老年非小细胞肺癌患者表皮生长因子受体基因19-21外显子突变研究

目的 研究老年非小细胞肺癌(NSCLC)患者表皮生长因子受体(epidermal growth factor receptor,EGFR)基因酪氨酸激酶区19-21外显子的突变状态,并对其临床特征进行初步分析.方法 选取46例病理确诊的老年非小细胞肺癌患者,提取肺癌组织或胸腔积液及心包积液肿瘤细胞基因组DNA,通过巢式PCR基因扩增和直接测序的方法 .分析19、20、21外显子的突变情况,并与其临床特征及应用酪氨酸激酶抑制剂(TKI)疗效的关系进行了初步分析. 结果 46例中,26例检测出带有基因突变(56.5%),其中非沉默突变者为19例(41.3%).19号外显子突变6例(13.0%),20号外显子突变13例(28.2%),21号外显子突变14例(30.4%).其中7例带有2处突变,其余均为单处突变.不吸烟者的突变发生率显著高于吸烟者(P＜0.01).应用酪氨酸激酶抑制剂(TKI)临床获益的患者带有EGFR 19、20、21外显子的基因突变的几率显著高于未获益者(P＜0.05).60～69岁与70～85岁年龄组基因突变状态差异无统计学意义. 结论 老年NSCLC患者EGFR基因酪氨酸激酶区19-21外显子突变特征与肺癌患者总体类似,与年龄关系不大,老年NSCLC患者同样可以通过基因检测获得TKI治疗预测信息.     

非小细胞肺癌患者EGFR突变率及与临床病理关系和TKI靶向治疗效果

目的探讨非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)突变率及与临床病理关系和酪氨酸酶抑制剂(TKI)靶向治疗效果。 方法选取2014年5月至2016年8月我院收治的NSCLC患者100例为研究对象,采用聚合酶链反应-直接测序法检测患者肿瘤组织EGFR基因18-21号外显子突变情况,分析EGFR突变与临床病理的关系及其突变特点,比较EGFR突变型与野生型采用TKI靶向治疗的疗效及1年生存率、2年生存率。 结果本次纳入的100例NSCLC患者中共44例发生EGFR突变,EGFR突变率为44.00%;NSCLC患者EGFR突变率特点：女性高于男性,吸烟患者高于不吸烟患者,腺癌高于非腺癌,差异对比均有统计学意义(P<0.05);Logistic回归分析显示性别为女性、病理类型为腺癌是导致NSCLC患者发生EGFR突变的独立危险因素(P<0.05);EGFR突变类型包括18号外显子点突变4.54%(2/44)、19号外显子缺失突变43.19%(19/44)、20号外显子插入突变及点突变11.36%(5/44)、21号外显子点突变40.91%(18/44);EGFR突变型患者TKI治疗有效率68.18%明显高于EGFR野生型10.71%(P<0.05);EGFR突变型与野生型患者1年、2年生存率对比差异无统计学意义(P>0.05)。 结论性别、病理类型是导致NSCLC患者发生EGFR基因突变的独立危险因素,对于EGFR突变型患者采用TKI靶向治疗可获得较好疗效,但2年生存率与EGFR野生型患者尚无明显差异。     

大剂量EGFR-TKI治疗非小细胞肺癌脑转移的研究进展

非小细胞肺癌(non-small cell lung cancer,NSCLC)患者发生脑转移在肺癌中常见,预后较差,除了标准的全脑放射治疗,化疗在NSCLC脑转移患者中的治疗作用有限.表皮生长因子受体(epidermal growth factor receptor,EGFR)-酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)由于脑脊液药物浓度低,疗效不佳.近来个案报道大剂量EGFR-TKI为存在EGFR突变的NSCLC脑转移患者带来了很大获益.本文对NSCLC脑转移治疗现状、EGFR-TKI应用于NSCLC脑转移与存在的困惑、大剂量TKI治疗NSCLC脑转移药代动力学基础以及安全性和有效性进行综述.     

