Hepatocellularcarcinoma

,Hepatocellular carcinoma,Contents,Anatomic Structure and physiologic function of LiverEffect Factor of Liver Cancer SusceptibilitySymptom of Liver CancerChemical Therapy of Liver Cancer Action character and caution to some medicine (in our outpatient pharmacy)Other Information and knowledge about cancer,Part 1-1 Anatomic Structure of Liver,1.最大的腺体，成人1.5kg，2叶2.肝脏的位置3.肝脏上的管子有哪些？（上1低3）4.肝脏的血流方向？5.注意：首过效应；腹水；,Effect Factor of Liver Cancer Susceptibility,Liver Cancer,物理的因素,人类自身的因素,化学的因素,病毒？,The signs and Symptom of Liver Cancer,Because liver cancer is anumbrella termfor many types of cancer, the signs and symptoms depend on what type of cancer is present. Cholangiocarcinoma(胆管癌) is associated withsweating,jaundice(黄疸？),abdominal pain,weight lossandhepatomegaly（肝肿大及腹水）.Hepatocellular carcinoma is associated with, abdominal massabdominal pain,emesis,anemia（贫血）,back pain,jaundice,itching,weight lossandfever,Therapeuticprinciple of Liver Cancer,Operation + Chemical therapy,防止术后复发，但要注意局限性评价？,动脉化学栓塞(介入技术)冷冻手术经皮乙醇注射聚能刀消融全身或区域性化疗手术+放疗+化疗,局限性或局限性晚期 肿瘤小于5cm,动脉化学栓塞经皮乙醇注射化疗肝移植,复发性肝癌或不能手术的肝癌,局限性可切除的原位肝癌,为什么是动脉？,Transcatheter Arterial Chemoembolization,Chemical Therapy of Liver Cancer,The mostcommonchemical medicine wasDoxorubicin(Adriamycin) and 5-FU. But the effectiverate20%.,Other protocols of Chemical Therapy are on the base of above two medicine Such as PDF,AFP,AFM,EMP,LD-FP,AP,APC,GA FOLFOX- 4 OF,OG,OC,GO .etal.,Cis-Platinum;Mitomycin; Mitoxantrone; Capecitabine; Gemcitabine; Oxaliplatin,Mechanism of action and adverse reactions of chemical therapy protocol,Doxorubicin( Adriamycin ),The antibiotics of anti-tumor(broadspectrum)cell cycle non-specific drugs与其它抗肿瘤抗生素，如比柔比星，表柔比星，阿柔比星，柔红霉素和米托蒽醌一样结构中含有蒽醌结构，能够直接嵌 入DNA的碱基对之间，抑制m RNA的合成和DNA的复制。Myelosuppression and Cardiac toxicity lead to mycaroditis and heartfailure已有骨髓抑制的患者,心肺失代偿的患者及严重心脏病的患者不能使用.,Mechanism of action and adverse reactions of chemical therapy protocol,5-FU,抑制胸腺嘧啶核苷酸合成酶，抑制DNA的合成，该酶能够将甲酰四氢叶酸的一碳单位转移给脱氧尿嘧啶核苷一磷酸合成胸腺嘧啶核苷一磷酸。该药是目前应用最广的抗嘧啶类药物。主要不良反应是骨髓抑制，皮疹，色素沉积（少数）伴有水痘和带状疱疹的患者禁用使用本品是不能饮酒或同时服用阿司匹林类药物以减少肠道出血的发生。,Mechanism of action and adverse reactions of chemical therapy protocol,Cis-Platinum,能够与DNA形成交叉键，从而破坏DNA的功能不能进行复制（作用机制？与CI-有关）是目前联合化疗中最常用的药物主要是消化道不良反应、肾毒性、骨髓抑制和听力损伤。胰腺毒性可诱发尿糖。使用本品前应该检查肾功能及听力，注意多饮水或输液强迫利尿。,Mechanism of action and adverse reactions of chemical therapy protocol,Mitomycin,分子中的亚胺基团作为烷化剂与DNA分子中鸟嘌呤N7结合，形成链间交叉链接，抑制DNA的复制。高浓度时也能够抑制m RNA和蛋白质的合成。在体内经过还原酶活化后其作用主要作用与G1和早S期。有耐药性，主要是长时间使用细胞膜通透性降低。