放射性125I粒子植入联合内分泌治疗早期前列腺癌

目的:探讨经会阴超声引导放射性125I粒子植入联合去势治疗早期前列腺癌疗效和不良反应.方法: 39例早期前列腺癌实施经会阴超声引导和适时计划指导放射性125I粒子植入治疗,7例粒子术前行去势术,21例粒子植入后同时行去势术,11例粒子治疗后联合药物去势治疗.粒子治疗的匹配周边剂量(matched peripheral doses,MPD)为145-160Gy,尿道剂量低于400Gy.125I粒子活度0.35-0.50mCi,中位植入69颗(19-97颗).结果: 失败标准为前列腺特异抗原(prostate specific antigen,PSA)治疗后升高>4ng/ml,≤4ng/ml为生物化学无进展生存(biochemical disease-free survival,BDFS).全部患者顺利完成粒子植入术.36例粒子治疗后达到BDFS,3例分别在粒子治疗后6、8和36个月PSA升高,2例行内分泌治疗,1例行外放疗联合内分泌治疗.2年和3年BDFS分别为94.8%(37/39)和92.3%(36/39).粒子植入治疗后Ⅰ级和Ⅱ级直肠不良反应发生率分别为5.1%(2/39)和7.7%(3/39),没有Ⅲ级和Ⅳ级直肠反应.粒子植入治疗后Ⅰ级、Ⅱ级和Ⅲ级尿道不良反应发生率分别为53.8%(20/39)、17.9%(7/39)和2.6%(1/39),对症处理好转.2例粒子移位,没有相关并发症.结论: 经会阴超声引导放射性125I粒子植入治疗前列腺癌具有安全、微创、并发症发生率低等优点.     

放射性^125I粒子植入联合内分泌治疗早期前列腺癌

目的：探讨经会阴超声引导放射性^125I粒子植入联合去势治疗早期前列腺癌疗效和不良反应。方法：39例早期前列腺癌实施经会阴超声引导和适时计划指导放射性^125I粒子植入治疗,7例粒子术前行去势术,21例粒子植入后同时行去势术,11例粒子治疗后联合药物去势治疗。粒子治疗的匹配周边剂量（matched peripheral doses,MPD）为145—160Gy,尿道剂量低于400Gy。^125I粒子活度0．35—0．50mCi,中位植入69颗（19—97颗）。结果：失败标准为前列腺特异抗原（prostate specific antigen,PSA）治疗后升高〉4ng／ml,≤〈4ng／ml为生物化学无进展生存（biochemical disease—free survival,BDFS）。全部患者顺利完成粒子植入术。36例粒子治疗后达到BDFS,3例分别在粒子治疗后6、8和36个月PSA升高,2例行内分泌治疗,1例行外放疗联合内分泌治疗。2年和3年BDFS分别为94．8％（37／39）和92．3％（36／39）。粒子植入治疗后Ⅰ级和Ⅱ级直肠不良反应发生率分别为5．1％（2／39）和7．7％（3／39）,没有Ⅲ级和Ⅳ级直肠反应。粒子植入治疗后Ⅰ级、Ⅱ级和Ⅲ级尿道不良反应发生率分别为53．8％（20／39）、17．9％（7／39）和2．6％（1／39）,对症处理好转。2例粒子移位,没有相关并发症。结论：经会阴超声引导放射性^125I粒子植入治疗前列腺癌具有安全、微创、并发症发生率低等优点。     

