IL—2,5—Fu,MMC联合治疗癌性胸水38例报告

目的：观察细胞因子白细胞介素２（ Ｉ Ｌ２） 与５氟脲嘧啶（５ Ｆｕ） 、丝裂霉素（ Ｍ Ｍ Ｃ） 联合治疗癌性胸水的疗效。方法：所有患者化疗前排尽胸水,然后腔内注入药物,间隔１ 周,治疗１ ～２ 次。结果：总有效率９４ ．７ ％ （３６／３８） ,其中 Ｃ Ｒ４４ ．７ ％ （１７／３８） , Ｐ Ｒ５０ ％ （１９／３８） , Ｓ Ｄ５ ．３ ％ （２／３８） 。结论： Ｉ Ｌ２ 联用化学药物,疗效相加,能有效控制患者癌性胸水,毒副作用轻,效果优于腔内单用化疗药物。     

外源性IL—6对人脑髓母细胞瘤生长的促进作用

作者采用分子生物学和细胞免疫学手段，在国内外首次研究了ＩＬ－６基因在髓母细胞瘤内的表达和产生，及其对肿瘤细胞生长的作用。结果发现，１３例被检样本中１２例有ＩＬ－６信息传导基因－ＩＬ－６Ｒ和ｇｐ１３０的表达，但无一例表达ＩＬ－６。重组ＩＬ－６可明显促进细胞生长和ＤＮＡ合成。结果提示，ＩＬ－６可通过旁分泌途径促进髓母细胞瘤生长。由于髓母细胞瘤周围和内部存在ＩＬ－６分泌细胞，本研究对揭示肿瘤与其间质细胞     

急性白血病患者化疗后发热时IL—6检测的意义

目的：研究中性粒细胞缺乏伴发热患者血浆中ＩＬ－６浓度和Ｃ反应蛋白之间的关系，探讨ＩＬ－６在预测感染方面的作用。方法：对３２例接受化疗的急性白血病患者的５０例次发热，采用ＥＬＩＳＡ法检测患者血浆ＩＬ－６浓度。结果：有感染证据的病例ＩＬ－６水平均有不同程度的增高，且峰值较Ｃ反应白峰值提前１ｄ～３ｄ；在发热首日，革兰氏阴性菌血症患者ＩＬ－６水平（中位数１９５２ｎｇ／Ｌ，范围１０５３ｎｇ／Ｌ～２０７９４ｎ     

IL—2和（或）IL—3基因治疗对大剂量化疗后小鼠免疫功能恢复的影响

目的探讨ＩＬ－２、ＩＬ－３对化疗后小鼠免疫功能恢复的影响。方法正常小鼠腹腔注射大剂量环磷酰胺２４小时后,直接腹腔注射ＩＬ－２重组腺病毒（Ａｄ－ＩＬ－２）和（或）ＩＬ－３重组腺病毒（Ａｄ－ＩＬ－３）,观察小鼠腹腔巨噬细胞数量、杀伤活性、Ｉａ抗原表达、脾细胞增殖及ＮＫ细胞杀伤活性。结果腹腔注射Ａｄ－ＩＬ－３组小鼠,腹腔巨噬细胞数量明显增加,杀伤活性及Ｉａ抗原表达显著增强。腹腔注射Ａｄ－ＩＬ－２组小鼠,脾细胞增殖能力显著升高,ＮＫ细胞杀伤活性增强,但对小鼠腹腔巨噬细胞无激活作用。联合应用Ａｄ－ＩＬ－２及Ａｄ－ＩＬ－３组小鼠,腹腔巨噬细胞、脾细胞、ＮＫ细胞均被激活。结论腹腔直接注射Ａｄ－ＩＬ－２和Ａｄ－ＩＬ－３可促进化疗后小鼠免疫功能的恢复。     

