Effect of PSK and its subfractions on peripheral blood lymphocytes mediated cytotoxicity against urinary bladder tumor cells.

Our previous studies have indicated that the protein-bound polysaccharide Kreha (PSK) enhances the cytotoxic activity of peripheral blood lymphocytes (PBL) against the T24 human urinary bladder tumor cell line in patients with bladder tumor. Since PSK consists of a mixture of various kinds of protein-bound polysaccharides, the present study was designed to examine which subfractions of PSK mediated the enhancement of cytotoxicity. When PSK was separated according to size, treatment of PBL with the 50 kilodalton (kd) or less fraction killed T24 cells more efficiently than unfractionated PSK-treated PBL. The higher molecular weight fractions did not enhance killing above the control level. PSK was fractionated on a diethylaminoethyl (DEAE)-cellulose column to obtain a protein rich fraction that absorbed onto the column and a polysaccharide rich fraction that did not. PBL treated with the polysaccharide rich fraction were able to kill T24 cells more effectively than unfractionated PSK-treated PBL. The protein rich fraction had no effect on the killing. Further fractionation of the polysaccharide rich fraction was performed by differential precipitation with ammonium sulfate. PBL treated with the precipitated fraction at 70-80% saturation (PSK Fraction D) enhanced cytotoxicity equal to that of the polysaccharide rich fraction. Treatment of PBL with the other fractions did not augment the cytotoxicity. These enhancement by PSK fractions were observed in healthy donors and also in patients with bladder tumor. An increase of the proliferative response of PBL to PSK Fraction D as well as unfractionated PSK was observed. Treatment of PBL with PSK Fraction D had no effect on the proportion of PBL binding to T24 cells, thus suggesting a post-binding effect. The structure of PSK Fraction D as inferred from the results of methylation analysis was mainly an alpha-glucan. These results demonstrate that PSK mediated enhancement of cytotoxicity and proliferation of PBL may be largely due to an alpha-glucan of less than 50 kd.     

Adriamycin-mediated potentiation of cytotoxicity against freshly isolated bladder cancer cells by autologous non-activated peripheral blood lymphocytes and tumor infiltrating lymphocytes

PURPOSE: Previous studies indicated that cancer patients lack functional anti-tumor cytotoxic lymphocytes. However, anti-tumor cytotoxic lymphocytes may coexist with immunoresistant tumor cells. We reasoned that anti-tumor cytotoxic activity of lymphocytes may be revealed if the tumor cells are sensitized to killing. It has been reported that adriamycin (ADR) exhibits various immunomodulating activities. In the present study, we investigate the effect of ADR on the susceptibility of freshly isolated bladder cancer cells to lysis by autologous non-activated peripheral blood lymphocytes (PBL) and tumor infiltrating lymphocytes (TIL). MATERIALS AND METHODS: Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. RESULTS: Treatment of ADR-resistant fresh bladder cancer cells with ADR at 0.1 microg./ml. or more for 3 hours or more enhanced their susceptibility to lysis by autologous PBL. This ADR-induced enhancement of susceptibility of fresh bladder cancer cells to lysis by PBL was also observed when lymphokine activated killer cells, purified natural killer cells and T lymphocytes were used as effector cells. Furthermore, while cytotoxicity of freshly derived TIL against autologous bladder cancer cells was minimal, significant cytotoxicity was observed with ADR-treated bladder cancer cells. The ADR analogs, epirubicin and pirarubicin, also enhanced the susceptibility of bladder cancer cells to lysis by autologous PBL. Treatment of bladder cancer cells with ADR had no effect on the expression of MHC class I on the cancer cells or the frequency of bladder cancer target cell conjugates to autologous PBL. Treatment of bladder cancer cells with ADR augmented their sensitivity to anti-Fas monoclonal antibody and tumor necrosis factor-a. Pretreatment of effector cells with ADR had no effect on their cytotoxic function. CONCLUSIONS: These findings demonstrate that PBL and TIL in patients with bladder cancer exhibit anti-tumor cytotoxic function, but their function is not manifested due to development or acquisition of tumor cell resistance to killing. However, the resistance of bladder cancer cells to killing by cytotoxic lymphocytes is overcome if cancer cells are sensitized by subtoxic concentrations of ADR. These findings suggest that treatment of bladder cancer patients with low doses of ADR may sensitize the cancer cells to killing by autologous circulating and tumor infiltrating lymphocytes and may be a novel immunotherapeutic modality for the treatment of drug-resistant and/or immune-resistant bladder cancer.     

