新辅助化疗方案尼妥珠单抗联合奈达铂和5-氟尿嘧啶治疗下咽鳞癌初步临床分析

目的 探讨尼妥珠单抗联合奈达铂和5-氟尿嘧啶(fluorouracil,5-Fu)新方案,作为新辅助化疗来治疗下咽鳞癌患者术前的疗效和安全性。 方法 对初治的91例下咽鳞癌患者以尼妥珠单抗(300 mg第1天)联合奈达铂(90 mg/m²第1天)和5-Fu(750 mg/m²第1~5天)3周方案作为新辅助化疗,两个周期后予以手术和术后放射治疗。主要研究终点为肿瘤缓解率,次要研究终点为病理完全缓解率、保喉率和化疗相关毒性。 结果 所有入组对象的总体肿瘤缓解率为86.8%(79/91),52例(57.1%)影像学降期,其中47例次(51.6%)达T降期,20例次(22.0%)达N降期。新辅助化疗(1或2个周期)后共88例行手术治疗,其中68例为保留喉功能的下咽癌根治性手术,保喉率为77.3%。8例术后原发灶病理完全缓解,占总入组患者数的8.8%(8/91)。29例(31.9%)出现中性粒细胞减少,26例(28.6%)出现恶心呕吐等胃肠道反应。 结论 尼妥珠单抗联合奈达铂和5-Fu方案作为新辅助化疗可提高下咽鳞癌患者的肿瘤缓解率,且对其毒性耐受良好,多数患者通过新辅助化疗保留喉功能。     

西妥昔单抗联合放化疗治疗头颈部鳞状细胞癌

全世界每年确诊为头颈部鳞状细胞癌的患者超过50万例,占全身恶性肿瘤的5％.且头颈部鳞状细胞癌患者高表达表皮生长因子受体(epidermal growth factor receptor,EGFR),西妥昔单抗作为一种抗EGFR的新型人鼠嵌合性单克隆抗体能有效抑制肿瘤细胞的生长,联合放疗较单纯放疗降低了局部晚期头颈部鳞状细胞癌患者的死亡率,并可提高包括顺铂在内的多种化疗药物疗效.     

碳铂治疗头颈部癌优于顺铂

顺铂是治疗头颈部鳞癌最有效的药物之一,但总的毒性作用发生率较高,碳铂(car-bophtin)是一个很有希望的替代品。作者对未经治疗的头颈部进展期鳞癌,用碳铂、5-氟脲嘧啶联合诱导化疗与顺铂和5-氟脲嘧啶治疗结果进行了对照观察。52例病人,男46,女6,     

术前放疗并用顺铂治疗晚期头颈部鳞癌

顺铂是治疗头颈部癌的有效药物之一,一些包括顺铂在内的化疗方案,获得的肿瘤缓解率超过90％。近来的实验发现,该药还具有放射增敏用用,能有效地抑制放射后组织损伤的自身修复,综合应用顺铂与放疗,比单独应用上述放疗和化疗,肿瘤的缓解率更为显著。作者治疗18例Ⅲ,Ⅳ期头颈鳞癌病人,术前放射剂量4500拉德/5周(180拉德/次)。于放疗开始的第1～4天及第21～24天,每天按20mg/m~2静脉给予顺铂(给药前先给生理盐水500ml输液以保护肾脏)。放疗结束后4～8周手术。结果:16例完成放疗,1例未完     

不宜手术的头颈癌的热化学疗法

不宜手术的头颈癌的治疗,至今仍是一个最棘手的问题,这类病人虽然用化疗、放疗或综合治疗,局部复发及远处转移的危险性仍很大。作者采用高温与化疗结合的方法,对化疗无效并且有局部扩展和复发的头颈部鳞癌患者进行治疗获得了一定的疗效。病例条件如下:头颈部鳞癌(Ⅱ期)至少用了一个疗程的顺氯氨铂和5-Fu联合化疗,只能达到部份有效(肿瘤缩小50%);②正规治疗(如放疗、手术)后复发的头颈部鳞癌,用上述同样的药物化疗无效,同时已确定不再手术者,通过外科方法     

局部晚期头颈部鳞状细胞癌的化疗及靶向进展

局部晚期头颈部鳞状细胞癌目前主要采用手术、放疗和化疗相结合的综合治疗,但是器官功能保留率和5年生存率没有显著提高。从20世纪70年代末开始,以顺铂为基础的化疗药开始应用于局部晚期头颈部鳞状细胞癌治疗中,研究表明,顺铂联合氟尿嘧啶作为诱导化疗方案提高了喉功能保全率。后来随着紫杉醇的应用,有研究证实在PF方案基础上加用紫杉醇可提高诱导化疗的疗效。与PF方案相比,TPF方案在局部控制率及无进展生存期上有显著的优越性,因此,成为诱导化疗的首选方案。20世纪90年代初期,同步放化疗成为非手术治疗及保喉的新方式,因其在总体生存率、保喉率、局部控制率上有明确的优势,已被列入局部晚期头颈部肿瘤非手术治疗的标准治疗方案。2006年分子靶向治疗药物西妥昔单抗经美国食品和药物管理局批准运用于临床,因其预后的优势及较少的不良反应成为无法耐受化疗药物的新选择。就局部晚期头颈部鳞状细胞癌的化疗药物及靶向药物治疗进展进行综述。     

