α—2b干扰素瘤内注射治疗41例骨软组织肿瘤及转移癌

１９９３年１１月－１９９５年７月，以α－２ｂ干扰素治疗骨，软组织实体瘤及转移癌４１例，其中３１例瘤内注射，１０例肌肉或皮下注射。结果显示：１）α－２ｂ干扰素对多种骨，软组织肿瘤及转移癌有较明显的局部，及区域疗效，尤以恶性黑色素瘤为佳。２）瘤内注射疗效显著且肿瘤     

干扰能瘤内注射治疗实体瘤疗效观察

本文报告我科1993．11～1994．11期间应用干扰能(α-2b干扰素)瘤内注射(A组)及瘤外注射(B组)治疗13例肿瘤患者，其中恶性黑色素瘤及恶性纤维组织细胞瘤各3例，横纹肌肉瘤2例，平滑肌肉瘤、软骨瘤及骨肉瘤各1例，转移低分化腺癌1例，乳癌骨转移1例。隔日注射一次，共3～4周，每次剂量依瘤体大小而定，A组共11例均显效。     

α－2b干扰素瘤内注射治疗41例骨软组织肿瘤及转移癌

１９９３年１１月～１９９５年７月，以α－２ｂ干扰素治疗骨、软组织实体瘤及转移癌４１例。其中３１例瘤内注射，１０例肌肉或皮下注射。结果显示：１）α－２ｂ干扰素对多种骨、软组织肿瘤及转移癌有较明显的局部及区域疗效，尤以恶性黑色素瘤为佳。２）瘤内注射疗效显著且肿瘤细胞及亚细胞结构有明显变化，全身用药难达此效。３）决定局部疗效的重要因素为瘤内药物浓度，而它受肿瘤体积、范围及用药途径等因素影响。４）瘤内注射后瘤组织ＣＤ４／ＣＤ８变化比较外周血ＣＤ４／ＣＤ８明显，但与某些报告不一致，其变化与疗效间亦无平行关系。提示ＣＤ４／ＣＤ８可能不适合做为衡量疗效的确切指标。     

平阳霉素瘤内注射治疗顽固性残留淋巴瘤结节

目的：观察平阳霉素（ＢＬＭＡ５）中注大性残留淋巴瘤结节的临术疗效。方法：３８例患者,其中瘤内注射组（下称瘤内组）２６例,以ＢＬＭＡ５８ｍｇ,加生理盐水１～３ｍｌ,行瘤内注射。瘤旁注射组（下称瘤旁组）１２例,同剂量瘤周注射。用药前１０分钟,二组均肌注地塞米松（ＤＸＭ）５～１０ｍｇ。上述方法,２次／周,连续２周。结果：瘤内注射组,ＣＲ１７例,ＰＲ５例,ＲＲ８４．６％;瘤注射组１２例,仅１你ＰＲ,ＲＲ８     

自身骨髓移植在实体瘤中的应用

自身骨髓移植在实体瘤中的应用解放军福州总医院（福州市３５０００１）杨瑞芬综述陈捷审校近１０年来，随着医学的发展，已促使自身骨髓移植（Ａｕｔｏｌｏｇｕｓｂｏｎｅｍａｒｒｏｗｔｒａｎｓｐｌａｎｔａｔｉｏｎ，ＡＢＭＴ）广泛应用于治疗白血病和实体瘤。１９９１...     

良性肿瘤和恶性实体瘤患者血浆Lp（a）和其它脂类的变化

本文对５７例良性肿瘤、５２例恶性实体瘤患者和８０例正常人血浆中Ｌｐ（ａ）和ＴＣ、ＴＧ、ＡｐｏＢ、ＡｐｏＡ－Ⅰ的水平进行了比较。结果发现，上述指标在良性肿瘤与正常人之间无统计学差异。恶性实体瘤患者的Ｌｐ（ａ）水平明显高于良性肿瘤患者和正常人，ＴＣ水平明显低于良性肿瘤患者和正常人，ＡｐｏＢ和ＡｐｏＡ－Ⅰ明显低于正常人。本文认为，Ｌｐ（ａ）可能通过影响凝血系统而对肿瘤的生长和转移发挥一定的促进作用，Ｌｐ（ａ）和ＴＣ水平有可能成为恶性肿瘤辅助诊断的生化指标。脂质、脂蛋白和载脂蛋白与肿瘤的关系，值得进一步研究。     