IL—6R与脑胶质瘤的恶性增殖

白细胞介素－６（ＩＬ－６）与ＩＬ－６受体（ＩＬ－６Ｒ）的自分泌或旁分泌环路在肿瘤发生发展中的作用越来越受到重视。随着对ＩＬ－６Ｒ结构和功能及其与脑胶质瘤关系的研究不断深入，初步推测脑胶质瘤细胞及组织中也存在ＩＬ－６－ＩＬ－６Ｒ自分泌或旁分泌环路，这为脑胶质瘤的免疫治疗提供了新的思路。     

多发性骨髓瘤患者周围血单个核细胞培养上清液IL—6和TNF活性测定的…

本文测定了１８例ＭＭ患者ＩＬ－６和ＴＮＦ活性，同时分析其活性与ＭＭ病情有关参数相关性。结果显示ＴＮＦ、ＩＬ－６活性明显高于对照组（Ｐ〈０．０５）。ＩＬ－６与β２－ＭＧ、ＴＮＦ与血浆总钙浓度呈正相关（Ｐ〈０．０５）。提示该两种因子参与ＭＭ的发病，且有可能影响骨髓的代谢。     

人脑胶质瘤细胞中IL—6mRNA的表达及意义

目的 观察白细胞介素－６（ＩＬ－６）ｍＲＮＡ在脑胶质瘤细胞中的表达。方法 采用逆转聚合酶链反应（ＲＴ－ＰＣＲ）方法对２０例新鲜人脑胶持瘤标本进行了检测。结果 ２０例标本中有１７例表达ＩＬ－６ｍＲＮＡ，恶性程度高的肿瘤中ＩＬ－６ｍＲＮＡ的表达量明显高于恶性程度低的肿瘤。结论脑胶质瘤细胞中ＩＬ－６基因的表达与脑胶质瘤的发生发展有关。     

多发性骨髓瘤患者周围血单个核细胞培养上清液IL—6和TNF活性测定的初步研究

本文测定了１８例ＭＭ患者ＩＬ—６和ＴＮＦ活性，同时分析其活性与ＭＮ病情有关参数相关性。结果显示ＴＮＦ、ＩＬ一６活性明显高于对照组（Ｐ＜０．０５）。ＩＬ—６与β２—ＭＧ、ＴＮＦ与血浆总钙浓度呈正相关（Ｐ＜０．０５）。提示该两种因子参与ＭＮ的发病，且有可能影响骨髓的代谢。     

缓激肽对C6胶质瘤细胞分泌白细胞介素-6的影响

目的:白细胞介素-6(IL-6)与脑胶质瘤的恶性增殖密切相关,本文探讨缓激肽作用大鼠C6胶质瘤细胞后对IL-6表达的影响。方法:应用逆转录聚合酶链反应(RT-PCR)和放射免疫法分别检测1μmol·L^-1 缓激肽作用下,C6胶质瘤细胞内及细胞培养液中IL-6的表达水平。结果:RT-PCR结果显示缓激肽作用于C6胶质瘤细胞,在不同时相点(0,5,10,15,30,60min)均有IL-6mRNA的表达,各组间比较无显著性差异(P>0.05);放射免疫法结果显示,细胞培养液中未检测到IL-6的表达。结论:缓激肽作用C6胶质瘤细胞60min以内不引起IL-6的表达增强,这为缓激肽临床应用的安全性提供了有利的实验依据。     

FFL方案时辰化疗法治疗转移性大肠癌的临床观察

目的：探讨FFL(草酸铂 5-氟脲嘧啶 亚叶酸钙)方案对转移性大肠癌的近期疗效。方法：对22例大肠癌术后出现局部复发或转移的病人采用FFL方案化疗，其中初治6例，复发后治疗16例。结果：疗效为完全缓解(CR)2例，部分缓解(PR)8例；总有效率为45．5％。结论：对于转移性大肠癌FFL方案可获得较高的缓解率，同时化疗反应轻微。     

Real-World Effect of Maintenance and Intermittent Chemotherapy on Survival in Metastatic Colorectal Cancer

Background

With improved survival and longer duration of treatment, clinicians managing metastatic colorectal cancer (mCRC) increasingly consider intermittent (IC) or maintenance chemotherapy (MC), but the effect of these treatment modifications on real-world outcomes is unclear.

食管癌患者手术前后血清IL-6和SIL-6R检测及其临床意义

目的：探讨血清白介素6（IL－6）、可溶性白介素6受体（SIL－6R）在食管癌发病中的作用。方法：应用夹心酶联免疫吸附法（FAISA）测定了30例手术前后食管癌及30例健康对照者血清IL－6、SIL－6R水平，同时测定了血清C反应蛋白（CRP）。白介素4（IL－4）水平。结果：食管癌患者术前血清IL－6和SIL－6R水平显著高于健康对照者（27．2±7．9ng／L、41．3±12.0μg/L比16．1±1．3ng/L、31．5±127nμg/L，P均＜0．01）；食管癌患者术后血清IL－6和SIL－6R水平又高于术前（535±士22．0ng/L、53．3±14．0μg/L比27．2±7．9ng／L、41．3±12．0μg/L，P均＜0.01）。结论：血清IL－6、SIL－6R可能参与食管的发病过程；食管癌患者术后血清IL－6、SIL－6R升高可能与手术后应激有关。     

氟达拉滨对多发性骨髓瘤细胞系KM3细胞分泌IL-6的影响

目的：研究氟达拉滨（fludarabine）在体外对多发性骨髓瘤细胞KM3细胞生长的影响及对细胞上清液IL-6、sIL-6R的影响。方法：采用MTT法及细胞计数法分别观察不同浓度氟达拉滨对KM3细胞生长的影响；用双抗夹心法检测不同浓度氟达拉滨作用KM3细胞后上清液白细胞介素6（interleukin-6，IL-6）和可溶性白细胞介素6受体（soluble interleukin-6 receptor，sIL-6R）的表达水平。结果：MTT法及细胞计数法均显示氟达拉滨对KM3细胞有明显的抑制作用，氟达拉滨作用KM3细胞72h后，25、50、100、200、400nmol／L组的增殖抑制率均高于对照组（P〈0．01），且与浓度成正比。400nmol/L组对KM3细胞增殖抑制率随时间的延长而增加。双抗夹心法检测结果显示KM3细胞经氟达拉滨作用96h后，其IL-6水平先升高后明显下降，而sIL-6R水平随药物浓度的升高而逐渐下降。结论：氟达拉滨能明显抑制KM3细胞的增殖，同时能抑制KM3细胞自分泌IL-6和sIL-6R。     

Antitumor Effect of PSK at a Distant Site: Inductions of Interleukin-8-like Factor and Macrophage Chemotactic Factor in Murine Tumor

The antitumor effect of PSK, a Coriolus preparation, at a distant site was analyzed with the use of a double grafted tumor system in which male BALB/c mice received simultaneous intradermal inoculations of Meth-A tumor in the right (10⁶ cells) and the left (2 × 10⁵ cells) flanks and were then injected with PSK in the right tumor on the third day thereafter. The antitumor effect of intratumoral administration of PSK in the right tumor on days 3, 4 and 5 was compared with the effect of surgical resection of the right tumor on day 5. Three out of 8 mice given PSK intratumorally became tumor-free whereas no mouse tumor-free in the left flank was found among the surgically resected mice. As regards sinecomitant immunity, tumor inoculation into the right flank followed by intratumoral administration of PSK on days 3 and 5 and surgical excision of the primary tumor on day 6 resulted in complete rejection of a tumor challenge in the left flank on day 21. The combination of presurgical intratumoral injections of PSK (more than 2 times) and postoperative oral administration of PSK appeared to be most effective in eradicating secondary tumors. Isolated TILs (tumor-infiltrating lymphocytes), obtained from the right tumor (treated with PSK) and the left tumor on day 10 in the double grafted tumor system were cultured in RPMI1640 with 10% fetal calf serum for 24 h. The culture supernatants were harvested and tested for the presence of chemotactic activity for neutrophils or macrophages. Significant neutrophil chemotactic factor (NCF) and macrophage chemotactic factor (MCF) activities were detected in the culture media from PSK-treated TILs that had been cultured for 24 h. Neither significant neutrophil nor macrophage chemotactic activity was detected in the media from untreated TILs. NCF and MCF activities were also detected in the culture supernatant from PSK-treated tumor tissue on day 6. PSK-induced NCF in the murine tumor was neutralized by treatment with anti-human IL-8 IgG, and might be murine IL-8-like factor. Therefore, neutrophil and macrophage infiltrations of tumors following intratumoral injections of PSK are probably mediated by inductions of IL-8-like factor and MCF.     

Phase I trial of fluorouracil modulation by N-phosphonacetyl-L-aspartate and 6-methylmercaptopurine ribonucleoside

Inhibition of pyrimidine and purine synthesis has been demonstrated to potentiate 5-fluorouracil (5-FU) activity in preclinical models. Low-dose phosphonacetyl-l-aspartate (PALA) potentiates the incorporation of 5-FU into RNA, without detectably increasing its toxicity. 6-Methylmercaptopurine riboside (MMPR) results in inhibition of purine biosynthesis with elevation of phosphoribosyl pyrophosphate (PRPP), which in turn is believed to increase the phosphorylation and intracellular retention of 5-FU. We conducted a phase I clinical trial to determine the maximum tolerated dose of 5-FU in combination with low-dose PALA and a biochemically-optimized dose of MMPR. The regimen consisted of PALA 250 mg/m² given on day 1, followed 24 h later by MMPR 150 mg/m², and escalating doses of 5-FU from 1625 to 2600 mg/m² by 24 h continuous infusion. This regimen was repeated weekly. A group of 29 patients with a diagnosis of malignant solid tumor were entered; their median performance status was 1. The dose-limiting toxicity was mucositis, while other gastrointestinal toxicity was minimal. Two patients also experienced ischemic chest pain during the 5-FU infusion. The maximum tolerated dose of 5-FU in this combination was 2600 mg/m². Several responses were observed including a complete remission in a previously treated breast cancer patient and two partial responses in breast and colon cancer. MMPR pharmacokinetics were obtained from urine analyses in 21 patients on this trial; there was no correlation between the pharmacokinetics of MMPR and the toxicity observed. This regimen was well tolerated and phase II trials are warranted using PALA 250 mg/m², MMPR 150 mg/m², and 5-FU 2300 mg/m² by continuous infusion over 24 h.     

The Effect of Ketoconazole on the Phagocytosis and Intracellular Killing of Candida albicans by Polymorphonuclear Granulocytes

Summary: The synergism between the polymorphonuclear granulocytes and ketoconazole was studied in vitro. The phagocyte index proved to be 87.3 + 8.1. while the Candida killing index was 20.8 + 4.8. Treatment of granulocytes with ketoconazole did not influence their activity. However, the treatment of Candida albicans with ketoconazole led to unchanged phagocytosis, but a significantly higher killer activity. The results indicate that not the immunomodulating effect of the imidazole derivative, but its antimycotic effect, is responsible for the synergism observed between ketoconazole and the host defence mechanisms.
Zusammenfassung: Der Synergismus zwischen polymorphonukleären Granulozyten und Ketoconazol wurde in der vorliegenden Studie in vitro untersucht. Die Bestimmung des Phagozytosenindex ergab einen Wert von 87,3 + 8,1. und beim Candida-Abtötungsindex 20,8 + 4,8. Die Behandlung der Granulozyten mit Ketoconazol ließ die Aktivität dieser Zellen unbeeinflußt. Wird der Candida-Suspension Ketoconazol zugesetzt, beeinflußt es die Phagozytose der Candida-Zellen nicht, sondern erhöht signifikant die candidacide Aktivität. Die Ergebnisse weisen darauf bin, daß der zwischen dem Arzneimittel und dem Abwehrsystem des Wirtes bestehende Synergismus sich nicht aus einem immunomodulierenden Effekt der Imidazol-Derivate erklärt, sondern auf die antimykotische Wirkung von Ketoconazol zurückgeht.     

Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion,Extranodal Extension,and Lower Disease-Free Survival in Thai Breast Cancer Patients

Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients.