rIL－2／LAK细胞治疗晚期恶性肿瘤

胎儿来源的ＬＡＫ细胞／ｒＩＬ－２对５例失去手术、化疗、放疗机会的晚期恶性肿瘤病人进行了过继免疫治疗。结果都取得了一定的疗效，黑色素瘤病人肺转移结节基本消失，局部瘤细胞全部坏死，组织细胞正常；淋巴瘤病人转移灶消退５９％；小肠平滑肌肉瘤病人在没进行此疗法之前２年半复发、手术三次。第三次手术后用此疗法治疗一个疗程，三年后第一次复发。为晚期恶性肿瘤病人延长了生命，提高了生存质量争得了再次治疗的机会。     

电化学治疗体表恶性肿瘤（附36例临床分析）

本文报道自1994年12月至1996年10月，应用CIAs－505型电脑电化学治仪及钻电极针，对36例各种类型晚期及术后复发转移的恶性肿瘤进行电化学治疗，取得了良好效果，其中Ⅰ级28例（7778％），Ⅱ级5例（13.89％），Ⅲ级2例（5.55％），Ⅳ级1例（2.78％），总有效率97.22％。本文认为电化学治疗简便易学，安全有效，创伤性小，对于许多晚期恶性肿瘤，已失去手术机会或术后局部复发、有远处转移的患者以及其它疗法无效者，不失为一种较理想的治疗方法，且对于患者的疼痛症状，亦有明显的缓解作用。     

体外放疗在肝癌治疗中的应用进展

原发性肝癌（简称＂肝癌＂）是我国高发恶性肿瘤,发病率位居恶性肿瘤第3位,每年肝癌死亡人数达20万以上,死亡率居第2位[1-3]。临床诊治断时80%肝癌患者已失去手术切除机会。肝癌恶性程度高,易转移、复发,手术切除的病人中约50%会出现复发或远处转移[3]。另外大多数肝癌患者合并肝硬化、肝功能不全,使临床治疗困难,总体疗效差。近年来综合治疗肝癌取得了令人满意的临床疗效,肿瘤局部控制率和患者生存率均有不同程度的提高。     

体外放疗在肝癌治疗中的应用进展

原发性肝癌(简称"肝癌")是我国高发恶性肿瘤,发病率位居恶性肿瘤第3位,每年肝癌死亡人数达20万以上,死亡率居第2位[1-3]。临床诊治断时80%肝癌患者已失去手术切除机会。肝癌恶性程度高,易转移、复发,手术切除的病人中约50%会出现复发或远处转移[3]。另外大多数肝癌患者合并肝硬化、肝功能不全,使临床治疗困难,总体疗效差。近年来综合治疗肝癌取得了令人满意的临床疗效,肿瘤局部控制率和患者生存率均有不同程度的提高。放疗在其中的作用越来越受到重视。结合国内外相关文献,本文对肝癌体     

晚期非小细胞肺癌化疗和靶向治疗的现状

肺癌是一种恶性程度极高且易复发、转移的恶性肿瘤,Rivera[1]报道在新诊断的肺癌中,非小细胞肺癌(NSCLC)占80%～85%,而其中1/3初诊时已为局部晚期,不能手术的中晚期NSCLC约占全部NSCLC的3/4.治疗必须采用针对全身兼顾局部的多学科治疗方法(包括手术、化疗、放疗等).我国肺癌的发病率与死亡率逐年增长[2],发病率已居各种恶性肿瘤的首位,晚期NSCLC失去了手术根治的机会,化疗成为主要的治疗方法.     

电化学治疗恶性肿瘤：（附32例报道）

本文报道自1988年11月至1991年12月,应用WL型直流电肿瘤治疗仪和L系列铂电极针,对32例14种不同类型晚期和术后复发转移的恶性肿瘤进行电化学治疗,取得较满意疗效,并有缓解疼痛作用。其中Ⅰ级6例(18.75),Ⅱ级18级(56.25％),Ⅲ级2例(6.25％),Ⅳ级6例(18.75％),总有效率为81.25％。我们认为采用电化学治疗晚期恶性肿瘤,对失去手术机会或术后局部复发、远处转移的患者以及对放、化疗无效者,是一较理想的新的治疗手段。     

改良FOLFIRI方案治疗晚期胃癌

胃癌是我国最常见的恶性肿瘤之一，早期诊断、早期治疗是提高治愈率的关键。然而胃癌患者中Ⅳ期胃癌占37％～39％，Ⅰ～Ⅲ期可切除的胃癌患者有半数以上术后复发转移变成晚期胃癌。晚期胃癌失去彻底手术切除、治愈疾病的机会，以化疗为主的内科综合疗法显得尤为重要。收集我院2004年5月～2007年5月24例晚期胃癌，采用改良FOLFIRI方案化疗取得一定疗效，现报告如下。     

