CN104955452B - 含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 - Google Patents
含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途 Download PDFInfo
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- CN104955452B CN104955452B CN201380071525.8A CN201380071525A CN104955452B CN 104955452 B CN104955452 B CN 104955452B CN 201380071525 A CN201380071525 A CN 201380071525A CN 104955452 B CN104955452 B CN 104955452B
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Abstract
本发明公开了一种含有亚铁氨基酸螯合物的组合物及其在制备抗癌症的药物中的用途,其中药物包含有效抗癌症剂量的含有亚铁氨基酸螯合物的组合物以及其药学上可接受的载剂。本发明所述的含有亚铁氨基酸螯合物的组合物中,氨基酸可与亚铁维持螯合状态通过胃,且不影响受体的体重变化;由含有亚铁氨基酸螯合物的组合物制备而得的药物具有抑制或治疗癌症的效果。
Description
技术领域
本发明涉及含有亚铁氨基酸螯合物的组合物的用途,还涉及该组合物在制备抗癌症的药物中的用途。
背景技术
癌症或恶性肿瘤是全世界人口主要死亡原因之一,其中癌症致死率的排名主要为肺癌、胃癌、肝癌、结肠直肠癌、乳腺癌及子宫颈癌,依据世界卫生组织的统计,近二十年又以肺癌死亡率增加最快,其中肺癌依据其细胞特性及临床表现分为小细胞肺癌(smallcell lung cancer)和非小细胞肺癌(non-small cell lung carcinoma,NSCLC)两大类,其中小细胞肺癌多发生于男性,且与抽烟息息相关,占全部肺癌患者总数的25%;且小细胞生长快,并容易由淋巴或血路扩散到其他器官。非小细胞癌则占全部肺癌患者总数的75%,常见的包括:鳞状细胞癌、腺癌、大细胞癌。鳞状细胞癌又称类表皮样癌,常见于男性吸烟者,早期多为局部向外延伸的转移,后期则通过血路扩散;腺癌为目前肺癌数量最多的类型,经常在远处转移后才出现临床症状,且无吸烟者所罹患肺癌常为此类;大细胞癌,生长速度较慢,但亦经由血路及淋巴扩散。小细胞肺癌对于化学及放射线治疗相当敏感,但经治疗缓解后,大多数病例在两年内会复发并产生抗药性;非小细胞肺癌虽生长较缓慢,但可早期开刀治疗的病例仅约四分之一,且对于化学药物及放射线治疗大多不敏感;由于上述原因,肺癌病人愈后普遍不佳。此外,至今研究显示,化疗药物对病人往往是一种伤害,长期服用会造成患者免疫力下降、正常细胞凋亡而使得病人存活率下降,因此,寻找一种对于正常细胞无毒性且能够促进肺癌肿瘤细胞生长或凋亡的药物是目前极需的课题。
此外,肝癌是十大癌症前几名,除了外科切除手术之外,不外乎以化学治疗或放射线治疗等方式,但以上治疗方式往往造成病患难以忍受的痛苦及副作用,因此现有技术是以标靶治疗药物用于抗肝癌治疗,并通过抑制肝癌细胞进展过程中所涉及的突变、增殖或扩散的通路、抑制肝癌细胞血管新生或促进肝癌细胞死亡或防止癌细胞扩散为治疗目的。由于肝癌初期并无明显症状,因此预防上也越来越受重视。
Singh等人(Life Science,70 49-56,2001)揭示当细胞内铁离子浓度高时,双氢青蒿素(dihydroartemisinin)与全运铁蛋白(holotransferrin)结合后,可将全运铁蛋白及双氢青蒿素送入细胞,以达到抑制人类乳癌细胞的功效;Green等人(Clin Cancer Res7:3574-3579,2001)揭示吡哆醛异烟碱酰基类(pyridoxal isonicotinoyl)的铁螯合剂311(2-hydroxyl-naphthyladehyde benzoyl hydrazon)通过抑制核苷酸还原酶(ribonucleotide reductase)的R2亚基(subunit)以用于抑制乳癌细胞、膀胱癌细胞、头颈癌细胞以及T淋巴母细胞淋巴瘤生长;欧洲专利EP2306187 A1揭示亚铁(Fe2+)或三价铁(Fe3 +)的铁化合物可抑制乳癌细胞生长。