局部晚期喉咽鳞状细胞癌紫杉醇+顺铂+氟尿嘧啶方案诱导化疗#br# 的近期疗效观察

目的　观察紫杉醇+顺铂+氟尿嘧啶（TPF）方案诱导化疗对局部晚期喉咽鳞状细胞癌（简称鳞癌）的近期疗效及毒副反应。方法　选取2011 年1 月～2013 年10 月于 本院首次治疗的局部晚期喉咽鳞癌患者78例,采用TPF方案诱导化疗2周期,复查影像学检查,评价疗效。结果  全组78例患者共完成156周期化疗,均可评价疗效。其中 完全缓解（complete remission,CR）4例（5.1%）,部分缓解（partial remission,PR）55例（70.5%）,稳定（stable disease,SD）17例（21.8%）,进展（progression disease,PD）2例（2.6%）。总有效率（CR+PR）75.6%,Ⅲ/Ⅳ度副反应发生率低。Logistic回归分析显示,有效率与肿瘤中低分化有显著相关性。结论　对于局部晚期喉咽鳞癌患者,TPF方案诱导化疗显示了良好的疗效及安全性,可作为局部晚期喉咽癌诱导化疗的选择。同时提示病理分化程度为中低分化的肿瘤患者,更可能从诱导化疗中获益。     

T3、T4喉及喉咽鳞癌的化疗与放疗

目的用化疗与放疗综合治疗10例晚期喉和喉咽鳞癌,保留器官,替代手术治疗.方法化疗与放疗按一定程序给予顺铂和5-氟尿嘧啶3个周期,放疗总量至70Gy.结果原发灶肿块完全消退者(CR)7例,肿块最大直径和最小直径乘积缩小≥50%者(PR)3例;颈部转移淋巴结CR5例,PR3例.2年生存率70%.结论对晚期喉、喉咽鳞癌,化放疗不仅疗效好,并且保留了器官,提高了患者生存质量.     

头颈部癌诱导化疗后细胞凋亡与DNA含量的研究

目的：了解头颈部癌手术前诱导化疗后肿瘤细胞的凋亡情况及ＮＤＡ含量的变化，为诱导化疗后及手术切缘的设计提供理论基础。材料与方法：对３０例未经治疗的头颈部鳞状细胞癌应用顺铂、平阳霉素、甲氨喋呤的联合化疗方案，化疗一周后手术，取肿瘤组织及肿瘤退缩区组织进行常规病理及流式细胞仪检查。结果 化疗肿瘤组织及退缩区组织细胞凋恨较化疗前明显增高（分别为１１．４７％、１４．９２％及０．６９％，Ｐ〈０．０５），化疗后     

Antioxidants Reduce Cellular and Functional Changes Induced by Intense Noise in the Inner Ear and Cochlear Nucleus

The present study marks the first evaluation of combined application of the antioxidant N-acetylcysteine (NAC) and the free radical spin trap reagent, disodium 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), as a therapeutic approach for noise-induced hearing loss (NIHL). Pharmacokinetic studies and C-14 tracer experiments demonstrated that both compounds achieve high blood levels within 30 min after i.p injection, with sustained levels of radiolabeled cysteine (released from NAC) in the cochlea, brainstem, and auditory cortex for up to 48 h. Rats exposed to 115 dB octave-band noise (10–20 kHz) for 1 h were treated with combined NAC/HPN-07 beginning 1 h after noise exposure and for two consecutive days. Auditory brainstem responses (ABR) showed that treatment substantially reduced the degree of threshold shift across all test frequencies (2–16 kHz), beginning at 24 h after noise exposure and continuing for up to 21 days. Reduced distortion product otoacoustic emission (DPOAE) level shifts were also detected at 7 and 21 days following noise exposure in treated animals. Noise-induced hair cell (HC) loss, which was localized to the basal half of the cochlea, was reduced in treated animals by 85 and 64 % in the outer and inner HC regions, respectively. Treatment also significantly reduced an increase in c-fos-positive neuronal cells in the cochlear nucleus following noise exposure. However, no detectable spiral ganglion neuron loss was observed after noise exposure. The results reported herein demonstrate that the NAC/HPN-07 combination is a promising pharmacological treatment of NIHL that reduces both temporary and permanent threshold shifts after intense noise exposure and acts to protect cochlear sensory cells, and potentially afferent neurites, from the damaging effects of acoustic trauma. In addition, the drugs were shown to reduce aberrant activation of neurons in the central auditory regions of the brain following noise exposure. It is likely that the protective mechanisms are related to preservation of structural components of the cochlea and blocking the activation of immediate early genes in the auditory centers of the brain.     

对我国变应性鼻炎动物实验研究的评价与思考

目的　通过对我国变应性鼻炎动物模型研究现状进行分析,以期对今后变应性鼻炎动物实验研究提出一些设想和建议。方法　回顾分析1998年1月～2014年12月国内有关变应性鼻炎模型所用实验动物种类、品系、复制动物模型方法及其判断标准。结果　137篇文章中所用实验动物种类、品系、复制动物模型的方法及其判断标准各异。 结论　只有标准化、统一化的实验前提,才能保证科研工作的顺利实施和实验结果的可靠性。     

非变应性鼻炎与变应性鼻炎临床特点初步分析

目的 探讨高反应性非变应性鼻炎(hyperreactivity non-allergic rhinitis,HNAR)与变应性鼻炎(allergic rhinitis,AR)在性别、年龄分布、发病季节、诱因及临床表现的差异.方法 选择2009年1-8月398例以高反应性鼻部症状首诊的诊断为HNAR及AR的连续患者,以SPSS 17.0软件对其性别、年龄、发病季节、分型、诱发因素及临床症状等因素进行统计分析.结果 HNAR与AR的性别分布差异有统计学意义(χ2=6.415,P=0.01),HNAR女性患者居多,AR以男性为主;在发病年龄上,HNAR以中青年为主,高发年龄在30～39岁(χ2=51.533,P=0.00),AR以青少年为主,高发年龄在10～19岁(χ2=12.772,P=0.00);HNAR发病无明显季节性,AR发病多在秋季.AR变应原以艾蒿和豚草为主.AR以中-重度持续性为主(χ2=123.991,P=0.00),HNAR以中-重度间歇性为主(χ2=97.420,P=0.00);除鼻痒外,AR较HNAR鼻部及眼部的临床症状重(P值均<0.05);非特异性诱发因素在AR与HNAR患者发病过程中的作用大致相似(统计值,P>0.05).结论 AR与HNAR在性别构成、主要发病年龄、鼻炎分型及发病季节上有明显差异,除鼻痒外AR鼻部及眼部临床症状较HNAR重,但在发病诱因上呈一致性.     

喉癌组织中Survivin和p63的表达及临床意义

目的：探讨Survivin、p63在喉鳞状细胞癌（LSCC）组织中的表达及与LSCC发生、发展的关系和生物学意义。方法：应用原位分子杂交方法,检测Survivin mRNA、p63 mRNA在47例LSCC组织、癌旁组织及14例正常喉组织中的表达。结果：①Survivin mRNA在正常喉组织中不表达;在LSCC组织、癌旁组织中的阳性表达率分别为59．6％（28／47）、25．5％（12／47）,其差异有统计学意义（P〈0．05）;组织分化程度越低、TNM分期越晚、淋巴结转移率越高,则Survivin mRNA表达越强（均P〈0．05）。②p63mRNA在LSCC组织、癌旁组织中的阳性表达率分别为91.5％（43／47）、93．6％（44／47）,分别与正常喉组织（57．1％）比较,差异有统计学意义（P〈0．05）;p63 mRNA与喉癌临床病理特征无关。结论：Survivin在LSCC中表达上调,提示其通过抑制细胞凋亡在LSCC的发生、发展过程中起重要作用,可能成为LSCC基因治疗的新靶点;其高表达预示肿瘤有较高的侵袭性和不良预后。p63对LSCC生物学行为的影响较小。     

Humming in Tune: Sex and Species Recognition by Mosquitoes on the Wing

Mosquitoes are more sensitive to sound than any other insect due to the remarkable properties of their antennae and Johnston’s organ at the base of each antenna. Male mosquitoes detect and locate female mosquitoes by hearing the female’s flight tone, but until recently we had no idea that females also respond to male flight tones. Our investigation of a novel mechanism of sex recognition in Toxorhynchites brevipalpis revealed that male and female mosquitoes actively respond to the flight tones of other flying mosquitoes by altering their own wing-beat frequencies. Male–female pairs converge on a shared harmonic of their respective fundamental flight tones, whereas same sex pairs diverge. Most frequency matching occurs at frequencies beyond the detection range of the Johnston’s organ but within the range of mechanical responsiveness of the antennae. We have shown that this is possible because the Johnston’s organ is tuned to, and able to detect difference tones in, the harmonics of antennal vibrations which are generated by the combined input of flight tones from both mosquitoes. Acoustic distortion in hearing organs exists usually as an interesting epiphenomenon. Mosquitoes, however, appear to use it as a sensory cue that enables male–female pairs to communicate through a signal that depends on auditory interactions between them. Frequency matching may also provide a means of species recognition. Morphologically identical but reproductively isolated molecular forms of Anopheles gambiae fly in the same mating swarms, but rarely hybridize. Extended frequency matching occurs almost exclusively between males and females of the same molecular form, suggesting that this behavior is associated with observed assortative mating.     

