Optimize Gynecologic Cancer Care –From Prevention to Treatment

• Main Authors: Chien-Hsing Lu, 呂建興
• Other Authors: Chia-Chen Chang
• Format: Others
• Language: en_US
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/rh877n

博士 === 國立中興大學 === 生物醫學研究所 === 100 === This dissertation includes two different themes. These themes involved difficult handling issues in gynecologic oncology, which include: 1. Quality issues in cervical cytology (Pap smear): Pap smear play most important role in cervical cancer prevention. Only satisfactory (good quality) Pap smear can ensure accurate detection of cervical lesions. However, there were no researches on what clinical conditions will result in more unsatisfactory Pap smears. After reviewed and analyzed of medical history of 5,662 cases, we found that the clinical parameters correlated with unsatisfactory smears were postpartum status (OR=1.92), vaginal bleeding (OR= 2.02), and endocervical polyps (OR= 2.62). If any of these parameters are noted prior to obtaining a Pap smear, optimal collecting devices, better sampling techniques, and liquid-based cytology should be considered to decrease the incidence of unsatisfactory smears. Another issue is in Cses of pelvic irradiation, chemotherapy, and/or hysterectomy, the cellularity in Pap smear will decrease. Therefore, cytopathologists were allowed to lower their criteria of satisfactory Pap smear. After reviewed and analyzed the medical history of 1,337 cases with history of pelvic irradiation, chemotherapy, and hysterectomy, we found hysterectomy was not associated with increased unsatisfactory Pap smear. For age more than 50 years with history of pelvic irradiation, or chemotherapy, the threshold of satisfactory Pap smear can be reset at 2,000 per slide. By doing this, the unsatisfactory rate will not increased, at the same time the sensitivity will not be compromised. Thus, cervical cancer prevention can be more effective by Pap smears. Moreover, the troubles between medical services and patients will decrease. 2. Use of Src inhibitor to treat ovarian clear carcinoma cell line: ovarian clear cell carcinoma is chemoresistant and highly malignant. We used Src inhibitor dasatinib to treat ovarian cancer clear cell carcinoma cell line. We found the activity of Src can be effectively inhibited, at the same time E-cadherin expression was increased. Dasatinib can inhibit invasiveness and resulted in cell cycle arrest a G1 phase. From in vitro and in vivo studies, we found increased cytotoxic effects of dasatinib to paclitaxel. From these data, we suggested that for clear cell carcinoma with increased Src activity, dasatinib combination with paclitaxel provide another potential effective option. With the results of these studies, we understand more about the qualities issues of cervicovaginal screening, the clinical conditions associated with unsatisfactory Pap smear, the need and degree of criteria modification in special clinical conditions during sampling of Pap smears. We also found a promising molecule Src for target therapy in combination with paclitaxel in highly malignancy and lethal ovarian clear cell carcinoma with clinical available Src inhibitor dasatinib.