晚期非小细胞肺癌TKI耐药后治疗进展

<正>在非小细胞肺癌(NSCLC)中约15%白种人患者存在表皮生长因子受体(EGFR)突变〔1〕,而亚裔人种的EGFR突变率较高,约为30%〔2〕。多项大型临床资料显示以EGFR-酪氨酸激酶抑制剂(TKI)为代表的分子靶向药物治疗晚期NSCLC可提高患者的生活质量,延长患者的生存期,已成为临床治疗肺癌的手段之一。IPASS、NEJ002、WJTOG3405、EURTAC等研究已证     

EGFR基因突变及其预测酪氨酸激酶抑制剂对非小细胞肺癌疗效的作用

肺癌是目前发病率、死亡率最高的肿瘤之一，其中约80％是非小细胞肺癌fnon—smallcellungcancer,NSCLC）．而且大部分患者确诊时已属晚期。尽管手术、化疗、放疗等综合治疗有所进步，但总的治疗效果并不理想。近年来随着分子生物学的进展和对癌症发病机制的深入研究．出现了以特定分子为靶点的抗肿瘤药物。表皮生长因子受体（epidermalgrowtllfactorreceptor．EGFR）在多种上皮肿瘤中过表达．在肿瘤的发生发展中起重要作用．成为抗肿瘤药物的重要靶点之一。目前肺癌分子靶向治疗中研究较多的是以gefitinib（Iressal和erlotinib（Tarceva）为代表的EGFR酪氨酸激酶抑制剂fEGFR—tyrosinekinaseinhibitor。早期临床试验表明,EGFR-TKI）EGFR-TKI在部分化疗耐药的NSCLC中仍然有较好的效果．统计显示EGFR—TKI在女性、腺癌、不吸烟患者和东亚人群中疗效更佳。有研究表明EGFR酪氨酸激酶区突变与TKI疗效密切相关。本文综述了EGFR突变和它在预测EGFR—TKI疗效中的进展。     

非小细胞肺癌患者表皮生长因子受体酪氨酸激酶抑制剂耐药机制及其治疗方案的研究进展

表皮生长因子受体酪氨酸激酶抑制剂(EGFR TKIs)是伴有表皮生长因子受体(EGFR)基因突变的非小细胞肺癌(NSCLC)患者的一线治疗药物之一,其可有效延长患者总生存期,但部分患者存在耐药问题。新型EGFR TKIs、EGFR TKIs联合治疗、免疫治疗及个体化治疗有望解决NSCLC患者EGFR TKIs耐药问题。本文就NSCLC患者EGFR TKI耐药机制及其治疗方案的研究进展进行综述。     

泉州地区非小细胞肺癌人群中表皮生长因子受体基因突变分析

目的探讨泉州地区非小细胞肺癌(NSCLC)患者表皮生长因子受体(EGFR)基因突变的情况。方法收集130例泉州地区NSCLC组织或胸腔积液,用ADx-ARMS技术检测NSCLC患者石蜡组织标本EGFR DNA突变19、20及21的突变,同时分析其突变与临床特征的关系。结果130例NSCLC中共检出37例EGFR基因突变,EGFR突变阳性率为28.46%(37/130),女性EGFR基因突变率(26/54)48.15%,显著高于男性(12/78)15.4%(P0.05);EGFR突变外显子19和21突变占总突变的100.0%;腺癌突变发生率为89.19%(33/37)。结果泉州地区NSCLC患者EGFR基因突变以外显子19和21突变为主。结论临床上对未进行EGFR检测的晚期NSCLC腺癌女性患者,可考虑先予EGFR酪氨酸激酶抑制剂进行诊断性治疗。     

智能扩增检测法检测非小细胞肺癌患者血浆及肿瘤组织中表皮生长因子受体突变的研究

近年来,非小细胞肺癌(non-small cell lung cancer,NSCLC)的发病率逐年增高,严重威胁着人类的健康.表皮生长因子受体(epidermal growth factor receptor,EGFR)酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)改变了NSCLC患者的治疗策略.EGFR突变是该类药物的预测因子,在NSCLC的治疗决策中起重要作用[1].对晚期患者而言,获取肿瘤组织检测EGFR突变存在困难,有学者曾尝试在NSCLC患者体液中检测EGFR突变,但标本中肿瘤细胞DNA含量少且不稳定,对检测技术要求高.因此,本研究设计了相应的智能扩增检测(smart amplification process,SMAP)体系,检测晚期NSCLC患者肿瘤组织及外周血浆中EGFR突变,以传统测序及扩增阻滞突变富集技术(amplification refractory mutation system,ARMS)作为对照,并用克隆测序进一步验证结果,探讨SMAP法检测EGFR突变的稳定性和可靠性.     

非小细胞肺癌表皮生长因子受体基因突变与分子靶向治疗

肺癌分子靶向治疗近年来取得较大进展.特别是针对表皮生长因子受体(EGFR)分子靶向药物表现出确定的临床效果.临床应用表明,EGFR基因酪氨酸激酶域体细胞突变与非小细胞肺癌患者对酪氨酸激酶抑制剂吉非替尼的敏感性相关.本文就EGFR生物学特点、EGFR在肺癌中的表达、EGFR基因突变率、EGFR基因突变与EGFR酪氨酸激酶抑制剂疗效的关系作一综述.     

中国人原发性肺腺癌EGFR基因突变分析

目的 探讨原发性肺腺癌表皮生长因子受体(EGFR)基因突变特点,及其与临床特征(性别、临床分期、吸烟情况)的关系.方法 采用PCR扩增和基因测序,检测133例原发性肺腺癌EGFR外显子18,19,20和21的突变情况,同时分析其突变与临床特征的关系.结果 133例中检测到EGFR基因突变50例(37.6%,50/133),EGFR 基因突变与性别和吸烟史相关,与临床分期无关.结论 使用EGFR酪氨酸激酶抑制剂治疗前进行EGFR基因检测非常必要.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

N-acetyl-L-cysteine combined with mesalamine in the treatment of ulcerative colitis： Randomized,placebo-controlled pilot study

AIM： To evaluate the effectiveness and safety of oral N-acetyl-L-cysteine （NAC） co-administration with mesalamine in ulcerative colitis （UC） patients.
METHODS： Thirty seven patients with mild to moderate UC were randomized to receive a four-wk course of oral mesalamine （2.4 g/d） plus N-acetyl-L-cysteine （0.8 g/d） （group A） or mesalamine plus placebo （group B）. Patients were monitored using the Modified Truelove-Witts Severity Index （MTWSI）. The primary endpoint was clinical remission （MTWSI ≤ 2） at 4 wk. Secondary endpoints were clinical response （defined as a reduction from baseline in the MTWSI of ≥ 2 points） and drug safety. The serum TNF-α, interleukin-6, interleukin-8 and MCP-1 were evaluated at baseline and at 4 wk of treatment. RESULTS： Analysis per-protocol criteria showed clinical remission rates of 63% and 50% after 4 wk treatment with mesalamine plus N-acetyl-L-cysteine （group A） and mesalamine plus placebo （group B） respectively （OR = 1.71; 95% CI： 0.46 to 6.36; P = 0.19; NNT = 7.7）. Analysis of variance （ANOVA） of data indicated a significant reduction of MTWSI in group A （P = 0.046） with respect to basal condition without significant changes in the group B （P = 0.735） during treatment. Clinical responses were 66% （group A） vs 44% （group B） after 4 wk of treatment （OR = 2.5; 95% CI： 0.64 to 9.65; P = 0.11; NNT = 4.5）. Clinical improvement in group A correlated with a decrease of IL-8 and MCP-1. Rates of adverse events did not differ significantly between both groups.
CONCLUSION： In group A （oral NAC combined with mesalamine） contrarily to group B （mesalamine alone）, the clinical improvement correlates with a decrease of chemokines such as MCP-1 and IL-8. NAC addition not produced any side effects.     

Delorme's transrectal excision for internal rectal prolapse

Surgical therapy of functional outlet obstruction in patients with internal rectal intussusception may include abdominal, perineal, or transrectal procedures. Because abdominal procedures often result in significant physiologic impact but unrelieved constipation, the authors have elected Delorme's transrectal excision for management of these patients. Since a short-term placebo effect attends many therapies, this report describes results of transrectal excision only after a threeyear postoperative period. Delorme's transrectal excision of internal intussusception accomplished sustained symptomatic relief in over 70 percent of otherwise refractory constipated patients. The association of internal intussusception with other abnormalities underscores the importance of defining both anatomic and functional components when selecting patients whose constipation may require surgical therapy. Critical technical elements, surgical pitfalls, and potential complications of the procedure are discussed.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Toronto, Canada, June 11 to 16, 1989.     

The oral glucose tolerance test: A comparison of the time points on the basis of limit values,normal dispersion,and reproducibility

Summary Time points in the glucose tolerance test (GTT) are compared on the basis of limit values, dispersion within a reference population, and reproducibility. We suggest using the distance between a limit value and the median reference value as a measure of the magnitude of abnormality. The distance between 140 mg/100 ml and the median fasting plasma glucose value is chosen as a standard distance and limits for other points in the GTT are calculated to equal this standard distance of abnormality. We suggest that the probability of correctly interpreting an inividual result is directly related to the reproducibility of the test and inversely related to the percentage of the total range of values which is dispersed among the normal population. The ratio of reproducibility to percentage normal dispersion is proposed as an index of the probability of correctly interpreting an individual result. According to this index, the probability of correct interpretation varies in order: fasting plasma glucose concentration>3-h>2-h>0.5-h>1-h plasma glucose concentration.