Different Cellular and Genetic Basis of Noise-Related Endocochlear Potential Reduction in CBA/J and BALB/cJ Mice

The acute and permanent effects of noise exposure on the endocochlear potential (EP) and cochlear lateral wall were evaluated in BALB/cJ (BALB) inbred mice, and compared with CBA/J (CBA) and C57BL/6 (B6) mice. Two-hour exposure to broadband noise (4–45 kHz) at 110 dB SPL leads to a ~50 mV reduction in the EP in BALB and CBA, but not B6. EP reduction in BALB and CBA is reliably associated with characteristic acute cellular pathology in stria vascularis and spiral ligament. By 8 weeks after exposure, the EP in CBA mice has returned to normal. In BALBs, however, the EP remains depressed by an average ~10 mV, so that permanent EP reduction contributes to permanent threshold shifts in these mice. We recently showed that the CBA noise phenotype in part reflects the influence of a large effect quantitative trait locus on Chr. 18, termed Nirep (Ohlemiller et al., Hear Res 260:47–53, 2010b). While CBA “EP susceptibility” alleles are dominant to those in B6, examination of (B6 × BALB) F1 hybrid mice and (F1 × BALB) N2 backcross mice revealed that noise-related EP reduction and associated cell pathology in BALBs are inherited in an autosomal recessive manner, and are dependent on multiple genes. Moreover, while N2 mice formed from B6 and CBA retain strong correspondence between acute EP reduction, ligament pathology, and strial pathology, N2s formed from B6 and BALB include subsets that dissociate pathology of ligament and stria. We conclude that the genes and cascades that govern the very similar EP susceptibility phenotypes in BALB and CBA mice need not be the same. BALBs appear to carry alleles that promote more pronounced long term effects of noise on the lateral wall. Separate loci in BALBs may preferentially impact stria versus ligament.     

变应性真菌性鼻-鼻窦炎的诊断与治疗

目的 探讨变应性真菌性鼻-鼻窦炎（allergic fungal rhino sinusitis, AFRS）的临床特点及治疗方法。方法 回顾性分析确诊的16例AFRS的临床表现、CT扫描结果、血清检测、皮肤点刺实验、术后病理结果以及鼻内镜手术治疗效果。结果 AFRS患者临床表现不典型,CT有特异性表现,病理切片可见真菌菌丝。16例患者中有5例复发,再次治疗后无复发。结论 诊断AFRS主要依据病史、CT表现、病理学检测。鼻内镜手术结合激素应用是治疗AFRS的有效手段。     

Altered dipeptidyl peptidase IV and prolyl endopeptidase activities in chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia

Objective

To analyse peptidase activities in the removed tonsils and adenoids from patients with chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia.

Methods

We have analyzed 48 tissue samples from patients undergoing tonsillectomy and adenoidectomy for chronic tonsillitis, tonsillar hyperplasia or adenoid hyperplasia. Tonsillectomy and adenoidectomy samples were collected and frozen for later enzyme analysis. The catalytic activity of a pool of peptidases (dipeptidyl peptidase IV, prolyl endopeptidase, aminopeptidase A, aminopeptidase N, aspartyl aminopeptidase, aminopeptidase B, neutral endopeptidase, pyroglutamyl peptidase I, puromycin-sensitive aminopeptidase and cystinyl aminopeptidase) was measured fluorometrically.

Results

The activity of prolyl endopeptidase was higher in tonsillar hyperplasia and adenoid hyperplasia than in chronic tonsillitis. On the contrary, dipeptidyl peptidase IV activity was higher in chronic tonsillitis than in hypertrophic tissues. When data were stratified by age and gender, dipeptidyl peptidase IV was also found to be more active in adult and male chronic tonsillitis tissues. Inversely, dipeptidyl peptidase IV activity was higher in tissues of females with tonsillar hyperplasia.

Conclusions

These data indicate the involvement of dipeptidyl peptidase IV and prolyl endopeptidase in the mechanisms underlying chronic tonsillitis, tonsillar hyperplasia and adenoid hyperplasia.