消化道癌最常用的药物主要不良反应：骨髓抑制及肾、肺毒性，服药期间严格检查血象有局部刺激作用，输液时不可侧漏水痘和带状疱疹患者禁用，用药期间禁用活病毒疫苗接种和避免口服脊髓灰质炎疫苗,Mechanism of action and adverse reactions of chemical therapy protocol,蒽醌结构，镶嵌如DNA，抑制DNA的合成，对RNN的合成也有抑制作用。为周期非特异性药物主要的不良反应是：骨髓抑制，白细胞减少心脏毒性低于多柔比星，但大剂量的时候心脏毒性明显脱发不良反应也低于多柔比星注意既往蒽环类药物的用药总量，按规定禁止超过总限制量（？）,Mitoxantrone,Capecitabine！,Mechanism of action and adverse reactions of chemical therapy protocol,5-FU的前药首先在肝脏转化为没有活性的中间体5-脱氧-5氟胞苷，最后在肿瘤组织内经胸苷磷酸化酶催化为5-FU主要的不良反应：麻木，感觉迟钝，有麻刺感；皮肤肿胀或红斑，水泡或严重的疼痛，皮炎和脱发常见与香豆素和华法林合用，凝血参数改变或出血；其能够增加苯妥英钠的血药浓度和毒性；由于会导致致命的氟尿嘧啶毒性，本品禁止与索利夫定（？）及类似物联用；抗酸药增加其血药浓度；与亚叶酸和干扰素-a合用时，最大耐受量降低,Gemcitabine,Mechanism of action and adverse reactions of chemical therapy protocol,嘧啶为抗肿瘤药物为前药，作用机制与阿糖胞苷一样，体内代谢物掺入DNA，主要作用于G1/S期。但与阿糖胞苷有所不同：1.双氟脱氧胞苷除了掺入DNA以外，还抑制核苷酸还原酶，使细胞内脱氧核苷三磷酸酯减少；2.它能够抑制脱氧胞嘧啶脱氨酶减少细胞内代谢物的降解，具有自我增效的作用。作为氟尿嘧啶化疗失败的二线药物骨髓抑制，中性粒细胞抑制和血小板抑制有肾毒性临床上主要根据血液毒性调整剂量，参照肝肾毒性化疗+放疗时，本品可加重放疗敏化的可能，所以本品与化疗的间隔周期要大于4周,Oxaliplatin,Mechanism of action and adverse reactions of chemical therapy protocol,为第三代铂类抗肿瘤药物以DNA为靶点，抑制器复制和转录对顺铂耐药的肿瘤有效，与5-FU有协同作用，与顺铂之间无交叉耐药性有神经毒性：感觉迟钝，感觉异常，遇冷加重；胃肠道的反应勿与存在潜在神经毒性的药物联用，不能用生理盐水溶解，用药期间不要吃生冷的东西，禁用冰水漱口。严禁与碱性药物或碱性溶酶联用，制备药液或输液时勿与铝制品接触与伊立康唑合用，发生胆碱能综合征的危险升高，注意观察并使用阿托品预防,Some special medicine in our outpatient pharmacy Mechanism of action and adverse reactions of Monoclonal antibody,(targeting preparation and monoclonal antibody),Trastuzumab( trade namesHerclon,Herceptin)Ranibizumab(trade nameLucentis)Infliximab(INN; trade name Remicade)Etanercept(trade nameEnbrel),Trastuzumab( trade namesHerclon,Herceptin),It is amonoclonal antibodythat interferes with theHER2/neureceptor. Its main use is to treat certain breast cancers.The HER receptors are proteins that are embedded in the cell membrane and communicate molecular signals from outside the cell (molecules calledEGFs) to inside the cell, and turn genes on and off.The HER proteins stimulate cell proliferation. In some cancers, notably certain types of breast cancer, HER2 is over-expressed, and causes cancer cells to reproduce uncontrollably.Some of the common side effects of trastuzumab are flu-like symptoms (such as fever, chills and mild pain),nausea(恶心，呕吐)anddiarrhoea（腹泻）. One of the significant complications of trastuzumab is its effect on the heart, although this is rare.9Trastuzumab is associated with cardiac dysfunction in 2-7% of cases.Trastuzumab downregulates neuregulin-1 (NRG-1)（神经营养素-1）, which is essential for the activation of cell survival pathways in cardiomyocytes and the maintenance of cardiac function. NRG-1 activates the MAPK pathway and the PI3K/AKT pathway as well as focal adhesion kinases (FAK).Approximately 10% of patients are unable to tolerate this drug because of pre-existing heart problems,Mechanism of action of Trastuzumab,Ranibizumab(trade nameLucentis),It is amonoclonal antibodyfragment (Fab) derived from the same parent mouse antibody asbevacizumab(Avastin). It is much smaller than the parent molecule and has beenaffinity maturedto provide stronger binding toVEGF-A.By blocking VEGF-A in the eye, ranibizumab may prevent and reverse vision lossThe most common side effects in clinical trials were conjunctival hemorrhage(结膜出血), eye pain, vitreousfloaters（玻璃体混浊）, increasedintraocular pressure（眼内压）, and intraocular inflammation（眼内炎症）.Although there is a theoretical risk for arterial thromboembolic （血栓）events in patients receiving VEGF-inhibitors by intravitreal injection, the observed incidence rate was low ( 4%) and similar to that seen in patients randomized to placebo（安慰剂）.,Mechanism of action of Ranibizumab,Infliximab(INN; trade name Remicade),Itis achimericmonoclonal antibodyagainst tumour necrosis factor alpha (TNF-) used to treatautoimmunediseases. Infliximab is an artificialantibodyInfliximab was approved by theU.S. Food and Drug Administration(FDA) for the treatment ofpsoriasis（牛皮癣）,Crohns disease（克罗恩氏病，节段性肠炎）,ankylosing spondylitis（强直性脊柱炎）,psoriatic arthritis（银屑病关节炎）,rheumatoid arthritis, andulcerative colitis（溃疡性结肠炎）. Infliximab won its initial approval by the FDA for the treatment ofCrohns diseasein August 1998.Infliximab works by binding to TNF-. TNF- is a chemical messenger (cytokine) and a key part of the autoimmune reaction. In rheumatoid arthritis, infliximab seems to work by preventing TNF- from binding to itsreceptorin the cell.Infliximab has adverse effects, some life-threatening, common to drugs in the class ofimmunosuppressants(which also includes etanercept (依纳西普Enbrel) and adalimumab (阿达木单抗). Some of the most severe are:serious and sometimes fatalblood disorders；seriousinfections；lymphomaand solid tissue cancers；reports of serious liver injury；reactivation ofhepatitis B,It is abiopharmaceuticalthat treats autoimmune diseases by interfering withtumor necrosis factor(TNF; a soluble inflammatory cytokine) by acting as aTNF inhibitor and is afusion proteinproduced byrecombinant DNA.Soluble TNF receptorPegsunerceptAnti-TNFmonoclonal antibodiesInfliximabAdalimumabCertolizumab pegolGolimumab,Etanercept(trade nameEnbrel),Mechanism of action of Etanercept,Mechanism of action of Ranibizumab,Oncogene,Oncogene：是控制细胞生长和分裂的正常基因的一种突变形式，能够引起 正常细胞的癌变 。Oncogene的发现：最早发现于能够诱发肿瘤的劳氏肉瘤病毒（Rous sarcoma vir