基因治疗在头颈恶性肿瘤的应用

头颈鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)是头颈部恶性肿瘤的主要病理类型,约占所有头颈部肿瘤的90%,其发病率在过去20年内逐渐上升。据美国癌症学会2007年公布的数据,HNSCC位居恶性肿瘤发病率的     

解读WHO(2017)鼻咽部肿瘤分类

<正>鼻咽为口腔上方颅底至腭帆平面以上管状结构,经后鼻道连接口咽。鼻咽顶壁与后壁交界处的淋巴组织称腺样体或咽扁桃体,在IARC(国际癌症研究机构)2017年2月发行的第4版《WHO头颈部肿瘤分类》~([1])(简称新版)中归于口咽部。尽管鼻咽面积有限,疾病/肿瘤类型较少,但鳞状细胞癌 (squamous cell carcinoma, SCC)在头颈部占首位,显著多于鼻腔鼻窦或口咽,与口咽同名肿瘤多与HPV感染引起不同~([2]),鼻咽SCC肿瘤发生与     

KLF6、p21及c-Jun在头颈部肿瘤组织芯片中的表达

目的:了解Krüppel样因子6(Krüppel-like factor 6,KLF6)、p2l及c-Jun在头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)的表达及临床病理学意义.方法:应用高通量组织芯片结合免疫组化,半定量检测分析HNSCC组织芯片中KLF6、p21及c-Jun的表达水平.结果:KLF6在正常组织、良性肿瘤及恶性肿瘤的表达分别为83.33%、64.29%、57.14%,3组间表达差异有显著性(P＜0.05);恶性肿瘤p21的表达明显低于正常组织和良性肿瘤;c-Jun在正常组织、良性肿瘤及恶性肿瘤的表达分别为33.33%、64.29%、92.86%,3组间表达差异有显著性(P＜0.05).KLF6与c-Jun表达呈正相关(P＜0.05);KLF6与p21的表达也呈正相关(P＜0.05).结论:KLF6、p21和c-Jun与HNSCC的发生发展有关,在病理学诊断上联合检测3个指标有重要的参考价值.     

头颈部鳞状细胞癌相关基因的生物信息学分析

目的从基因和分子水平探讨头颈部鳞状细胞癌(head and neck squamous cell carcinoma,HNSCC)的发生机制。方法从GEO数据库下载人HNSCC相关基因芯片数据,使用BRB-Array Tools软件筛选差异表达基因,采用DAVID、ToppGene、STRING、Cytoscape工具进行生物信息学分析。结果 BRB分析共筛选出263条差异表达基因,其中上调基因134个,下调基因共129个,对其进行生物信息学分析发现COL1A1、MMP9、COL1A2、COL3A1、MMP1等基因调节HNSCC细胞外基质受体相互作用、小细胞肺癌、肿瘤通路等,影响肿瘤的发生发展。结论利用生物信息学分析能有效挖掘基因芯片内在数据,为进一步探讨HNSCC的发生机制提供理论参考。     

局部或区域晚期头颈鳞癌放化疗联合治疗现状和展望

头颈部鳞状细胞癌的全身治疗包括细胞毒药物治疗（简称化疗）、靶向治疗和支持治疗;而局部治疗主要包括放射治疗和手术。放化疗联合是局部晚期或区域晚期头颈部鳞癌主要治疗模式,包括同步化放疗、诱导化疗、序贯化放疗。本文综述了原发于口腔、口咽、下咽、喉的鳞癌的化放疗联合治疗现状和进展。     