Augmentation of cytotoxicity of tumor infiltrating lymphocytes by interleukin-2 in gastric cancer patients

Lymphocyte infiltration into tumor has been regarded as an expression of host reaction against tumor, but the natural cytotoxicity of tumor infiltrating lymphocytes (TLL) is often very low. In order to augment this low cytotoxicity, TIL of gastric cancer patients were cultured with interleukin-2 (IL-2) in vitro. On the other hand, immunopotentiators (OK432, PSK) were injected into gastric cancer intralesionally under endoscopy. By the in-vitro culture with IL-2, the cytotoxicity of TIL was augmented against both targets of K562 and MNN28 (gastric carcinoma cell line). In particular, the augmentation of cytotoxicity against MKN28 was more obvious in TLL than PBL (peripheral blood lymphocytes). In the ascitic lymphocytes, the in-vitro culture with IL-2 induced autologous tumor cell killing. Intralesional injection of OK432 or PSK augmented the natural cytotoxicity of TIL, and the ratio of OKT8 and Leu7 cells increased in the TIL of OK432-injected group.     

Role of natural killer cells in bladder tumor

The role of natural killer (NK) cells in bladder tumors was assessed from the aspect of local and systemic immune responses. The NK cell activity was measured in a 4-hour 51Cr-release assay. The NK activity in patients with bladder tumor was lower, though not significantly, than that in normal individuals. In patients with bladder tumor, the NK activity was significantly lower in invasive tumors and lymph node metastases. Moreover, the NK activity was lower in those who died (n = 4) than it was in survivors (n = 21). In an in vitro experiment, OK432 significantly augmented the NK activity in peripheral blood lymphocytes (PBL), however, this augmentation was not always OK432 dose-dependent. The augmented NK activity induced by OK432 occurred even in patients with invasive tumors. On the other hand, the spontaneous NK activity in tissue-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) was significantly lower than that in PBL. In these three groups, the NK activity was significantly increased by OK432, this rate of increase was highest in TIL, followed by LNL and PBL. Further studies are required to elucidate the role of NK cells in bladder tumor, from the aspect of local and systemic immune responses.     

Cellular immune response of bladder tumor patients: effects of aging on cytotoxic activity against T24

The cytotoxic activity of peripheral blood lymphocytes of 39 control subjects, 42 bladder tumor patients and 15 patients with urological cancer other than bladder tumor against human bladder tumor cultured cell T24 was tested by a 51Cr-release assay. In the healthy donor group, high cytotoxic activity was found in younger people and negative correlation was significantly found between the cytotoxicity and age. On the other hand, high cytotoxic activity was frequently found in older patients with bladder tumors and no correlation between the cytotoxicity and age was found in this group. The mean % cytotoxicity for patients over 50 years old in the bladder tumor group was significantly higher than that for the healthy donor group and other carcinoma group. A large proportion of the cytotoxicity of the control subjects and the bladder tumor patients to T24 was due to lymphocytes that did not form spontaneous rosettes with sheep erythrocytes.     

Cellular cytotoxicity in transitional cell carcinoma of the human urinary bladder — A summary

Summary The cytotoxicity in vitro of peripheral blood lymphocytes from patients with carcinoma of the urinary bladder (TCC-bladder) against allogeneic target cells from established cell lines was studied by the ⁵¹Cr-release assay. Lymphocytes from both untreated and treated TCC-bladder patients have a significantly elevated mean cytotoxicity to TCC-bladder target cells. Tumour cell destruction by lymphocytes from TCC-bladder patients shows a clear disease related specificity. In TCC-bladder patients a superimposed cytotoxicity exists, probably reflecting reactions against one or several tumour-associated antigens. In treated patients this cytotoxicity may be masked by higher incidence of cross reaction.     

Studies on the cellular immune response in patients with urinary bladder carcinoma. XI: Evaluation of specific ADCC activity

We previously reported that the activity of antibody dependent cell-mediated cytotoxicity (ADCC) of lymphocytes from the patients with urinary bladder carcinoma was lower than that of normal subjects. We performed the specific ADCC assay using SRBC as the target cells, coated with tumor extract from the urinary bladder carcinoma. At the same time, the antiserum was collected from the immunized rabbit by the same tumor extract. The addition of the antiserum from the immunized rabbit gave the highest value for the patient sub-group that produced a precipitin band (Ouchterlony gel diffusion assay). Therefore it is suggested that the reaction of lymphocytes to tumor associated antigens is maintained to a considerable extent, although ADCC activity of the patient group was decreased. However, the antibody producing phenomenon toward the tumor associated antigen might be restrained.     