超声引导^125I粒子植入治疗前列腺癌方法的建立与近期疗效

目的探讨超声引导放射性^125I粒子治疗前列腺癌方法建立和近期疗效。方法26例前列腺癌全身或硬膜外麻醉下行经直肠超声引导粒子植入治疗。经直肠超声获取前列腺图像,将图像直接传输到计算机治疗计划系统,术中适时计算机计划,肿瘤周边匹配剂量（matched peripheral doses,MPD）145～160Gy。根据治疗计划插植粒子针,利用Mick植入器植入粒子,粒子植入总数为19—90颗,粒子活度0．35～0．4mCi。术后1个月行盆腔CT扫描,质量验证。结果26例患者成功实施会阴超声和模板引导放射性^125I粒子组织间近距离治疗前列腺癌手术。手术历时1—1．5h。术后验MPD为（137．73±36．5014）Gy。26例前列腺癌患者^125I粒子治疗后生物化学控制率92．3％,2例患者术后6个月出现骨转移。^125I粒子植入治疗,34．6％无尿道副反应,Ⅰ、Ⅱ、Ⅲ、Ⅳ和Ⅴ级尿道副反应分别为38．5％、11．5％、11．5％、0和0。Ⅰ级直肠副反应发生率为3．9％。1例患者1颗粒子移位,没有引起临床相关并发症,无粒子移位到肺。结论经会阴超声引导放射性粒子治疗前列腺癌具有微创、精确度高和副反应发生率低等优势。     

超声引导放射性125I粒子植入治疗舌癌的方法建立与近期疗效

目的探讨超声引导放射性125I粒子组织间植入治疗舌癌技术的可行性和近期疗效.方法9例舌癌患者,除1例为T2N0M0,其余均为局部晚期(T3～T4)或术后放疗后局部复发患者.4例采用全身麻醉,5例采用局部麻醉.舌后1/3经颌下超声引导,舌前2/3经口腔直视下行放射性125I粒子植入治疗,肿瘤周边匹配剂量(matched peripheral dose,MPD)90～110 Gy,每颗粒子活度0.40～0.60 mCi,每个病灶植入125I粒子4～84颗.术后即刻拍头颈正侧位平片或CT行质量验证.术后24～48 h拍胸部X-线片了解有无粒子移位或游走.结果随访1～31个月,1例完全缓解,3例部分缓解,4例稳定,1例进展,局部控制率88.8%.1例粒子移位至上颚,2例患者在随访过程中发生粒子脱失,但无治疗相关并发症发生.结论经颌下超声引导放射性粒子植入治疗舌癌可行、安全、微创.     

辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌

 目的 探讨辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌的安全性和有效性。方法 22例T1 ~ T2c前列腺癌患者在采用直肠超声引导经会阴穿刺放射性125I粒子组织间植入治疗前后，给予辅助内分泌治疗4 ~ 7个月。术前2 ~ 4个月，术后1 ~ 4个月。结果 22例手术均顺利完成，手术时间60 ~ 120 min，植入125I粒子40 ~ 75枚，术后随访12 ~ 48个月，前列腺特异性抗原（PSA）＜1 ng／ml 15例，1 ng／ml≤PSA＜2 ng／ml 2例，PSA≥2 ng／ml 5例。结论 辅助内分泌治疗配合放射性粒子组织间植入治疗局限性前列腺癌安全有效     

联合间歇性内分泌与125I放射性粒子植入术治疗局部晚期前列腺癌(附20例报告)

目的:探讨联合125I放射性粒子植入术和间歇性内分泌治疗局部进展期前列腺癌的临床价值.方法:前列腺癌患者20例,年龄52～80岁,中位年龄74岁,PSA:6.83～643.8ng/mL,Gleason Score:7～9分,临床分期T3NOM0.连续硬膜外麻醉,截石位,直肠超声从前列腺基底到尖部进行扫描,图像传送至计算机计划系统进行三维重建和术中计划,根据计划行直肠超声引导下经会阴125I放射性粒子植入术,术后结合雄激素全阻断疗法.当PSA达到0ng/mL,并稳定2个月后停止内分泌治疗,当PSA连续3次上升,则重新开始内分泌治疗.结果:所有患者手术均顺利,术中使用穿刺针26～36根,植入粒子57～99粒,平均73粒.术后随访8～51个月,平均22月.1例术后16个月发生骨转移,1例术后22个月死亡.术后3～5个月所有患者的PSA都降到正常范围,其中3例PSA未达到0ng/mL,未停药.4例术后5～26个月,出现PSA反弹,再次用药3～5个月PSA值达到0ng/mL:目前12例未出现PSA反弹,第一周期脱离治疗时间2～44个月,平均16.9个月.近期出现的并发症有轻至中度尿路刺激症30%(6/20),急性尿潴留5%(1/20),直肠刺激症和血便25%(5/20),多数患者症状随访1年后缓解.目前18例患者的PSA值在0～1.2ng/mL之间,其中17患者PSA≤0.17ng/mL.结论:对于局部晚期前列腺癌,125I放射粒子植入术结合间歇性内分泌是一种安全有效的治疗方法.     

