ArcCHECK系统在食管癌螺旋断层放疗计划验证中的应用

目的 探讨ArcCHECK系统在食管癌断层治疗旋转照射和固定野照射计划验证中的应用,总结相关经验。方法 对32例不同部位食管癌分别制作Helical旋转照射和Direct固定野照射验证计划,并通过ArcCHECK测量、分析,对比验证结果通过率。分析靶体积与计划验证通过率的相关性。将靶体积较小的治疗验证计划分别放在ArcCHECK模体中心和外周探测点处,分析验证通过率差异。结果 Helical计划验证通过率高于Direct计划(P<0.01),其靶体积与验证通过率的相关系数分别为-0.364和-0.042,P值分别为0.041和0.819。Helical计划采用3%/2mm标准时,高剂量区放在模体中心和外周探测点处测得的通过率不同(P=0.005),后者通过率更高;采用3%/3mm标准时与Direct计划的3%/3m、3%/2mm标准的相近(P均>0.05)。结论 Helical计划验证通过率普遍高于Direct计划,原因可能与ArcCHECK探测器的角度响应以及因更多参考点受到低剂量辐射而未参与计算有关,另外还可能跟Direct计划对断层治疗剂量控制系统要求更高有关。在Helical验证计划中,当采用3%/3mm标准时,靶体积越大,验证时出现较低通过率的可能性增加,但相关系数较低。验证计划的高剂量区位于模体中心或者探测点处都可以实现计划验证,综合考量建议放在模体等中心处。     

梨状窝癌局部扩展的病理学研究

目的 探讨梨状窝癌局部扩展的规律,为梨状窝癌的手术治疗提供病理学依据。方法 应用石蜡包埋大体标本连续切片的方法,对２６例梨状窝癌全喉及次全喉及次全喉切除的标本进行了观察。结果 位于梨状窝外侧壁的肿瘤（４例）主要向外侧咽侧壁扩展,位于梨状窝内侧壁的肿瘤（５例）容易向喉腔及对侧梨状窝扩展。累及整个梨状窝１７例。声门旁间隙及甲状软骨是最易受侵犯的喉结构,环状软骨受侵较少;会厌及会厌前间隙的侵犯未见超过中     

梨状窝癌局部扩展的病理学研究

目的　探讨梨状窝癌局部扩展的规律 ,为梨状窝癌的手术治疗提供病理学依据。方法　应用石蜡包埋大体标本连续切片的方法 ,对 2 6例梨状窝癌全喉及次全喉切除的标本进行了观察。结果　位于梨状窝外侧壁的肿瘤 ( 4例 )主要向外侧咽侧壁扩展 ,位于梨状窝内侧壁的肿瘤 ( 5例 )容易向喉腔及对侧梨状窝扩展。累及整个梨状窝 17例。声门旁间隙及甲状软骨是最易受侵犯的喉结构 ,环状软骨受侵较少 ;会厌及会厌前间隙的侵犯未见超过中线 ,声门旁间隙及会厌前间隙的侵犯途径有2个 ,肿瘤沿杓会厌襞向前及在甲状软骨板内侧直接向前侵犯声门旁间隙 ;肿瘤沿杓会厌襞向内上方及在甲状软骨板内侧上部侵入会厌前间隙。结论　会厌前间隙的受侵并不是喉部分切除的禁忌证 ,大部分位于梨状窝外侧壁的肿瘤及部分梨状窝内侧壁的肿瘤保留喉功能是可行的 ;位于梨状窝内侧壁及环后区的肿瘤易在环后区向对侧侵犯 ,对累及环后区的梨状窝癌 (Ⅰ ,Ⅲ型 ) ,应注意肿瘤在环后区粘膜下向对侧侵犯。     

保留颈外静脉同期双侧颈淋巴结清除术治疗头颈部癌

自１９８９年１月至１９９４年１２月对１９例头颈部癌并双侧颈淋巴结转移的病人采取保留颈外静脉同期双侧颈淋巴结清除术（以下简称颈清术）治疗。包括喉癌、下咽癌、舌癌、口底癌、甲状腺癌及双侧原发灶不明的颈部转移癌。本文对其手术指征及手术方法作了简单介绍，并对其意义及可行性进行了讨论。     

Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells

Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER⁺) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER⁺ breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER⁺ breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER⁺ breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.     

Pre-clinical use of isogenic cell lines and tumours in vitro and in vivo for predictive biomarker discovery; impact of KRAS and PI3KCA mutation status on MEK inhibitor activity is model dependent

Studies to identify predictive biomarkers can be carried out in isogenic cancer cell lines, which enable interrogation of the effect of a specific mutation. We assessed the effects of four drugs, the PI3K–mammalian target of rapamycin inhibitor dactolisib, the PI3K inhibitor pictrelisib, and the MEK (MAPK/ERK Kinase) inhibitors PD 0325901 and selumetinib, in isogenic DLD1 parental, KRAS^+/−, KRAS^G13D/−, PIK3CA^+/− and PIK3CA^E545K/− colorectal carcinoma cell lines. Importantly, we found substantial differences in the growth of these cells and in their drug sensitivity depending on whether they were studied under 2D (standard tissue culture on plastic) or 3D (in vitro soft agar and in vivo xenograft) conditions. DLD1 KRAS^+/− and DLD1 PIK3CA^+/− cells were more sensitive to MEK inhibitors than parental, DLD1 KRAS^G13D/− and DLD1 PIK3CA^E545K/− cells under 2D conditions, whereas DLD1 KRAS^G13D/− and DLD1 PIK3CA^E545K/− xenografts were sensitive to 10 mg/kg daily ×14 PD 0325901 in vivo (p ≤ 0.02) but tumours derived from parental DLD1 cells were not. These findings indicate that KRAS and PIK3CA mutations can influence the response of DLD1 colorectal cancer cell lines to MEK and PI3K inhibitors, but that the effect is dependent on the experimental model used to assess drug sensitivity.