局部晚期头颈部鳞状细胞癌术后同期放化疗的疗效分析

目的观察局部进展期头颈部鳞状细胞癌术后放疗,同期多西他赛联合顺铂方案化疗的疗效,探讨提高术后放疗疗效的方法。方法回顾性分析2008年3月至2011年12月行术后同期放化疗的79例头颈部鳞状细胞癌患者治疗资料,原发灶位于口咽、喉或喉咽,术后有以下高危因素:淋巴结包膜外侵犯;手术切缘阳性;病理学为T4或N2、N3。根据复发风险处方照射剂量,同期多西他赛联合顺铂方案化疗,3周1次。用Kaplan-Meier法分析生存获益及无进展生存率,RTOG毒性标准评价放疗引起的急性与晚期毒性反应,NCI化疗毒性标准评价化疗毒性反应。结果中位随访38个月,全组共9例发生局部区域复发。2年局部区域控制率92%,2年无进展生存率75%,2年总体生存率87%。Ⅲ度或以上治疗相关毒性反应:粒细胞缺乏(59%),黏膜损伤(47%),口干(6%),肌纤维化(10%),吞咽困难(8%)及皮肤损伤(13%),9例患者发生咽瘘,无治疗相关死亡。结论局部进展期头颈部鳞状细胞癌术后放疗,同期多西他赛联合顺铂方案化疗是安全、有效的治疗手段。     

子宫颈鳞状细胞癌浅表性扩散临床病理观察

<正>子宫颈鳞状细胞癌仅在毗邻宫腔子宫内膜表面浅表性扩散蔓延而不浸润子宫内膜间质及内膜下肌层称为浅表扩散性鳞状细胞癌(Superficial spreading squamous cell carcinoma,SSSCC),鲜见报道。本文回顾性分析了1例子宫颈鳞状细胞癌浅表性扩散累及双侧输卵管病例,并结合文献探讨此类病变的临床表现、组织学特征、生物学行为及其诊断、鉴别诊断、治疗和预后。     

HPV16/18、P16蛋白在头颈部鳞状细胞癌中的表达及意义

目的探讨头颈部鳞状细胞癌中高危型HPV感染、P16蛋白表达及临床病理意义。方法采用组织原位杂交及免疫组化Envision技术检测头颈部鳞状细胞癌中高危型HPV16/18及P16蛋白的表达,并进行临床病理分析。结果 (1)HPV16/18在口腔癌中的表达率为80%(8/10)、下咽癌78%(11/14)、鼻咽癌0(0/7)、唇癌33.3%(1/3)、头颈部皮肤鳞癌33.3%(2/6),口腔癌、下咽癌中HPV16/18表达率显著高于鼻咽癌、唇癌及头颈部皮肤鳞癌(P=0.001<0.05);(2)P16蛋白在口腔癌中的表达率为70%(7/10)、下咽癌71.4%(10/14)、鼻咽癌0(0/7)、唇癌33.3%(1/3)、头颈部皮肤鳞癌33.3%(2/6)。口腔癌、下咽癌中P16表达率显著高于鼻咽癌、唇癌及皮肤鳞癌,鼻咽癌为阴性表达,差异具有统计学意义(P=0.001<0.05);(3)临床病理分析:组织学分级中HPV16/18在高分化、中分化及低分化鳞状细胞癌的阳性率分别为25%(2/8)、76.1%(16/21)、36.3%(4/11),P16在高分化、中分化及低分化鳞状细胞癌的阳性率分别为87.5%(7/8)、42.9%(9/21)、36.3%(4/11),差异具有统计学意义(P均<0.05);二者在年龄、性别中表达差异无显著性(P均>0.05)。结论 (1)头颈鳞状细胞癌中,HPV16/18、P16与肿瘤发生部位及肿瘤分化程度差异有显著性,分化程度越低,HPV16/18及P16蛋白表达越低;(2)HPV16/18的感染与P16蛋白的表达具有一致性。     

以颈部囊性转移为首发症状的扁桃体鳞状细胞癌一例及文献复习

目的：探讨以颈部囊性转移为首发症状的扁桃体鳞状细胞癌的临床病理组织学特点、诊断及鉴别诊断。方法复习1例以颈部囊性转移为首发症状的扁桃体鳞状细胞癌的相关临床资料,对其进行免疫组织化学及HPV基因分型检测,并结合文献进行探讨。结果患者临床症状与体征酷似颈部淋巴结核,病理组织学与鳃裂癌相似。免疫组织化学染色 p16阳性,P53（＋）,Ki-67指数约20%,HPV 基因分型HPV16型阳性。结论扁桃体鳞状细胞癌以首发颈部囊性转移性包块症状者少见,其临床需要与颈部淋巴结核及鳃裂癌鉴别,避免误诊。     