Microwave coagulation therapy for urinary bladder tumors

A new device has been developed for microwave coagulation of urinary bladder tumors. Twenty-one patients with urinary bladder tumors were treated by irradiation with microwave energy of 2,450 MHz. Results were obtained as follows: (1) microwave coagulation was performed in 21 patients with transitional cell carcinoma of the urinary bladder. Excluding 4 patients who subsequently received radical cystectomy, 17 patients showed a complete response, although 2 patients subsequently developed recurrences in different parts of the bladder within the following several months. Histological examination of the excised specimen revealed complete eradication of the tumor in 2 patients. In the remaining 2 patients with high-stage tumor (T4), viable tumor cells were noted in the urethra or vaginal wall. (2) Although neither technical difficulties nor severe complications were encountered, transient urinary frequency and calcification of the bladder wall were noted. The results of this study indicate that microwave coagulation may be used in the treatment of both superficial and invasive tumors.     

超抗原SEA联合树突状细胞诱导特异性抗膀胱肿瘤研究

目的 观察超抗原金黄色葡萄球菌肠毒素A(SEA)联合树突状细胞(Dc)诱导CTL对膀胱肿瘤高效特异性的免疫杀伤作用和对肿瘤局部免疫提呈功能的改善情况.方法 用GM-CSF和IL-4联合刺激诱导外周血单个核细胞分化为DC.将Dc与同源淋巴细胞(DC-L组)、超抗原SEA淋巴细胞(DC-SEA-L组)共培养,用FCS分析DC供刺激分子表型,酶联免疫吸附测定法检测细胞因子IL-2,MTT法测定激活的CTL对膀胱癌E-J细胞的体外杀伤效应.结果 在体外,DCSEA-L对膀胱癌细胞具有相对特异的杀伤作用,SEA-L和Dc-L则无明显特异性.结论 SEA和Dc联合应用可诱导产生高效并具有相对特异性的抗膀胱癌效应,并改善膀胱癌组织局部的DC抗原提呈功能.     

Prognostic relevance of preoperative circulating CD8-positive lymphocytes in the urinary bladder recurrence of urothelial carcinoma

ObjectiveTumor-infiltrate lymphocytes (TIL) have been associated with favorable outcomes in various tumors including urothelial carcinoma (UC). There is little literature about peripheral blood lymphocytes (PBL). Our objective is to investigate the clinical significance and relevance of PBL on the outcomes of UC patients.Materials and methodsNinety UC treated patients at Chia-Yi Christian hospital were enrolled. Preoperative PBLs were collected and analyzed for the percentage of each subpopulation of lymphocyte using flow cytometry. The prognostic values were calculated by using Kaplan-Meier curve and Cox progression model for univariate and multivariate analyses, respectively. Furthermore, available tumor specimens from 27 patients were further analyzed for number of CD8⁺ tumor infiltrating lymphocytes (TIL) using immunohistochemistry. The correlation between percentage of CD8+ PBL and number of CD8+ TIL was analyzed using a linear regression model.ResultsThe log-rank test showed that tumor location (urinary bladder vs. upper urinary tract), enrolled status (primary or recurrent), and CD8⁺ PBL were significant prognostic indicators of recurrence (P values, 0.043, 0.039, and 0.018, respectively). Cox analyses showed that CD8⁺ PBL was the sole independent prognostic indicator for recurrence-free survival (P = 0.048). The results using a linear regression analysis showed there was a reverse correlation between CD8⁺ TIL and PBL (r² = 0.635, P < 0.0001).ConclusionsIn our investigation, preoperative CD8⁺ PBL was an independent predictor for bladder recurrence. The percentages of CD8⁺ PBL were reversely correlated with the number of TIL. Such findings may benefit in the decision for subsequent intravesical therapy after surgery.     

Comparative sensitivity of urinary CYFRA 21-1, urinary bladder cancer antigen, tissue polypeptide antigen, tissue polypeptide antigen and NMP22 to detect bladder cancer

PURPOSE: We compare the individual and combined sensitivity of urinary CYFRA 21-1, urinary bladder cancer antigen, tissue polypeptide antigen and NMP22 to detect bladder cancer, evaluate the false-positive rates for different pathological conditions, and assess differential sensitivity regarding histological and clinical characteristics of disease. MATERIALS AND METHODS: A total of 267 subjects entered the study. Sensitivities of the tests were evaluated in 111 patients with active bladder cancer and 76 with no evidence of disease. False-positive rates were evaluated in 80 symptomatic and asymptomatic controls, including patients with benign urological conditions and nonbladder malignancies, and healthy subjects. CYFRA 21-1 was determined by electrochemoluminescent immunoassay in the Elecsys 2010, urinary bladder cancer antigen was quantified by enzyme linked immunosorbent assay (IDL Biotech), tissue polypeptide antigen was measured by the Prolifigen TPA-IRMA and NMP22 was assayed by enzyme linked immunosorbent assay (Matritech). Cutoffs were obtained by the 95% percentile in patients with no evidence of disease, which gave a 95% specificity for all biomarkers. Differences in sensitivity of urinary biomarkers regarding stage, grade, tumor size, pattern of growth, focality and recurrence were evaluated. RESULTS: At a specificity of 95% cutoffs were 5.4 ng./ml. for CYFRA 21-1, 15.5 microg./l. for urinary bladder cancer antigen, 760.8 U./l. for tissue polypeptide antigen and 14.6 U./ml. for NMP22. Using these cutoffs sensitivities were 75.7% for NMP22, 83.8% for CYFRA 21-1, 73.9% for urinary bladder cancer antigen quantitative and 80.2% for tissue polypeptide antigen. The additional determination of cytokeratins increased the sensitivity of NMP22. Cytokeratins did not appear to be specific for bladder cancer, and false-positives rates were between 20% for urinary bladder cancer antigen and 36% for tissue polypeptide antigen for benign urological conditions, and between 40% and 52%, respectively, for nonbladder malignancies. NMP22 showed lower false-positives rates, mainly for benign diseases. Urinary tumor markers appeared to be associated with some of the most relevant histological and clinical parameters of bladder cancer. CONCLUSIONS: Our preliminary evaluation showed the tests to be potential noninvasive adjuncts to help determine the need for cystoscopy. The combination of 2 tumor markers, NMP22 and 1 cytokeratin (CYFRA 21-1 or urinary bladder cancer antigen), seemed to be the most effective. Further comparative studies are needed to assess the promising diagnostic role of these markers.     

Antiproliferative effects of interferons against human bladder carcinoma cell lines in vitro

In order to evaluate the antiproliferative effects of recombinant human interferon-gamma 2c (rHu IFN-gamma 2c), recombinant human interferon-gamma (rHu IFN-gamma), natural interferon-beta (IFN-beta), and their combination with cytotoxic agents, 17 different human bladder carcinoma cell lines were tested in vitro. The antiproliferative effects were compared in evaluating the tumor cell inhibiting potency of the different interferon (IFN) classes. It could be demonstrated that interferons have inhibiting effects on the bladder cancer cell multiplication rate, yet there are significant differences in the susceptibility of different IFN preparations on different cell lines. The cell lines BT1, RT4, EJ, 468P, 253J, SD, TCCSUP, and SW1738 can be defined as sensitive, T24, 647V, VM-CUB2, and J82 as semisensitive, HT1376, 5637, VM-CUB1, 639V and SW1710 as resistant upon treatment with IFN. The combination of rHu IFN-alpha 2c, IFN-beta, and rHu IFN-gamma seems to be more effective than treatment with rHu IFN-alpha 2c alone. The cytotoxic effect of doxorubicin on bladder cancer cells can be intensified by combining it with IFN.     

T-cell bearing IgG-Fc receptor in patients with bladder cancer

The T-cell bearing Fc receptor (IgG-FcR+ T cell) has been considered as a suppressor or a part of the killer cell, as determined by its function. The population of IgG-FcR+ T cells was determined by Moretta 's method in patients with urinary bladder cancer, urological benign diseases and in normal subjects. The population of IgG-FcR+ T cells in the peripheral lymphocytes of 16 patients with urinary bladder cancer was 20.5 +/- 10.1%, that of 7 patients with urological benign diseases was 9.5 +/- 3.2%, and that of 8 normal subjects was 9.0 +/- 2.1. The population of IgG-FcR+ T cells in the peripheral lymphocytes patients with high stage bladder cancer was significantly higher than that of patients with low stage cancer. In low stage bladder cancer cases, the population of IgG-FcR+ T cells was decreased to the normal range at three weeks after removal of the tumor. But in high stage bladder cancer cases, it was not changed at 3 weeks.     