然而,Kato等人(Int.J.Cancer:80,693-698,1999)揭示大肠直肠癌的风险是随着高脂肪饮食结合较多总铁摄入相关;Simonart等人(Gynecologic Oncology 85,95-102,2002)揭示排铁剂(DFO及deferiprone)以时间依赖性(time-dependent)及剂量依赖性(dose-dependent)的方式抑制人类乳突病毒相关癌细胞生长,并可将人类乳突病毒相关癌细胞停止于细胞周期的G0/G1期,以及促进人类乳突病毒相关癌细胞死亡或凋亡(apoptosis)。
综上所述,现有技术并无法确认铁离子或铁化合物是否具有抑制或治疗癌症的功效,然而化学药物用于治疗诸如肺癌或肝癌等癌症往往会产生副作用,并引起患者不适而导致放弃治疗;因此,寻找可抗癌症、无副作用且可被人体吸收的药物是当务之急。
发明内容
鉴于现有技术化学药物的治疗癌症产生副作用的缺点,故本发明的目的在于提供一种含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途,其中含有亚铁氨基酸螯合物的组合物具有可抗癌的功效。
为达上述目的,本发明提供一种含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途,其中药物包含有效抗癌症剂量的含有亚铁氨基酸螯合物的组合物以及其医药学上可接受的载剂。
依据本发明,“含有亚铁氨基酸螯合物的组合物”是由无机铁与氨基酸混合所制得的含有亚铁氨基酸螯合物(ferrous amino acid chelate)的组合物;较佳的,所述的无机铁包括,但不限于硫酸亚铁、氯化亚铁及焦磷酸亚铁;较佳的,所述的氨基酸是甘胺酸。
更佳的,所述的含有亚铁氨基酸螯合物的组合物是含有重量百分比为95%至100%的亚铁甘胺酸螯合物;又更佳的,为重量百分比为98%至99.9%的亚铁甘胺酸螯合物。
较佳的,亚铁氨基酸螯合物的组合物是将硫酸亚铁(ferrous sulfate)与甘胺酸(glycine)经60℃至90℃加热8小时至48小时所获得,其中硫酸亚铁与甘胺酸的重量比例介于1∶1.2至1∶1.5之间。依据本发明,所述的含有亚铁氨基酸螯合物的组合物包含至少一种亚铁氨基酸螯合物,亚铁氨基酸螯合物的亚铁与氨基酸的螯合比例介于1∶1至1∶4之间;更佳的,亚铁氨基酸螯合物的亚铁与氨基酸的螯合比例介于1∶1.5至1∶2.5之间。
较佳的,所述的含有亚铁氨基酸螯合物的组合物中包括还原剂,该还原剂可维持含有亚铁氨基酸螯合物的组合物的亚铁的氧化态,亦可提升含有亚铁氨基酸螯合物的组合物于受体的肠道吸收率,其中还原剂包括,但不限于抗坏血酸(ascorbic acid)、柠檬酸(citric acid)、乙酸(acetic acid)、丙酸(propionic acid)、丁酸(butyric acid)、乳酸(lactic acid)、羟琥珀酸(malic acid)、磺酸(sulfonic acid)及丁二酸(succinicacid)。
依据本发明,“抗癌症”是指有效抑制或舒缓癌症;“有效剂量”是指在剂量上及对于所需要的时间段而言对达成所要抑制或舒缓癌症结果有效的量;依据本发明,是指能够使得肺癌或肝癌肿瘤的生长减缓、停止,甚致死亡,其如本发明所例示者,有效抑制或舒缓肺癌或肝癌肿瘤的剂量可通过施予特定范围量的含有亚铁氨基酸螯合物的组合物,并于特定时间范围内测量肿瘤体积变化而得。
依据本发明,“医药学上可接受的载剂”包括生理上兼容的任意及所有溶剂、分散介质、衣料、抗菌剂及抗真菌剂、等张剂及吸收延缓剂及其类似物。药学上可接受的载剂的实例包括水、盐水、磷酸盐缓冲生理食盐水、右旋糖、甘油、乙醇及其类似物的一或多种及其组合。在许多情况中,较佳的组合物包括等张剂,例如糖、甘露醇、山梨糖醇的多元醇或氯化钠。药学上可接受的载剂可进一步包含微量辅助物质,诸如湿润剂或乳化剂、防腐剂或缓冲剂。
较佳的,所述的含有亚铁氨基酸螯合物的组合物的有效剂量是介于0.2毫克/公斤/天(mg/kg/day)至15mg/kg/day;更佳的,介于0.3mg/kg/day至14mg/kg/day;较佳的,介于0.4mg/kg/day至12mg/kg/day。
本发明所述的药物可以多种形式存在。该等形式包括,但不限于液体、半固体及固体药剂形式,诸如液体溶液(例如可注射及可输注溶液)、分散液或悬浮液、锭剂、丸剂、粉剂、脂质体及栓剂。较佳的形式取决于预期的投药模式及治疗应用;较佳的,本发明的药物是呈可口服或可输注溶液形式,且较佳的投药模式为经肠模式,诸如口服。在本发明的实施例中,包含有效抗癌症剂量的含有亚铁氨基酸螯合物的组合物的药物是通过口服施予。
较佳的,所述的药物更包括一赋形剂(excipient),使药物适用于经肠道的或非经肠道的剂型。
较佳的,所述的经肠道的剂型是口服剂型,其包括,但不限于溶液、悬浮液、锭剂及胶囊。
较佳的,所述的癌症包括,但不限于黑色素瘤(melanoma)、肝癌(liver cancer)、结肠癌(colon cancer)、肺癌(lung cancer)、胃癌(gastric cancer)、食道癌(esophagealcancer)、乳癌(breast cancer)、前列腺癌(prostate cancer)及血癌(leukemia)。
更佳的,所述的癌症包括,但不限于脑部肿瘤(brain tumor)、低度星状细胞瘤(low-grade astrocytoma)、高度星状细胞瘤(high-grade astrocytoma)、垂体腺瘤(pituitary adenoma)、脑脊髓膜瘤(meningioma)、中枢神经淋巴瘤(CNS lymphoma)、寡树突神经胶细胞瘤(oligodendroglioma)、颅咽管瘤(craniopharyngioma)、室管膜瘤(ependymoma)、胶质细胞肿瘤(brain stem tumor)、头颈瘤(head and neck tumor)、喉癌(laryngeal cancer)、口咽癌(oropharyngeal cancer)、鼻咽癌(nasopharyngeal tumor)、唾液腺肿瘤(salivary gland tumor)、下咽癌(hypopharyngeal cancer)、甲状腺癌(thyroid cancer)、口腔肿瘤(oral cavity tumor)、胸廓肿瘤(chest wall tumors)、小细胞肺癌(small cell lung cancer)、非小细胞肺癌(non-small cell lung cancer,NSCLC)、胸腺瘤(thymoma)、纵隔肿瘤(mediastinal tumor)、男性乳癌(male breastcancer)、腹骨盆(abdomen-pelvis tumor)、肝细胞癌(hepatoma)、肝腺癌(liveradenocarcinoma)、胆囊癌(gallbladder cancer)、胆道癌(biliary tract cancer)、胰脏癌(pancreatic cancer)、小肠肿瘤(small intestinal tumor)、大肠肿瘤(largeintestinal tumor)、肛门癌(anal cancer)、膀胱癌(bladder cancer)、肾细胞癌(renalcell carcinoma)、子宫颈癌(cervix cancer)、子宫内膜癌(endometrial cancer)、卵巢癌(ovarian cancer)、子宫肉瘤(uterine sarcoma)及皮肤癌(skin cancer)。
较佳的,所述的癌症是肝癌或肺癌。
本发明所述的含有亚铁氨基酸螯合物的组合物中,由于氨基酸分子量小,可与亚铁维持螯合状态通过胃,且经本发明证实施予含有亚铁氨基酸螯合物的组合物并不影响受体的体重变化;此外,在本发明施予含有亚铁氨基酸螯合物的组合物相较于施予市售的氨基酸亚铁及无机铁(诸如硫酸亚铁)更具有抑制或舒缓肺癌或肝癌肿瘤的效果,因此,本发明所述的含有亚铁氨基酸螯合物的组合物的药物可做为用于抑制或舒缓癌症,尤其是肺癌或肝癌。
附图说明
图1是裸鼠(BALB/c nu/nu mice)施予含有亚铁氨基酸螯合物的组合物1周后,再注射肺癌肿瘤细胞的肺癌肿瘤体积变化曲线图;
图2是将含有亚铁氨基酸螯合物的组合物施予裸鼠6周后的体重变化柱状图;
