Cellular immunity indices of ovarian cancer patients

The dynamics of functional indexes of T-cell immunity was studied in 47 patients with extended ovarian tumor. The said parameters were found to be adversely affected in primary patients as a result of surgery and chemotherapy. They came back to normal during remission but were badly deranged in relapsing patients.     

Reductive effect on ascites, of neocarzinostatin in patients with ovarian cancer

Neocarzinostatin (NCS) was administered intravenously by drop infusion to 16 patients with ovarian cancer, and intrathoracically to one patient. In addition to evaluation of the efficacy of the chemotherapy, we mainly investigated its effect on ascites and pleural effusion, and carried out continuous measurements of the abdominal circumference in 3 patients. NCS relieved thoracic effusion in 1 patient. We observed that abdominal circumference decreased in 10 patients after administration of NCS. The results obtained from continuous measurement of abdominal circumference revealed that NCS significantly reduced ascitic retention in ovarian cancer.     

Doxorubicin levels in the serum and ascites of patients with ovarian cancer.

AIMS: To investigate the diffusion and accumulation of doxorubicin metabolites in the ascites of patients with ovarian cancer following intravenous injection, as a model for intraperitoneal accumulation of drugs. METHODS: The concentrations of doxorubicin and its metabolites [Doxorubicinol (Dox-ol), 7-deoxydoxorubicinolone (7d-Dox-ol-on) and 7-deoxydoxorubicinone (7d-Dox-on)] were measured using high-performance liquid chromatography in the serum and in the ascites of seven patients with recurrent ovarian carcinoma suffering from symptomatic ascites and treated with intravenous doxorubicin. RESULTS: Doxorubicin metabolites accumulated in the peritoneal cavity. The concentrations of the doxorubicin metabolites were initially higher in the serum compared to the ascitic fluid, but following several hours the doxorubicin metabolites became higher in the ascites, and remained detectable in the ascites for up to 168h, long after disappearance from the serum. CONCLUSIONS: Doxorubicin metabolites accumulate in the ascites and are cleared more slowly from the peritoneal compartment than from the serum. Accumulation in the peritoneal cavity with prolonged half-life should be considered when administering medication in patients with ascites.     

Influence of ascites on the pharmacokinetics of hexamethylmelamine andN-demethylated metabolites in ovarian cancer patients

Levels of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N₂N₂N₄N₆ tetramethylmelamine (TMM) and N₂N₄N₆ trimethylmelamine (TriMM) were determined in plasma of 31 patients with advanced ovarian cancer receiving HMM. In 14 of them with ascites the drug metabolites PMM, TMM and TriMM were assayed in this fluid. Both in plasma and in ascites a GLC method with nitrogen detection was applied after extraction with n-hexane and ethyl acetate at pH11.5. Plasmatic HMMT/2α and T/2β were respectively 47 ± 6 and 403 ± 37 min. Mean AUC_{o→12 hr} values ±S.E.M., expressed in μ g/ml × min, were 312 ± 95 for HMM, 117 ± 32 for PMM, 260 ± 50 for TMM and 311 ± 82 for TriMM. AUCs of HMM, PMM, TMM and TriMM in ascites calculated up to 6 hr were 78 ± 13, 31 ± 7, 60 ± 12 and 129 ± 38 μg/ml × min respectively. The presence of ascites, the patient's age, the concomitant administration of adriamycin and cyclophosphamide and fatness did not appear to influence the kinetic behaviour of HMM and metabolites. HMM was not detectable in urine and PMM, TMM and TriMM accounted for less than 1% of the HMM dose.     

乳腺癌患者免疫指标检测及其临床意义

目的:分析乳腺癌及乳腺良性疾病患者机体免疫指标的特点及临床意义。方法:应用流式细胞术对30例乳腺癌患者、45例乳腺良性疾病患者外周血T细胞亚群及NK细胞进行检测。结果:乳腺癌患者CD3 、CD4 细胞百分比显著低于乳腺良性疾病组(P<0.05);CD8 细胞百分比以及CD4 /CD8 比值在乳腺癌组和乳腺良性疾病组之间无显著差异(P>0.05);乳腺癌患者NK细胞百分比显著高于乳腺良性疾病组(P<0.05);乳腺癌腋淋巴结转移组CD3 细胞百分比及CD4 /CD8 比值明显低于腋淋巴结无转移组(P<0.05),而NK细胞百分比显著高于腋淋巴结无转移组(P<0.05)。结论:乳腺癌患者存在细胞免疫功能紊乱,检测外周血T淋巴细胞亚群表达可能对评估患者的细胞免疫功能及疾病的预后具有一定意义。     