吉西他滨联合氟尿嘧啶和草酸铂治疗晚期进展期食管癌近期疗效观察

食管癌是常见消化道恶性肿瘤,在我国为高发肿瘤之一,其病死率占我国恶性肿瘤的第4位。手术治疗是食管癌的标准治疗手段,但不能手术或手术后及放化疗后复发、转移的晚期食管癌,联合化疗仍是主要治疗手段。自2005年1月至2006年12月,我科采用吉西他滨联合氟尿嘧啶、草酸铂治疗晚期     

重组白细胞介素2联合化疗治疗卵巢癌复发和转移灶的探讨

卵巢癌是常见的妇科恶性肿瘤之一,由于缺乏早期诊断的手段,很多患者在诊断时已达晚期.而晚期病人由于手术难以彻底及化疗药物的耐受性,患者常于术后1～2年中复发.虽然二线药物泰素对复发患者有30%的疗效,但仍不能解决药物的耐受性问题.而白细胞介素2作为免疫调节剂不受药物的耐受性的限制,可望对复发及转移的晚期卵巢癌有一定的治疗作用.本研究应用重组白细胞介素2及化疗联合应用治疗卵巢癌的复发及转移灶,探讨重组白细胞介素2治疗实体肿瘤的作用效果,为有效冶疗复发和转移的卵巢癌提供一种方法.     

消化道肿瘤分子靶向治疗临床进展

消化道肿瘤是常见的恶性肿瘤，早期均以手术治疗为主，但因早期诊断困难，根治性手术切除率不高，预后差。晚期和术后复发、转移的病人以化疗为主。虽然近年来广泛采用5-FU持续静注及生化调节疗法和一些有独特作用机制的新药，有些消化道肿瘤疗效有所改善，但目前总体仍处姑息治疗水平。     

胎脾LAK细胞联合rlL－2治疗癌性胸水临床观察

以人胎脾淋巴细胞体外在ｒＩＬ－２存在下诱导成ＬＡＫ细胞并与ｒｌＬ－２联合胸内注入，治疗７例癌性胸水患者。其中１例胸水完全消失，其余患者胸水明显减少，出现胸膜肥厚，连续观察８个月胸水未见进一步增多；胸水内肿瘤细胞也明显减少。７例患者均未出现任何不良反应。结果提示：胎脾ＬＡＫ细胞与ｒＩＬ－２胸腔内联合应用治疗癌性胸水有效，可延长患者生存期。     

晚期肺癌癌性胸水的免疫治疗

Ten patients with advanced lung cancer complicated by malignant pleural effusion were treated by intrapleural transfer of autologous LAK cells induced from lymphocytes of malignant effusions in the presence of rIL-2 and by administration of rIL-2 10 days before and after the transfer of LAK cells. The pleural effusions disappeared in 8 patients and significantly reduced in the other two. The number of tumor cells in the pleural effusion was obviously decreased while the number of lymphocytes was significantly increased. No changes were found in 4 responders during 4 months follow-up after treatment. No serious side effects were observed in all these 10 patients. The results indicated that transfer of LAK cells combined with rIL-2 in the treatment of patients with malignant pleural effusion due to advanced lung cancer is effective, safe and feasible.     

LAK细胞和IL－2联合化疗治疗晚期肺癌的近期疗效观察

ＬＡＫ细胞和ＩＬ－２是目前常用的肿瘤生物制剂。自１９９２年以来，对１８例晚期肺癌，男１５例，女３例，年龄２９～６４岁，进行ＬＡＫ细胞和重组ＩＬ－２联合化疗治疗。选择胎脾、胸腺的淋巴细胞做前体细胞，体外用重组ＩＬ－２诱导制备ＬＡＫ细胞，每输３次ＬＡＫ细胞为一疗程、每次输入细胞数０．５～１．０×１０９。化疗采用环磷酰胺，长春新碱，阿霉素为主的方案。治疗结果：完全缓解（ＣＲ）５例，部分缓解（ＰＲ）７例，无效（ＮＲ）３例，病情平稳３例，有效率ＣＲ＋ＰＲ达６６％。采用本疗法后病人精神及饮食好转，能有效缓解胸痛、减轻病人痛苦。提示ＬＡＫ细胞和重组ＩＬ－２联合化疗对晚期肺癌是一种可行的有效治疗，但在临床应用中要注意毒性反应。     

靶动脉灌注NaHCO3提高部分抗肿瘤药物疗效的基础及临床研究

Objective: To observe the influence of pH value on the proliferation of LAK cells and on the killing effect of rIL-2,IFN-α2b, TNF-α, LAK cells and doxorubicin on malignant tumor cells, and investigate the possibility of increasing the efficacy of rIL-2 or IFN-α2b and doxorubicin by infusing sodium bicarbonate (NaHCO3) through target arteries. Methods: Separating single nucleus cells from peripheral blood of healthy men, and observing the influence of pH on the activation of single nucleus cells by rIL-2. MTT assay was used to measure the killing effect of rIL-2, IFN-α2b and TNF-α on 7404 cells and the increased effect of doxorubicin on rIL-2 and IFN-α2b, the cytotoxity of LAK cells in different pH. Forty-two patients with advanced primary liver cancer were obtained by stratified random, NaHCO3, rIL-2/IFN-α2b and doxorubicin were infused through target arteries. The efficacy was estimated after two cycles. Results: The conditions of pH 7.3 and pH 7.6 in vitro helped the proliferation of LAK cells and the killing effect of rIL-2, IFN-α2b and LAK cells on 7404 cells. In the condition of pH 6.8 there was almost no killing effect for LAK cells. In the condition of pH 7.0, 7.2, 7.4 and 7.6, the killing rate of TNF-α to 7404 cells increased by degrees, and in pH 7.4 the killing effect was the optimum. After two cycles treatments in the 42 patients with advanced primary liver cancer,the response rate (CR PR) was 88% (37/42). The median overall response and median overall survival were increased, and no complication associated with infusing sodium bicarbonate was observed. Conclusion: The killing effect of rIL-2, IFN-α2b, TNF-αand doxorubicin on malignant tumor cells was enhanced by increasing the pH value.     

Inducible lymphokine-activated killer (LAK) cell activity in the peripheral blood of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL)

Therapy with recombinant interleukin-2 (rIL-2) induces clinical response in a significant number of patients with refractory malignant disease. Very few patients with non-Hodgkin's lymphoma (NHL) have been treated with rIL-2. The present study sought to determine if peripheral blood mononuclear cells (PBM) from patients with relapsed/refractory non-Hodgkin's lymphoma could be induced in vitro to generate LAK cell activity. PBM from 28 patients with relapsed/refractory NHL were incubated for 7 days in rIL-2 to determine their ability to lyse the LAK cell sensitive Daudi cell line. The PBM from all patients were able to generate LAK activity after in vitro incubation in rIL-2. Approximately one third of the patients' PBM samples generated less activity than activity generated in the PBM sample from normal control donors. However, two-thirds of patient samples were able to generate activity equal to or greater than that of the controls. The degree of LAK activity generated by the patients' PBM did not correlate either with histologic subtype or amount of prior chemotherapy. The amount of LAK activity an individual generated (control or patient) tended to remain stable over time.     

Adoptive immunotherapy for recurrent glioblastoma multiforme using lymphokine activated killer cells and recombinant interleukin-2

Thirteen patients with recurrent glioblastoma were treated with adoptively transferred autologous lymphokine activated killer (LAK) cells and recombinant interleukin-2 (rIL-2). Patients' blood mononuclear cells (MNC) obtained by leukapheresis were cultured at 2.5 million MNC per ml for 3 to 5 days in media containing 1000 U rIL-2/ml. After incubation, the nonadherent MNC from all cultures (0.5-5 X 10(9] were combined and concentrated for infusion in 5 to 10 ml saline containing 10(6) U rIL-2. Nine patients received one injection of LAK cells and rIL-2 into the brain tissue immediately surrounding the tumor cavity during craniotomy for subtotal tumor removal (Group 1). On each of the 3 days after surgery, patients received boosters of 10(6) U rIL-2 delivered into the tumor cavity through a skin flap or via an Ommaya reservoir. Approximately 1 to 2 weeks after this series of injections, these patients were treated with a second cycle of LAK cells and rIL-2 injected into the tumor cavity using the reservoir. Four patients received both adoptive immunotherapy cycles by intracavitary injection (Group 2). In this relatively small patient pool, neither age, sex, Karnofsky score, treatment history, nor anticonvulsant and steroid dosage appeared to influence a patient's ability to make LAK cells. The therapy, itself, was well-tolerated by all patients although they all displayed symptoms of aseptic meningitis and increased intracranial pressure, i.e., headache, fever, malaise on the days of LAK cell and/or rIL-2 infusion. The therapy did not appear to have a significant impact on patient survival (mean, 30 weeks) especially for those patients with a high postsurgical tumor burden. As the therapy is safe, the authors believe its efficacy can best be tested in patients with a newly diagnosed or recurrent glioblastoma which lies in an area where a near-total resection is possible.     

Splenic versus hepatic artery infusion of interleukin-2 in patients with liver metastases

In an attempt to improve the therapeutic index of recombinant interleukin-2 (rIL-2) by generating or activating lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) regionally and/or in situ, we randomly assigned 28 patients with liver metastases to receive rIL-2 by continuous infusion for 5 days via either the splenic artery or the hepatic artery. Clinically significant and lasting tumor regression was observed only in two of 28 patients (7%), one in each of the two treatment arms. The maximum-tolerated daily dosage of rIL-2 was 3 x 10(6) U/m2; beyond this dosage, toxicity was excessive. Peripheral LAK cell activity measured in vitro and clinical tumor regression did not correlate. This observation, coupled with the equal distribution of regressions between the two treatment arms, raises the possibility that tumor regression, rare though it may be in response to rIL-2 administration, is largely mediated by TIL activation and not by LAK cell generation.     

A phase II study of the administration of recombinant interleukin 2 (rIL-2) plus lymphokine activated killer (LAK) cells in stage IV melanoma patients

From January 1987 to February 1988, 15 stage IV melanoma patients were treated with two courses of bolus injection of rIL-2 plus LAK cell infusions at the National Cancer Institute of Milan. The original treatment regimen included a first course of rIL-2 administration (400 micrograms/m2 bolus injection 3 times a day [TID] for 4 days) and a second course of rIL-2 administration (800 micrograms/m2 bolus injection TID for 7 days) separated by 4 consecutive daily leukaphereses. Autologous lymphokine activated killer (LAK) cells were reinfused into each patient on three occasions during the second period of rIL-2 administration. Due to the appearance of grade III-IV neurological, hepatic and cardiopulmonary toxicity, 7 patients discontinued dosing before the end of treatment, one patient desired to be withdrawn and one patient died from rapidly progressive disease, although complications of rIL-2 administration may have contributed to her death. Only 6 patients completed the schedule without evidence of major intolerance, even though the planned dose during the second course of rIL-2 was reduced to 400 micrograms/m2. The complete duration of treatment ranged from 11 to 19 days. The total dose of rIL-2 injected ranged from 12.6 to 30.4 mg. The number of infused LAK cells ranged from 15.5 x 10(9) to 60 x 10(9)/patient. Two of the 14 evaluable patients showed a minor anti-tumor response. In 5 patients new metastases in other sites were documented from 2 to 5 months after completion of dosing. No apparent association was found between progression of the disease (or the appearance of new metastases) and the total dose of rIL-2 injected, the number of LAK cells administered or the number of days of treatment. By December 1988, all patients had died of their disease in a period ranging from 3 to 14 months from the last injection of rIL-2. The lack of significant clinical responses in this study and the high toxicity of this treatment lead us to conclude that at least as far as melanoma patients are concerned, adoptive immunotherapy with rIL-2 plus LAK cells (as described here) is not a justifiable treatment option unless new evidence presents itself.     

Functional and phenotypic characteristics of recombinant interleukin-2 or T-cell growth factor-activated splenic lymphoid cells from patients with gastric or hepatocellular carcinoma

Fourteen days' culture of human spleen cells with recombinant interleukin-2 (rIL-2) or T-cell growth factor (TCGF) results in the generation of lymphokine-activated killer (LAK) effector cells that have the unique property of lysing natural killer (NK)-resistant human tumor cells, Daudi, and NK-sensitive K562 cells. LAK cells were generated from patients with advanced cancer or liver cirrhosis. The splenic LAK-effector cell types were analyzed by two-color flow cytometry. The rIL-2-induced LAK cells showed an increased proportion of CD8+CD11- and CD57+CD16- and a decreased proportion of CD4+Leu-8- cells. In contrast, TCGF-induced LAK cells revealed a significantly increased proportion of CD8+CD11- and CD4+Leu-8- cells and a decreased proportion of CD57+CD16- cells. Thus, splenic LAK cells with different surface phenotypes were induced by the cultivation with rIL-2 or TCGF. Furthermore, TCGF-induced LAK cell activities in patients with cancer were found to be lower than the rIL-2-induced LAK cell activities. It was noted that the TCGF-activated splenic lymphoid cells did not inhibit the effector process of tumor cell lysis by LAK cells that had been activated by rIL-2. Other mechanisms of lower LAK cell activities of TCGF-activated splenic lymphoid cells from patients with cancer were discussed. The findings suggest that spleens of examined patients with gastric or hepatocellular carcinoma do not seem to be responsible for suppression of cell-mediated antitumor immunity.