口腔鳞癌中Angiopoietin的表达及功能的研究进展

口腔鳞状细胞癌(oral squamous cell carcinoma)是一种常见的实体肿瘤,占所有恶性肿瘤的4%.有研究显示[1-2]:在下一个十年,许多癌症的发生率会下降,而口腔鳞状细胞癌的发生率却会显著上升.虽然手术和放疗在不断改进,但口腔鳞状细胞癌的治疗仍然存在困难,生存率未发生大的改观.肿瘤的生长和转移是依赖于血管生成(angiogenesis)的.     

Is chemoimmunotherapy a game changer in the treatment of locally advanced head and neck squamous cell carcinoma?

Pembrolizumab and chemotherapy (chemoimmunotherapy) were administered to 2 head and neck squamous cell carcinoma (HNSCC) patients with extremely advanced local tumors and distant metastases with palliative intent. However, they demonstrated strikingly good responses and achieved remission. Expanded application of induction chemoimmunotherapy may be useful for locally advanced HNSCC.     

探测前哨淋巴结在乳腺癌、早期宫颈癌和头颈鳞癌中的应用

目的评价核素淋巴显像和γ探针定位在乳腺癌、宫颈癌和头颈鳞癌中确定前哨淋巴结(SLN)的应用价值。方法女性乳腺癌116例,体检腋窝未扪及肿块。应用99Tcm-DX37~74MBq(1~2mCi)经皮下注射,或术中注射专利兰1ml,术中用γ探针定位并行前哨淋巴结活检,与手术、病理对照。宫颈癌27例,体检盆腔未扪及肿块。应用99Tcm-DX74MBq(2mCi)在宫颈肿瘤周围2°或10°处或99Tcm-SC74MBq(2mCi)阴道镜直视下四点注射,行核素淋巴显像后,手术后的标本用γ探针行体外定位,并与病理的结果加以对照。N0头颈鳞癌10例,99Tcm-DX74MBq(2mCi)肿瘤周围成分下注射,术中用γ探针定位并行前哨淋巴结活检,与手术、病理对照。结果116例乳腺癌中活检SLN108例,灵敏度为92.6%(22/27例),特异性100%(81/81例)。27例宫颈癌中SLN的灵敏度为100%(6/6例),特异性100%(21/21例)。10例N0头颈鳞癌中SLN转移3例,NSLN转移1例。结论核素淋巴显像和γ探针定位应用于乳腺癌、宫颈癌和N0头颈鳞癌是切实可行和可能的,这是一种简便、安全、易被病人接受的探测前哨淋巴结的检查方法,对预测腋窝淋巴结、盆腔淋巴结等转移有很大的临床实用价值。     

Rethinking the head and neck cancer population: the human papillomavirus association

Head and neck squamous cell carcinoma (HNSCC) is the tenth most commonly diagnosed form of cancer in males worldwide. Although the incidence of HNSCC is relatively low in the United States, the affected population is changing from older males to young Caucasian males. High-risk strains of the human papillomavirus (HPV) already are associated with cervical, oral, and anal cancers; however, HPV DNA has been detected in about a third of head and neck malignancies. Nurses play major roles in educating the public and treating patients with HPV and HNSCC. Many possibilities for outreach and research exist that could decrease HPV and HNSCC rates.     

