化疗周期对埃克替尼一二线化疗耐药的表皮生长因子受体突变不明的非小细胞肺癌临床疗效分析

<正>非小细胞肺癌(non-small cell lung cancer,NSCLC)是肺癌的常见类型,占肺癌比例的85%。其中,超过50%的患者病理类型为非鳞状细胞癌[1-3]。除此之外,60%～70%的患者一经诊断即为晚期,大部分晚期或术后复发的患者已不适合手术和放疗,对于这类患者首选的治疗方式为以铂类为基础的化疗。一线化疗失败或疾病进展的患者会选择无交叉耐药的二线化疗方案。目前,对于二线化疗治疗失败的非鳞NSCLC患者,一般情况下,再也没有可以使用的有效化疗药物。因此,近年来生物靶向治疗成为这类患者治疗的主要方式。然而,靶向治疗基于基因突变,表皮生长因子受体(epidermal growth factor receptor,EGFR)基因是NSCLC中最     

BIM与EGFR突变非小细胞肺癌吉非替尼耐药的关系

BIM是Bcl-2中含BH3碱基亚家族的成员,是一种重要促凋亡调节蛋白.表皮生长因子受体(epidermal growth factor receptor,EGFR)突变的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者对EGFR-酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)治疗敏感、疗效显著,但无论近期疗效如何,最终患者都不可避免地产生耐药及病情进展.BIM参与许多癌细胞(乳腺癌、肺癌、骨肉瘤、黑色素瘤)凋亡.近年来,有研究发现BIM表达与EGFR突变NSCLC吉非替尼耐药有关.因此,了解BIM与EGFR-TKIs耐药关系有利于临床指导.本文综述了近年来BIM与EGFR突变NSCLC吉非替尼耐药的关系.     

表皮生长因子受体突变对肺癌吉非替尼耐药的机制

肺癌是目前发病率和病死率最高的恶性肿瘤之一,化疗是其主要治疗手段,但以铂类为基础的化疗方案在晚期肺癌中缓解率为30％～40％,中位生存期为8～10个月。近年来,随着分子生物学技术的发展,针对细胞特定分子的靶向治疗药物陆续上市,这些药物具有针对性强、能特异性地杀伤肿瘤细胞的特点。如表皮生长因子受体（ EGFR）阻滞剂吉非替尼,用于治疗化疗失败或不适于化疗的局部晚期或远处转移的非小细胞肺癌（ NSCLC ）患者。但几乎所有对吉非替尼治疗有效的患者会产生耐药性,其机制可能与EGFR的二次突变有关。故EG-FR基因突变对肺癌吉非替尼耐药性的作用机制成为目前肺癌治疗的热点之一。本文就近年来有关肺癌吉非替尼耐药机制的研究进展综述如下。     

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。     

长链非编码RNA在非小细胞肺癌耐药机制中的研究进展

正肺癌仍是最常见且死亡率最高的恶性肿瘤,对于EGFR基因敏感突变的晚期NSCLC患者,EGFR-酪氨酸激酶抑制剂(EGFR-TKIs)能够有效延长生存期并提高生活质量,该类患者疾病进展往往源于肿瘤细胞对EGFR-TKIs的耐药。对于驱动基因阴性或靶向治疗后进展的晚期NSCLC患者,化疗是最主要的治疗手段,由于肿瘤细胞对化疗药物的耐药使     

从耐药机制分析ALK-TKI序贯治疗ALK重排非小细胞肺癌的理论基础

<正>肺癌是全球最常见的恶性肿瘤,其病死率居恶性肿瘤的首位~([1])。肺癌的85%为非小细胞肺癌(non-small cell lung cancer,NSCLC)。随着分子医学的进展和靶向药物的不断涌现,NSCLC治疗已经进入了个体化治疗的时代。间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)最初是在间变性大细胞淋巴瘤中的一种亚型中被发现,由此得名为。2007年     

非小细胞肺癌EGFR靶向治疗的研究进展

肺癌是目前世界上发病率和病死率最高的癌症,其中非小细胞肺癌(NSCLC)占肺癌的85％以上.近10年来,随着对肿瘤生物学的深入研究,作为NSCLC治疗靶点的多个基因突变已被识别,其中表皮生长因子受体(EGFR)基因的突变频率最高,因此,EGFR基因的靶向治疗也逐渐成为NSCLC治疗的主力军.本文将就目前NSCLC中的EGFR基因突变及其靶向治疗药物进行简要阐述.     

非小细胞肺癌接受奥希替尼靶向治疗后出现间质性肺病1例报道

我国是肺癌大国,发病率和死亡率都很高,其中非小细胞肺癌(non-small cell lung cancer,NSCLC)占绝大部分。表皮生长因子受体(EGFR)突变型肺癌属于NSCLC,第一代表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKIs)(如吉非替尼及厄洛替尼)为其首选治疗方案。但有学者报道,尽管接受EGFR-TKIs治疗的病人在初期反应显著,但由于获得性耐药,常在接受治疗后9~13个月内发生疾病进展,超过60%进展病人的肿瘤细胞中可检测到T790M突变,是EGFR-TKIs最常见的耐药机制[1]。     

晚期非小细胞肺癌中老年患者胸水表皮生长因子受体基因突变及其酪氨酸激酶抑制剂靶向治疗效果

目的分析晚期非小细胞性肺癌(NSCLC)中老年患者胸水表皮生长因子受体(EGFR)基因突变及EGFR-酪氨酸激酶抑制剂(EGFR-TKIs)靶向治疗的临床效果。方法共纳入NSCLC患者74例,均为一线化疗方案无效,行EGFR 19和21位点检测,对EGFR野生型41例(对照组)更改化疗方案,对EGFR突变型33例(观察组)采用靶向药物吉非替尼250 mg/d,疗程为3个月,对比临床效果。结果 EGFR突变与患者性别、年龄、肿瘤分期及直径无相关性(P0. 05)。观察组的无进展生存时间延长,客观有效率和疾病控制率高于对照组,差异有统计学意义(P0. 05)。两组化疗严重不良反应发生率比较无显著差异(P0. 05)。结论 EGFR基因突变的靶向治疗可改善晚期NSCLC患者的生存预后。     

EGFR-TKI治疗非小细胞肺癌EGFR突变阳性脑转移的临床对比观察

目的探讨EFGR-TKI(厄洛替尼与吉非替尼)治疗非小细胞肺癌(NSCLC)EGFR突变阳性脑转移患者的临床疗效。方法回顾收集分析我科73例EGFR突变阳性的肺腺癌脑转移患者的临床病历资料,患者均口服厄洛替尼150mg/d(39例)或吉非替尼250 mg/d(34例),服药直至患者颅内外病情进展、死亡、出现不可耐受的副反应或不能控制的新发病灶。结果厄洛替尼组与吉非替尼组颅内病变的有效率(RR)和疾病控制率(DCR)分别为51.3%,94.9%和53.0%,94.1%(P=0.861),两组颅外病变的有效率和疾病控制率分别为59.0%,97.4%和50.0%,97.1%(P=0.793),两组患者的中位无进展生存期(PFS)和总生存期(OS)分别为11.3个月和15.1个月vs12.1个月和16.4个月(P=0.913,P=0.641)。两种药物的副反应均较小,患者都可以耐受。结论 EGFR-TKI对EGFR突变阳性的NSCLC脑转移均具有较好地疗效,可作为EGFR突变阳性脑转移患者的一线或二线治疗,药物副反应较小,两种药物对患者的预后无明显差异。     

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.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

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.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.