羟基脲致皮肤顽固性溃疡5例报告

1．1一般情况 5例羟基脲所致的皮肤顽固性溃疡中男3例、女2例。年龄25岁-60岁,平均45岁,其中慢性粒细胞性白血病(CGL)4例、真性红细胞增多症(PV)1例。初诊时间为1990年-1997年。     

慢性粒细胞白血病并发皮肤鳞癌1例报道

0 引言 皮肤癌是常见的恶性肿瘤之一,大多数是由于太阳辐射中的紫外线照射所致.某些因素也可能与皮肤癌的发生有关,如电离辐射,经常接触砷、柏油或沥青,各种癌前病变以及免疫抑制和种族等.羟基脲是一种核苷二磷酸还原酶抑制剂,广泛应用于慢性粒细胞白血病的治疗.现报道1例慢性粒细胞白血病患者使用羟基脲10年后并发皮肤鳞癌,使用CAP方案化疗后取得较好疗效,可为晚期皮肤鳞癌患者的全身化疗提供依据. 1 病例资料 患者,男,45岁.于1996年6月确诊为慢性粒细胞白血病(CML),1996年6月 2007年9月长期口服羟基脲治疗.患者自2007年9月开始出现右手背及右手掌处多发疣状物、伴溃疡形成,行原发灶切除+植皮术,术后病理示皮肤高分化鳞状细胞癌.术后停服羟基脲,2007年10月开始口服格列卫(400毫克/日)治疗,2011年9月复查染色体及融合基因无改变,开始改服尼洛替尼胶囊(800毫克/日)治疗,CML病情稳定.     

粒细胞集落刺激因子治愈化学性皮肤坏死1例

化疗药物渗漏到皮下组织,轻者可引起局部红肿、疼痛,严重可损伤神经、肌腱,甚至造成皮肤组织坏死、肢体功能障碍。我们采用以粒细胞集落刺激因子（G-CSF）为主的综合治疗治愈表阿霉素外渗导致皮肤坏死1例,现报告如下。     

外用重组人粒细胞-巨噬细胞集落刺激因子治疗肿瘤内科常见并发症效果观察

目的观察重组人粒细胞．巨噬细胞集落刺激因子（rhGM—CSF）治疗肿瘤内科常见的皮肤黏膜组织损伤并发症的疗效。方法外用rhGM—CSF治疗化疗后口腔溃疡、手术切口不愈合、化疗药物外渗致皮肤组织坏死脱落,观察其治疗效果。结果rhGM—CSF外用对化疗后口腔溃疡效果好,各期溃疡均在10d内愈合,最快3d,平均5．5d。对其他肿瘤内科常见的皮肤黏膜组织损伤并发症也有较好疗效。结论rhGM-CSF外用对肿瘤内科常见的皮肤黏膜组织损伤具有较好的修复和治疗作用。     

重组粒细胞-巨噬细胞集落刺激因子上市

美国食物和药品管理局于1991年3月批准重组粒细胞-巨噬细胞集落刺激因子(GM-CSF)—沙莫司订(Sargramostim)上市。此药可用于治疗正在接受自体骨髓移植的何杰金氏病、非何杰金氏淋巴瘤或急性成淋巴细胞白血病(ALL)病人,藉以促进患者的自体骨髓恢     

重组人粒细胞集落刺激因子治疗药物所致急性粒细胞缺乏症

重组人粒细胞集落刺激因子（ｒｈＧ－ＣＳＦ）具有调节粒系细胞增殖、分化的功能,已被广泛应用于骨髓移植、白血病及其他肿瘤化疗后引起的骨髓抑制。应用ｒｈＧ－ＣＳＦ治疗非抗肿瘤药物所致的粒细胞缺乏症（粒缺）报告较少。我们治疗他吧唑和复方氨基比林所致的急性粒缺...     

国产基因重组人粒细胞／巨噬细胞集落刺激因子治疗化疗致白细…

本文作者采用配对分组的方法，观察了国产基因重组人粒细胞／巨噬细胞集落刺激因子（ＲＨＧＭ－ＣＳＦ）对乳腺癌和癌化疗所致白细胞减少症的治疗效果。结果表明，国产ｒｈｇｍ－ｃｓｆ对白细胞减少有确切的治疗作用，且毒副反应轻微，价格便宜，适合国同推广应用。     

羟基脲长期维持治疗慢性粒细胞白血病疗效观察

我们应用羟基脲作一线药物 ,长期维持治疗慢性粒细胞白血病患者 11例 ,现将结果报告如下。1　资料与方法1.1　病例　慢性粒细胞白血病 11例 ,均系我院住院和门诊病人 ,经血常规、骨收稿日期 :1999-10 -2 6;修回日期 :2 0 0 0 -0 1-2 0作者单位 :杭州市第二医院 ,浙江　杭州　3 10 0 15髓及其他化验检查 ,结合临床表现 ,符合1998年张之南主编的《血液病诊断及疗效标准》中关于慢性粒细胞白血病的诊断。其中男 8例 ,女 3例 ,年龄 16岁～ 73岁 ,平均 46岁。白细胞最高者达 2 0 0×10 9/ L 以上 ,一般在 140× 10 9/ L 左右 ,近半数患者同时伴…     

重组人粒细胞—巨噬细胞集落刺激因子的临床新用途

粒细胞－巨噬细胞集落刺激因子（ｇｒａｎｕｌｏｃｙｔｅ ｍａｃｒｏｐｈａｇｅ ｃｏｌｏｔｒｙ ｓｔｉｍｕｌａｔｉｎｇ ｆａｃｔｏｒ,ＣＭ－ＣＳＦ）是一个具有多项潜能的造血生长因子,因为它不仅能够促进造血前体细胞的增殖、分化和成熟,而且对其他的细胞,如抗原递呈细胞（ＡＰＣ）、成纤维细胞、角质细胞皮肤粘膜细胞等,均有着不同程度的刺激作用,由于ＣＭ－ＣＳＦ对骨髓抑制的修复作用,目前在临床上的用途主要有用于     

Effect of human recombinant granulocyte/macrophage colony-stimulating factor and native granulocyte colony-stimulating factor on clonogenic leukemic blast cells

The effects of human recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF) and human native purified granulocyte colony-stimulating factor (G-CSF) on the growth of clonogenic leukemic blast cells from eight Japanese patients with acute myeloblastic leukemia were studied, using an in vitro leukemic blast colony assay. The results showed that GM-CSF stimulated leukemic blast colony formation in all cases examined, whereas G-CSF stimulated colony formation in four of the eight cases. The maximum stimulating activity of GM-CSF on the growth of clonogenic leukemic blast cells was higher than that of G-CSF in the majority of cases, while sometimes GM-CSF and G-CSF worked synergistically. Thus, the clonogenic leukemic blast cell populations seemed to be heterogeneous with respect to their in vitro response to growth regulators.     

Differential effect of recombinant granulocyte macrophage colony-stimulating factor on human monocytes and alveolar macrophages

The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF), a pluripotent cytokine, on tumoricidal activity of alveolar macrophages and monocytes from nonsmoking normal volunteers was compared using [3H]thymidine-labeled human tumor cells (SK-MEL-28, melanoma) as targets. A dose-response study (500-5000 units/ml) of recombinant GM-CSF indicated dramatic differences between cytotoxicity of alveolar macrophages and blood monocytes. Macrophages exhibited significant (P less than 0.01) tumoricidal activity at all GM-CSF doses tested. In contrast, monocytes showed no significant tumoricidal activity at 500 units/ml and significantly (P less than 0.01) less activity than alveolar macrophages at doses of 1000-5000 units/ml. Maximal activity in alveolar macrophages occurred 72-96 h after exposure to 1000-5000 units/ml GM-CSF. Tumoricidal activity may be related to the state of maturation, because monocytes matured in vitro for 7 days displayed enhanced tumoricidal activity after GM-CSF exposure. Tumor necrosis factor alpha and interleukin 1 beta were measured in supernatant fluids of 24-h GM-CSF-treated cells. No significant increase in either cytokine was detected after GM-CSF treatment of alveolar macrophages. Monocyte interleukin 1 beta secretion was not enhanced by GM-CSF; however, tumor necrosis factor alpha secretion was enhanced in some donors (three of five). Superoxide anion production of alveolar macrophages was not enhanced by GM-CSF. These data suggest that alveolar macrophage tumoricidal activity is induced by GM-CSF and is not dependent on oxidative metabolism or secreted forms of interleukin 1 beta or tumor necrosis factor alpha.     

化疗前应用重组人粒细胞集落刺激因子预防白细胞减少

 【摘要】　目的　观察重组人粒细胞集落刺激因子（rhG-CSF）预防化疗后中性粒细胞减少症的有效性和安全性。方法　采用随机对照方法，初治恶性肿瘤患者接受1个周期的化疗，其中治疗组化疗前24 h给予rhG-CSF 150 μg皮下注射1次，对照组不给予rhG-CSF。结果　入组52例肿瘤患者，分为治疗组和对照组各26例，WBC＜4.0×109／L的发生率分别为19.23 %和53.85 %（P＜0.05），白细胞减少发生率Ⅰ度分别为7.69 %和19.23 %，Ⅱ度7.69 %和15.39 %，Ⅲ度3.85 %和1.54 %，Ⅳ度0和7.69 %； 持续时间分别为1.27 d和4.04 d（P＜0.05）；抗生素使用率分别为7.69 %和26.92 %（P＜0.05）；发热性中性粒细胞减少发生率分别为3.85 %和26.92 %（P＜0.05）。rhG-CSF的毒副作用主要为骨骼肌肉疼痛、乏力、头晕等。结论　化疗前应用rhG-CSF能有效控制肿瘤化疗后白细胞减少的发生，降低肿瘤化疗后白细胞减少的程度。     

重组人粒细胞集落刺激因子混合液治疗化疗引起口腔溃疡的临床观察

目的 观察重组人粒细胞集落刺激因子（rhG-CSF）混合液治疗恶性肿瘤化疗引起口腔溃疡的临床效果。方法 将50例恶性肿瘤患者按数字表法随机分为观察组和对照组,每组25例。对照组采用0.9％氯化钠注射液100 ml加冰硼散3 g、锡类散1 g配制的含漱液。观察组为在对照组基础上加入rhG-CSF 100 μg、庆大霉素16 万U、地塞米松5 mg及2％利多卡因10 ml配制的含漱液。两组患者均予10 ml／次含漱,每日3～5次,每次3 min;从发生口腔溃疡24 h内开始用药,至口腔溃疡愈合或治疗7d后停药。观察并记录两组患者口腔溃疡的治疗有效率、疼痛缓解率、疼痛缓解时间及溃疡愈合时间。结果 观察组口腔溃疡的治疗有效率为92.0％,高于对照组的60.0％（P＜0.05）;观察组的疼痛缓解率优于对照组（84.0％ vs. 52.0％）,差异有统计学意义（P＜0.05）;给药后观察组不同时间点的口腔溃疡疼痛评分均显著低于对照组（P＜0.05）;观察组的口腔溃疡平均愈合时间明显短于对照组［（3.5±1.2） d vs.（5.7±1.3） d,P＜0.05］。结论 rhG-CSF混合液含漱治疗化疗后引起的口腔溃疡效果显著,能有效减轻患者的疼痛程度和时间,加快创面愈合,明显缩短口腔溃疡的愈合时间。     

Effect of surgery on granulocyte/macrophage colony-stimulating factor.

Eighteen surgical patients were studied to determine the effect of anesthesia (general or spinal) and surgery on serum and urinary colony-stimulating factor(s) (CSF). CSF is a leukopoietin that stimulates proliferation of macrophages and granulocytes from bone marrow precursor cells. CSF was assayed by adding aliquots of serum or urine to semisolid agar cultures of bone marrow cells and scoring the number of colonies developing after 7 days of incubation. In all but 1 case, a 3- to 30-fold increase in the 24 hour excretion of urinary CSF was seen on the day of surgery and the first postoperative day. CSF urinary excretion began declining toward normal by the second postoperative day. A parallel increase in granulocyte count, a delayed rise in monocytes, and a decline in absolute lymphocyte counts were also observed. The data suggest that immediately postoperatively there may be a strong stimulus to granulocyte/macrophage proliferation. More rapidly proliferating cells would be anticipated to have increased vulnerability to toxicity from cell cycle-active chemotherapeutic agents.     

Oral administration of recombinant human granulocyte macrophage colony-stimulating factor in the management of radiotherapy-induced esophagitis.

Radiation-induced esophagitis often results in treatment interruption, which may severely affect the probability of control of the local disease in patients undergoing chest radiotherapy (RT). No effective regimen that would reduce the incidence and severity of this complication has been identified up to now. Although acceleration of oral mucosal healing using topical recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) has been reported, the mechanism of such an interaction remains obscure. Effective topical application of rhGM-CSF for the treatment of radiation-induced esophagitis has never been reported in the past. In pharmacological studies, we observed that glycerol exerts a remarkable stabilizing effect on rhGM-CSF immunoreactivity. After studying the kinetics of esophageal emptying with nuclear imaging, we proposed a rhGM-CSF regimen that could be applied for topical treatment of esophagitis during RT. The regimen was applied for 5 consecutive days in a cohort of 36 patients undergoing chest RT, immediately after the documentation of grade 3 esophagitis. RT was not interrupted. Mucosal biopsies were performed endoscopically and examined immunohistochemically. Regression of dysphagia to grade 0/1 was observed in 19 of 36 (52%) patients, whereas grade 2 dysphagia persisted in 12 of 36 (33%) patients. Progression of dysphagia was seen in 5 of 36 (14%) patients. Recurrence of severe esophagitis within 5-8 days after rhGM-CSF therapy was observed in 7 of 31 (22%) patients with initial response to rhGM-CSF. Four of these patients presented significant improvement of symptomatology after additional rhGM-CSF medication. In immunohistochemical studies, active intraepithelial neovascularization and thymidine phosphorylase and vascular endothelial growth factor overexpression were observed in the damaged epithelium, which was not accompanied by macrophage or neutrophil infiltration. We conclude that rhGM-CSF topical therapy (p.o. administration) exerts a significant therapeutic effect against RT-induced esophagitis. The rhGM-CSF mucosa healing effect is probably due to its direct angiogenic activity and/or to the potentiation of the activity of other angiogenic factors released by the damaged epithelium.     

重组人粒细胞集落刺激因子治疗急性放射性口腔黏膜损伤的临床观察

目的　观察重组人粒细胞集落刺激因子（ｒｈＧ-ＣＳＦ）对鼻咽癌急性放射性口腔黏膜损伤的作用。方法　将５０例鼻咽癌住院患者随机分为对照组和ｒｈＧ ＣＳＦ治疗组,每组２５例。对照组用生理盐水每次１０ｍｌ含漱,治疗组用生理盐水１００ｍｌ＋ｒｈＧ-ＣＳＦ９００μｇ溶液每次１０ｍｌ含漱;每日３～５次,每次１０分钟。两组均采用标准分割方式放疗,观察急性口腔黏膜损伤的发生率、严重程度及其疗效。结果　放疗２０Ｇｙ时治疗组的黏膜损伤发生率为４０％,对照组为６８％（Ｐ＝０.０４７）。放疗结束治疗组的１～４级黏膜损伤发生率分别为４４％、２４％、１２％和０,对照组分别为１６％、２８％、４４％和８％（Ｐ＜０.０５）。治疗组患者的生活质量各项指标均较对照组有明显改善（Ｐ＜０.０５）。结论　ｒｈＧ-ＣＳＦ能够降低鼻咽癌急性放射性黏膜损伤的发生率,并减轻其损伤程度,值得推广。     

Weekly CODE chemotherapy with recombinant human granulocyte colony-stimulating factor for relapsed or refractory small cell lung cancer

We used cisplatin, vincristine, doxorubicin, and etoposide (CODE) plus recombinant human granulocyte colony-stimulating factor (rhG-CSF) weekly for salvage chemotherapy in relapsed or refractory small cell lung cancer (SCLC). We reviewed the medical charts of patients between January 1993 and December 1996 at the National Nishi-Gunma Hospital. Twenty patients were treated with salvage chemotherapy. The overall response rate was 55.0%. The median survival time of extensive disease patients from the start of CODE therapy was 23 weeks and the 1-year survival rate was 21.0%. Toxicities were severe, especially in myelosuppression. CODE could be selected as a salvage therapy for chemotherapy- relapsed SCLC cases.