Effect of leukocyte activation on the formation of heterotypic tumor-cell aggregates in vitro

Walker tumor cell (1 x 10(6) cells/ml) were incubated at 37 degrees C in a stirred cuvette with rat peritoneal exudate cells (9 x 10(6) cells/ml) with or without the synthetic leukocyte chemo-attractant fMLP (2 x 10(6) M) or biologically active concentrations of the major endogenous chemo-attractant, C5a. Aggregation, induced by the chemo-attractants, was detected after 3 min by a platelet aggregometer and by studying cytocentrifuge preparations. The response was amplified in the presence of cytochalasin B (5 micrograms/ml). Tumor cells could be identified in the aggregates by their morphology or by autoradiography after labeling with 3H-thymidine. Although tumor cells were incorporated into the leukocyte aggregates, there was no appreciable change in the number of aggregates formed between tumor cells themselves. Levine III human breast tumor cells (1 x 10(6)/ml) in heparinized human blood were incorporated into leukocyte aggregates within 30 min of adding 50 U cobra venom factor to activate complement. Aggregation correlated with a decrease in complement hemolytic activity (CH50). The aggregation reaction was not cytotoxic to tumor cells when evaluated by Trypan blue exclusion or by 51Cr release. We conclude that local tumor cells can be incorporated into aggregates formed when leukocytes are stimulated by chemo-attractants. We postulate that intravascular activation of neutrophils might affect the localization of circulating tumor cells by incorporating them into microembolic cell aggregates and by causing damage to the pulmonary endothelium.     

Inhibition of melanoma growth in hamsters by type-2 adenovirus.

Type-2 adenovirus was shown to inhibit the growth of transplantable hamster melanoma in 70% of Syrian hamsters without any injurious effect to the host. Greatest inhibition of tumor formation was seen when animals were injected with 10(6) TCD50 of adenovirus and 2.5 x 10(5) tumor cells, or 10(6) TCD50 of virus and 5.0 x 10(5) tumor cells followed either 1 or 7 days later by a second injection of a similar dose of virus. Significant inhibition in tumor growth was also noted when 2 injections of virus (10(6.2) TCD50/injection) were given on 2 separate occasions as late as 7 and 10 days after the inoculation of tumor cells. The mechanism of tumor inhibition is not known but it could be due to a combination of factors such as viral toxicity, viral oncolysis, and antitumor immunity.     

磁激活细胞分选结合荧光激活细胞分类检测胃癌骨髓微转移的临床价值

背景与目的:检测胃癌患者骨髓微转移有多种方法,但不同的方法差异很大。在乳腺癌中,以磁激活细胞分选(m agnetic activated cellsorting,M ACS)结合荧光激活细胞分类(fluorescentactivated cellsorting,FACS)检测血细胞中的肿瘤细胞,有较高的敏感性和特异性。本研究探讨应用这一方法检测胃癌骨髓微转移的临床意义。方法:选择2002年12月～2003年6月行手术治疗的胃癌患者35例,提取其骨髓有核细胞,以结合抗细胞角蛋白(cytokeratin,CK)7/8抗体的M ACS微型免疫磁珠、标记异硫氰酸荧光素(fluorescein isothiocyanate,FITC)的抗CK抗体,以及标记叶绿素蛋白的抗CD45抗体标记后,以M S /RS 型阳性分选柱进行两次肿瘤细胞富集。取富集前后的细胞样本进行FACS检测,将检测结果与各临床病理学参数进行比较。结果:M ACS富集前,仅3例(8.6%)检测到骨髓中存在的微转移细胞;而富集后,有25例(71.4%)患者检测到了骨髓微转移细胞。组织学分级为中分化、低分化和未分化的患者中,肿瘤细胞频数分别为1.4×10-8～2.4×10-5、2.2×10-7～3.7×10-5和4.0×10-6～8.6×10-5,3组比较,有显著性差异(P=0.026)。骨髓微转移状况与肿瘤TNM分期密切相关(r=439,P=0.008),而与肿瘤大小、浸润深度等参数无关。结论:M ACS结合FACS可提高胃癌患者骨     

The vascular response of tumor and normal tissues in the rat to the vascular targeting agent,combretastatin A-4-phosphate,at clinically relevant doses

The antivascular actions of disodium combretastatin A-4 3-O-phosphate (CA-4-P) were investigated in the rat P22 carcinosarcoma after single doses of 10 or 30 mg x kg(-1). Pharmacokinetic data showed that 10 mg x kg(-1) in the rat gave a plasma exposure similar to that achieved in the clinic. Blood flow rate to the tumor and normal tissues was measured using the uptake of radiolabelled iodoantipyrine (IAP). Quantitative autoradiography was used to determine changes in spatial distribution of tumor blood flow. Both doses caused an increase in mean arterial blood pressure (MABP) and a reduction in heart rate 1 h after treatment. Blood flow rate to the tumor decreased to below 15% of control for both doses at 1 h, whereas the normal tissues were much less affected. A further reduction (to 2% of control at 6 h) was found for 30 mg x kg(-1). Recovery was essentially complete by 24 h for both doses. Vascular resistance increased 80-fold in tumor at 6 h after 30 mg x kg(-1), compared with a maximum 5-fold increase in normal tissues. Analysis of the spatial distribution of tumor blood flow illustrated an overall reduction in all areas of the tumor at 1 h after 10 mg x kg(-1), with a tendency for blood flow in the peripheral regions of the tumor to recover more quickly than in central regions. Tumor blood flow reduction was related to vascular damage including vessel distension, coagulation and haemorrhage, and tumor cell damage culminating in necrosis. No pathology was evident in any of the normal tissues following treatment. The data provide an insight into the mechanisms underlying tissue blood flow changes occurring after clinically relevant doses of CA-4-P. It is currently being used to aid interpretation of pharmacodynamic data obtained from phase I/II clinical trials of CA-4-P and is relevant for future drug development in this area.     

大鼠树突状细胞融合瘤苗的特异性抗骨肉瘤作用

背景与目的:树突状细胞(dendriticcells,DCs)是目前已知的功能最为强大的抗原呈递细胞,但以DC为基础的针对骨肉瘤的免疫治疗未见报道。本研究旨在探讨大鼠树突状细胞融合瘤苗诱导的特异性抗骨肉瘤作用。方法:应用重组大鼠rGM-CSF、rIL-4和rTNF-α培养大鼠骨髓前体细胞获得大量DCs,用标记抗大鼠OX62单抗免疫磁珠分离纯化DCs,经形态学观察、表型检测、功能学实验鉴定,然后通过电融合的方法将细胞系UMR-106与异基因或同基因大鼠DCs相融合制备肿瘤疫苗,观察其抗肿瘤的效果。结果:预防接种异基因肿瘤疫苗组和同基因肿瘤疫苗组大鼠的存活率分别为70%和50%,存活的大鼠经历了第2次大剂量骨肉瘤细胞的免疫攻击,7周之后继续得以存活。在针对骨肉瘤动物模型进行主动免疫治疗的研究中,60%的荷瘤大鼠瘤体萎缩、消失而得以长期存活。结论:大鼠骨肉瘤细胞系UMR-106与同种异基因树突状细胞的融合瘤苗有较强的特异性抗骨肉瘤作用。     

Inhibitory effects of canthaxanthin on in vitro growth of murine tumor cells.

The antitumorigenic effects of carotenoids, in addition to their immuno-enhancing effects, may occur by their direct action on growing tumor cells. To test this hypothesis the direct inhibitory effect of various concentrations of canthaxanthin (CX; 4,4'-diketo-beta-carotene), a non-provitamin A carotenoid, was tested on the in vitro growth of JB/MS, B16F10 melanomas and PYB6 fibrosarcoma and murine non-transformed NIH-3T3 (ATCC CRL 1658) cells. At concentrations of 1 x 10(-8) M up to 1 x 10(-4) M, CX significantly reduced the overall number of tumor cells. The greatest inhibition was observed at a CX concentration of 1 x 10(-4) M after 72 h and 96 h of incubation. However, CX had no inhibitory effect on the growth of the non-transformed NIH-3T3 cell line; rather it significantly enhanced growth of this cell line (P less than 0.05) after 96 h of incubation. Thus, the inhibitory action of CX on growing tumor cells appears to be due to its direct actions on tumor cells and not via its conversion to vitamin A or its immuno-enhancing effects.     

Iridium-192 brachytherapy for hemorrhagic angiosarcoma of the scalp: a case report

A 60-year-old woman presented with multicentric skin tumors of the head. The histologically proven hemangioendothelioma was bleeding as a result of disseminated coagulopathy. In addition to immunotherapy, 6 MeV electron beam radiotherapy was used for the purpose of hemostasis with a single portal, 20 x 20 cm in size, covering the whole scalp from the top of the head. The radiotherapy was discontinued after 39 Gy/13 fractions/20 days because of the progress in size of a peripheral tumor and the stability of coagulopathy. After another electron boost delivery by two portals focused to exophytic parietal and temporal tumors of 20 Gy/10 fractions, high dose rate brachytherapy with a surface mold technique was performed, 3 Gy/fraction, four fractions/week, for a total of 36 Gy. It induced partial regression of the tumor and complete recovery of platelet counts from 2.5 x 10(4) to 18.2 x 10(4). The tumor disappeared in 3 months. No late side effects occurred, except for permanent alopecia. The patient developed a cervical lymph node metastasis 1 year after and marginal recurrence 2 years after the initial treatment. Both recurrent tumors were successfully treated by 4 MV external photons of 60 Gy/20 fractions/46 days and electron beam irradiation of 60 Gy/20 fractions/29 days, respectively. She has remained disease free for 3 years after the initial presentation.     

Adoptive transfer via immune T-lymphocytes of effective anti-tumor immunity against a malignant rat glioma in the brain

The aim of the present study was to develop an animal model to test the therapeutic potential of purified CD4 and CD8 T-lymphocytes against the intracerebrally implanted rat glioma cell line TZ363. Peripheral immunization of donor rats was performed by subcutaneous injection of viable TZ363 tumor cells while control animals received buffer injection. Donor splenic T-lymphocytes were prepared 14 days later and enriched by immune-bead MACS sorting. FACScan analysis revealed that of the pooled and sorted cells 91% of the tumor immune group were T-lympocytes and from the control animals 96%. The purified immune CD4/CD8 T-lymphocytes (1.2 to 5x10(7) cells) were injected intraperitoneally into 12 adult rats (three groups; each four animals), which were challenged five days later by an intracerebral injection of 5x10(4) TZ363 glioma cells. Four rats received 1.4x10(7) T-cells from control animals. While 3 of 4 animals developed a brain tumor and died in the control group, all animals, which received 5x10(7) immune T-cells survived the intracerebral tumor challenge. In the other groups survival rate depended on the amount of T-cells given. All other rats were sacrificed 32 days after intracerebral grafting. No tumor was found in these animals. Our data demonstrate that an anti-tumor T-cell response can be raised against the malignant rat glioma TZ363 and that purified CD4 and CD8 T-lymphocytes from tumor immunized donors can transfer protective immunity across the blood-brain barrier into recipient rats which are tumor challenged intracerebrally.     

Protective effect of irradiated renal carcinoma expressing hepatitis B surface antigen against renal-cell carcinoma-mediated tumors

Radiation therapy and chemotherapy have little effect on renal-cell carcinomas (RENCAs). We investigated the effect of the tumor vaccination strategy on preventing tumor formation after a challenge with RENCA. The hepatitis surface antigen (HBsAg) was used to enhance the antitumor immunity and tumor vaccination efficiency. RENCA cells expressing HBsAg (RENCA/HBS) were completely susceptible to HBsAg vaccination, which implies that HBsAg vaccination induces specific antitumor immunity against HBsAg- expressing cancer cells. As with HBsAg vaccination, vaccination with irradiated RENCA/HBS retarded tumor formation following a RENCA/HBS challenge. After HBsAg vaccination, the irradiated RENCA/HBS tumor vaccine completely prevented the tumor formation by RENCA/HBS. Tumor vaccination with irradiated RENCA/HBS (5 x 10(4) cells), but not with RENCA, reduced the tumor rate after a challenge with 5 x 10(6) RENCA cells, whereas a lower tumor load was overcome by the RENCA vaccination alone. These results confirm the postulate that RENCA/HBS vaccination elicits an antitumor immune response to some putative antigens or enhances the general immune competence in immunosuppressed renal tumor patients.     

Immunomodulating activity of natural killers in patients with breast tumors using vasopressin and interleukin 2 in vitro

The study included 10 female donors, 12 patients with benign and 59 with malignant tumors of the breast at various stages before and after treatment. The immunomodulating effect of vasopressin and interleukin-2 on blood-natural killer functional activity was studied in vitro. Vasopressin dose of 4 x 10(-1) IU/5 x 10(5) cells exerted an immunosuppressive effect while 4 x 10(-5) IU/5 x 10(5) cells stimulated immunity. The stimulating effect of optimal interleukin-2 dosage (20-40 U/5 x 10(5) cells) on natural killer functional activity appeared 1.5-2-times higher than that optimal vasopressin dose (4 x 10(-5)/5 x 10(5) cells). Combined administration of the agents was not followed by increase in overall effect. Sensitivity of blood-natural killer cells in breast cancer patients to vasopressin and interleukin-2 depended upon clinical pattern, stage of tumor and treatment modality.     

Rejection of parental meth-a tumor on concomitant inoculation of meth-a cells infected retrovirally with the interferon-gamma gene into (balb/cxc57bl/6)f-1 mice

The IFN-gamma gene was introduced retrovirally into Meth A cells. IFN-gamma gene infected Meth A (K gamma) cells were highly antigenic and regressed in CB6F(1) mice. Concomitant immunization of CB6F(1), mice with IFN-gamma gene infected Meth A (K gamma) cells after inoculation of parental Meth A protected the mice from parental tumor growth. 1x10(6) infectant Meth A (K gamma) cells protected the mice from growth of 1x10(6) parental Meth A cells, but 2x10(6) infectant cells did not, suggesting that there was an optimal dose of infectant cells for rejection of the parental tumor. Specificity analysis revealed that growth of CMS13 tumor was slightly inhibited by Meth A (K gamma) cells but that of CMS5 was not inhibited. The findings are consistent to those obtained with parental Meth A cells and indicated that the relevant rejection antigen on Meth A (K gamma) cells was identical to the parental Meth A rejection antigen.     

Anti-tumor effects of human peripheral gammadelta T cells in a mouse tumor model

Peripheral gammadelta T cells derived from healthy donors were found to exhibit cytotoxicity against a variety of tumor cell lines in vitro, including CNE2, which was established from nasopharyngeal carcinoma (NPC). The anti-tumor effects were further studied in a mouse model. Control nude mice inoculated s.c. with 5 x 10(6) CNE2 cells regularly developed hypodermal tumors, which progressively increased in size, and animals had a mean survival of 35 +/- 3.4 days. Tumor growth was arrested and tumor size was reduced after animals were infused with 5 x 10(7) gammadelta T cells derived from a healthy donor. The anti-tumor effects were temporary, however, and tumor growth was resumed after about 1 week in a group of the animals that had been given a single dose of gammadelta T cells. In another group of animals given 2 doses of gammadelta cells 1 week apart, resumption of tumor growth was delayed for a further week. Mean survival of the 2 groups was increased to 61 +/- 15.7 and 74 +/- 12.9 days, respectively. Immunohistology revealed an accumulation of infused cells in tumors attended by focal tumor necrosis in specimens taken 2 days after infusion. Infiltrative cells virtually disappeared from tumor tissues 6 days after infusion, accompanied by increased mitotic indices of tumor cells. These temporal relationships suggested that the accumulation of infused gammadelta T cells in hypodermal tumors was responsible for the observed anti-tumor effects.     

The inhibition of growth and angiogenesis in heterotransplanted esophageal carcinoma via intratumoral injection of arsenic trioxide

To investigate the antitumor action of arsenic trioxide (As2O3) by intratumoral injection into solid tumors, tumor growth inhibition (TGI) and angiogenesis of heterotransplanted esophageal carcinoma in mice was carried out. The cultured human esophageal carcinoma cells were inoculated into both laterals of the abdominal wall of severe combined immunodeficient (SCID) mice. When both lateral tumors had grown to about 10x8x5 mm(3), the right tumors were treated with an intratumoral injection of As2O3 in dosage of 1, 5 and 10 microg per day, respectively, for 10 days sequentially. Left tumors were treated with PBS (phosphate buffer solution) as control. The weight of transplanted tumor masses were measured and counted for TGI. The tissue of tumor, liver, kidney, heart, lung and brain was examined histopathologically and tumor tissues were examined by light- or electron-microscope. Ki-67 and CD34 were assessed by immunohistochemistry and positive nuclei of Ki-67 and microvessel density (MVD) labeled by CD34 were measured. The results revealed that on the 20th day after the first injection, As2O3-treated tumors were suppressed markedly as compared with the contrarily situated tumor, accompanied by a marked apoptosis and necrosis in tumor cells. The tissue of liver, kidney, heart, lung and brain was unaffected by As2O3. MVD in tumor tissue was decreased in the right side tumor with the significant difference in the 5 micro g and 10 micro g group (p<0.01). TGI was 5.80 (p>0.05), 58.66 (p<0.01) and 73.97% (p<0.01) in the 1, 5 and 10 micro g groups respectively, but 2.21% (p>0.05) in the control group. Conclusively, a repeated administration of As2O3 (5 and 10 microg x 10) induced an increase of tumor growth inhibition and decrease of angiogenesis in the solid tumor in tumor progressive periods. These results suggest that intra-tumoral injection of As2O3 may be investigated as a modality to treat some solid tumors.     

Interferon-induced inhibition of Moloney sarcoma virus-transformed cells: requirement for T-cells

We previously demonstrated that although natural killer (NK) cells participated in interferon (IFN)-induced inhibition of growth of the Moloney sarcoma MSC cell tumor, the need for NK cells could be circumvented by using a small tumor cell challenge or an increased amount of IFN. These studies were performed in normal, euthymic mice. The role of T-cells remained undefined. In the present study, nude mice were used to evaluate the role of T-cells. Investigation of various treatment regimens revealed that IFN could not totally inhibit tumor growth in nude mice. A significant delay in tumor growth was observed when 1 x 10(5) units of IFN were administered at the site of tumor on days 1-4 after tumor challenge. Increasing the dose of IFN or extending therapy to 7 days did not afford any further inhibition of tumor growth. In vivo depletion of NK cells with anti-asialo monoganglioside antibody revealed that the delay in tumor growth was dependent on NK cells when IFN was given on days 1-4. Treatment for days 1-7, however, still inhibited tumor growth in the NK cell-depleted nude mice. In order to further ascertain the role of T-cells in IFN-induced tumor inhibition, T-cell reconstitution studies of nude mice were performed. Nude mice were reconstituted with 1 x 10(7), 2 x 10(7), and 5 x 10(7) T-cells on day -1 to tumor challenge and treated with IFN on days 1-7. The extent of the observed decrease of tumor sizes and tumor incidences among the T-cell-reconstituted groups was dependent on the dose of T-cells being administered in both IFN-treated and untreated animals. These data indicate that T-cells are essential for maintaining the growth-inhibitory effects of IFN. This is in contrast to NK cells whose role in IFN-induced inhibition of MSC tumor growth can be circumvented by increasing the dose of IFN.     

33例头颈部恶性肿瘤患者局部过继免疫治疗的疗效观察

目的评价ＩＬ－２／ＬＡＫ细胞局部过继免疫疗法在头颈部恶性肿瘤治疗中的疗效。方法对３３例头颈部恶性肿瘤患者进行局部过继免疫治疗,采用ＩＬ－２每日１０～２０万单位局部注射,共１０天;于ＩＬ－２治疗的第４～８天同时于局部注射ＬＡＫ细胞１．０×１０８～５．０×１０８／ｄ。结果完全缓解１例,部分缓解６例,好转２０例,稳定６例,治疗总缓解率２１．２％,总有效率８１．８％。治疗后１,２,３年生存率分别为９６．３％、８３．３％、和７５．０％。组织病理学检查证实免疫治疗后肿瘤局部大量ＣＤ３、ＣＤ４阳性Ｔ淋巴细胞浸润。治疗过程中未见严重的毒副作用。结论局部应用ＬＡＫ细胞与ＩＬ－２治疗头颈部恶性肿瘤疗效明显,方法安全。     

Murine liver metastasis model using L5178Y-ML lymphoma and the effect of antitumor agents on the metastasis

A reproducible tumor model for liver metastasis has been developed from murine L5178Y lymphoma line by sequential cycles of subcutaneous inoculation of liver tumor cells, that were originally generated in livers of female (BALB/c x DBA/2)F1 mice by injecting the parental cells into the tail vein. This variant (L5178Y-ML) metastasized predominantly to the liver after intravenous or subcutaneous injection. The livers of the animals killed 9 days after intravenous implantation of 5 x 10(5) tumor cells were about 3 times the weight of control livers. All tumor-bearing mice died 10 to 12 days after inoculation. Subcutaneous implantation of L5178Y-ML in the side flank of mice induced metastatic nodules spontaneously in the livers. The tumor cells proliferated more in livers than in the implanted sites, compared with the parental L5178Y cells. The effects of 5-fluorouracil, mitomycin C, cis-platinum and doxorubicin on the liver metastasis of L5178Y-ML were examined at subtoxic doses; 5-fluorouracil was the most effective in both inhibiting the tumor growth in livers and prolonging the survival period of mice. This model provides a useful tool for the experimental therapy of hepatic tumors in mice.     

Novel allogeneic granulocyte-macrophage colony-stimulating factor-secreting tumor vaccine for pancreatic cancer: a phase I trial of safety and immune activation.

PURPOSE: Allogeneic granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor vaccines can cure established tumors in the mouse, but their efficacy against human tumors is uncertain. We have developed a novel GM-CSF-secreting pancreatic tumor vaccine. To determine its safety and ability to induce antitumor immune responses, we conducted a phase I trial in patients with surgically resected adenocarcinoma of the pancreas. PATIENTS AND METHODS: Fourteen patients with stage 1, 2, or 3 pancreatic adenocarcinoma were enrolled. Eight weeks after pancreaticoduodenectomy, three patients received 1 x 10(7) vaccine cells, three patients received 5 x 10(7) vaccine cells, three patients received 10 x 10(7) vaccine cells, and five patients received 50 x 10(7) vaccine cells. Twelve of 14 patients then went on to receive a 6-month course of adjuvant radiation and chemotherapy. One month after completing adjuvant treatment, six patients still in remission received up to three additional monthly vaccinations with the same vaccine dose that they had received originally. RESULTS: No dose-limiting toxicities were encountered. Vaccination induced increased delayed-type hypersensitivity (DTH) responses to autologous tumor cells in three patients who had received >or= 10 x 10(7) vaccine cells. These three patients also seemed to have had an increased disease-free survival time, remaining disease-free at least 25 months after diagnosis. CONCLUSION: Allogeneic GM-CSF-secreting tumor vaccines are safe in patients with pancreatic adenocarcinoma. This vaccine approach seems to induce dose-dependent systemic antitumor immunity as measured by increased postvaccination DTH responses against autologous tumors. Further clinical evaluation of this approach in patients with pancreatic cancer is warranted.     

99mTcOAADT]-(CH2)2-NEt2: a potential small-molecule single-photon emission computed tomography probe for imaging metastatic melanoma

Evaluation of [99mTc]oxotechnetium(V) complexes of the amine-amide-dithiol (AADT) chelates containing tertiary amine substituents as small-molecule probes for the diagnostic imaging of metastatic melanoma has shown that technetium-99m-labeled AADT-(CH2)2-NEt2 (99mTc-1) has the highest tumor uptake and other favorable biological properties. We have, therefore, assessed this agent in a more realistic metastatic melanoma model in which, after i.v. tail injection, a highly invasive melanoma cell line, B16F10, forms pulmonary tumor nodules in normal C57BL6 mice. Small melanotic lesions develop in the lungs and, on histologic examination, appear as small black melanoma colonies, increasing in size and number with time after tumor cell injection. Groups of mice received tumor cell inocula of 2 x 10(5), 4 x 10(5), or 8 x 10(5) B16F10 cells; 14 days later, 2 hours after 99mTc-1 administration, lung uptake of 2.83 +/- 0.21%, 3.63 +/- 1.07%, and 4.92 +/- 1.61% injected dose per gram of tissue (% ID/g), respectively, was observed, compared with normal lung uptake of 2.13 +/- 0.2% ID/g (P < 0.05). Additionally, a higher level of 99mTc-1 accumulation was seen 17 days after tumor cell inoculation as the lung lesions grew. These in vivo studies coupled with additional in vitro and ex vivo assessment show that 99mTc-1 has high and specific uptake in melanoma metastases in lungs and can potentially follow the temporal growth of these tumors.     

腺病毒介导的内皮抑素基因治疗小鼠肺癌

目的 探讨内皮抑素对小鼠肺癌生长和转移的抑制作用及其对肿瘤内部新生血管的影响.方法 在C57BL/6小鼠背部皮下注射2×106 lewis肺癌(LLC)细胞,建立小鼠肺癌种植瘤模型,2周后,瘤内注射2×109 pfu内皮抑素腺病毒载体,观察内皮抑素对肿瘤生长、转移及生存率的影响,检测内皮抑素在肿瘤组织的原位表达和血液循环中的表达水平及持续时间.用免疫组化方法,检测肿瘤内部血管密度,观察治疗对肿瘤血管的影响.用透射电镜观察肿瘤细胞的凋亡情况.结果 免疫组化检测结果显示,内皮抑素蛋白在内皮抑素组的肿瘤组织中呈强阳性表达,而在空载体对照组和阴性对照组中呈阴性表达或很少量表达.用酶联免疫吸附实验(ELISA)法检测内皮抑素组血清内皮抑素浓度,第2周可达1540±560 ng/ml;1个月后,血清内皮抑素浓度降至对照水平.内皮抑素组的肿瘤体积和生存率,与空载体对照和阴性对照组比较,差异有统计学意义(P＜0.05).抗CD31抗体标记的肿瘤内血管密度(MVD)在内皮抑素组、空载体对照组和阴性对照组中,分别为37.5±4.6、65.2±5.8和68.5±4.5个/200倍视野,抗CD105抗体标记的肿瘤内MVD分别为10.5±3.2、39.7±5.6和42.4±4.8个/200倍视野,内皮抑素组与空载体对照组和阴性对照组比较,差异有统计学意义(P＜0.05).内皮抑素组的组织在电镜下呈凋亡相的肿瘤细胞多见.结论 腺病毒介导的内皮抑素基因可在体内高效、较长时间表达内皮抑素蛋白,对小鼠皮下种植瘤有一定的治疗作用,其作用的靶点是抑制新生血管的生成.     

Giant renal cell carcinoma: a case report

Though renal cell carcinoma is a fairly common disease, it is extremely rare to encounter a case providing a resected mass as large as over 2,000 g in weight. We report a case in which a giant 2,200 g tumor was resected after renal arterial embolization and interferon treatment for reduction of its size. A forty-three-year-old woman was first seen at a certain hospital with a chief complaint of fever and right flank pain. Under suspicion of right renal tumor, nephrectomy by extraperitoneal flank incision was attempted. However, the tumor was too large to be resected. After transfer to our department, she was treated by renal arterial embolization with absolute ethanol and steel coil and by the administration of interferon (rIFN-alpha A). As the tumor shrank to 77% of its original size on CT measurements and became mobile, transperitoneal nephrectomy was performed. The resected mass was as large as 12 x 12 x 21 cm. Pathologically, it was a clear cell type tumor showing mucinous degeneration and hyaline degeneration of tumor cells. Interferon used amounted to as high as 864 x 10(6) units, but no particular side effect occurred. No recurrence has been detected so far.