these differences disappeared when the depression score was used as a co-variant. No significant differences were obtained for personality traits or depression among the AN-R only patients irrespective of their duration of illness.</p> <p>Conclusion</p> <p>The present findings suggest a tendency toward obesity among patients who cross over from AN-R to BN. Low self-directedness and high parental criticism may be associated with the development of BN by patients with AN-R, although the differences may also be associated with depression.</p