CPC/氨磷汀复合体理化性能和体外细胞学实验研究

对复合有氨磷汀的磷酸钙骨水泥用作骨缺损填充材料进行基础性研究。本研究采用混合-模压法将不同质量比的氨磷汀载入磷酸钙骨水泥制备磷酸钙骨水泥/氨磷汀复合体,分别对其固化时间、力学强度、孔隙率、电镜扫描、对骨肉瘤细胞、血管内皮细胞是否具有保护作用进行观察。研究表明磷酸钙骨水泥中载入0.1%和0.5%氨磷汀不影响磷酸钙骨水泥的固化时间、强度、孔径、孔隙率,对骨肉瘤细胞不具有保护作用,不影响血管内皮细胞的增殖分化。因此在磷酸钙骨水泥中载入0.1%和0.5%氨磷汀在肿瘤性骨缺损的化学治疗中可能是有意义的。     

氨磷汀在头颈部肿瘤放、化疗中应用的观察与护理

放射治疗是头颈部肿瘤最重要的治疗手段之一，尤其在鼻咽癌中，其处于主导地位。而在放疗过程中伴发的放疗副反应，如放射性咽炎、反射性皮炎等放疗反应，无疑会增加患者的痛苦。随者放疗技术的不断进步，头颈部肿瘤的预后越来越好[1]，如何最大限度减轻患者的痛苦示现今我们医务工作者共同探讨的话题。作为美国FDA批准上市的第一个泛细胞保护剂-阿米福汀[2]，近来逐渐应用于临床，但由于其相对副反应较重，也限制了临床应用范围。我院2008~2014年先后收治50例头颈部肿瘤患者，放、化疗过程中应用氨磷汀，有效减轻了放射性咽炎、放射性皮炎的发生率，同时伴发不同程度的副反应，现将护理体会介绍如下。     

放射治疗下实体肿瘤演变的数学模型和数值模拟

目的数值模拟研究放射治疗下放射敏感性系数、治疗频率、肿瘤细胞成熟年龄等因素对实体肿瘤放射治疗效果的影响。方法建立放射治疗下实体肿瘤演变的连续-离散混合数学模型,模型考虑肿瘤的微环境(氧、细胞外基质、基质降解酶)以及自身行为(增殖、凋亡、黏附)对肿瘤演变的影响,并引入线性二次模型描述肿瘤对放射治疗的响应,采用数值模拟方法模拟不同条件下肿瘤演变的过程,评价放射治疗的疗效。结果肿瘤的放射治疗效果与放射敏感性系数、肿瘤细胞成熟年龄正相关,而在放射剂量总量不变的情况下,高频治疗和低频治疗效果并没有特别明显的区别。结论模拟结果与临床结果相吻合,可为肿瘤放射治疗的理论及临床研究提供一种新的方法。     

Fas、Bcl-2在放射损伤小鼠骨髓细胞的表达及意义和川芎嗪对其影响的研究

目的：探讨放射损伤小鼠骨髓细胞Fas、Bcl-2的表达和骨髓细胞凋亡以及川芎嗪对其影响。方法：健康昆明小鼠经6.0Gy^60Coγ照射后立即喂饲川芎嗪并设对照组和正常组，在放射损伤后第3、7、14、21天检测其骨髓细胞Fas、Bcl-2的表达和骨髓细胞凋亡率。结果：照射后骨髓细胞Fas表达增强，Bcl-2表达减弱，骨髓细胞凋亡增加，但川芎嗪能够减轻放射损伤后小鼠骨髓细胞凋亡率，与对照组有显著差异。结论：放射损伤后小鼠骨髓细胞Fas、Bcl-2的表达变化在细胞凋亡过程中起重要作用。川芎嗪具有减轻放射损伤后小鼠骨髓细胞凋亡的作用。     

应用剂量体积直方图分析放疗对心脏毒性影响

目的:本文回顾性研究一组连续收治行放射治疗的恶性胸腺肿瘤病例,应用剂量体积直方图分析心脏受照情况,同时结合临床随访放射性心脏损伤的结果,探讨了影响心脏损伤的因素和避免或减少心脏损伤的有效方法。方法:1983年3月至2001年9月,50例胸腺肿瘤患者在北京大学临床肿瘤学院放射治疗科接受放射治疗。Masaoka分期Ⅱ期14例,Ⅲ期22例和Ⅳ期14例。47例患者接受普通二维技术放射治疗,三例患者接受三维适形放射治疗。治疗的剂量范围为10Gy～84.5Gy穴中位剂量为55Gy雪。根治性放疗20例,术后放疗14例,术前放疗2例和姑息性放疗14例。对所有病例均在三维治疗计划系统上模拟进行CT图象的三维重建和剂量分布的计算,由心脏的剂量体积直方图,借助于正常组织和器官并发症概率模型,计算心脏1/3等效体积的等效剂量,进而导出放射相关心脏疾患发生的概率,并与临床观测结果进行比较。结果:普通照射技术治疗组的心脏等效1/3体积中位剂量为57.9Gy穴21.6Gy～83.3Gy雪;三维适形放射治疗的心脏等效1/3体积中位剂量为26.3Gy穴22.7Gy～52.0Gy雪。全组病例中位随访期为13个月(0.6～111.3个月)。在45例有心脏状况记录的病例中发现7例有放射相关的心脏疾患,SOMA分级1～3级。结论:该研究结果表明,心脏损伤随着心脏等效体积剂量增大而明     

质子和其他放射治疗肿瘤的比较

质子加速器是目前世界上最先进的放射治疗设备。本文对质子和目前各国常用的常规射线(兆伏特级的光子和电子),在肿瘤的放射治疗方面进行了比较。并复习了世界各国用质子治疗肿瘤的经验,介绍质子治疗肿瘤的优点、发展历史以及发展前景。质子束进入人体组织时,其大量的能量集中在接近射程终点,称为Bragg峰。放射治疗医生可以通过调节质子加速器能量的方式,使高能量区集中在病人体内一定的区域;在此高量区的后方,放射剂量骤降为零。因此,医生可以使放射线的高剂量区集中在靶区(肿瘤区),避免周围正常组织部受到照射。而用常规射线照射时,周围正常组织仍受到较高量的照射。用目前先进的三维适形放射治疗和调强放射治疗技术,只需用少数的照射野,即可达到非常满意的放射剂量分布。到2004年2月,世界上已有11个国家正在开展质子治疗工作;已用质子治疗病人35838例。所治疗的肿瘤有眼葡萄膜黑色素瘤、中枢神经系统肿瘤、颅底肿瘤、前列腺癌、非小细胞肺癌、胃肠道肿瘤、鼻咽癌、乳腺癌和官颈癌等,均取得较好的效果。目前已引起世界各国放射治疗学界的重视。     

立体定向放射治疗可抑制肺部癌细胞生长

德国放射肿瘤学会指出，对因年老体弱或有其他重病无法接受手术治疗的肺癌患者来说，立体定向放射治疗是一个有效的治疗选择。     

肿瘤放射治疗物理学的进展

(一)放射物理对肿瘤放射治疗的贡献自X线和镭被发现以来.在九十多年的时间里,放射治疗发展很快。特别是最近三十年,由于放疗设备的发展,肿瘤的放射治疗获得了较好的疗效。其原因有三:(1)放射物理学的进展,特别是射线剂量学精确性和可靠性的提高:(2)高能射线,如钴60治疗机和医用加速器的普遍使用;(3)对肿瘤生物学     

头颈肿瘤放疗后失聪之谜揭开

头颈肿瘤放疗后失聪之谜揭开头颈肿瘤患者放射治疗后，感音神经性耳聋的发生率往往高达３０％～５０％，但这种损伤的机理和防治一直未得到人们的重视。杨新明于１９９３年在导师卢永德教授的指导下，开展内耳电离辐射损伤及防护研究。他采用不同剂量和分割剂量的γ射线照...     

我国立体定向放疗技术治疗肿瘤进展显著

在2005年10月29日至30日第二届全国肿瘤靶向治疗技术大会暨首届立体定向放射治疗技术学术研讨会上获悉，我国在引进国外放射技术的基础上，在临床立体定向放射治疗技术治疗颅内、肺部、肝部等肿瘤方面取得明显进展。本次会议有王忠诚院士、林达院士等来自全国的400多位医务、科研工作者参加。     

In vitro three‐dimensional culture systems of salivary glands

Dry mouth can be caused by salivary gland hypofunction due to Sjögren's syndrome (SS) or radiation therapy for head and neck cancer, and it can also be a side effect of medications. The use of sialagogues effectively increases saliva secretion in patients with dry mouth. However, the application of sialagogues is not always satisfactory because of their side effects, such as sweating, nausea, runny nose and diarrhea. Two‐dimensional (2D) cell cultures have been used not only for drug screening and discovery but also to clarify disease mechanisms. However, three‐dimensional (3D) cell cultures are expected to be even more advantageous than 2D cell cultures. Therefore, we have tried to develop an in vitro cell culture system that can reconstitute 3D salivary glands. Sox9 and Foxc1 were identified as important genes that differentiate mouse embryonic stem cell‐derived oral ectoderm into salivary gland placode. Using these genes and organoid culture systems, we succeeded in generating salivary gland organoids that exhibited a morphology and gene expression profile that were similar to those of the embryonic rudiment from which salivary glands arise in normal mice. These organoids are expected to be a promising tool for disease modeling, drug discovery and regenerative medicine in salivary glands.     

PSA immunoreactivity in a parotid oncocytoma: A diagnostic pitfall in discriminating primary parotid neoplasms from metastatic prostate cancer

Prostate-specific antigen (PSA) is secreted by both normal and neoplastic acinar cells of the prostate gland, and the immunohistochemical detection of PSA is widely accepted as an excellent method for confirming the prostatic origin of metastatic tumor implants in men with prostate cancer. Less recognized is the observation that certain nonprostatic tissues and their neoplastic counterparts also secrete PSA. As one example, salivary gland ducts and certain salivary gland neoplasms have been reported to be immunoreactive for PSA. Potentially, this nonspecificity could be a diagnostic pitfall when using immunoperoxidase on fine-needle aspiration (FNA) biopsy specimens to differentiate metastatic prostate cancer from primary salivary gland tumors. We report on a case where strong PSA immunoreactivity of a parotid oncocytoma led to its confusion with metastatic prostate cancer. Diagn. Cytopathol. 1998;19:221–225. © 1998 Wiley-Liss, Inc.     

Effects of EGF and bFGF on Irradiated Parotid Glands

Radiotherapy is common treatment for head-and-neck cancer, during which the salivary glands are often included within the radiation field. The most common side effect of this treatment is the development of oral dryness (xerostomia). This study considers the administration of epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF or FGF2) at physiological concentrations before and after irradiation in order to repair radiation-induced damage in salivary gland cells. As a preliminary examination of the efficacy of this approach we have characterized the effects of EGF and bFGF on the apoptotic response of 15-Gy irradiated rat salivary glands in vitro. Also, we have developed a controlled-release delivery system to effectively administer the growth factor to the gland since local delivery is essential to avoid unwanted protection of cancer cells. In vitro administration of bFGF prior to and immediately after irradiation partially protected (44%) the rat parotid gland. EGF did not show any significant radioprotective effect on parotid glands after a single 15-Gy irradiation dose. Encapsulation, storage and release of bFGF from biodegradable 50/50 PLGA microspheres did not affect the functionality of the growth factor in vitro.     

Immunohistopathology of Sjögren's syndrome

Sj?gren's syndrome (SS) is characterized by keratoconjunctivitis sicca and xerostomia, which occur in an autoimmune lacrimal and salivary gland disease characterized by lymphocyte infiltrates of exocrine glands and/or Sj?gren's syndrome autoantibody production. It has been reported that aquaporin-5 distribution is abnormal in SS, perhaps as a result of paracrine effect of TNF-alpha. Also the neurogenic regulation of the salivary gland is impaired in SS. Apart from functional changes, the syndrome is also characterized by structural abnormalities of the secretory acinar apparatus. The acinar basement membrane is abnormal as it lacks laminin alpha1 chain, which may impair its capability to induce the progenitor cells to differentiate to acinar cells. CRISP-3 and TMPRSS-2 can be used as androgen markers and LIV-1 and Cyr61 as estrogen markers to study the sexual dimorphism of the salivary glands. Patients with SS seem to have low concentrations of dehydroepiandrosterone, which may predispose women and the exocrine glands to this syndrome.     

Peroxynitrite formation in radiation-induced salivary gland dysfunction in mice

Xerostomia frequently arises in patients with head and neck malignancies that are treated by radiation. However, the mechanisms responsible for the destruction of the salivary gland remain unknown. We previously established a xerostomia model of mice and identified the pathway through which nitric oxide (NO) affects the pathogenesis of radiation-induced salivary gland dysfunction. Although the toxicity of NO alone is modest, NO with superoxide anion (O2(*-)) rapidly forms peroxynitrite (ONOO), a more powerful toxic oxidant. In this study, we used the experimental model to examine: 1) when NO and O2(*-) production is maximum in the salivary gland after irradiation;2) whether peroxynitrite, as assessed by nitrotyrosine production, is responsible for salivary gland dysfunction; and 3) the effect of the iNOS selective inhibitor, aminoguanidine (AG), on nitrotyrosine formation. The increases in production of NO and O2(*-) in the salivary gland peaked on day 7 after irradiation. Nitrotyrosine detected immunohistochemically was significantly reduced by AG in the salivary gland. On the basis of these results, we concluded that NO together with O2(*-) forms the more reactive ONOO, which might be an important pathogenic factor in radiation-induced salivary gland dysfunction.     

Immunotherapy for adenoid cystic carcinoma of salivary glands: Cancer/testis antigens and 5-aza-2′-deoxycytidine

Adenoid cystic carcinoma of salivary glands is the epithelial tumor. There are amount of malignant occurrences of adenoid cystic carcinoma of salivary glands in the head and neck area.Cancer/testis antigens can be found in various malignant tumors, normal adult testis and occasionally placenta, but not in the other normal adult tissues. This characteristic makes Cancer/testis antigens as potential markers to be applied in immunotherapeutic strategies against cancer. It has been shown that in different tumors, the expression of certain Cancer/testis antigens is activated treated with 5-aza-CdR via the demethylation of their promoter CpG islands.It is logical that multiple Cancer/testis antigens may correlate with the clinicopathologic factors of adenoid cystic carcinoma of salivary glands and be the potential markers of prognosis treated with 5-aza-CdR. So the hypothesis will provide the new direction that we can use Cancer/testis antigens as candidate antigens for adenoid cystic carcinoma of salivary glands immunotherapy due to the high expression rate activated with 5-aza-CdR.     

Histopathological study of the human submandibular gland in graft versus host disease

Major salivary gland dysfunction and severe xerostomia is one of the manifestations of graft versus host disease (GVHD). The histopathological evaluation of the major salivary gland in patients with GVHD has never been reported. The pathological findings of the submandibular glands in a GVHD patient who succumbed to the disease are described. Lymphocytic infiltration, parenchymal destruction, and fibrosis were observed, which may provide the pathophysiological mechanism for the xerostomia and hyposalivation observed in GVHD.     

Expression of alpha-methylacyl-CoA racemase (P504s) in various malignant neoplasms and normal tissues: astudy of 761 cases

Alpha-methylacyl CoA racemase (AMACR), also known as P504S, plays an important role in peroxisomal beta-oxidation of branched-chain fatty acids. It has recently been shown that AMACR is highly expressed in prostate cancer and that it may be an important diagnostic marker for prostate carcinoma. However, little is known about expression of AMACR in normal tissues and other malignant tumors. In this study, we investigated expression of AMACR in 539 malignant tumors and 222 normal human tissues of various types by immunohistochemical analysis. mRNA levels of AMACR in normal organs and in selected tumors were assessed by real time PCR. In normal tissue, high expression of AMACR mRNA was identified in liver, kidney and salivary gland, while AMACR protein was detected in liver (hepatocytes), kidney (tubular epithelial cells), lung (only bronchial epithelial cells), and gallbladder (only mucosal epithelial cells). High expression of AMACR mRNA was found in prostate, liver, and kidney cancers but rarely in stomach and bladder cancers. A high percent of adenocarcinomas arising from these organs express AMACR, including 17 of 21 (81%) of hepatocellular carcinomas and 18 of 24 (75%) of renal cell carcinomas. In addition, carcinomas arising from tissues normally not expressing AMACR were also positive for the antigen, including 17 of 18 (94%) prostate carcinomas, 9 of 29 (31%) of urothelial carcinomas, and 4 of 15 (27%) of gastric adenocarcinomas. Two hundred and fifty cases of adenocarcinomas from lung, breast, pancreas, bile duct, adrenal gland, salivary gland, ovary, thyroid and endometrium were negative or rarely positive for AMACR. Neuroendocrine carcinomas rarely expressed AMACR. Melanomas, squamous cell carcinomas, basal cell carcinomas, soft tissue tumors (including epithelioid sarcomas and synovial sarcoma), thymomas, and germ cell tumors were negative for AMACR. Our data provide important baseline information for using AMACR in clinical practice and also are valuable in furthering understanding of the pathogenic role of AMACR in malignant neoplasms.     

Expression and amplification of neu oncogene in pleomorphic adenomas of salivary gland.

Amplification of the neu oncogene and overexpression of its product was found to be a potential marker for aggressive biological behavior in breast cancer. However, the expression of the neu oncoprotein in normal breast ducts and myoepithelial cells has also been demonstrated. Hence, we examined normal salivary gland tissue and 15 cases of pleomorphic adenoma for the expression of the neu oncoprotein by immunohistochemistry using two polyclonal antibodies and 12 cases for the amplification of the neu oncogene using slot blot hybridization. Immunohistochemistry in the normal salivary gland revealed positive staining of all ductal cells. In the pleomorphic adenomas all cellular elements stained to a variable degree. The positive staining was seen in the ductal cells, in the solid sheets, and in chondroid, myxoid, and metaplastic foci. The normal salivary gland and 11 of 12 cases of pleomorphic adenoma showed no increase in copy number of the neu oncogene, whereas one case showed threefold amplification. These results indicate that the neu oncoprotein is expressed but the neu copy number is not increased in normal salivary gland epithelium and in most pleomorphic adenomas. The threefold amplification of the gene in one case may indicate an aggressive biological behavior.