Influence of preoperative bladder capacity and compliance on the outcome of artificial sphincter implantation in patients with neurogenic sphincter incompetence.

We performed a retrospective study of 23 patients with neurogenic sphincteric incompetence who had undergone implantation of an artificial urinary sphincter to determine if bladder capacity and compliance as determined by cystometrography could predict the need for enterocystoplasty. Study criteria were neurogenic sphincteric incompetence, no previous operations on the lower urinary tract, and performance of preoperative and postoperative cystometrography. Patients were 5 to 17 years old at implantation. Incontinence was caused by myelomeningocele (18 patients), sacral agenesis (3) and spinal cord tumor (2). The 8 patients for whom preoperative cystometric bladder capacity was greater than 60% of the expected capacity for age have been followed for a mean of 60 months. All 8 patients are continent and none required enterocystoplasty. Preoperative bladder compliance exceeded 2 ml./cm. water in all patients (group 1). Of the 15 patients for whom preoperative cystometric bladder capacity was less than 60% of the expected value (group 2, small bladders) 8 followed an average of 72 months had a compliance greater than 2 ml./cm. water and have done well without bladder augmentation. In contrast, 7 patients in this group (46%) required enterocystoplasty: 6 for persistent or recurrent incontinence and 1 for upper tract changes. The average interval between artificial sphincter placement and enterocystoplasty was 14 months. Patients with a small bladder that required augmentation had a preoperative bladder compliance of less than 2 ml./cm. water. We conclude that small bladder capacity, as determined by cystometrography in patients with neurogenic sphincteric incompetence but a bladder compliance of less than 2 ml./cm. water predicts the future need for bladder augmentation. In all other patients, with good medical treatment and followup, the possible adverse effects of a small capacity bladder can be prevented or corrected. With this strategy we have been able to avoid enterocystoplasty with its attending potential complications in 70% of our patients with neurogenic incontinence and favorable urodynamics regardless of preoperative cystometric bladder capacity.     

Anti-tumor effect of LAK (lymphokine activated killer) cells against human bladder tumors transplanted to nude mouse

The effect of lymphokine-activated killer (LAK) cells on bladder tumor was examined in vivo and in vitro. In the in vitro experiment, 51Cr-cytotoxic assay was performed for which PBL were used as effector cells. A LAK activity of 26.6% was observed in PBL cultured with IL2 for 4 days, whereas OK-432-induced LAK activity was 22%. Furthermore, in the in vivo experiment, the anti-tumor effect of LAK cells was evaluated in human bladder tumor transplanted into nude mouse. IL2, OK432-induced LAK cells were injected intratumorally. In the LAK-treated group, inhibition of tumor growth was seen. Histologically, it was demonstrated that infiltrating lymphocytes were scattered around tumor cells. The augmentation of NK activity in spleen cells was observed in the LAK-treated group. Although further studies are required to establish its full significance, these findings suggest that immunotherapy against bladder tumors is hopeful.     

Ex vivo host response to gastrointestinal cancer cells presented by autologous dendritic cells

BACKGROUND: Dendritic cells (DCs) capture apoptotic tumors and cross-present their antigens in the MHC class I and class II pathways for recognition by CD4+ and CD8+ T lymphocytes. Here we have tested the ability of fresh surgically resected colon and gastric cancer tumors to specifically activate host T lymphocytes when presented by autologous DCs. METHODS: DCs derived from adherent blood mononuclear cells of five patients, after a 7-day culture with GM-CSF and IL-4, were exposed to apoptotic autologous tumor (AAT) or apoptotic autologous peritumor normal (AAN) cells and cultured 24 h with monocyte-conditioned medium to achieve full DC maturation. Tumor-specific response was evaluated as single-cell cytokine release in an enzyme-linked immunospot (ELISPOT) and as cytotoxicity in a cold target inhibition (51)Cr-release assay. RESULTS: AAT-DCs induced specific IFN-gamma by T lymphocytes of two patients (rectal and gastric cancer), whereas in another two patients (rectal and gastric cancer) this response was depressed with a similar tumor-specific pattern and in one patient (rectal cancer) there was no response. Activation of IFN-gamma release was accompanied by tumor cytotoxicity and both responses were enhanced by IL-12, indicating the functional integrity of patients' lymphocytes. CONCLUSION: These data show that T-cell memory against rectal/gastric carcinoma antigens can be triggered by tumor-loaded autologous DCs. However, escape mechanisms may exist among tumors of the same histological origin that can inhibit this host response. A DC-based antitumor immunological monitoring assay with autologous tumor biopsies may allow patients to be screened to determine those who are suitable candidates for immune-based immunotherapy.     

Surgical treatment of urinary bladder cancer

Ultrasonic transabdominal and transrectal investigations, computed tomography, endoscopic photodynamic studies, polyfocal biopsy of the urinary bladder were used in examination of 1238 patients which were diagnosed to have urinary bladder cancer. 894 patients underwent transurethral resection of the bladder. Morphologically, cancer of the urinary bladder has an inductory effect on intact parts of the bladder mucosa. This means that even most radical resection does not eliminate grounds for a new tumor growth. Radical cystectomy was performed in diffuse papillomatosis, multiple stage T2 tumors of high-grade malignancy, tumors at stage T3, T4, Nx, MO, in rapid recurrent tumors after conservative or operative treatment.     

Endosurgery in treatment of urinary bladder cancer in elderly patients

Treatment of 162 patients with micro- and macrohematuria was analyzed. Urinary bladder cancer was diagnosed in 156 of them (men--127, women--29). All patients received endoscopic treatment (transurethral resection). An average age of patients was 74.4±7.9 years. 142 (91.1%) of patients were older then 60 years. The transitional cell carcinoma was diagnosed in 118 patients. The urinary bladder cancer recurrence was diagnosed in 13 (9.2%) patients steged T1 and in 24 (16.9%) staged T2. Only 2 patients with T3 stage of the disease were considered to be unsuitable for endoscopic transurethral resection and received an open argon tumor vaporization.     

The essential role of interferon-gamma during interleukin-12 therapy for murine transitional cell carcinoma of the bladder

PURPOSE: Recombinant interleukin (IL)-12 and adenoviral IL-12 gene therapy have been shown to be potent therapeutic interventions for murine transitional cell carcinoma (TCC) of the bladder in vivo. We investigated the mechanisms through which IL-12 induces antibladder cancer immunity. MATERIALS AND METHODS: The ability of IL-12 to enhance interferon-gamma (IFN-gamma) expression, a major T-helper type 1 cytokine, was analyzed in murine serum, urine and splenocyte cultures. MB49, a murine TCC line, was treated with IFN-gamma and evaluated for its proliferation, surface molecule expression and sensitivity to splenocyte mediated cytotoxicity. Neutralizing antiIFN-gamma antibody was applied to test the role of IFN-gamma in the IL-12 therapy of MB49 tumor. RESULTS: IL-12 was observed to significantly increase IFN-gamma concentrations in serum and urine as well as in splenocyte cultures. While IL-12 had no direct activity against TCC in vitro, IFN-gamma showed potent dose dependent antiproliferative and pro-apoptotic activity, which was further enhanced by supplementation of tumor necrosis factor-alpha. In addition, IFN-gamma substantially up-regulated the expression of surface immune molecules on TCC cells, including MHC-I, MHC-II, ICAM-I, B7.1, B7.2 and Fas. Maximum splenocyte mediated cytotoxicity against TCC was enhanced by pretreatment of target bladder cancer cells with IFN-gamma plus tumor necrosis factor-alpha. Furthermore, IL-2 in combination with IL-12 further enhanced splenocyte mediated cytotoxicity. The in vivo antibladder cancer activity of IL-12 was abolished by concurrent treatment with antibodies to IFN-gamma. CONCLUSIONS: This study strongly suggests that IFN-gamma has an essential role in IL-12 induced antibladder tumor immunity. Activation of host effector immune cells by IL-12 is also required for induction of optimal tumor destruction in IL-12 therapy.     

膀胱小细胞癌的诊断与治疗(附6例报告)

目的：探讨膀胱小细胞癌的临床特点及诊治疗效。方法：对6例膀胱小细胞癌患者的临床资料进行回顾性分析。结果：6例患者，男4例，女2例，平均年龄63岁（51～71岁）。肿瘤分期T2N0M02例，T3N0M0 1例，T4N0M0 2例，T4N2M1 1例。肿瘤电切加化疗1例，根治性膀胱全切2例，姑息膀胱切除加化疗2例，肿瘤电切、髂动脉栓塞及全身化疗1例。4例死于肿瘤复发或转移，平均存活时间7个月（2～15个月），2例分别随访18个月及21个月仍存活。结论：膀胱小细胞癌预后差，治疗应以手术结合放化疗。