成人型喉乳头状瘤中PCNA的表达及意义

目的探讨细胞增殖活性与成人型喉乳头状瘤生物学行为的关系。方法４２例手术及活检标本，分为四组：正常喉粘膜组（ｎ＝５）、喉乳头状瘤组（ｎ＝２１）、喉乳头状瘤伴不典型增生组（ｎ＝９）及喉乳头状瘤癌变组（ｎ＝７），应用抗增殖细胞核抗原（抗ＰＣＮＡ）单克隆抗体ＰＣ１０，采用ＡＢＣ免疫组织化学染色技术，评价其细胞增殖活性。结果经ＰＣＮＡ阳性反应计算出的ＰＣＮＡ增殖指数分别为３．８５０±０．６３６％、８．５８８±１．４０９％、１１．２２０±１．６０２％、１６．８１７±２．８９９％，各组间经统计学分析有差异（Ｐ＜０．０５）。结论ＰＣＮＡ表达可作为喉部良、恶性病变的鉴别，检测癌前病变及观察肿瘤生物学行为较好的参考指标。     

瘤体内注入LAK／IL－Ⅱ治疗恶性肿瘤12例

瘤体内注入ＬＡＫ／ＩＬ－Ⅱ治疗恶性肿瘤１２例朱床余副主任医师陈永清，杨淑丽通辽市第二医院我院于１９９３年７月至１２月，用ＬＡＫ细胞和白细胞介素Ⅱ（以下简写成ＬＡＫ／ＩＬ－Ⅱ）瘤体内注射治疗经病理证实的恶性肿瘤１２例，男１１例，女１例，最小年龄５４岁，...     

LMWNTS体外培养净化ABMT治疗11例晚期恶性淋巴瘤

目的探讨体外有效净化骨髓中残存肿瘤细胞的方法,减少恶性淋巴瘤的复发。方法用体外液体培养联合低分子天然抑瘤物净化骨髓移植物后作自体骨髓移植（ＡＢＭＴ）治疗１１例中高度晚期恶性淋巴瘤。结果移植后均造血重建,白细胞恢复至≥１．０×１０９／Ｌ和血小板恢复至≥２０×１０９／Ｌ的平均时间分别为１４．８（１１～２２）ｄ和１５．５（１２～２３）ｄ。９例持续缓解（ＣＣＲ）,中位ＣＣＲ时间４１（１２～７２）个月。１例ＡＢＭＴ４个月后复发。１例ＡＢＭＴ后达到部分缓解并于１７个月死于复发。结论认为该法治疗晚期淋巴瘤能获得造血重建并取得满意疗效。     

卵巢恶性中胚叶混合瘤12例临床分析

目的探讨卵巢恶性中胚叶混合瘤的临床特点、治疗及预后因素。方法对我院１９８３年～１９９７年收治的１２例卵巢恶性中胚叶混合瘤的临床资料进行回顾性分析。按ＦＩＧＯ分期（１９８５年）,Ⅱ期４例,Ⅲ期６例,Ⅳ期１例,不详１例。组织学分类：同源性８例,异源性４例。１２例均接受肿瘤细胞减灭术。术后辅助化疗１１例,其中３例又追加盆腔放疗。结果全组平均生存２４个月,２,５年生存率分别为３３．３％（４／１２）和８．３％（１／１２）。Ⅱ和Ⅲ期生存２年以上者均为２例,Ⅳ期１例在１年内死亡。同源性８例中,４例生存２年以上,异源性４例均在２年内死亡。综合治疗１１例中,５例在１年内死亡。单纯手术１例在６个月内死亡。结论卵巢恶性中胚叶混合瘤恶性度高,预后差。其组织学类型、分期及治疗方法与预后有关,应采用手术与化疗和（或）放疗的综合治疗     

荷非小细胞肺癌裸鼠体内131^I-17-AAG的分布及其抗癌潜力

目的：探讨131^I-17-丙基胺基-17-去甲氧基格尔德霉素（131^I-17-AAG）在荷瘤裸鼠体内的生物学分布及其抗癌机制。方法：通过不同给药方式（131^I-17-AAG间质给药或静脉给药、Na131I间质给药对照及竞争性显像）,显像比较12只模型鼠体内分布情况,每只5.55MBq0.1mL。1周后处死取瘤,电镜和免疫组化检测细胞凋亡和Ki-67、Bcl-2蛋白表达情况,设空白对照组（n=3）。另取24只,分别通过间质或尾静脉注射131^I-17-AAG（每只1.85MBq0.1mL）,不同时间处死,取血并测主要组织脏器的放射性计数率值。结果：显像提示,间质注射131^I-17-AAG瘤体内放射性浓聚并长时间滞留,体内分布实验进一步证实;尾静脉给药瘤体内存在一定放射性摄取,药物体内清除较快;Na131I注射后迅速排出体外,无瘤内滞留;竞争性显像示瘤内摄取降低。电镜观测给药组较对照组肿瘤增长抑制显著。Bcl-2和Ki-67阳性表达率131^I-17-AAG给药组要低于对照组。不同给药组组间比较及与对照组比较差异有统计学意义,Pmax=0.004。结论：131^I-17-AAG间质给药在瘤组织内有明确药代学分布和药效学作用,可行进一步肿瘤治疗研究。     