Reversal of cisplatin resistance with a BH3 mimetic, (-)-gossypol, in head and neck cancer cells: role of wild-type p53 and Bcl-xL

Organ preservation protocols in head and neck squamous cell carcinoma (HNSCC) are limited by tumors that fail to respond. We observed that larynx preservation and response to chemotherapy is significantly associated with p53 overexpression, and that most HNSCC cell lines with mutant p53 are more sensitive to cisplatin than those with wild-type p53. To investigate cisplatin resistance, we studied two HNSCC cell lines, UM-SCC-5 and UM-SCC-10B, and two resistant sublines developed by cultivation in gradually increasing concentrations of cisplatin. The cisplatin-selected cell lines, UM-SCC-5PT and UM-SCC-10BPT, are 8 and 1.5 times more resistant to cisplatin than the respective parental cell lines, respectively. The parental lines overexpress p53 and contain p53 mutations but the cisplatin-resistant cell lines do not, indicating that cells containing mutant p53 were eliminated during selection. Bcl-x(L) expression increased in the cisplatin-resistant lines relative to the parental lines, whereas Bcl-2 expression was high in the parental lines and decreased in the cisplatin-resistant lines. Thus, cisplatin selected for wild-type p53 and high Bcl-x(L) expression in these cells. We tested a small-molecule BH3 mimetic, (-)-gossypol, which binds to the BH3 domain of Bcl-2 and Bcl-x(L), for activity against the parental and cisplatin-resistant cell lines. At physiologically attainable levels, (-)-gossypol induces apoptosis in 70% to 80% of the cisplatin-resistant cells but only in 25% to 40% of the parental cells. Thus, cisplatin-resistant cells seem to depend on wild-type p53 and Bcl-x(L) for survival and BH3 mimetic agents, such as (-)-gossypol, may be useful adjuncts to overcome cisplatin resistance in HNSCC.     

Associations Between [18F]FDG-PET and Complex Histopathological Parameters Including Tumor Cell Count and Expression of KI 67, EGFR,VEGF, HIF-1α, and p53 in Head and Neck Squamous Cell Carcinoma

Molecular Imaging and Biology - Head and neck squamous cell carcinoma (HNSCC) is one of common cancers worldwide. Positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG)...     

A Standardized Framework for Fluorescence-Guided Margin Assessment for Head and Neck Cancer Using a Tumor Acidosis Sensitive Optical Imaging Agent

Molecular Imaging and Biology - Intra-operative management of the surgical margin in patients diagnosed with head and neck squamous cell carcinoma (HNSCC) remains challenging as surgeons still have...     

头颈部鳞状细胞癌术后早期吞咽障碍的临床相关因素

目的 了解头颈部鳞状细胞癌(HNSCC)患者术后早期吞咽障碍的临床相关因素。 方法 对2019年10月至2021年4月在重庆医科大学附属第一医院颌面外科首次接受根治性外科手术治疗HNSCC患者80例,术后2周采用洼田饮水试验、功能性经口摄食量表(FOIs)和M.D.安德森吞咽困难评分量表(MDADI)对患者吞咽功能进行筛查和评价,收集相关随访资料,进行回顾性分析。 结果 HNSCC患者吞咽障碍发生率91.25%。单因素分析显示,肿瘤T分期、部位,同期进行皮瓣修复、颈清扫均会对术后早期吞咽功能产生影响(P < 0.05)。多因素分析显示,肿瘤T分期是吞咽障碍的独立影响因素(B = -5.092, t = -6.770, P < 0.001)。 结论 建议常规评估HNSCC患者术后的吞咽功能,特别是恶性程度高的患者,以便及早干预。     

Head and Neck Cancer: A Review of the Impact of Treatment Delay on Outcome

Delay between the initial symptoms, diagnosis, and the definitive treatment of head and neck cancers is associated with tumor progression and upstaging. These delays may lead to poor outcomes and may mandate more aggressive treatments with unnecessary morbidity and even mortality. The multidisciplinary team approach for the treatment of patients with head and neck cancers has improved organization of standard clinical guidelines, but this development has yet to translate into a demonstrable impact on survival. We review the association between waiting times (time between diagnosis and initiation of treatment) and clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC).