32P-胶体内照射治疗浅表实体瘤的疗效观察

目的:评价32P胶体内照射治疗浅表实体瘤的临床效果.方法:对23例浅表实体肿瘤进行32P胶体瘤内注射,按照每cm3肿瘤应用18.5MBq32P胶体进行计算,注射总量不超过740MBq,2个月后评价疗效.结果:瘤体内注射32P制剂后肿瘤生长明显受到抑制,抑瘤率达到69.5%.肿瘤完全缓解的2例(8.69%),部分缓解14例(60.86%),无变化7例(30.43%).结论:32P胶体治疗实体肿瘤的疗效肯定,值得进一步研究.     

聚合白蛋白和^32P胶体内照射治疗肝癌的疗效观察

目的 探讨聚合白蛋白（MAA）和^32P胶体内照射治疗肝癌的疗效和副作用。方法 26例肝癌患者受B超引导下瘤内注射MAA和^32P胶体治疗，观察治疗前后患者的临床表现、肿物大小、甲胎球蛋白（AFP)水平、组织病理学以及肝肾功能、血常规和免疫指标。结果 治疗后临床症状减轻，AFP水平下降；组织学显示治疗区肿瘤组织完全或部分坏死、纤维化。完全缓解（CR）2例，部分缓解（PR）13例，好转（MR）2例，稳定（SD）7例，进展（PD）2例，总有效率为57．7％。5例治疗后行二期手术。1、2、3年生存率分别为88．5％、76．9％、38．5％，中位生存期16个月。局部无并发症，治疗前后肝肾功能、血常规和免疫指标无变化。结论 MAA和胶体^32P内照射治疗肝癌是一种简单、安全和有效的新方法，副作用小、适应证广。     

聚合白蛋白和^32P胶体治疗原发性肝癌的临床分析

目的：观察超声引导下瘤内注射聚合白蛋白（MAA）和^32P胶体治疗原发性肝癌（PHC）的疗效和不良反应。方法：观察26例PHC患者治疗前后的临床表现、肿块大小、血清AFP水平、组织病理学以及肝肾功能、血常规和免疫指标的变化。结果：治疗后,PHC患者临床症状减轻,21例AFP升高者的血清AFP水平明显下降;肿块均见缩小,肿块缩小率≥50％者占78．38％,平均肿块缩小率为53．25％,组织学检查发现治疗区内肿瘤组织出现完全或部分坏死和纤维化。患者1、2、3年生存率分别为88．46％、76．92％、38．46％,平均生存期为16．5个月。局部无并发症。治疗前后ECG、肝肾功能、血常规和免疫功能均无变化。结论：瘤内注射聚合白蛋白和^32P胶体是1种简单、安全而有效的治疗PHC的新方法,不良反应轻、适应证广。     

放射性同位素^32P治疗脑肿瘤的初步观察

目的：探讨放射性同位素^32P治疗脑肿瘤的疗效。方法：采用立体定向仪和开颅手术方法,通过肿瘤囊内注入和术中肿瘤残腔内放入放射性同位素^32P胶体。结果：14例患者中,3例颅咽管瘤瘤体缩小。3例脑转移瘤和8例脑胶质瘤疗效满意,毒副反应轻微。结论：放射性同位素^32P胶体治疗脑肿瘤有良好的效果。     

手术后早期腹腔内β粒子内照射治疗进展期胃贲门癌近期疗效观察

目的：对进展期胃贲门癌术后早期腹腔β粒子内照射治疗的方法及疗效进行评价。方法：３５例进展胃贲门癌患者，於术中完成切除吻合程序后，将软硅胶管置于上腹腔瘤床部位，经上腹壁截孔引出，缝合固定，术后一周消化道功能恢复后开始治疗，将＾３２Ｐ胶体４８－２２２ＭＢｑ（４～６ｍＣｉ）与盐水（２５０～５００ｍｌ）混合经导管注入腹腔结果：腹腔内照射组１、２、３年生存率分别为：８２．８６％、７７．１４％、６８．５８％。     

32P胶体联合激素治疗海绵状血管瘤临床分析

海绵状血管瘤是一种先天性良性肿瘤，在各种血管瘤中危害最大。笔者自2004年1月～2006年12月观察了^32P胶体联合激素内照射治疗海绵状血管瘤治疗疗效，现报道如下。     

32P胶体介入治疗甲状腺囊腺瘤临床分析

目的:探讨32P胶体联合地塞米松治疗甲状腺囊腺瘤的疗效。方法:收集自2008年1月至2012年5月于本院确诊的甲状腺囊腺瘤患者112例,全部患者随机分为两组:32P胶体联合地塞米松治疗组56例,32P胶体治疗组56例。患者治疗前后均查游离三碘甲状腺原氨酸（FT3）、游离甲状腺素（FT4）、血清促甲状腺素（TSH）、甲状腺球蛋白(TG)、甲状腺微粒体(TM)及血常规。用超声及甲状腺显像测量囊腺瘤大小。用药1个疗程之后,经医学影像检测未发现瘤体,则判定治愈;经医学影像检测发现囊腺瘤直径缩小超过1/2,则判定有效;经医学影像检测发现囊腺瘤缩小不到治疗前1/2或无变化,则判定无效。结果:两组的治疗疗效比较有显著差异（P＜0.05）。两组治疗前后甲状腺激素及血常规检查未发现异常变化,穿刺液未检出癌细胞。治愈病例随访2年未复发。结论:32P胶体联合地塞米松治疗甲状腺囊腺瘤安全且无创,疗效确切,治愈率高,可避免手术损伤,值得临床推广应用。     

32p胶体联合地塞米松治疗甲状腺囊肿的疗效

目的:探讨32p胶体联合地塞米松治疗甲状腺囊肿的疗效及临床价值.方法:采用32p胶体联合地塞米松治疗甲状腺囊肿患者103例,患者按甲状腺囊肿的直径大小分为三组,甲状腺囊肿＜2 cm患者45例,2～ ＜3 cm患者38例,3～ ＜4cm患者20例.患者治疗前后均查FT3、FT4、TSH、TG(甲状腺球蛋白)、TM(甲状腺微粒体)及血常规.用超声及甲状腺显像测量囊肿大小.用药1个疗程之后,经医学影像资料未发现囊肿,则判定治愈;经医学影像资料发现囊肿直径缩小超过1/2,则判定有效;囊肿缩小不到治疗前1/2或无变化,则判定无效.采用卡方检验对结果进行统计.结果:三组的治疗效果比较有显著差异,P ＜0.05.三组治疗前后甲状腺激素及血常规检查未发现异常变化,穿刺液未检出癌细胞.治愈病例随访2年未复发.结论:32p胶体联合地塞米松治疗甲状腺囊肿安全,疗效确切,治愈率高,易被患者接受,具有重要的临床价值.     

^32P持续低剂量率辐射敷贴治疗的胶片剂量验证

目的：对^32P的敷贴治疗进行胶片剂量验证。方法：直线加速器建立25—575cGy的胶片辐射剂量曲线。放射性核素^32P溶液4．14MBq吸附在1．1cm×1．2cm的长方形滤纸上制成放射性敷贴器。将20张1．5cm×1．5cm的辐射直接显色（RC）胶片（胶片厚0．225mm）重叠放置（总厚度4．5mm）,把放射性敷贴器放置在最顶端,辐射0．5小时。通过辐射剂量曲线计算每张胶片辐射剂量,根据胶片厚度推算距离敷贴器不同距离处的辐射剂量,并绘制相应的剂量-距离曲线。结果：距离敷贴器0、0．225、0．45、0．675、0．9、1．125、1．35、1．8、2．025、2．25、2．475mm处的0．5小时辐射测量吸收剂量为265、175、120、98、68、55、39、25、19、16、12、5cGy,拟合曲线为Y：257．28e^-1.4521X。结论：放射性核素^32P敷贴器的辐射剂量随距离增加呈指数方式衰减,敷贴器表面和2．5mm处的辐射剂量相差约53倍。     

用胶体Cr^32PO4—碘油混悬液行肝动脉栓塞并放射治疗原发性肝癌的临床观察

我们采用胶体Ｃｒ＾３２ＰＯ４－碘一混悬液用肝动脉栓塞并内放射治疗原发性肝癌１８例，１３例术后肿瘤有所上，４例稳定。１３例ＡＦＰ术后明显下降。４例获得Ⅱ期切除，切除标本中１例的肿瘤及其卫星结节均未见残留癌细胞。所有病例均能耐受该项治疗。无严重并发症。半年生存率为６１％，３例已逾１年仍生存。     

立体定向穿刺引流联合32P囊内注射治疗囊性脑转移瘤

目的 观察立体定向穿刺引流联合32P囊内注射治疗囊性脑转移瘤的疗效.方法 研究设3个组:A组25例,采用立体定向穿刺引流联合32P囊内注射治疗;B组21例,采用立体定向穿刺引流联合X刀治疗;C组26例,单纯采用X刀治疗.结果 A组、B组和C组总有效率分别为76.0%、66.7%和7.7%,A组和B组总有效率显著高于C组(χ2＝24.163,P＝0.000).1年、2年生存率A组分别为52.0%、16.0%,B组为42.8%、14.3%,C组为19.2%、0,A组和B组1年生存率显著高于C组(χ2＝6.116,P＝0.047).A组1例患者出现癫痫小发作,B组2例患者出现头痛、1例患者出现脑水肿,C组3例患者出现脑水肿.未见其他严重并发症.结论 立体定向穿刺引流联合32P囊内注射治疗囊性脑转移瘤有较好的临床疗效.     

白细胞介素32与肿瘤关系的研究进展

IL-32已发现9种mRNA剪接变异体以及4种主要蛋白亚型,作为新晋促炎细胞因子,IL-32与炎症的关系已逐步明确,但是与肿瘤之间的相关性仍需进一步研究。目前的研究结果表明,IL-32虽然有促癌和抑癌两种作用,但仍以促癌为主。因此,进一步研究IL-32各蛋白亚型与NK-κB的作用机制,探究促癌与抑癌作用转换的关键环节,有望为肿瘤的治疗和预防提供新的思路。     

Inhibitory KIR-HLA receptor-ligand mismatch in autologous haematopoietic stem cell transplantation for solid tumour and lymphoma

Genes that encode killer Ig-like receptors (KIRs) and their HLA class I ligands segregate independently; thus, some individuals may express an inhibitory KIR gene but not its cognate ligand. We hypothesised that these patients with KIR-HLA receptor-ligand mismatch have a low risk of relapse after an autologous haematopoietic stem cell transplantation (HCT). Sixteen consecutive patients with lymphoma or solid tumour were enrolled onto a prospective study. They received high-dose busulphan and melphalan followed by autologous CD133(+) HCT. We found that 8 of the 16 patients experienced disease progression after autologous HCT, including 5 of the 6 patients (83%) with no inhibitory KIR-HLA mismatch and 3 of the 6 patients (50%) with 1 mismatched pair; none of the 4 (0%) patients with 2 mismatched pairs experienced disease progression. Survival analyses showed that inhibitory KIR-HLA mismatch was the only significant prognostic factor (P=0.01). The potential applicability of the receptor-ligand mismatch model to autologous HCTs and to patients with lymphoma or solid tumour is clinically significant because of the prevalence of the HCT procedure.     

Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumour angiogenesis

The brain-specific angiogenesis inhibitor 1 gene has been isolated in an attempt to find fragments with p53 "functional" binding sites. As reported herein and by others, brain-specific angiogenesis inhibitor 1 expression is present in some normal tissues, but is reduced or lost in tumour tissues. Such data and its particular structure prompted the hypothesis that brain-specific angiogenesis inhibitor 1 may act as a mediator in the local angiogenesis balance. We herein demonstrate that brain-specific angiogenesis inhibitor 1 over-expression suppresses tumour angiogenesis, delaying significantly the human tumour growth in immunodeficient mice. The inhibitory effect of brain-specific angiogenesis inhibitor 1 was documented using our intravital microscopy system, strongly implicating brain-specific angiogenesis inhibitor 1 as a mediator in the control of tumour angiogenesis. In contrast, in vitro tumour cell proliferation was not inhibited by brain-specific angiogenesis inhibitor 1 transfection, whereas some level of cytotoxicity was assessed for endothelial cells. Immunohistochemical analysis of tumour samples confirmed a reduction in the microvessel density index in brain-specific angiogenesis inhibitor 1-overexpressing tumours. At messenger level, moderate changes could be detected, involving the down-regulation of vascular endothelial growth factor and collagenase-1 expression. Furthermore, brain-specific angiogenesis inhibitor 1 expression that was lost in a selection of human cancer cell lines could be restored by wild-type p53 adenoviral transfection. Brain-specific angiogenesis inhibitor 1 should be considered for gene therapy and development of efficient drugs based on endogenous antiangiogenic molecules.     

Apoptosis,cancer and the p53 tumour suppressor gene

One of the most commonly detected abnormalities in human cancer is mutation of the p53 tumour suppressor gene. Intrinsic to the function of p53 is its ability to induce apoptotic cell death and to cause cell cycle arrest. Moreover, p53 plays an important role in controlling the cellular response to DNA damaging agents such as ionizing radiation and cancer chemotherapeutic drugs. Loss of p53 function causes increased resistance to radiation and chemotherapeutic agents, and there is increasing evidence that p53 mutational status is an important determinant of clinical outcome in cancer. This review will focus on recent data describing the biochemistry of p53 function, its role in mediating apoptosis and cell cycle arrest and in the control of tumour growth and death.     

Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation

Background:

Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development.

Methods:

To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53^lox/lox/FAK^+/+/WapCre, p53^lox/lox/FAK^flox/+/WapCre and p53^lox/lox/FAK^flox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53^R270H, the mouse equivalent of human p53^R273H hot spot mutation, together with conditional deletion of FAK, P53^R270H/+/FAK^lox/+/WapCre and p53^R270H/+/FAK^flox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours.

Results:

Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53^R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures.

Conclusions:

Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion kinase deletion reduced proliferative capacity of p53 null and p53^R270H mammary epithelial cells but did not lead to increased apoptosis in vivo. Our data identify FAK as an important regulator in mammary epithelial cell proliferation in p53-mediated and p53^R270H-induced mammary tumour development.