图3是重症联合免疫缺陷小鼠(Severe Combined Immunodeficiency Mice;SCIDmice)(以下注记为SCID小鼠)施予含有亚铁氨基酸螯合物的组合物1周后,再注射肝癌肿瘤细胞的肝癌肿瘤体积变化倍数曲线图;
图4是SCID小鼠注射肝癌肿瘤细胞5周内的存活率曲线图;
图5是将裸鼠分成五个组别,其中对照组施予磷酸盐溶液、A为含有亚铁氨基酸螯合物的组合物,剂量分别为1.2mg/kg/day含有亚铁氨基酸螯合物的组合物、12mg/kg/day含有亚铁氨基酸螯合物的组合物;B为氨基酸亚铁,剂量为1.2mg/kg/day;C为硫酸亚铁,剂量为1.2mg/kg/day。以上各组分别施予裸鼠7天后,再注射肺癌肿瘤细胞的肺癌肿瘤体积变化曲线图;
图6是将裸鼠分成五个组别,其中对照组施予磷酸盐溶液、A为含有亚铁氨基酸螯合物的组合物,剂量分别为4mg/kg/day含有亚铁氨基酸螯合物的组合物、为12mg/kg/day含有亚铁氨基酸螯合物的组合物;B为氨基酸亚铁,剂量为4mg/kg/day;C为硫酸亚铁,剂量为剂量为4mg/kg/day。以上各组分别施予裸鼠7天后,再注射肝癌肿瘤细胞的肝癌肿瘤体积变化倍数曲线图。
具体实施方式
以下配合图式及本发明的较佳实施例,进一步阐述本发明为达成预定发明目的所采取的技术手段。
本发明的一种含有亚铁氨基酸螯合物的组合物被使用对抗癌症,其中所述含有亚铁氨基酸螯合物的组合物是与其医药学上可接受的载剂相互混合而作为抑制或治疗癌症的药物。
所述的含有亚铁氨基酸螯合物的组合物是由无机铁与氨基酸混合并历经加热一时间所制得的含有亚铁氨基酸螯合物的组合物。
在本发明的一较佳实施例中,含有亚铁氨基酸螯合物的组合物包括还原剂;其中还原剂是坏血酸、柠檬酸、乙酸、丙酸、丁酸、乳酸、羟琥珀酸、磺酸或丁二酸。
在本发明的较佳实施例中,其中无机铁是硫酸亚铁、氯化亚铁或焦磷酸亚铁,所述的氨基酸是甘胺酸,藉以形成含有亚铁甘胺酸螯合物的组合物,且经证实具有抑制癌细胞细胞的功效。
制备例1制备含有亚铁氨基酸螯合物的组合物
本实施例是用以制备含有亚铁氨基酸螯合物的组合物,其是以下述方式制备。首先,将硫酸亚铁与甘胺酸以重量比1∶1.3混合并历经60℃至90℃加热8小时至48小时,以获得该含有亚铁氨基酸螯合物的组合物,其中亚铁氨基酸螯合物的亚铁与氨基酸螯合比例介于1∶1至1∶4之间;再将所获得的含有亚铁氨基酸螯合物的组合物调制成浓度为0.1μg/μl(即每100微升含有10微克)、0.3μg/μl、1μg/μl及3μg/μl的组合物。
制备例2肺癌细胞培养
将肺癌细胞株(A549)以含有10%胎牛血清(fetal bovine serum,FBS)、1%青霉素(100U/mL)-链霉素(100g/mL)(penicillin-streptomycin)以及1%麸酰胺酸(glutamine)(200mM)的杜氏改良英格尔培养基(Dulbecco′s Modified Eagle′s medium,DMEM)培养于37℃、5%二氧化碳的培养箱中,待细胞贴附7至8分满时,再进行继代培养。
制备例3肝癌细胞培养
将肝癌细胞株(SK Hep1)以含有10%胎牛血清(fetal bovine serum,FBS)、1%非必需氨基酸(non-essential amino acid,NEAA)以及1%青霉素-链霉素的杜氏改良英格尔培养基(Dulbecco′s Modified Eagle′s medium,DMEM)培养于37℃、5%二氧化碳的培养箱中,约3天至4天继代培养一次。
实施例1测量肿瘤细胞的体积
将制备例1所制得的浓度为0.1μg/μl、0.3μg/μl、1μg/μl的含有亚铁氨基酸螯合物的组合物分别以剂量为0.4mg/kg/day、1.2mg/kg/day或4mg/kg/day施予喂食裸鼠(BALB/cnu/nu mice)[购自于国家实验动物中心(台湾台北),约5周至6周龄],并以无菌水作为对照组,施予亚铁氨基酸螯合物或无菌水历经7天后,再将前述制备例2培养所得的1×107cell/mL的肺癌细胞注射至裸鼠后腿动脉肱附近皮下组织,之后每7天以游标阀尺测量肿瘤大小及体积,并于6周后牺牲小鼠。
其中肿瘤体积计算公式如下:
假设最长径为a,最短径为b,则肿瘤体积大小为(a x b2)/2,单位为毫米立方(mm3)。
如图1所示,肺癌肿瘤体积随着天数增加,但施予剂量为1.2mg/kg/day或4mg/kg/day的含有亚铁氨基酸螯合物的组合物具有较佳抑制肺癌肿瘤体积的效果。此外,如图2所示,喂食前述浓度的含有亚铁氨基酸螯合物的组合物并不会抑制裸鼠正常生长。
将4mg/kg/day亚铁氨基酸螯合物以每周施予5次喂食SCID小鼠(购自于台湾大学医学院动物中心)(约6周龄),并以无菌水作为对照组,历经1周后,将SCID小鼠麻醉并施予0.75Gy放射线照射,再将前述制备例3培养所得的107cell/mL的肝癌细胞(100μl)注射至SCID小鼠下背部附近皮下组织,之后每7天以游标阀尺测量肿瘤大小及体积,并于4周后牺牲小鼠。
如图3所示,肝癌肿瘤体积随着周数增加,且于第4周时,对照组SCID小鼠的肝癌肿瘤的体积已增加为原始3.5倍,然而,施予浓度4mg/kg/day的含有亚铁氨基酸螯合物的组合物的SCID小鼠的肝癌肿瘤的体积仅增加为原始1.8倍,据此,本案所述的含有亚铁氨基酸螯合物的组合物具有抑制肝癌肿瘤体积的效果。
实施例2分析受体存活率
如图4所示,施予浓度为4mg/kg/day含有亚铁氨基酸螯合物的组合物4周后,对照组的SCID小鼠的存活率为75%,然而施予浓度4mg/kg/day的含有亚铁氨基酸螯合物的组合物的存活率为100%,由此显示,施予含有亚铁氨基酸螯合物的组合物可提高SCID小鼠的存活率。
实施例3其他含铁化合物的对照实验
将裸鼠分成5个组别,第一组施予缓冲生理食盐水(phosphate buffered saline,PBS)为对照组,第二组施予剂量为1.2mg/kg/day含有亚铁氨基酸螯合物的组合物,第三组施予剂量为12mg/kg/day含有亚铁氨基酸螯合物的组合物,第四组施予剂量为1.2mg/kg/day氨基酸亚铁(购于美国Albion公司),第五组施予剂量为1.2mg/kg/day硫酸亚铁(无机铁)历经7天后,再将前述制备例2培养所得的1X107cell/mL的肺癌细胞(100μl)注射至裸鼠后腿动脉肱附近皮下组织,之后每7天以游标阀尺测量肿瘤大小及体积,并于6周后牺牲小鼠。
如图5所示,虽然肺癌肿瘤体积随天数增加,但施予剂量分别为12mg/kg/day或1.2mg/kg/day含有亚铁氨基酸螯合物的组合物(A组)5周后,含有亚铁氨基酸螯合物的组合物相较于氨基酸亚铁(B组)、硫酸亚铁及对照组具有较佳抑制肺癌肿瘤体积的效果。
将裸鼠分成5个组别,第一组施予缓冲生理食盐水为对照组,第二组施予剂量为4mg/kg/day含有亚铁氨基酸螯合物的组合物,第三组施予剂量为12mg/kg/day含有亚铁氨基酸螯合物的组合物,第四组施予剂量为4mg/kg/day氨基酸亚铁,第五组施予剂量为4mg/kg/day硫酸亚铁历经2周后,再将前述制备例2培养所得的107cell/mL的肝癌细胞(注射100μl)注射至裸鼠下背部附近皮下组织,之后每7天以游标阀尺测量肿瘤大小及体积,并于5周后牺牲小鼠。
如图6所示,施予剂量为4mg/kg/day或12mg/kg/day含有亚铁氨基酸螯合物的组合物(A组)5周后,含有亚铁氨基酸螯合物的组合物相较于氨基酸亚铁(B组)、硫酸亚铁(C组)及对照组具有较佳抑制肝癌肿瘤体积的效果。
以上所述仅是本发明的较佳实施例而已,并非对本发明做任何形式上的限制,虽然本发明已以较佳实施例揭露如上,然而并非用以限定本发明,任何熟悉本专业的技术人员,在不脱离本发明技术方案的范围内,当可利用上述揭示的技术内容作出些许更动或修饰为等同变化的等效实施例,但凡是未脱离本发明技术方案的内容,依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均仍属于本发明技术方案的范围内。
Claims (14)
1.一种含有亚铁氨基酸螯合物的组合物在制备抗癌症的药物中的用途,其中所述的药物包含有效剂量的含有亚铁氨基酸螯合物的组合物以及其医药学上可接受的载剂。
2.根据权利要求1所述的用途,其中含有亚铁氨基酸螯合物的组合物中的亚铁氨基酸螯合物的亚铁与氨基酸的螯合比例是介于1:1至1:4之间。
3.根据权利要求1所述的用途,其中含有亚铁氨基酸螯合物的组合物中的亚铁氨基酸螯合物的亚铁与氨基酸的螯合比例是介于1:1.5至1:2.5之间。