CT引导放射性125I粒子组织间植入治疗复发直肠癌的疗效观察

目的探讨CT引导下放射性^125I粒子组织间植入治疗复发直肠癌的技术可行性、疗效和副反应.方法23例直肠癌术后复发患者行CT引导下^125I粒子植入术,其中3例行2次粒子植入.20例手术采用硬膜外麻醉,3例局部麻醉.20例腹卧位,3例仰卧位.术前通过治疗计划系统行三维治疗计划,确定粒子数目、空间分布和粒子针数目.既往放疗者肿瘤匹配周边剂量为90～120Gy,未行放疗者为140～160Gy.治疗PTV为CTV外加1 cm.粒子活度18.5～25.9 MBq（0.5～0.7 mCi）.植入粒子33～137颗,术后即刻行CT扫描进行质量验证.术后1周3例患者加三维适形放疗,2～3 Gy/次,总剂量45～50Gy.每3个月复查1次CT.结果随访3～28个月.术后平均7 d疼痛缓解,其中完全缓解12/15,部分缓解2/15,无变化1/15,总有效率为93%.肿瘤局部控制率为87%.中位生存时间14个月,1、2年生存率分别为93%和50%.4例全身合并全身转移,2例8个月和12个月时死于肺转移.无治疗相关严重并发症发生.结论CT引导放射性^125I粒子植入治疗复发直肠癌具有安全、微创、并发症率低和疗效肯定等优势,疗后配合外放疗和全身化疗有望进一步提高疗效.     

CT引导放射性~(125)Ⅰ粒子组织间植入治疗复发直肠癌的疗效观察

目的探讨CT引导下放射性~(125)Ⅰ粒子组织间植入治疗复发直肠癌的技术可行性、疗效和副反应。方法23例直肠癌术后复发患者行CT引导下~(125)Ⅰ粒子植入术,其中3例行2次粒子植入。20例手术采用硬膜外麻醉,3例局部麻醉。20例腹卧位,3例仰卧位。术前通过治疗计划系统行三维治疗计划,确定粒子数目、空间分布和粒子针数目。既往放疗者肿瘤匹配周边剂量为90～120 Gy,未行放疗者为140～160 Gy。治疗PTV为CTV外加1 cm。粒子活度18．5～25．9MBq(0．5～0．7mCi)。植入粒子33～137颗,术后即刻行CT扫描进行质量验证。术后1周3例患者加三维适形放疗,2～3 Gy/次,总剂量45～50 Gy。每3个月复查1次CT。结果随访3～28个月。术后平均7 d疼痛缓解,其中完全缓解12/15,部分缓解2/15,无变化1/15,总有效率为93%。肿瘤局部控制率为87%。中位生存时间14个月,1、2年生存率分别为93%和50%。4例全身合并全身转移,2例8个月和12个月时死于肺转移。无治疗相关严重并发症发生。结论CT引导放射性~(125)Ⅰ粒子植入治疗复发直肠癌具有安全、微创、并发症率低和疗效肯定等优势,疗后配合外放疗和全身化疗有望进一步提高疗效。     

