恶笥血液病患者游离Fas的检测及意义

目的 了解游离Ｆａｓ（ｓＦａｓ）在恶性血液病中的水平及临床意义。方法 用酶联免疫吸附法测定６０例恶笥血液病患者血ｓＦａｓ水平。结果 恶性血液病患者血清ｓＦａｓ水平高于正常人，治疗后ｓＦａｓ水平下降，下降的程度与疗效有关，但治疗前水平高低与疗效无关。结论ｓＦａｓ对恶性血液病的诊断及产判定有一定意义，并可能对其发病机制产生影响。     

胃癌患者治疗前后血清可溶性肿瘤坏死因子受体Ⅰ的变化及其意义

目的探讨胃癌患者治疗前后血清可溶性坏死因于受体（ｓＴＮＦ－Ⅰ）水平的临床意义。方法应用酶联免疫吸附测定（ＥＬＩＳＡ）的方法测定了３４例胃癌患者ｓＴＮＦＲ－Ⅰ水平。结果胃癌患者血清ｓＴＮＦＲ－Ⅰ水平明显高于正常人（Ｐ＜０．０１），且与临床分期有关，病情越晚，ｓＴＮＦＲ－Ⅰ水平越高，ｓＴＮＦＲ－Ⅰ水平超过３．００ｎｇ／ｍｌ者预后不良；治疗有效者ｓＴＮＦＲ－Ⅰ均显著下降（Ｐ＜０．０１），２４例治疗后４～８个月再次采血检验，８例无瘤生存者ｓＴＮＦＲ－Ⅰ水平降至正常，其余１６例肿瘤未控制或复发转移者血清ｓＴＮＦＲ－Ⅰ水平升高。结论血清ｓＴＮＦＲ－Ⅰ测定对胃癌疗效观察、病情监测及预后判断有重要意义。     

消化系癌症手术前后的血清可溶性肿瘤坏死因子受体Ⅰ的变化和意义

用双抗体夹心ＥＬＩＳＡ方法测定了６０例消化系癌症患者血清可溶性肿瘤坏死子受体Ⅰ的水平，。结果表明：消化系癌症患者血清ｓＴＮＦＲ－Ⅰ水平均明显高于正常人，且血清ｓＴＮＦＲ－Ⅰ水平与临床分期有关；手术切除肿瘤后，血清ｓＴＮＦＲ－Ⅰ水平明显下降，术后２－８月，１６例无癌患者血清ｓＴＮＦＲ－Ⅰ水平继续下降；另３２例局部未控制伴复发转移患者血清ｓＴＮＦＲ－Ⅰ水平上升。提示：血清ｓＴＮＦＲ－Ｉ测定对消化系癌症     

肝癌患者HBxAg与Fas/FasL表达的研究

目的：探讨肝癌患者肝组织中 ＨＢｘＡｇ与 Ｆａｓ／ＦａｓＬ的表达状况及血清中 ＨＢＶ Ｘ基因与 Ｆａｓ／ＦａｓＬ的水平。方法：用ＳＰ法对３４例肝癌组织ＨＢｘＡｇ、Ｆａｓ与ＦａｓＬ表达状况进行分析,用ＥＬＩＳＡ法对３０例肝癌、３２例肝硬化及２０例正常人血清ｓＦａｓ与 ｓＦａｓＬ含量进行分析,并用ＰＣＲ法对肝癌与肝硬化患者血清ＨＢＶ Ｘ基因表达进行检测。结果：ＨＢｘＡｇ、Ｆａｓ与ＦａｓＬ在肝癌表达的阳性率分别为９７．０６％、８５．２９％及１００％。阳性信号均主要位于胞浆,且三者可在同一癌组织的相同区域出现阳性染色,Ｒｅｄｉｔ分析示三者的阳性程度无统计学差异（Ｐ＞０．０５）。血清ｓＦａｓ在肝癌、肝硬化与正常人中的含量分别为（７２２．９７±３２１．１３）μｇ／Ｌ、（８０１．９０±４１９．９４）μｇ／Ｌ和（２２４．０７±１４８．２３）μｇ／Ｌ,其中肝癌与肝硬化组显著高于正常人（Ｐ＜ ０． ０１）;血清 ｓＦａｓＬ在肝癌、肝硬化与正常人中的含量分别为（１５２． ２７±７． ９９）μｇ／Ｌ、（ １６２． ９７±１２． ４０）μｇ／Ｌ和（１５４．９９± ６．９６）μｇ／Ｌ,其中肝硬化组含量高于肝癌与正常人（ Ｐ＜０．０１）。血清ＨＢＶ　Ｘ基     

恶性血液病患者血清免疫抑制酸性蛋白的测定及临床意义

目的：分析恶性血液病患者血甭免疫抑制酸性蛋白（ＩＡＰ）的变化及临床意义。方法：应用单向免疫琼脂扩散法检测５０例恶性血液病和１５例非恶性血液病２者血清ＩＡＰ水平。结果：垩是血液病患者血清ＩＡＰ水平明显增高,与健康对照组相比有差异（Ｐ〈０．０１＿。非恶性血液病患者与健康对照组无统计学差异。动态观察急慢性白血病不同病期ＩＡＰ变化表明,初始与未缓解病人ＩＡＰ增高明显,缓解期水平下降,ＩＡＰ持续增高病人往往     

恶性血液病患者的非甲状腺疾病综合征

为了探讨恶性血液病非甲状腺疾病综合征的临床意义，采用放射免疫分析法测定１１８例恶性血液病患者和４０例正常人的甲状腺功能，并对恶性血液病的相关因素与非甲状腺疾病综合征进行单因素和多因素分析。结果显示，在１１８例恶性血液病中有８６例存在非甲状腺疾病综合征，占７２．９％。统计分析表明，血清甲状腺素水平在病情复发和恶化时降低。贫血、慢性肝肾功能不良、化学治疗和细胞因子治疗与非甲状腺疾病综合征的发生密切相关。提示动态检测血清甲状腺素水平将有助于评估恶性血液病的发展和转归。     

恶性血液病患者血一氧化氮、内皮素及超氧化物歧化酶的变化

目的：探讨恶性血液病患者血一氧化氮（NO）、内皮素（ET）及超氧化物歧化酶（SOD）的变化。方法：采用RIA法、硝酸还原法对26例恶性血液病患者和20例正常对照进行NO、ET、SOD测定。结果：26例初治恶性血液病患者NO、ET水平明显高于正常对照（P＜0．05），SDO低于正常水平（P＜0．05）。26例恶性血液病患者治疗后，10例完全缓解，8例部分缓解，8例未缓解，其中完全缓解组NO、ET、SOD与正常对照组差异无显著性（P＞0．05）；而部分缓解与未缓解组三者水平仍与正常对照差异有显著性（P＜0．05）。结论：NO、ET、SOD可能与恶性血液病发病有关，对三者动态监测有利于判断疗效。     

CYFRA21—1,CEA及Gastrin组合动态检测在肺癌临床评估中的价值

目的 探讨ＣＹＦＲＡ２１－１，ＣＥＡ和Ｇａｓｔｒｉｎ组合动态检测在肺癌诊断，分型分期，疗效观察和预后判断的临床价值，方法 选自本院３１例肺癌，２８例肺癌良性疾病住院患者和２８例本院健康志愿者，应用放射免疫分析法（ＩＲＭＡ）检测血清ＣＹＦＰＡ２１－１，ＣＥＡ水平，应用放射免疫～ＰＥＧ法检测血清ＣＥＡ和Ｇａｓｔ，水平，肺癌患者在化疗和／或放疗１～２个疗程前后各检测一次，以本院同位素实验室提供的临床值为     

64例肺癌血清胃泌素和锰超氧化物歧化酶检测结果分析

同时检测了６４例原发性肺癌，３２例肺良性疾病，３２例健康成人血清胃泌素（Ｇａｓｔｒｉｎ）含量和血清锰超氧化物歧化酶（Ｍｎ－ＳＯＮ）活力。Ｇａｓｔｒｉｎ的阳性率为７３．４４％，诊断正确率为７３．４４％，ＭＮ－ＳＯＤ的阳性率为８１．２５，诊断正确率为８６．２５％。Ｇａｓｔｒｉｎ对小细胞肺癌，Ｍｎ－ＳＯＤ对各型肺癌均有较高的阳性检出率。二者的血清水平及阳性率与肺癌病期相关，晚期患者高于早期病人（Ｐ＜０．０１），１５例肺癌患者Ｇａｓｔｒｉｎ和Ｍｎ－ＳＯＤ水平在手术切除肿块后明显下降（Ｐ＜０．０１）。结果提示Ｇａｓｔｒｉｎ和Ｍｎ－ＳＯＤ在肺癌的诊断、判断病期和病理类型，手术疗效监测方面有重要的临床实用价值。     

G－CSF不同时机应用对恶性血液病化疗副反应的作用

Ｇ－ＣＳＦ不同时机应用对恶性血液病化疗副反应的作用王开泰，周柱，邬伟秀Ｇ－ＣＳＦ对化疗后粒细胞减少的治疗作用业已肯定，选择何时应用对比疗后血液学恢复更为有利未见专门报道，我们对３１例恶性血液病化疗后应用Ｇ－ＣＳＦ的疗效作了观察，现将结果报告如下。材料...     

Serum soluble Fas antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients

We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25 (mean+/-SD) in the high grade malignant group (n=9) that demonstrated diffuse large cell (DL) components and 2.53+/-0.46 (mean+/-SD) in the low grade malignant group (n=12) that did not demonstrate DL components. Among 12 patients who underwent HP eradication therapy, the blood sFas antigen level lowered after eradication in 7 out of 10 patients who showed complete response or partial response, while sFas antigen level did not decrease in the 2 patients who showed no change or progression of the disease. In the high grade malignant group, 2 of 3 patients who underwent HP eradication treatment showed a mild decrease in the sFas antigen level as well as an improvement on endoscopic and histological examinations, but these sFas level were not normalized. The blood sFas antigen level tended to coincide with pathological activity and malignancy, suggesting that the sFas antigen level may be a prognostic indicator and useful index for the response of HP eradication treatment in gastric MALT lymphoma.     

Changes of cytokines in cirrhosis patients with advanced hepatocellular carcinoma treated by intra-arterial chemotherapy

INTRODUCTION: Tumor necrosis factor (TNF) induces cancer cell-specific apoptosis by binding to a TNF-related apoptosis-inducing ligand. Binding of the Fas ligand on cytotoxic T lymphocytes to the Fas receptor on hepatocytes is also known to induce apoptosis. The aim of this study was to clarify changes of cytokines in patients with liver cirrhosis (LC) and advanced hepatocellular carcinoma (aHCC) receiving intra-arterial combination chemotherapy. METHODS: Twenty-one adult Japanese LC patients with aHCC received intra-arterial combination chemotherapy. The serum levels of TNF-alpha, soluble TNF receptor-I (sTNFr-I), soluble Fas ligand (sFas L), and soluble Fas (sFas) were evaluated. RESULTS: Thirteen of the 21 patients (group R) showed an objective response, while the other eight patients (group N) showed no response. The serum level of TNF-alpha was lower after chemotherapy than before chemotherapy in group N, but there was no difference of serum sTNFr-I levels between before and after chemotherapy and there were also no differences between the two groups. The serum sFas levels were higher after chemotherapy than before chemotherapy in group N, while there was no difference among groups. CONCLUSIONS: These results indicate that a high serum TNF-alpha level and a low serum sFas level might be important for successful combined arterial chemotherapy in LC patients with aHCC.     

大肠癌患者血清癌胚抗原、可溶性 Fas、白细胞 介素 -6水平测定及其临床意义

目的探讨大肠癌患者血清癌胚抗原（carcinoembryonic antigen,CEA）、可溶性Fas(solubleFas,sFas)、白细胞介素-6(interleukin-6,IL-6)水平的临床意义。方法采用双抗体夹心ELISA方法检测162例大肠癌患者术前、术后血清中sFas、IL-6表达水平,同时测定了相关免疫指标及血清CEA水平。结果大肠癌患者血清sFas水平为（20.97±8.19）ng/L,阳性率为53.70％;IL-6水平为（36.87±11.20）ng/L,阳性率67.91％;CEA水平为（32.52±10.81）μg/L,阳性率41.98％,三者均非常显著高于良性病变及对照组。大肠癌患者术前血清CEA、sFas、IL-6水平均显著高于术后（P<0.01),以sFas、IL6水平升高更明显。血清sFas水平与癌转移相关,而血清IL6与肿瘤大小及癌转移明显相关（P<0.01)。仅血清sFas水平与淋巴细胞转化率、LAK及NK活性呈显著负相关。CEA、IL6、sFas三者之间均呈显著正相关。结论大肠癌患者血清sFas、IL6检测阳性率高于CEA。sFas、IL6反映了肿瘤的增殖和转移情况,这可能与sFas抑制了免疫功能和肿瘤细胞的凋亡有关;IL6有促进肠癌细胞的增殖作用。三者联合检测对大肠癌患者的临床诊断、判断预后及监测疗效有重要作用。     

大肠癌患者血清可溶性FAS(sFAS)水平表达

目的　探讨可溶性Fas(sFas)在大肠癌及良性病变患者中的表达及其临床意义。方法　用双抗体夹心ELISA法检测 46例大肠癌、15例息肉或腺瘤、10例溃疡性结肠炎患者血清中可溶性Fas(sFas)表达水平 ,并比较 15例大肠癌患者术前、术后sFas的变化。结果　大肠癌患者血清sFas水平 ( 16 2 8± 3 5 3ng ml)明显高于良性病变及正常人 (P <0 0 1) ,随着临床分期的上升 ,sFas水平上升明显 ;sFas与年龄、性别、肿瘤大小及组织学分级无明显相关 (P >0 0 5 )。sFas与CEA呈正相关 (P <0 0 5 )。大肠癌患者术后血清Fas水平较术前明显下降 (P <0 0 5 )。结论　sFas可以作为大肠癌一种新的肿瘤检测指标 ,与大肠癌的发生、发展密切相关     

Serum soluble Fas levels and prediction of response to platinum-based chemotherapy in epithelial ovarian cancer

Epithelial ovarian cancer (EOC) is treated mainly by platinum-based combination chemotherapy. Chemotherapy induces apoptosis in which the Fas/Fas ligand pathway is important. Serum soluble Fas (sFas) is a biomarker of this pathway and functionally inhibits Fas-/FasL-mediated apoptosis. In this study, we have investigated the role of sFas in prediction of response to chemotherapy in EOC. Thirty-five patients were recruited and their serum sFas levels were estimated by ELISA at 4 time points-preoperative (sFas1), postoperative (sFas2), midchemotherapy (sFas3) and at the end of chemotherapy (sFas4). The response to chemotherapy was documented clinically, radiologically and by CA-125 levels, based on which, 2 groups were identified: primary chemosensitive (n = 24) and primary chemoresistant (n = 11). Based on the disease status at last follow-up, 2 groups were identified: No Evidence of Disease (n = 15) and Evidence of Disease (n = 20). The primary chemoresistant tumors showed significantly higher median sFas2 levels (p = 0.033) with the sFas2/sFas1 ratio > or =1 (p = 0.001). A multivariate Cox proportional hazards regression model identified sFas2/sFas1 ratio as a significant factor for the prediction of response to platinum-based chemotherapy (p = 0.011). Receiver operating characteristic (ROC) analysis showed that at a ratio of 1.2, sFas2/sFas1 achieved a sensitivity of 82% and specificity of 100% for prediction of chemotherapeutic response. sFas2/sFas1 and sFas3/sFas1 ratio was also higher in patients with evidence of disease (p = 0.018 and p = 0.028, respectively). Progression-free survival rates in patients with sFas2/sFas1 ratio <1 exceeded those with ratio > or =1 (p = 0.004). In conclusion, serum sFas is a useful biomarker for predicting response to platinum-based chemotherapy in EOC.     

Serum neuron-specific enolase is a useful tumor marker for small cell lung cancer

Small cell lung cancer (SCLC) may be potentially curable. A correct diagnosis of cancer cell type is important and serum markers are of great value. Although several markers have been suggested, they have been of limited value because of insufficient specificity. To assess the value of serum neuron-specific enolase (S-NSE) as a possible marker of SCLC, the serum levels of 81 patients with SCLC (59 patients with extensive disease and 22 patients with limited disease) were compared with the serum levels of patients with non-small cell lung cancer (N-SCLC) and 93 patients with nonmalignant lung diseases. The S-NSE level also was measured in 104 patients with extensive disease of various other malignancies, including 71 solid tumors and 33 malignant hematologic disorders. From 105 healthy control subjects, the upper limit of the normal range (x + 2 standard deviations [SD]) was determined as 12.3 ng/ml. The S-NSE level was elevated in 78% of patients with SCLC, including 11 of 22 (50%) with limited disease and 52 of 59 (88%) with extensive disease. In contrast, the S-NSE level was raised only in 18% of patients with advanced N-SCLC (nine of 50) and 6% of patients with nonmalignant lung diseases (six of 93). Twelve patients (17%) with other solid malignant tumors and two patients (6%) with malignant hematologic disorders had raised S-NSE levels. Serial N-NSE levels were obtained in 13 patients with SCLC. S-NSE levels fell in all patients responding to chemotherapy and increased again with progression of disease. Our results indicate that S-NSE seems to be specific for SCLC (85%), whereas sensitivity seems to be dependent on the stage of disease. Further, S-NSE may be a useful marker for monitoring treatment and predicting relapse in patients with SCLC.     

Serum soluble fas level as a prognostic factor in patients with gynecological malignancies.

The Fas-Fas ligand system is important in apoptosis mediated by CTLs and natural killer cells. The suppression of apoptosis contributes to carcinogenesis, as well as to a resistance to chemotherapy and radiotherapy. Circulating soluble Fas (sFas), which is generated by alternative mRNA splicing, can antagonize cell-surface Fas function. We investigated sFas levels in 64 patients with gynecological malignancies (28 cervical carcinomas, 18 endometrial carcinomas, and 18 ovarian carcinomas) and in 24 healthy female donors by using a Fas-specific ELISA. In each carcinoma group, serum sFas demonstrated a statistically significant elevation relative to levels in normal controls (P < 0.0001). Levels of serum sFas in patients with advanced cancer (FIGO stages III and IV) significantly exceeded those in patients with localized cancer (FIGO stages I and II) or those in normal control subjects (P < 0.0001). We divided the patients into two groups based on the level of serum sFas and examined the relationship between serum sFas levels and survival. No deaths occurred in the groups with cervical and endometrial cancer with a serum sFas level < 1.5 ng/ml. Survival rates in groups with cervical carcinoma, endometrial carcinoma, and ovarian carcinoma with a serum sFas level < 1.5 ng/ml exceeded those in groups with sFas levels of 21.5 ng/ml (P < 0.001, P = 0.128, and P = 0.012, respectively). Proportional hazard models demonstrated that serum sFas level was a statistically significant factor (P = 0.0196) for survival, as well as histological grade (P = 0.0168) in ovarian carcinoma.     

Myelosuppression in patients benefiting from imatinib with hydroxyurea for recurrent malignant gliomas

Reports suggest reasonable efficacy and minimal myelosuppression from combination imatinib and hydroxyurea for recurrent malignant glioma. We retrospectively reviewed 16 patients treated with this regimen who were evaluable for toxicity; 14 were also evaluable for response. The incidence of grade 3–4 hematologic toxicity was 25%. The best radiographic response, by Macdonald criteria, was partial response (PR) in three patients (21%), stable disease (SD) in four (29%), and progressive disease (PD) in seven (50%). One patient with a PR developed therapy-limiting hematologic toxicity on day 19 of treatment, progressing to grade 4 on day 64, and persisting until death on day 127 despite discontinuing both drugs. Another patient with PR and two of four patients with SD also developed grade 3 hematologic toxicity. All patients with grade 3–4 hematologic toxicity had disease control (PR or SD) as best radiographic response, whereas none with PD suffered grade 3–4 hematologic toxicity. Combining imatinib with hydroxyurea is effective in some patients with malignant glioma. However, myelosuppression can persist for months after discontinuing the regimen, precluding further chemotherapy. Disease control may also correlate with hematologic toxicity (p = 0.08), suggesting that glioma and marrow stem cells may share a common sensitivity to this chemotherapy regimen.     

A high serum soluble Fas/APO-1 level is associated with a poor outcome of aggressive non-Hodgkin's lymphoma.

Soluble Fas (sFas) in the serum is believed to be able to inhibit apoptosis of lymphocytes. It has been reported that the serum sFas level is increased in various diseases, including malignant lymphoma and systemic lupus erythematosus. We studied the association between sFas and the prognosis of patients with aggressive non-Hodgkin's lymphoma (NHL). Compared with normal controls, the serum sFas level was increased significantly in patients with aggressive NHL and adult T cell leukemia/lymphoma. Among patients with aggressive NHL, the complete remission rate was significantly decreased in the subgroup having high serum sFas levels. Both the overall survival rate and the disease-free survival (DFS) rate were significantly lower for this subgroup than for patients with low serum sFas levels. The 5-year survival rates estimated by the Kaplan-Meier method for patients with high and low serum sFas levels were 27.6% and 68.3%, respectively (P = 0.0001). The 5-year DFS rates estimated for patients with high and low serum sFas levels were 44.7% and 71.9%, respectively (log-rank test: P = 0.0023, and generalized Wilcoxon test: P = 0.0014). Among patients with a low and low-intermediate risk group according to the International Prognostic Index (IPI), the 5-year survival rates for low and high serum sFas subgroups were 72.8% and 42.0%, respectively, showing a significant difference (Wilcoxon test: P = 0.0163, log-rank test: P = 0.0115). Among patients with a high-intermediate and high risk group, the 5-year survival rates for low and high serum sFas subgroups were 51.6% and 17.4%, respectively, again showing a significant difference (Wilcoxon test: P = 0.0001, log-rank test: P = 0.0002). Multivariate analysis of a series of prognostic factors, including the five used to calculate the IPI, showed that the serum sFas level was an independent prognostic factor for the overall survival. Based on these results, a serum sFas level of 10 ng/ml or more can be considered to indicate a poor prognosis in patients with advanced NHL, and this finding may be useful for developing strategies for further treatment.     

The Clinical Significance of Serum Soluble Fas and p53 Protein in Breast Cancer Patients: Comparison with Serum CA 15-3

Serum sFas and p53 protein have been observed in breast cancer patients, but their clinical usefulness for diagnosis and therapy monitoring has not been clarified. The aim of this study was to compare the clinical utility of serum sFas and p53 protein with that of serum CA 15-3 as the most commonly used breast cancer tumor marker. Serum samples were taken from 35 normal healthy controls and 35 breast cancer patients before surgery, after 2?weeks of surgery and after six cycles of FAC chemotherapy. Serum sFas and p53 protein levels were measured using ELISA kits. Serum CA 15-3 levels were determined using IRMA kit. Mean Serum levels of sFas and CA 15-3 were significantly elevated while p53 protein was significantly declined in breast caner patients than controls. Serum p53 protein showed the greatest significant area under the ROC curve (84.3%) followed by sFas (80.5%), then CA 15-3 (78%). The sensitivity, specificity and cut-off value for diagnosing breast cancer patients were 84.2%, 82.6% and 2.88?U/ml for p53 protein, 83.3%, 68.2% and 497.3?pg/ml for sFas and 45.8%, 100% and 23?U/ml for CA15-3. Surgical removal of breast resulted in a significant decline in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. Six cycles of chemotherapy resulted in a significant elevation in serum sFas level with no effect on serum p53 protein and CA 15-3 levels. sFas was significantly correlated with tumor grade. It could be concluded that although serum p53 protein is superior to sFas and CA15-3 for diagnosis of breast cancer patients, only sFas is useful for monitoring the response of breast cancer patients to surgery and chemotherapy if the effect of systemic inflammatory reactions is excluded.