4.根据权利要求1所述的用途,其中含有亚铁氨基酸螯合物的组合物的有效剂量介于0.2mg/kg/day至15mg/kg/day。
5.根据权利要求1所述的用途,其中含有亚铁氨基酸螯合物的组合物的有效剂量是介于0.4mg/kg/day至12mg/kg/day。
6.根据权利要求1至5中任一项所述的用途,其中含有亚铁氨基酸螯合物的组合物是由无机铁与氨基酸混合并历经60℃至90℃加热8小时至48小时所制得的含有亚铁氨基酸螯合物的组合物,其中无机铁与氨基酸的比例是介于1:1.2至1:1.5之间。
7.根据权利要求6所述的用途,其中无机铁是硫酸亚铁、氯化亚铁或焦磷酸亚铁;该氨基酸是甘氨酸。
8.根据权利要求6所述的用途,其中含有亚铁氨基酸螯合物的组合物中包括还原剂,该还原剂是抗坏血酸(ascorbic acid)、柠檬酸(citric acid)、乙酸(acetic acid)、丙酸(propionic acid)、丁酸(butyric acid)、乳酸(lactic acid)、羟琥珀酸(malic acid)、磺酸(sulfonic acid)或丁二酸(succinic acid)。
9.根据权利要求1所述的用途,其中药物是经肠道的或非经肠道的剂型。
10.根据权利要求9所述的用途,其中该经肠道的剂型是口服剂型。
11.根据权利要求10所述的用途,其中,所述口服剂型为溶液、悬浮液、锭剂或胶囊。
12.根据权利要求1所述的用途,其中癌症是黑色素瘤(melanoma)、肝癌、结肠癌(coloncancer)、肺癌、胃癌(gastric cancer)、食道癌(esophageal cancer)、乳癌(breastcancer)、前列腺癌(prostate cancer)或血癌(leukemia)。
13.根据权利要求1所述的用途,其中癌症是脑部肿瘤(brain tumor)、低度星状细 胞瘤(low-grade astrocytoma)、高度星状细胞瘤(high-grade astrocytoma)、垂体腺瘤(pituitary adenoma)、脑脊髓膜瘤(meningioma)、中枢神经淋巴瘤(CNS lymphoma)、寡树突神经胶细胞瘤(oligodendroglioma)、颅咽管瘤(craniopharyngioma)、室管膜瘤(ependymoma)、胶质细胞肿瘤(brain stem tumor)、头颈瘤(head and neck tumor)、喉癌(laryngeal cancer)、口咽癌(oropharyngeal cancer)、鼻咽癌(nasopharyngeal tumor)、唾液腺肿瘤(salivary gland tumor)、下咽癌(hypopharyngeal cancer)、甲状腺癌(thyroid cancer)、口腔肿瘤(oral cavity tumor)、胸廓肿瘤(chest wall tumors)、小细胞肺癌(small cell lung cancer)、非小细胞肺癌(non-small cell lung cancer,NSCLC)、胸腺瘤(thymoma)、纵隔肿瘤(mediastinal tumor)、男性乳癌(male breastcancer)、腹骨盆(abdomen-pelvis tumor)、肝细胞癌(hepatoma)、肝腺癌(liveradenocarcinoma)、胆囊癌(gallbladder cancer)、胆道癌(biliary tract cancer)、胰脏癌(pancreatic cancer)、小肠肿瘤(small intestinal tumor)、大肠肿瘤(largeintestinal tumor)、肛门癌(anal cancer)、膀胱癌(bladder cancer)、肾细胞癌(renalcell carcinoma)、子宫颈癌(cervix cancer)、子宫内膜癌(endometrial cancer)、卵巢癌(ovarian cancer)、子宫肉瘤(uterine sarcoma)或皮肤癌(skin cancer)。
14.根据权利要求1所述的用途,其中癌症是肝癌或肺癌。
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