进展期胃癌术前卡铂腹腔,静脉化疗肿瘤组织聚积浓度的比较及药…

探讨不同给药途径抗癌药在肿瘤组织内药物浓度的聚积性。方法：对２０例可切除进展期胃癌比较研究了术前卡铂腹腔,静脉化疗化代动力学。术前卡铂３００ｍｇ／ｍ＾２加生理盐水７５０ｍｌ分别腹腔、静脉给药,注射后１６０－１８０取腹腔液、门静脉及外周血,２４０－２７０取癌组织,癌旁正常组织大网膜,腹膜及转移阴性淋巴结,应用高效液相色谱法（ＨＰＬＣ）测定总铂浓度。结果腹腔给药各组织内聚积较高的药物浓度,其中腹膜浓度     

术前腹腔和静脉卡铂化疗肿瘤组织聚积浓度的比较研究

目的：探讨不同给药途径卡铂在肿瘤组织内药物浓度的聚积性。方法：采用高效液相色谱法对２０例可切除进行期胃癌进行腹腔和静脉卡铂术前化疗药代动力学研究。卡铂３００ｍｇ／ｍ２加生理盐水７５０ｍｌ分别静脉、腹腔１次注射，给药后２４０～２７０ｍｉｎ手术取癌组织、癌旁正常组织、腹膜、大网膜、阴性淋巴结，测定总铂浓度。结果：腹腔给药组各组织浓度明显高于静脉给药组（Ｐ＜０．０１），其中腹膜浓度最高，其次为癌组织、大网膜、癌旁正常组织及阴性淋巴结，分别超出静脉给药的３．６、２．５、３．０、２．８、１．９倍。癌组织含量高于正常组织。结论：术前卡铂腹腔化疗大大提高腹膜、肿瘤组织内浓度，延长药物作用时间，使对药物敏感癌细胞得到控制。对杀灭腹腔亚临床病灶，控制医源性转移，提高治愈性手术切除率颇有意义     

胃癌术前卡铂腹腔化疗肿瘤组织浓度测定及药代动力学研究

作者采用高效液相色谱法对１０例可切除进展期胃癌进行腹腔卡铂术前化疗药代动力学研究。卡铂３００ｍｇ／ｍ２加生理盐水７５０ｍｌ快速腹腔注射，１６０～１８０ｍｉｎ取腹腔液、门静脉及外周血，２４０～２７０ｍｉｎ取癌组织、癌旁正常组织、腹膜、大网膜、阴性淋巴结，测定总铂浓度。结果表明，腹腔液浓度最高，平均４８．１４μｌ／ｍｌ，门静脉次之为１０．１μｌ／ｍｌ，分别是外周血的８、１．６倍。被测组织中，腹膜浓度超出其它组织浓度（Ρ＜０．０５），癌组织含量高于正常组织。研究证明，卡铂术前腹腔化疗不仅提高腹腔、门静脉药物浓度，而且，在腹膜、癌组织内有一定聚积性，对于杀灭腹腔亚临床病灶，改善临床分期，控制医源性转移，提高治愈性手术切除率发挥重要作用。     

术有腹腔和静脉卡铂化疗肿瘤组织聚积浓度的比较研究

目的：探讨不同给药途径卡铂在肿瘤组织内药物浓度的聚积性。方法：采用高效液相色谱法对２０例可切除进行期胃癌进行腹腔和静脉卡铂术前化职药代动力学研究。卡铂３００ｍｇ／ｍ＾２加生理盐水７５０ｍｌ分别静脉、腹腔１次注射，给药后２４０￣２７０ｍｉｎ手术取癌组织、癌旁正常组织、腹膜、大网膜、阴性淋巴结，测定总铂浓度。结果：腹腔给药组各组织浓度明显高于静脉给药组（Ｐ〈０．０１），其中腹膜浓度最高，其次为癌组织、     

卡铂腹腔化疗药代动力学实验研究

应用高效液相色谱法（ＨＰＬＣ）对６只犬体内卡铂腹腔内给药药代动力学进行研究。卡铂３０ｍｇ／ｋｇ加生理盐水５００ｍｌ，快速腹腔给药，不同时间取腹腔液、门静脉及股静脉血测定总铂浓度。结果表明：大剂量、大容量卡铂经腹腔给药后，２４０分钟内腹腔液浓度最高，峰值浓度和平均浓度分别为股静脉浓度的１３９倍和６４倍；门静脉次之，分别为股静脉浓度的１３．３倍和６．５倍。卡铂腹腔给药可为腹腔、门静脉和肝脏提供恒定持久的高药物浓度，大大提高抗癌药对肿瘤细胞的杀伤作用，减少其到达体循环量，从而减轻全身毒副作用，对胃肠道恶性肿瘤术后腹腔复发和肝转移的预防和治疗颇有意义。     

~(131)I-3H11经腹腔、门静脉和外周静脉给药的药代学比较研究

目的将１３１Ｉ－３Ｈ１１经不同给药途径的药代学进行比较研究，证实其腹腔内给药治疗胃肠癌的合理性。方法３组家兔分别经耳静脉、门静脉和腹腔注射１３１Ｉ－３Ｈ１１。检测系列耳静脉血、门静脉血及腹腔液中药物含量。结果（１）耳静脉给药后，门静脉与外周静脉血内药物浓度没有明显差别；腹腔液内药物浓度为血液内的１／３。（２）门静脉给药后，门静脉血内药物浓度高于外周静脉内药物浓度；３０分钟后，其差别不明显。腹腔液内药物浓度为血液内的１／３。（３）腹腔给药后，腹腔液中的药物浓度保持最高，其峰值分别是外周静脉和门静脉血的３７．２倍和５．４倍；门静脉血次之，峰值浓度是外周静脉血的６．９倍；外周静脉血药物浓度始终在较低水平。结论１３１Ｉ－３Ｈ１１腹腔给药与外周静脉及门静脉给药相比具有明显的药代学优点，有利于预防和治疗胃肠癌术后腹腔内复发和肝转移。     

碳铂腹腔给药HPLC测定法及犬的药代动力学研究

应用高压液相色谱(HPLC)法对6只犬腹腔内灌注碳铂(30mg/kg),不同时间取腹腔液、门静脉、外周血测定总铂浓度。结果表明,4小时内腹腔浓度最高,峰值浓度及平均浓度分别为外周血浓度的139倍和64倍,门静脉浓度为外周血浓度的13.3倍和6.5倍.证明腹腔给药可大大提高腹腔、门静脉及肝脏浓度,减低到达体循环量。对有效地杀灭腹腔亚临床转移、门静脉癌栓、防治肝转移十分重要,并对控制术后复发、医源性转移颇有意义。     

胃癌术前卡铂腹腔化疗肿瘤细胞浓度测定及药代动力学研究

作者采用高效液相色谱法对１０例可切除进展期胃癌进行腹腔卡铂术前化疗药代动力不研究。卡铂３００ｍｇ／ｍ＾３加生理盐水７５０ｍｌ快速腹腔注射，１６０－１８０ｍｉｎ聚腹腔液，门静脉及外周血，２４０－２７０ｍｉｎ取癌组织，癌旁正常组织，腹膜，大网膜，阴性淋巴结，测定总铂浓度。     

卡铂腹腔化疗卵巢中药物浓度的初步研究

１５例卵巢肿瘤患者于术前２４小时内的不同时间，接受腹腔穿刺注射卡铂（３００ｍｇ／ｍ２），手术切除卵巢肿瘤取得组织标本，用无火焰原子吸收光谱法测定肿瘤组织内的总铂浓度。其结果表明，注药后卡铂可迅速分布到卵巢肿瘤组织中去，３０分钟即在肿瘤组织中达到较高的药物浓度，并在给药后４小时内呈上升趋势，最高值达１７１．０７ｕｇ／ｇ。组织药物浓度与给药时间、肿瘤组织学类型及肿瘤大小等有关。病理检查显示仅内胚窦瘤有大片细胞坏死，认为疗效不仅与药物浓度有关，还与肿瘤本身的敏感性、药物作用时间等因素有关。     

^131I—3H1经腹腔,门静脉和外周静脉给药的药代学比较研究

目的 将＾１３１Ｉ－３Ｈ１１经不同给药途径的药代学进行比较研究,证实其腹腔内给药治疗胃肠癌的合理性。方法 ３组家兔分别经耳静、门静脉和腹腔注射＾１３１Ｉ－３Ｈ１１。检测系列耳静脉血、门静脉血及腹腔注中药物含量。结果 （１）耳静脉给药后,门静脉与外周静脉血内药物浓度没有明显差别;腹腔内药物浓度为血液内的１／３。（２）门静脉给药后,门静脉血内药物浓度高于外周静脉内药物浓度;３０分钟后,其差别不明显。腹     

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.     

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.     

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     

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.