Yu Kang

Publications (2)12.61 Total impact

• Article: Biological significance of HORMA domain containing protein 1 (HORMAD1) in epithelial ovarian carcinoma.

  Mian M K Shahzad, Yong-Hyun Shin, Koji Matsuo, Chunhua Lu, Masato Nishimura, De-Yo Shen, Yu Kang, Wei Hu, Edna M Mora, Cristian Rodriguez-Aguayo, Arvinder Kapur, Justin Bottsford-Miller, Gabriel Lopez-Berestein, Aleksandar Rajkovic, Anil K Sood
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  ABSTRACT: The present study was undertaken to determine the expression and biological significance of HORMAD1 in human epithelial ovarian carcinoma. We found that a substantial proportion of human epithelial ovarian cancers expressed HORMAD1. In vitro, HORMAD1 siRNA enhanced docetaxel induced apoptosis and substantially reduced the invasive and migratory potential of ovarian cancer cells (2774). In vivo, HORMAD1 siRNA-DOPC treatment resulted in reduced tumor weight, which was further enhanced in combination with cisplatin. HORMAD1 gene silencing resulted in significantly reduced VEGF protein levels and microvessel density compared to controls. Our data suggest that HORMAD1 may be an important therapeutic target.
  Cancer letters 07/2012; · 4.86 Impact Factor
• Article: Metronomic activity of CD44-targeted hyaluronic acid-paclitaxel in ovarian carcinoma.

  Sun Joo Lee, Sukhen C Ghosh, Hee Dong Han, Rebecca L Stone, Justin Bottsford-Miller, De Yue Shen, Edmond J Auzenne, Alejandro Lopez-Araujo, Chunhua Lu, Masato Nishimura, Chad V Pecot, Behrouz Zand, Duangmani Thanapprapasr, Nicholas B Jennings, Yu Kang, Jie Huang, Wei Hu, Jim Klostergaard, Anil K Sood
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  ABSTRACT: Most primary human ovarian tumors and peritoneal implants, as well as tumor vascular endothelial cells, express the CD44 family of cell surface proteoglycans, the natural ligand for which is hyaluronic acid. Metronomic dosing, the frequent administration of chemotherapeutics at substantially lower than maximum tolerated doses (MTD), has been shown to result in reduced normal tissue toxicity and to minimize "off-treatment" exposure resulting in an improved therapeutic ratio. We tested the hypothesis that hyaluronic acid (HA) conjugates of paclitaxel (TXL; HA-TXL) would exert strong antitumor effects with metronomic (MET) dosing and induce antiangiogenic effects superior to those achieved with MTD administration or with free TXL. Female nude mice bearing SKOV3ip1 or HeyA8 ovarian cancer cells were treated intraperitoneally (i.p.) with MET HA-TXL regimens (or MTD administration) to determine therapeutic and biologic effects. All MET HA-TXL-treated mice and the MTD group revealed significantly reduced tumor weights and nodules compared with controls (all P values < 0.05) in the chemotherapy-sensitive models. However, the MTD HA-TXL-treated mice showed significant weight loss compared with control mice, whereas body weights were not affected in the metronomic groups in HeyA8-MDR model, reflecting reduced toxicity. In the taxane-resistant HeyA8-MDR model, significant reduction in tumor weight and nodule counts was noted in the metronomic groups whereas the response of the MTD group did not achieve significance. While both MTD and metronomic regimens reduced proliferation (Ki-67) and increased apoptosis (TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling), only metronomic treatment resulted in significant reductions in angiogenesis (CD31, microvessel density). Moreover, metronomic treatment resulted in substantial increases in thrombospondin-1 (Tsp-1), an inhibitor of angiogenesis. This study showed that MET HA-TXL regimens have substantial antitumor activity in ovarian carcinoma, likely via a predominant antiangiogenic mechanism.
  Clinical Cancer Research 06/2012; 18(15):4114-21. · 7.74 Impact Factor