荷非小细胞肺癌裸鼠体内131I-17-AAG的分布及其抗癌潜力

目的:探讨131I-17-丙基胺基-17-去甲氧基格尔德霉素(131I-17-AAG)在荷瘤裸鼠体内的生物学分布及其抗癌机制。方法:通过不同给药方式(131I-17-AAG间质给药或静脉给药、Na131I间质给药对照及竞争性显像),显像比较12只模型鼠体内分布情况,每只5.55MBq0.1mL。1周后处死取瘤,电镜和免疫组化检测细胞凋亡和Ki-67、Bcl-2蛋白表达情况,设空白对照组(n=3)。另取24只,分别通过间质或尾静脉注射131I-17-AAG(每只1.85MBq0.1mL),不同时间处死,取血并测主要组织脏器的放射性计数率值。结果:显像提示,间质注射131I-17-AAG瘤体内放射性浓聚并长时间滞留,体内分布实验进一步证实;尾静脉给药瘤体内存在一定放射性摄取,药物体内清除较快;Na131I注射后迅速排出体外,无瘤内滞留;竞争性显像示瘤内摄取降低。电镜观测给药组较对照组肿瘤增长抑制显著。Bcl-2和Ki-67阳性表达率131I-17-AAG给药组要低于对照组。不同给药组组间比较及与对照组比较差异有统计学意义,Pmax=0.004。结论:131I-17-AAG间质给药在瘤组织内有明确药代学分布和药效学...     

瘤内注射紫杉醇脂质体对小鼠H22移植瘤抑制作用的研究

目的比较瘤内注射和静脉注射紫杉醇脂质体对小鼠H22肝细胞癌皮下移植瘤的抑瘤作用,探讨瘤内注射微球化疗药物应用的可行性。方法采用ICR小鼠建立H22皮下移植瘤模型,随机分为瘤内注射紫杉醇脂质体组（IT-PL）、静脉注射紫杉醇脂质体组（IV-PL）和瘤内注射5％葡萄糖溶液组（IT-GS）。10天后待瘤体生长至直径10mm左右,分别予经超声引导瘤内注药及尾静脉给药处理。紫杉醇脂质体的给药浓度为3mg／ml,剂量为75mg／kg,每周1次,共2周。采用近红外荧光活体显像法观察注药24h内药物在小鼠体内的分布情况。隔日记录瘤体积变化并观察小鼠的不良反应,计算各组的抑瘤率。瘤体组织石蜡包埋后行HE染色。结果超声引导下瘤内注射紫杉醇脂质体时,针头附近区域见回声增高有助于确认药物分布于瘤体内。近红外荧光活体显像示瘤内注射24h药物持续集中在瘤体内,无明显全身分布;静脉注射药物则逐渐集中至瘤体,但瘤体内的药物浓度低于瘤内注射组。IT-PL组与IV-PL组的抑瘤率分别为95.0％和56.1％,差异有统计学意义（P＜0.05）。病理组织学检查示IT GS组的肿瘤细胞生长旺盛,而IT-PL组的瘤体内及周边有脂质沉积,仅边缘少量残存肿瘤细胞。瘤内注射部位皮下组织未见溃破、糜烂;未观察到明显全身不良反应。结论紫杉醇脂质体瘤内注射有可能成为针对局部实体肿瘤安全、有效的给药模式。     

Intratumoral administration of neocarzinostatin conjugated to monoclonal antibody A7 in a model of pancreatic cancer

We investigated the following in athymic nude mice with xenografts of a human pancreatic carcinoma: 1) clearance of the murine monoclonal antibody A7 from the carcinoma; and 2) the antitumor effect of neocarzinostatin conjugated to MAb A7 (A7-NCS) on the carcinoma following intratumoral injection. Compared with ¹²⁵I-labeled normal mouse IgG, a significantly larger amount of ¹²⁵I-labeled A7 remained in the tumor after intratumoral injection. Neocarzinostatin conjugated to MAb A7 showed a greater antitumor activity against human pancreatic cancer than neocarzinostatin alone after intratumoral administration. The conjugate completely suppressed tumor growth macroscopically during the experiment. Tumor tissue in mice became necrotic 32 days after injection with A7-NCS. These observations suggest that the intratumoral injection of A7-NCS offers promise in treating pancreatic carcinoma. © 1993 Wiley-Liss, Inc.     

吉西他滨化疗联合树突状细胞瘤内注射对小鼠巨大淋巴瘤的治疗作用

目的：观察吉西他滨对荷B细胞淋巴瘤小鼠脾脏中髓源抑制性细胞（myeloid derived suppressor cell, MDSC）的影响,以及吉西他滨化疗联合树突状细胞（dendritic cells, DCs）治疗巨大淋巴瘤的疗效。方法：小鼠皮下接种A20淋巴瘤细胞,30 d后形成巨大肿瘤,流式细胞仪分析吉西他滨化疗前后荷瘤小鼠脾脏中Gr1+CD11b+ MDSC的比例,免疫磁珠纯化的脾脏MDSC体外加入吉西他滨共培养后,AnnexinV/PI标记法检测细胞凋亡;观察荷瘤小鼠接受吉西他滨化疗联合DCs瘤内注射后肿瘤生长情况及小鼠存活期。结果：荷A20淋巴瘤小鼠脾脏中MDSC的比例显著上调,是正常小鼠脾脏中的10倍以上。体外吉西他滨时间依赖性诱导MDSC凋亡与坏死;荷瘤小鼠体内注射吉西他滨后,脾脏中绝大部分的MDSC被清除。单独吉西他滨注射或DCs瘤内注射对肿瘤生长产生一定的抑制作用,小鼠平均存活天数分别为（48.8±3.6）d和（47.2±7.4）d,而对照组小鼠平均存活天数为（38.8±2.2）d;吉西他滨化疗联合DCs瘤内注射后瘤体持续显著缩小,60%小鼠存活时间均超过90 d。结论：吉西他滨可有效清除荷瘤小鼠脾脏MDSC,吉西他滨化疗与DCs瘤内注射免疫治疗具有协同效应,可以提高对巨大淋巴瘤的疗效,本实验为应用生物化疗综合治疗模式治疗复发、难治性淋巴瘤提供了实验依据。     

基因工程腺病毒(H101)瘤内注射联合化疗治疗头颈部及食管鳞癌的Ⅲ期临床研究

背景与目的：H101是利用基因重组技术得到的一种删除了E1B部分基因片段的溶瘤腺病毒,其在一定剂量范围内对肿瘤有明显的抑制作用。本研究目的是比较H101瘤内注射联合顺铂(c platin,DDP) 5-氟尿嘧啶(5-fluorouracil,5-FU)或阿霉素(adriamycin,ADM) 5-FU方案化疗与单纯化疗对头颈、食管鳞癌的治疗效果及毒副作用。方法：160例入选患者,根据过去化疗史分别选定不同化疗方案。未用过PF方案化疗或用过PF方案有效者采用PF方案化疗,已用过PF方案无效者则采用AF方案化疗。采用多中心随机对照分组,分别加用(A组)或不加用(B组)肿瘤浅表病灶内注射H101。两组均为21天一个周期,所有患者至少接受2个周期的治疗。结果：完全符合方案标准的病例123例,A1组(PF H101)有效率为78．8％,B1组(PF only)为39．6％,A2组(AF H101)为50％(7／14),B2组(AF only)50％(2／4)。A1、B1组间以及A1 A2、B1 B2组间疗效差异有显著性(P=0．000)。45．7％病例出现轻～中度发热,28．3％出现注射局部反应,9．8％出现流感样症状。结论：H101注射液瘤内局部注射联合化疗的客观有效率比单纯化疗组高,显示H101瘤内注射对于头颈、食管鳞癌具有明确的治疗作用,且具有较高的安全性。     

Combined intratumoral injection of bone marrow-derived dendritic cells and systemic chemotherapy to treat pre-existing murine tumors

Dendritic cells (DCs) are attractive candidates for innovative cancer immunotherapy by virtue of their potential to function as professional antigen-presenting cells for initiating cellular immune responses. In this study, we evaluated a possible synergy of conventional chemotherapy together with intratumoral injection of syngeneic bone marrow-derived DCs for the treatment of preexisting tumors. Using murine CT26 colon adenocarcinoma cells (parental or modified to express beta-galactosidase as a model tumor antigen) to produce s.c. tumors in syngeneic BALB/c mice, the data demonstrate that direct injections of DCs at the tumor site result in partial eradication of established tumors. Strikingly, the addition of systemic chemotherapy (cyclophosphamide) combined with local intratumoral injection of DCs led to complete tumor regression in the treated animals. The tumor-free mice were able to resist a repeat challenge with the same tumor, suggesting that the animals had acquired long term antitumor immunity. Supporting evidence for the paradigm of systemic chemotherapy and intratumoral administration of DCs was obtained using melanoma B16 syngeneic tumor treated with Adriamycin plus DCs. These novel findings raise the possibility of using this potent strategy of combined intratumoral injections of DCs and systemic chemotherapy for cancer treatment.     

经不同途径应用rAdp53对大肠癌裸鼠模型生长抑制差异性的研究

目的：研究经不同途径使用rAdp53对小鼠大肠癌肿瘤模型生长抑制作用的差异性。方法：应用人大肠癌-174细胞株经体外培养传代后,接种到SPF级BALB／c-nu裸鼠皮下,建立大肠癌动物模型;分别经由腹腔、静脉以及瘤内注射rAdp53,动态测量不同使用途径下肿瘤体积及肿瘤重量的变化。结果：经三种不同途径应用rAdp53后,大肠癌动物模型的生长明显较对照组减缓,但腹腔注射组与静脉注射组、瘤内注射组的抑瘤作用有统计学的差异性;同样经三种不同途径给药后,肿瘤模型瘤重抑制率均达50％以上,其中静脉注射组及瘤内注射组高达70％以上,与腹腔注射组有显著统计学差异。结论：经不同途径应用rAdp53均可以抑制大肠癌肿瘤模型的生长,但静脉注射组及瘤内注射组的抑瘤效果较腹腔注射组明显增强。     

Antitumor activity of murine tumor necrosis factor (TNF) against transplanted murine tumors and heterotransplanted human tumors in nude mice

The antitumor activity of highly purified tumor necrosis factor (TNF) was tested against eight kinds of murine tumor and five kinds of human tumor heterotransplanted into nude mice. Mice were treated by intravenous or intratumoral injection of TNF, commencing when the tumors were well established. TNF showed an excellent curative effect against all kinds of murine and human tumors tested. Meth A sarcoma, Colon 26, Ehrlich, sarcoma 180, MM 46, MH 134, B16 melanoma, and Lewis lung tumors transplanted into mice underwent tumor necrosis and regression following a single injection of TNF. Sometimes a complete cure was observed in Meth A sarcoma, sarcoma 180, Ehrlich, and MM 46 tumors. Human cancers, SEKI, HMV-I, KATO-III, MKN 45, or KB, heterotransplanted into nude mice, also exhibited tumor necrosis and regression in size following several intratumoral injections of TNF. A great difference in curative effects of TNF was observed in Meth A sarcomas between those transplanted into BALB/c nu/+ and into BALB/c nu/nu mice: following a single intravenous administration the effect was stronger in BALB/c nu/+ than in nu/nu mice. In contrast, tumor necrosis was almost the same in nu/+ and nu/nu mice following intratumoral administration. The present results thus indicate that TNF from mice had an antitumor activity against not only murine tumors but also human tumors. In addition to direct cytotoxicity against tumor cells, TNF induced a host-mediated factor which contributed to the antitumor effects.     

Therapeutic vaccination against murine lymphoma by intratumoral injection of recombinant fowlpox virus encoding CD40 ligand

The interaction between CD40 ligand (CD40L, CD154) and its receptor CD40 on antigen-presenting cells is essential for the initiation of cell-mediated and humoral immune responses. Malignant B cells also express CD40 and respond to CD40L by enhancing expression of costimulatory molecules. In this study, we investigated the therapeutic antitumor effect of intratumoral administration of recombinant fowlpox virus encoding murine CD40L (rF-mCD40L) in a murine B-cell lymphoma model. BALB/c mice with established s.c. and widely metastatic A20 lymphoma tumors were treated with intratumoral injections of rF-mCD40L together with systemic chemotherapy. This combined chemoimmunotherapy resulted in complete tumor regression and long-term survival of the mice. Some tumor cells in the injected sites expressed the CD40L transgene and had increased expression of the CD80 and CD86 costimulatory molecules. The therapeutic effect was dependent on CD8 but not on CD4 T cells. Moreover, there was a requirement that the recombinant CD40L virus be injected directly into the tumor, as opposed to peritumoral or distant sites. Thus, rF-mCD40L injected directly into the tumor microenvironment enhances the immunogenicity of tumor B cells. The results support future plans for intratumoral injection of rF-mCD40L in patients with lymphoma.