• 【骨髓嵌合体小鼠肿瘤浸润基质细胞的制备及功能分析。】 复制标题 收藏 收藏
    DOI:10.1111/j.1348-0421.2006.tb03830.x 复制DOI
    作者列表:Ishigaki H,Yamamoto Y,Ishida H,Kajino K,Itoh Y,Fujiyama Y,Ogasawara K
    BACKGROUND & AIMS: :Tumor-infiltrating stroma cells (TISC) as well as tumors themselves are thought to be involved in tumor-related immunosuppression, which is one of the critical mechanisms of tumor escape from immune surveillance. However, preparation of TISC is difficult because of the small proportion of TISC in established tumors. Thus, the cells thought to be involved in tumor-related immunosuppression are generally prepared from spleens or draining lymph nodes in tumor-bearing mice. In this study, we developed a method for directly preparing TISC from established tumors in order to analyze their function. Using green fluorescent protein (GFP) transgenic (Tg) mice and C57BL/6 mice transplanted with bone marrow (BM) cells of GFPTg mice, we detected three subpopulations of TISC: one is compatible with immature myeloid cells (ImC) derived from BM and the two other subpopulations, CD11b(+) cells and CD11b(-) cells, do not originate from BM. The TISC including these subpopulations but not each subpopulation independently after culturing with tumors in the presence of GM-CSF could suppress T cell proliferation induced by anti-CD3. In our system, tumors did not inhibit T cell responses directly, but unknown factors from tumors affected immunosuppression by TISC.
    背景与目标: : 肿瘤浸润的基质细胞 (TISC) 以及肿瘤本身被认为与肿瘤相关的免疫抑制有关,这是肿瘤逃避免疫监视的关键机制之一。然而,由于TISC在已建立的肿瘤中的比例较小,因此很难制备TISC。因此,被认为与肿瘤相关的免疫抑制有关的细胞通常是从荷瘤小鼠的脾脏或引流淋巴结中制备的。在这项研究中,我们开发了一种从已建立的肿瘤中直接制备TISC的方法,以分析其功能。使用绿色荧光蛋白 (GFP) 转基因 (Tg) 小鼠和C57BL/6小鼠移植了GFPTg小鼠的骨髓 (BM) 细胞,我们检测到了TISC的三个亚群: 一个与BM衍生的未成熟髓样细胞 (ImC) 相容,另外两个亚群,CD11b(+) 细胞和CD11b(-) 细胞不起源于BM。在gm-csf存在下用肿瘤培养后,包括这些亚群但不是每个亚群的TISC可以抑制anti-CD3诱导的T细胞增殖。在我们的系统中,肿瘤没有直接抑制T细胞反应,但是肿瘤的未知因素会影响TISC的免疫抑制。
  • 【P53基因的等位基因丢失与膀胱癌的肿瘤分级,分期和恶性进展的相关性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1442-2042.1997.tb00144.x 复制DOI
    作者列表:Tsutsumi M,Sugano K,Yamaguchi K,Kakizoe T,Akaza H
    BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.
    背景与目标:
  • 【PedsQL脑肿瘤模块: 初始信度和效度。】 复制标题 收藏 收藏
    DOI:10.1002/pbc.21026 复制DOI
    作者列表:Palmer SN,Meeske KA,Katz ER,Burwinkle TM,Varni JW
    BACKGROUND & AIMS: BACKGROUND:Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5-year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory (PedsQL) Brain Tumor Module. METHODS:The PedsQL 4.0 Generic Core Scales, PedsQL Multidimensional Fatigue Scale, and PedsQL Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range=2-18 years). The sample included children with tumors located in the posterior fossa/brainstem (N=62, 62.6%), supratentorial (N=15, 15.2%), and midline (N=22, 22.2%). Children were on treatment (N=46, 46.5%), off treatment<12 months (N=19, 19.2%), or off treatment>12 months/long-term survivor (N=34, 34.3%). Treatment included radiation (N=61, 61.6%), surgery (N=83, 83.8%), chemotherapy (N=87, 87.9%), and bone marrow transplant (N=5, 5.1%). RESULTS:Internal consistency reliability was demonstrated for the 24-item PedsQL Brain Tumor Module (average alpha=0.78-0.92, parent proxy-report, n=99; average alpha=0.76-0.87, child self-report, n=51). Construct validity for the PedsQL Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale. CONCLUSIONS:The findings provide support for the measurement properties of the PedsQL Brain Tumor Module.