超声引导下~125I放射性粒子植入治疗原发性肝癌的临床观察

目的:探讨超声引导下经皮穿刺植入125I放射性粒子治疗原发性肝癌的应用价值。方法:采用三维治疗计划系统(3D-TPS)计算48例肝癌患者51个病灶125I植入剂量,在超声显示肝脏病灶后,将125I粒子按外周密植、中间疏植的原则经皮穿刺植入肿瘤内。术后2周行超声检查,观察有无腹腔出血等并发症,术后2个月行AFP检测、彩超、CT或MR检查评价治疗效果。结果:125I放射性粒子治疗48例原发性肝癌后,12周内31例患者AFP降至正常,12例患者较术前下降一半,5例无变化,有效率为89.58%;51个病灶完全缓解23个,部分缓解21个,无变化6个,进展1个,总有效率为86.27%,无严重并发症。结论:超声引导下经皮穿刺植入125I放射性粒子治疗肝癌创伤小,布源合理,疗效肯定,并发症少,操作简单,实用性强。     

前列腺~(125)Ⅰ射粒子植入结合去势治疗C期前列腺癌(附10例报告)

目的　探讨前列腺12 5I放射粒子植入内放疗在前列腺癌治疗中的意义。方法　依据治疗计划 ,在直肠B超引导下 ,经会阴穿刺植入前列腺12 5I放射粒子对 10例C期前列腺癌行三维适形内放疗并结合手术去势治疗。结果　全组手术顺利 ,平均植入12 5I放射粒子 5 8粒 ,平均手术时间 80分钟 ,术后平均住院时间 5 .9天 ,随访 9例术后 3个月结果 :前列腺体积及PSA均有不同程度降低 ,前列腺平均体积由35 .2cm3 降至 2 4 .7cm3 ,平均PSA由 19.8ng/ml降至0 .74ng/ml,随访 6例术后 6个月结果 :5例PSA进一步降低 ,平均 0 .11ng/ml,1例升高 ,由 0 .5 1ng/ml升高至 1.6 5ng/ml,无一例出现严重的并发症。结论　采用永久性放射粒子植入前列腺三维适形内放疗是一种有效、微创的治疗前列腺癌的方法。     

Farnesyltransferase inhibitors: antineoplastic properties, mechanisms of action, and clinical prospects

Farnesyltransferase (FTase) inhibitors are among the current wave of molecularly targeted anti-cancer agents being used to attack malignancy in a rational manner. A large body of preclinical data indicates that FTase inhibitors block cancer cell proliferation through both cytostatic and cytotoxic effects. Interestingly, FTase inhibitors have rather limited effects on normal cell function, suggesting that they may target unique aspects of cancer cell pathophysiology. The development of FTase inhibitors was predicated on the discovery that the Ras oncoproteins must be post-translationally modified to transform cells. However, recent work indicates that the anti-neoplastic effects of FTase inhibitors depend on altering the post-translational modifications of non-Ras proteins as well. In particular, a critical target protein that responds to FTase inhibition by blocking tumor cell growth is RhoB, an endosomal Rho protein that functions in receptor trafficking. In this review, we survey the biological foundations for the clinical development of FTase inhibitors, and consider some of the latest mechanistic studies that reveal how these agents affect cellular physiology.     

Targeting tumor vasculature with homing peptides from phage display

Tumor vasculature expresses a number of molecular markers at much lower levels than those seen in the blood vessels of normal tissues, and in some cases, such markers are undetectable. The presence of these markers relates to angiogenesis; the same markers are shared by all blood vessels undergoing angiogenesis. The endothelial cells, pericytes and smooth muscle cells, and the vascular extracellular matrix in angiogenic vessels can each express such markers. Molecularly, they represent vascular growth factor receptors, cell adhesion proteins and their receptors. Screening of phage display libraries for peptides that home to tumor vasculature when injected into mice has recently provided a new tool for analyzing the distinguishing features of tumor vasculature. Tumor-homing peptides isolated in this manner, as well as an antibody against a form of fibronectin expressed in tumor blood vessels, have been found to serve as targeting devices to concentrate drugs and other therapeutic materials to tumors in in vivo models. Such a targeting strategy can therefore potentially improve the efficacy of drugs and reduce their side effects.     

Identification of EBV transforming genes by recombinant EBV technology

Epstein-Barr virus (EBV) is able to infect primary B-lymphocytes but usually does not proceed to replicate more virions. Instead, EBV persists as an incomplete virus and expresses 12 gene products that transform the growth of these cells into continuously proliferating lymphoblastoid cell lines. Because EBV is associated with several human malignancies, there is intense interest in delineating the molecular functions of these EBV gene products in transformation. This review focuses on the recombinant EBV technologies that have been developed to introduce specific mutations into EBV and test the functions of these EBV genes in primary B-lymphocyte growth transformation.     

Matrix metalloproteinases in tumor invasion and metastasis

Extensive work on the mechanisms of tumor invasion and metastasis has identified matrix metalloproteinases (MMPs) as key players in the events that underlie tumor dissemination. Studies using natural and synthetic MMP inhibitors, as well as tumor cells transfected with cDNAs encoding the MMPs characterized thus far have provided compelling evidence that MMP activity can induce or enhance tumor survival, invasion and metastasis. Because of the ability of MMPs to degrade extracellular matrix (ECM) proteins, the principal mechanism whereby MMPs promote tumor development has been thought to be the proteolytic breakdown of tissue barriers to invasion and the associated facilitation of circulating tumor cell extravasation. However, recent evidence stemming from the use of novel experimental approaches indicates that MMPs do not play a major role in the process of extravasation itself. Rather, they appear to promote intravasation (the process of penetrating the circulation following invasion of blood vessels) and regulate the relationship between tumor cells and host tissue stroma subsequent to extravasation. In addition, the discoveries that a growing number of proteolytically active MMPs may localize to the cell surface in association with adhesion receptors, and that MMP substrates include latent cytokines and growth factors, provide a new conceptual framework for the mechanisms whereby MMPs influence tumor behavior.     

New aspects of integrin signaling in cancer

Members of the integrin family of cell adhesion receptors influence several important aspects of cancer cell behavior, including motility and invasiveness, cell growth, and cell survival. Engagement of integrins with extracellular matrix (ECM) proteins can activate members of the Rho-family of small GTPases; conversely, Rho- and Ras-family proteins can influence the ability of integrins to bind their ligands. These events impinge on the control of cell motility, and ultimately on invasive and metastatic behavior. Integrin engagement with ECM also has important effects on cell survival, particularly for cells of epithelial origin. In some cases, specific integrins have selective effects on the efficiency of signal transduction in cell survival pathways.     

Role of LMP1 in immune control of EBV infection

The Epstein-Barr virus (EBV) encoded latent membrane protein (LMP1) plays a crucial role in the long-term persistence of this virus within the cells of the immune system. Not only is this protein critical for the transformation of resting B cells by EBV, it also displays pleiotropic effects on various cellular proteins expressed in the host cell. These include up-regulation of expression of B cell activation antigens, adhesion molecules and various components of the antigen processing pathway. Here we discuss how LMP1 acts like an expression 'switch' which, depending on the stage of EBV infection, manoeuvres various pathways that either modulate the immune system towards or against its survival.     

腹部压块对膈肌运动影响的研究

目的 :研究腹部压块对膈肌运动的影响。方法 :选择拟行立体适形放疗患有肺癌或肝脏肿瘤的患者 2 0例。按治疗体位仰卧于体部立体放疗定位负压袋内 ,待患者呼吸平稳后 ,将灯光野的中心点置于膈顶运动的最低点 ,在膈肌运动至最高位时拍摄照片 ,测量膈肌运动的最大幅度 ;然后 ,将心形腹部压块放置于患者剑突下 ,并用定位框架的腹带交叉固定 ,按压程度以不引起患者呼吸困难或其他不适为标准 ,5min后按上述方法再次测量膈肌运动的最大幅度。结果 :2 0例患者未加腹部压块的运动幅度为0 6 2～ 2 6 7cm ,平均 (1 4± 0 6 4)cm ,加腹部压块后的膈肌运动幅度为 0 2 8～ 2 0 8cm ,平均 (1 0±0 5 5 )cm ,加腹部压块后膈肌运动幅度平均减小 (0 4± 0 34)cm ,P =0 0 0 0。加腹部压块后 90 % (18/2 0 )的患者膈肌运动幅度受到不同程度的限制 ,但有 10 % (2 /2 0 )的患者膈肌运动幅度增加。结论 :腹部压块可使大部分患者膈肌运动的幅度减小 ,但少部分患者例外 ,即腹部压块并不能使所有膈肌周围肿瘤的照射容积减少。建议在制定放射治疗计划前应预先进行测量和评价     

ABCG2在肺癌中表达的定量研究

目的 观察ABCG2在肺癌和癌周肺组织的表达,从量化角度阐明其在肺癌组织中表达的病理学意义.方法 常规石蜡包埋、HE切片确诊,用免疫组化SP法检测ABCG2在肺癌和癌周肺组织的定位和表达,用LeicaQ500MC图像分析系统对其表达强度进行定量分析,并用表达的阳性单位(positive unit PU)反映其表达强度.结果 ABCG2蛋白在肺癌和癌周正常肺组织中的表达主要定位在细胞质和细胞膜.在癌周正常肺组织的支气管和细支气管上皮呈弥漫表达,腺上皮呈灶性表达;肺鳞癌和肺腺癌弥漫或大片表达,肺鳞癌表达的PU值高于肺腺癌(P＜0.001),肺大细胞癌和肺小细胞癌不表达,PU值接近于零.癌周肺组织表达的PU值高于各型肺癌(P＜0.05).ABCG2蛋白表达的PU值在肺癌原发灶和转移灶之间无差别(P＞0.05),且与肺癌患者的性别、年龄、转移和TNM分期未见明显相关性(P＞0.05),与肺癌分化程度有关(P＜0.001).分化程度越高,PU值越高,但高分化肺癌和癌周肺组织的表达PU值差异无显著性(P＞0.05).结论 ABCG2蛋白表达程度与肺癌类型及分化程度具有相关性,可能成为判断其指标之一.     

Telomerase and human tumorigenesis

Human cancer cells, unlike their normal counterparts, have shed the molecular restraints to limited cell growth and are immortal. Exactly how cancer cells manage this at the molecular level is beginning to be understood. Human cells must overcome two barriers to cellular proliferation. The first barrier, referred to as senescence, minimally involves the p53 and Rb tumor-suppressor pathways. Inactivation of these pathways results in some extension of lifespan. However, inactivation of these pathways is insufficient for immortalization. As normal cells undergo repeated rounds of DNA replication, their telomeres shorten due to the inability of traditional DNA polymerases to completely replicate the end of the chromosomal DNA. This shortening continues until the cells reach a second proliferative block referred to as crisis, which is characterized by chromosomal instability, end-to-end fusions, and cell death. Stabilization of the telomeric DNA through either telomerase activation or the activation of the alternative mechanism of telomere maintenance (ALT) is essential if the cells are to survive and proliferate indefinitely. Conversely, loss of telomere stabilization by an already-immortalized cell results in loss of immortality and cell death. Together this indicates that telomere maintenance is a critical component of immortality. In this review we attempt to describe our current understanding of the role of telomere maintenance in senescence, crisis, and tumorigenesis.     

Post-translational regulation of COX2 activity by FYN in prostate cancer cells

While increased COX2 expression and prostaglandin levels are elevated in human cancers, the mechanisms of COX2 regulation at the post-translational level are unknown. Initial observation that COX2 forms adduct with non-receptor tyrosine kinase FYN, prompted us to study FYN-mediated post-translational regulation of COX2. We found that FYN increased COX2 activity in prostate cancer cells DU145, independent of changes in COX2 or COX1 protein expression levels. We report that FYN phosphorylates human COX2 on Tyr 446, and while corresponding phospho-mimetic COX2 mutation promotes COX2 activity, the phosphorylation blocking mutation prevents FYN-mediated increase in COX2 activity.