PPI在肿瘤化疗期的应用价值.ppt

质子泵抑制剂与肿瘤耐药研究 肿瘤细胞外微环境的高度酸化是肿瘤细胞对化疗药物产生耐药的机制之一。改变肿瘤细胞内外的pH 梯度是逆转耐药的一种有效方法。 作为抗酸剂治疗胃病的质子泵抑制剂能够通过抑制质子泵的功能，改变pH 梯度而阻断肿瘤微环境的酸化，达到提高肿瘤对化疗药物敏感性的目的。 1　肿瘤酸化与耐药：细胞内pH(pHi)过低是诱导凋亡的因素之一，而较高pHi则是细胞分裂增殖的必要条件。为维持pHi的稳定，细胞在产酸和泌酸之间存在着动态平衡。实体瘤的重要特点之一是细胞间质呈酸性。 2　细胞内酸泡与耐药：在肿瘤细胞与酸相关的耐药机制中，细胞内的酸性囊泡也起了相关作用。人类恶性肿瘤分泌的微囊泡就起源于酸泡，其对肿瘤通过表达功能性凋亡分子的免疫逃避起着重要作用。 3　质子泵阻断剂与耐药逆转：研究发现，预先给予PPIs，在体 外可显著诱导肿瘤细胞对几种药物细胞毒作用的敏感性，如顺铂、5 - 氟尿嘧啶、长春新碱。 * * Breakthrough emesis presents a difficult situation as correction of refractory ongoing nausea/vomiting is often challenging to reverse. It isgenerally far easier to prevent nausea/vomiting than to treat it. The general principle of breakthrough treatment is to give an additional agent from a different drug class. No one drug class has been shown to be superior for the management of breakthrough emesis, and the choice of agent should be based on assessment of the current prevention strategies used. Some patients may require several agents utilizing differing mechanisms of action. One should strongly consider routine, around-the-clock administration rather than PRN dosing. The PO route is not likely to be feasible due to ongoing vomiting, therefore, rectal or IV therapy is often required. Multiple concurrent agents, perhaps in alternating schedules or by alternating routes, may be necessary. Dopamine antagonists (eg,metoclopramide, haloperidol , corticosteroids, and agents such as lorazepam may be required. Ensure adequate hydration or fluid repletion, simultaneously checking and correcting any possible electrolyte abnormalities. Prior to administering the next cycle of chemotherapy the patient should be reassessed, with attention given to various possible nonchemotherapy-related reasons for breakthrough emesis with the current cycle: Brain metastases Electrolyte abnormalities Tumor infiltration of the bowel or other gastrointestinal abnormality Other comorbidities Prior to the next cycle of chemotherapy, reassess both the day 1 and post-chemo antiemetic regimen w