Ganoderma lucidum exerts anti-tumor effects on ovarian cancer cells and enhances their sensitivity to cisplatin

Ganoderma lucidum is a herbal mushroom known to have many health benefits, including the inhibition of tumor cell growth. However, the effect of Ganoderma lucidum on epithelial ovarian cancer (EOC), the most fatal gynecological malignancy, has not yet been reported. In this study, we determined whether Ganoderma lucidum regulates EOC cell activity. Using several cell lines derived from EOC, we found that Ganoderma lucidum strongly decreased cell numbers in a dose-dependent manner. Ganoderma lucidum also inhibited colony formation, cell migration and spheroid formation. In particular, Ganoderma lucidum was effective in inhibiting cell growth in both chemosensitive and chemoresistant cells and the treatment with Ganoderma lucidum significantly enhanced the effect of cisplatin on EOC cells. Furthermore, Ganoderma lucidum induced cell cycle arrest at the G2/M phase and also induced apoptosis by activating caspase 3. Finally, Ganoderma lucidum increased p53 but inhibited Akt expression. Taken together, these findings suggest that Ganoderma lucidum exerts multiple anti-tumor effects on ovarian cancer cells and can enhance the sensitivity of EOC cells to cisplatin.     

腹腔热化疗治疗卵巢癌合并腹水临床疗效观察

目的探讨腹腔热化疗治疗卵巢癌合并腹水的疗效及毒副反应。方法将入选病例随机分为两组,治疗组采用腹腔热疗联合腹腔灌注化疗;对照组则仅行腹腔灌注化疗,剂量与治疗组相同,未进行腹腔热疗。结果治疗组卵巢肿瘤治疗总有效率60.5%（23/38）,对照组为28.6%（10/35）,两组比较差异有显著性（P〈0.05）;治疗组腹水治疗总有效率84.2%（32/38）,对照组为57.1%（20/35）,两组比较差异有显著性（P〈0.05）。而两组患者治疗前后T淋巴细胞亚群结果比较,差异有显著性（P〈0.05）。毒副反应主要为胃肠道反应、骨髓抑制及腹痛,两组毒副反应比较,差异无显著性（P〉0.05）。结论热疗联合化疗药物腹腔灌注治疗卵巢癌合并腹水具有协同效应,增强抗癌效果、提高免疫力并抑制肿瘤细胞活性,治疗毒副反应可耐受。     

Biochemical and immunologic characterization of galactosyltransferase purified from the ascites of ovarian cancer patients

Galactosyltransferase appears to be a promising marker for ovarian carcinoma. For an understanding of its role in this cancer, the enzyme was purified from the ascites of ovarian cancer patients, and its biochemical and immunologic properties were studied. For adequate recovery and stability, Triton X-100 (0.01%) was necessary in all the buffers used for the purification of this enzyme. Immunoglobulins were not detectable in this preparation, which showed a single band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Electrophoresis under nondenaturing conditions resolved the enzyme into two to three active components. An antiserum in rabbits, however, produced a single precipitin line suggesting a single determinant. By chromatography in concanavalin A-Sepharose 4B, the enzyme can be resolved into two components (F-1 and F-2). Purified galactosyltransferase and components F-1 and F-2 all catalyzed the transfer of galactose from UDP-galactose to alkali-stable beta-N-glycosidic acceptors, as well as to alkali-labile beta-O-glycosidic mucin-type acceptors. In addition, they catalyzed the N-acetyllactosamine synthetase reaction and, in the presence of alpha-lactalbumin, the lactose synthetase reaction. Galactosyltransferase and components F-1 and F-2 differed in their sensitivity to alpha-lactalbumin-induced inhibition of N-acetyllactosamine synthesis. Galactosyltransferase in the malignant ascites exists as different isoforms, which do not differ significantly in major biochemical and immunologic properties.     

Metronomic oral paclitaxel shows anti-tumor effects in an orthotopic mouse model of ovarian cancer

Objective

The purpose of this study was to compare the in vivo anti-tumor efficacy of a mucoadhesive, lipid-based, oral paclitaxel formulation (DHP107) with traditional, intraperitoneal (IP) paclitaxel using an orthotopic mouse model of chemotherapy-sensitive SKOV3ip1 ovarian cancer.

Methods

To determine the optimal therapeutic dose of oral paclitaxel, DHP107 was administered per os to female athymic nude mice at 0, 25, or 50 mg/kg twice per week. Control mice received 100 µL saline once per week. IP injections of paclitaxel at 5 mg/kg once per week were used for comparison. To evaluate the potential therapeutic effect of metronomic DHP107 chemotherapy, mice received DHP107 50 mg/kg once per week per os, which was compared with 25 mg/kg twice per week and with vehicle-treated controls.

Results

Low-dose DHP107 (25 mg/kg) twice per week was as effective as IP paclitaxel (5 mg/kg once a week) but high-dose DHP107 (50 mg/kg once per week) was less effective at inhibiting tumor growth in an orthotopic mouse model (88%, 82%, and 36% decrease in tumor weight, respectively). Mice that received 25 mg/kg DHP107 twice per week or 50 mg/kg DHP107 once per week per os had a significant decrease in tumor weight compared with vehicle-treated controls (p<0.01, both doses).

Conclusion

Metronomic oral chemotherapy with DHP107 showed anti-tumor efficacy in vivo similar to IP paclitaxel in an orthotopic mouse model.     

Circulating serum sVCAM-1 concentration in advanced ovarian cancer patients: correlation with concentration in ascites

Background

Vascular cell adhesion molecule-1 (VCAM-1) is associated with ovarian cancer progression but the origin of its soluble form (sVCAM-1) in serum is not well investigated. The purpose of this study was to elucidate whether the concentration of sVCAM-1 in serum correlates with the concentration in ascites, that represents local tumour environment, and with systemic inflammation, various clinicopathological characteristics, and patient outcome.

Patients and methods.

Thirty-six patients with advanced ovarian cancer were included in the study. Serum for sVCAM-1 analysis was obtained prior to surgery. Ascites samples were collected at the beginning of the operation. Clinical data were collected from patients’ medical records. sVCAM-1 in samples was analysed by flow cytometric bead-based assay. The mean follow-up period was 11 months (range 0–23) from the time of surgery.

Results

Serum sVCAM-1 concentrations are positively correlated to ascites sVCAM-1 concentrations. There was a weakly positive correlation of serum sVCAM-1 with tumour size and no correlation with inflammatory tumour markers, FIGO stage or grade. Higher concentrations of sVCAM-1 were associated with poor disease outcome (death from ovarian cancer) in almost all cases before chemotherapy was started.

Conclusions

This is the first study demonstrating that serum concentrations of sVCAM-1 in advanced ovarian cancer patients correlate with sVCAM-1 concentrations in ascites, thus expressing the biologic potential of malignant disease to metastasis, rather than systemic inflammation. Higher serum and ascites sVCAM-1 concentrations might have predictive potential for different biologic behaviour.     

Characterization of products synthesized by galactosyltransferase purified from the ascites of ovarian cancer patients

Galactosyltransferase purified from the ascites of ovarian cancer patients can use to an equal extent N-glycosidic glycoproteins, such as asialoagalactofetuin, and O-glycosidic mucin, such as asialo bovine submaxillary mucin (BSM), as acceptors. Thermal treatment and substrate competition experiments demonstrated that the same enzyme catalyzed the transfer of galactose to both types of acceptors. Alkaline borohydride treatment showed that, while the product with asialoagalactofetuin was totally resistant, about 90% of the product with asialo BSM was hydrolyzed by this treatment. Gel filtration of the released oligosaccharides on a calibrated Biogel P-2 column showed three peaks. One major oligosaccharide (O-2) of size 5.7 glucose U and two minor peaks (O-1 and O-3) of sizes 8.7 and 3.7 glucose U, respectively, were obtained. The oligosaccharides were doubly labeled, first by incubation with uridine-diphosphate [14C]galactose, followed by alkali treatment in the presence of [3H]borohydride. The doubly labeled oligosaccharides were separately purified by gel filtration and ion-exchange chromatography and digested with various exoglycosidases. The digested products were characterized by gel filtration and paper chromatography in three different systems. From these results, the structures of these oligosaccharides were computed as follows: O-1 = beta-galactosyl-beta-N-acetylglucosamine-galactosaminitol (sialic acid); O-2 = beta-galactose-beta-N-acetylglucosamine-galactosaminitol; O-3 = beta-galactose-galactosaminitol. These results suggest that the galactosyltransferase from the ascites of ovarian cancer patients catalyzes the transfer of galactose to N-acetylglucosamine, irrespective of whether it is a part of an N-glycan or an O-glycan.     

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Purpose

Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit.

Methods

We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection.

Results

Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise.

Conclusions

HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of ‘immune cold’ TNBCs.

     

Targeting immune checkpoints: releasing the restraints on anti-tumor immunity for patients with melanoma

Insight into the mechanisms of anti-tumor immunity has generated great enthusiasm for the treatment of patients with advanced melanoma. Particularly, negative regulators of the immune system, called immunologic checkpoints, have been found to play important roles in restraining otherwise effective anti-tumor immunologic responses. Therapies that target these negative regulator checkpoints, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death 1 receptor (PD-1), have demonstrated promising clinical results. Treatment is generally well tolerated, but a novel spectrum of side effects, termed immune-related adverse events, has been experienced. Unfortunately, not all patients respond to these therapies, and evaluation of biomarkers predictive of response is ongoing. Based on their unique mechanisms of action, radiographic assessment of response differs from methods traditionally applied to cytotoxic chemotherapy. We expect ongoing and future efforts combining agents that target immunologic checkpoints with other immunotherapeutic approaches, targeted therapy, chemotherapy, and radiotherapy may additionally be beneficial.     

Characterization of human kallikreins 6 and 10 in ascites fluid from ovarian cancer patients.

OBJECTIVES: Human kallikreins 6 (hK6) and 10 (hK10) are secreted serine proteases. We previously found that hK6 and hK10 are highly overexpressed in epithelial ovarian tumors and demonstrated that serum levels of hK6 and hK10 are valuable biomarkers for ovarian cancer diagnosis and prognosis. Our aim is to purify and characterize these two kallikreins from ascites fluid of ovarian cancer patients. METHODS: Protein concentrations of hK6 and hK10 in ovarian cancer ascites fluids were measured with ELISA-type immunoassays. hK6 and hK10 were purified from the ascites fluids with immunoaffinity columns, followed by reverse-phase high performance liquid chromatography. Purified hK6 and hK10 were then subjected to N-terminal sequencing. Enzymatic analyses were performed with synthetic fluorogenic peptides. RESULTS: hK6 and hK10 were present in ovarian cancer ascites fluid at concentrations ranging from 0.2-571 and 0.7-220 microg/l, respectively. The majority of hK6 and hK10 in the ascites fluids were present in the free (uncomplexed) form. Both hK6 and hK10 purified from the ascites fluid were zymogens with a molecular mass of 30 kDa. Purified hK6 exhibited trypsin-like enzymatic activity, whereas no enzymatic activity was observed for purified hK10. The enzymatic activity of hK6 could be suppressed by a neutralizing monoclonal antibody. CONCLUSIONS: The majority of hK6 secreted by the ovarian tumor cells into the ascites fluid are present in the uncomplexed, zymogen form, possessing weak trypsin-like enzymatic activity. All hK10 present in ovarian cancer ascites fluids are in the uncomplexed, zymogen form and have no detectable enzymatic activity.     

Profiling of cytokines in human epithelial ovarian cancer ascites

Background

The behavior of tumor cells is influenced by the composition of the surrounding tumor environment. The importance of ascites in ovarian cancer (OC) progression is being increasingly recognized. The characterization of soluble factors in ascites is essential to understand how this environment affects OC progression. The development of cytokine arrays now allows simultaneous measurement of multiple cytokines per ascites using a single array.

Methods

We applied a multiplex cytokine array technology that simultaneously measures the level of 120 cytokines in ascites from 10 OC patients. The ascites concentration of a subset (n = 5) of cytokines that was elevated based on the multiplex array was validated by commercially available ELISA. The ascites level of these 5 cytokines was further evaluated by ELISA in a cohort of 38 patients. Kaplan-Meier analysis was used to assess the association of cytokine expression with progression-free survival (PFS) in this cohort.

Results

We observed a wide variability of expression between different cytokines and levels of specific cytokines also varied in the 10 malignant ascites tested. Fifty-three (44%) cytokines were not detected in any of the 10 ascites. The level of several factors including, among others, angiogenin, angiopoietin-2, GRO, ICAM-1, IL-6, IL-6R, IL-8, IL-10, leptin, MCP-1, MIF NAP-2, osteprotegerin (OPG), RANTES, TIMP-2 and UPAR were elevated in most malignant ascites. Higher levels of OPG, IL-10 and leptin in OC ascites were associated with shorter PFS. IL-10 was shown to promote the anti-apoptotic activity of malignant ascites whereas OPG did not.

Conclusion

Our data demonstrated that there is a complex network of cytokine expression in OC ascites. Characterization of cytokine profiles in malignant ascites may provide information from which to prioritize key functional cytokines and understand the mechanism by which they alter tumor cells behavior. A better understanding of the cytokine network is essential to determine the role of ascites in OC progression.     

热疗联合顺铂对人卵巢癌细胞的毒性增效作用及治疗卵巢癌恶性腹腔积液的疗效观察

目的：探讨热疗联合顺铂对人卵巢癌细胞的毒性增效作用及治疗卵巢癌恶性腹腔积液的疗效。方法将79例卵巢癌伴恶性腹腔积液患者按照随机数字表法随机分为对照组（n=39）与观察组（n=40）,对照组仅采用顺铂进行常规治疗,观察组在此基础上联合热疗进行治疗。比较两组疗效、治疗48 h后SKOV3细胞凋亡情况、治疗前后免疫功能相关指标水平、生活质量及不良反应发生情况。结果①对照组临床总缓解率为58.97%,低于观察组的77.50%,差异有统计学意义（P＜0.05）;②观察组治疗48 h后SKOV3细胞凋亡率为72.5%,高于对照组的46.15%,差异有统计学意义（P＜0.05）;③观察组治疗后CD4及CD4/CD8水平均高于治疗前及对照组治疗后,差异有统计学意义（P＜0.05）,对照组治疗前后各免疫功能指标水平比较,差异均无统计学意义（P＞0.05）;④根据SF-12生活量表评分,观察组患者生活量表相关维度（总体健康、情感职能、躯体疼痛及精神健康）评分均高于对照组,差异有统计学意义（P＜0.05）;⑤对照组不良反应发生率为38.46%,观察组为35.00%,差异无统计学意义（P＞0.05）。结论热疗联合顺铂对人卵巢癌细胞的毒性增效作用及治疗卵巢癌恶性腹腔积液的疗效显著。     

PMN and anti-tumor immunity—The case of bladder cancer immunotherapy

Urothelial carcinoma of the bladder accounts for ∼5% of all cancer deaths in humans. The majority of bladder tumors are non-muscle invasive at diagnosis, and there is a high rate of tumor recurrence and progression even after local surgical therapy. Thus, many patients require lifelong follow-up examinations that include additional prophylactic treatments in the event of recurrence. Since its first use in 1976, Mycobacterium bovis bacillus Calmette–Guerin (BCG) has been the treatment of choice for non-muscle invasive bladder cancer. Despite nearly 40 years of clinical use, the mechanism(s) by which intravesical administration of BCG results in elimination of bladder tumors remains undefined. Granulocytes (polymorphonuclear neutrophils (PMN)) are the predominant immune cell (in number) that enters the bladder after BCG installation, and a number of studies have highlighted the importance of PMN in the antitumor activity of BCG. Studies from our laboratory demonstrated presence of intracellular stores of the apoptosis-inducing protein TNF-related apoptosis-inducing ligand (TRAIL) in PMN that are rapidly released after interaction with BCG cell wall components, along with a correlation between increased urinary levels of TRAIL and BCG responsiveness. Mature PMN in circulation are terminally differentiated cells with limited biosynthetic capacity, so the proteins located in the distinct PMN granule populations are compartmentalized concomitant with their synthesis during myelopoiesis. Thus, understanding PMN production, localization, and release of TRAIL is important in the design of future BCG-based bladder tumor immunotherapy protocols.     

Establishment of a human ovarian cancer cell line capable of forming ascites in nude mice and effects of tranexamic acid on cell proliferation and ascites formation

The present study was designed to obtain an experimental tumor model as similar as possible to human ovarian cancer which often had a large amount of ascites and to assess the therapeutic value of tranexamic acid. Human tumor cell lines which form ascites in nude mice were established from ascites of patient with serous cystadenocarcinoma of the ovary. Two cloned cell lines designated HRA and HR-1 were obtained from the parent cell line designated HR. All of these cultured cell lines had about 2.5-3.5 times higher lactate dehydrogenase activities than the original tumor. The original tumor and the tumor grown in nude mice had all 5 bands of lactate dehydrogenase isoenzymes, while all cultured cell lines had only a marked lactate dehydrogenase-3 in addition to a faint lactate dehydrogenase-2. Modal chromosome numbers of HR cells ranged from 50-76, while that of HRA cells ranged widely from 40-140. The DNA histograms of HR and HRA cells were similar to each other, showing predominant G1 and S phases. Although these cell lines had ability to produce ascites in the nude mice when the cells were inoculated i.p., the HRA cell inoculation made ascites most rapidly and brought about the shortest median survival (39 days). The proliferations of all three cell lines were dose-dependently inhibited by tranexamic acid. However, the concentration of this drug required for 50% inhibition of the proliferation of HRA cells was about one-half of that of HR and HR-1 cells. In addition, i.p. injections of tranexamic acid to nude mice treated with cisplatin resulted in a significant inhibition of the ascites formation and prolongation of 50% survival.     

自杀性肿瘤疫苗对大鼠卵巢癌的治疗作用及其安全性研究

目的 将自杀基因修饰的卵巢癌细胞与树突状细胞（DC）融合制备成自杀性肿瘤疫苗（FC／TK）,观察FC／TK对大鼠卵巢癌的免疫治疗作用,并探讨对FC／TK进行体内灭活的可行性。方法 以聚乙二醇法,用大鼠骨髓来源的DC与转导有自杀基因（HSV1-TK基因）的大鼠卵巢癌上皮细胞株NuTu-19细胞融合制备成FC／TK,在扫描电镜下观察FC／TK的形态;用^3H—TdR渗入法,检测FC／TK刺激T细胞增殖的能力。在大鼠体内的免疫治疗实验中,以FC／TK治疗大鼠卵巢癌皮下瘤,观察肿瘤形成及肿瘤大小,分别设立经^60Co照射的FC／TK组、未经自杀基因修饰的卵巢癌细胞与DC融合的疫苗（FC）组和PBS对照组。在体内灭活实验中,将FC／TK以荧光染料标记后进行大鼠体内示踪,腹腔注射羟甲基无环鸟苷（GCV）7d后,采用末端脱氧核苷酸转移酶（TdT）介导的d-UTP缺口末端标记技术,对大鼠淋巴组织的冰冻切片做原位细胞凋亡检测。结果 FC／TK为多形性,扫描电镜下可见不规则的突起。与对照组相比,FC／TK能明显刺激T细胞增殖（P〈0．01）。大鼠体内的免疫治疗实验结果显示,FC／TK组与FC组大鼠的成瘤时间晚于经^60Co照射的FC／TK组（P〈0．05）,较PBS组明显延迟（P〈0．01）;接种NuTu-19细胞90d后,FC／TK组大鼠的平均肿瘤体积较经^60Co照射的FC／TK组和PBS组明显缩小（P〈0．01）,但FC／TK组与FC组之间,差异无统计学意义（P〉0．01）。荧光显微镜下,经红色荧光标记的FC／TK出现在大鼠脾脏;进-步TUNEL染色显示,经GCV处理后,进入大鼠体内的FC／TK已发生凋亡。结论 FC／TK对大鼠卵巢癌有免疫治疗作用,并可由自杀基因系统控制其在体内的存活.