    背景与目标:
  • 【调节自噬的途径及其在介导肿瘤对治疗反应中的作用。】 复制标题 收藏 收藏
    DOI:10.4161/auto.2835 复制DOI
    作者列表:Paglin S,Yahalom J
    BACKGROUND & AIMS: :In addition to their role in cellular homeostasis, pathways that regulate autophagy affect both tumorigenesis and tumor response to treatment. Therefore, understanding the regulation of autophagy in treated cancer cells is relevant to the discovery of molecular targets for the development of anti-cancer drugs. Our recent report points to radiation-induced inactivation of the mTOR pathway as an underlying mechanism of radiation-induced autophagy in the human breast cancer cell line MCF-7. Most importantly, radiation-induced inactivation of this pathway was detrimental to cell survival and was associated with reversal of mitochondrial ATPase activity and mitochondrial hyperpolarization, decreased level of eukaryotic initiation factor 4G (eIF4G) and increased phosphorylation of p53. Future analysis of the interrelationship among these events and the role each of them plays in cell survival following radiation will increase our ability to employ the mTOR pathway in anti-cancer therapy.
    背景与目标: : 除了它们在细胞内稳态中的作用外,调节自噬的途径还影响肿瘤发生和肿瘤对治疗的反应。因此,了解治疗癌细胞中自噬的调控与发现抗癌药物开发的分子靶标有关。我们最近的报告指出,辐射诱导的mTOR途径失活是辐射诱导的人乳腺癌细胞系MCF-7自噬的潜在机制。最重要的是,辐射诱导的该途径的失活对细胞存活有害,并且与线粒体ATPase活性和线粒体超极化的逆转,真核起始因子4G (eIF4G) 水平降低和p53磷酸化增加有关。对这些事件之间的相互关系以及它们在辐射后的细胞存活中所起的作用的未来分析将提高我们在抗癌治疗中采用mTOR途径的能力。
  • 【视频内窥镜经肛门直肠肿瘤切除术。】 复制标题 收藏 收藏
    DOI:10.1016/S0002-9610(97)00076-7 复制DOI
    作者列表:Swanstrom LL,Smiley P,Zelko J,Cagle L
    BACKGROUND & AIMS: BACKGROUND:Transanal resection of benign and selected malignant rectal tumors is a well accepted surgical technique. The use of a stereoscopic microsurgical technique, as originally described by Buess et al in 1984, has been shown to improve the results of standard transanal resection by allowing precise, full thickness resections up to 24 cm from the anal verge. Transanal endoscopic microsurgery (TEM) has failed to gain widespread popularity for two reasons: The proprietary instrument set is expensive and complex ($68,000 and 30 components), and the procedure is difficult to master technically. We present our results with a modification of the TEM instrument that incorporates a standard laparoscope and video camera as well as standard laparoscopic instruments.

    METHODS:Four surgeons have been trained to date. Details of the training curriculum are presented. The technique of videoendoscopic transanal tumor resection (VTEM) is described. A prospective data base was maintained of all VTEM cases. This was reviewed for this study to determine indications, operative times, complications and outcomes.

    RESULTS:Four surgeons performed 27 VTEM cases between August 1994 and June 1996. The average age was 69 years and the majority (16) of patients were ASA III. Pre-op diagnosis was benign polyp in 25 patients and adenocarcinoma in 2. Average operating time was 127 minutes (49 to 280 minutes), and was longer during a surgeon's first 5 cases and for lesions more than 16 cm from the anal verge. Operative problems were rare (4%) and post-op complications (incontinence 2, late bleeding 1, adenoma recurrence 1) were seen in 15%.

    CONCLUSIONS:VTEM can be taught successfully to GI and colorectal surgeons using a format similar to that used for advanced laparoscopic courses. The use of already available laparoscopes and instruments decreases the initial costs of the set-up. Results are good, with low rates of complications and recurrence and a very short hospital stay. The patient benefits from an effective, minimally invasive alternative to open surgery.

    背景与目标: 背景 : 经肛门切除良性和选定的恶性直肠肿瘤是一种公认的手术技术。如Buess等人1984年最初描述的那样,使用立体显微外科技术已被证明通过允许从肛门边缘最多24厘米个精确的全厚度切除来改善标准经肛门切除的结果。经肛门内窥镜显微外科手术 (TEM) 未能获得广泛的欢迎,原因有两个: 专有仪器套件昂贵且复杂 (68,000美元和30个组件),并且该程序在技术上难以掌握。我们通过对TEM仪器的改进来展示我们的结果,该TEM仪器结合了标准的腹腔镜和摄像机以及标准的腹腔镜仪器。
    方法 : 迄今为止,已经对四名外科医生进行了培训。介绍了培训课程的详细信息。描述了视频内窥镜经肛门肿瘤切除术 (VTEM) 的技术。保留了所有VTEM病例的前瞻性数据库。本研究对此进行了审查,以确定适应症,手术时间,并发症和结果。
    结果 : 四名外科医生在1994年8月和1996年6月之间进行了27例VTEM病例。平均年龄为69岁,大多数 (16) 患者为ASA III。术前诊断为良性息肉25例,腺癌2例。平均手术时间为127分钟 (49至280分钟),并且在外科医生的前5例病例中较长,并且对于肛门边缘的病变超过16厘米。手术问题很少见 (4%),15% 术后并发症 (失禁2,晚期出血1,腺瘤复发1)。
    结论 :VTEM可以使用类似于高级腹腔镜课程的格式成功地教给GI和结肠直肠外科医生。使用已经可用的腹腔镜和仪器可以降低设置的初始成本。结果良好,并发症和复发率低,住院时间短。患者受益于开放手术的有效,微创替代方法。
  • 【大鼠横纹肌肉瘤R1H的放射生物学: 照射场大小对肿瘤反应,肿瘤床效应和新血管形成动力学的影响。】 复制标题 收藏 收藏
    DOI:10.1016/0360-3016(90)90411-c 复制DOI
    作者列表:Würschmidt F,Beck-Bornholdt HP,Vogler H
    BACKGROUND & AIMS: :R1H tumors were irradiated with a single dose of 15 Gy X rays using varying sizes of treatment fields. Damage to tumor cells and tumor stroma was determined separately by analysis of growth delay to ten times treatment volume (GD10vo) and net growth delay. GD10vo comprises irradiation effects on tumor parenchymal cells and on tumor stroma, whereas net growth delay only measures effects on tumor parenchymal cells. Stromal damage was observed to increase with increasing field size; the effect on the tumor parenchymal cells, however, was independent of the field size. An increase of GD10vo of 13 days per cm increase of field size diameter was observed. From this the velocity of neovascularization of the irradiated tumor bed was calculated to be 0.30 to 0.38 mm per day.
    背景与目标: : 使用不同大小的治疗场,用15 Gy x射线的单剂量照射R1H肿瘤。通过分析生长延迟至十倍治疗量 (GD10vo) 和净生长延迟,分别确定对肿瘤细胞和肿瘤基质的损害。GD10vo包括对肿瘤实质细胞和肿瘤基质的辐射作用,而净生长延迟仅测量对肿瘤实质细胞的影响。观察到基质损伤随着视野大小的增加而增加; 然而,对肿瘤实质细胞的影响与视野大小无关。观察到每增加cm的场尺寸直径,GD10vo增加13天。由此计算出照射肿瘤床的新血管形成速度为每天0.30至0.38毫米。
  • 【WT1 Wilms' 肿瘤抑制基因是PC12细胞中胰岛素样生长因子-I (igf-i) 作用的下游靶标。】 复制标题 收藏 收藏
    DOI:10.1111/j.1471-4159.2006.04119.x 复制DOI
    作者列表:Sarfstein R,Werner H
    BACKGROUND & AIMS: :The biological actions of the insulin-like growth factors, IGF-I and IGF-II, are mediated by the ligand-induced activation of the IGF-I receptor (IGF-IR), a transmembrane heterotetramer linked to the ras-raf-mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3 kinase (PI3K)-protein kinase B (PKB)/Akt signal transduction cascades. The Wilms' tumor suppressor gene (wt1) encodes a zinc finger transcription factor, WT1, which has been implicated in various cellular processes including proliferation, differentiation and apoptosis. In the present study we demonstrated that IGF-I modulates the WT1 gene expression in neurally derived PC12 cells in a dose- and time-dependent manner. This effect was mediated through both the MAPK and PI3-kinase signaling pathways, as shown by the ability of the specific inhibitors UO126 and LY294002 to abrogate IGF-I action. Moreover, using RT-PCR and transient transfection assays, we demonstrated that the IGF-I effect was associated with corresponding changes in WT1 mRNA levels and WT1 promoter activity. In addition, the results of the present study revealed that high WT1 levels were associated with the induction of apoptosis, whereas low WT1 levels were correlated with the inhibition of apoptosis, as demonstrated by poly ADP ribose polymerase (PARP) cleavage, Bax expression, Annexin V-FITC staining, and by the use of antisense oligonucleotides against WT1. In summary, our results show that the wt1 gene is a novel target for IGF-I action in neurally derived cells.
    背景与目标: : 胰岛素样生长因子igf-i和igf-ii的生物学作用是由配体诱导的igf-i受体 (igf-ir) 激活介导的,与ras-raf-有丝分裂原活化蛋白激酶 (MAPK) 和磷脂酰肌醇3激酶 (PI3K)-蛋白激酶B (PKB)/Akt信号转导级联连接的跨膜异四聚体。Wilmss的肿瘤抑制基因 (wt1) 编码锌指转录因子WT1,该因子与各种细胞过程有关,包括增殖,分化和凋亡。在本研究中,我们证明igf-i以剂量和时间依赖性方式调节神经源性PC12细胞中WT1基因的表达。这种作用通过MAPK和PI3-kinase信号通路介导,如特异性抑制剂UO126和LY294002消除igf-i作用的能力所示。此外,使用rt-pcr和瞬时转染分析,我们证明了igf-i效应与WT1 mRNA水平和WT1启动子活性的相应变化有关。此外,本研究的结果表明,高WT1水平与诱导凋亡有关,而低WT1水平与抑制凋亡有关,如聚ADP核糖聚合酶 (PARP) 切割,Bax表达,Annexin V-FITC染色,并通过使用针对wt1的反义寡核苷酸。总之,我们的结果表明wt1基因是神经源性细胞中igf-i作用的新靶标。
  • 【外阴复发性增生性毛囊瘤1例。】 复制标题 收藏 收藏
    DOI:10.1097/LGT.0b013e31824c199a 复制DOI
    作者列表:Moraloğlu Ö,Güngör T,Ozyer S,Eryilmaz ÖG,Özdener T,Toğrul C,Bayramoğlu H
    BACKGROUND & AIMS: :Proliferating trichilemmal tumor (PTT) is a rare but morphologically distinct tumor that usually arises on the scalp of elderly women. It is composed of multiple cysts consisting of squamous epithelium with trichilemmal keratinization without granular layer interposition. Vulvar proliferating trichilemmal cyst is very rare, with, to the best of our knowledge, only 3 cases previously reported in the literature. We describe a 39-year-old woman with recurrent PTT on the left labium majus of the vulva, which had been excised from the same side 5 years before. She had a palpable nodule, approximately 2 cm in size, which was firm, mobile, and nontender; without erythema and ulceration; and covered by normal skin on the vulva. There was no inguinal lymphadenopathy. The lesion was removed by wide surgical excision; because of the tissue elasticity, primary closure was possible. The pathology result was reported as proliferating trichilemmal carcinoma with tumor-free margins. Although local recurrence after wide excision is rare, we recommend complete excision for treatment of PTT and long-term follow-up because of the possibility of recurrence.
    背景与目标: 增生性毛囊瘤 (PTT) 是一种罕见但形态上不同的肿瘤,通常发生在老年妇女的头皮上。它由多个囊肿组成,由鳞状上皮组成,具有三鞘角化,没有颗粒层插入。外阴增生的毛囊囊肿非常罕见,据我们所知,以前文献中仅报道了3例。我们描述了一名39岁的女性,在外阴的左阴唇上复发性PTT,该女性在5年前从同一侧切除。她有一个可触及的结节,大小约2厘米,坚硬,可移动且不触痛; 没有红斑和溃疡; 外阴被正常皮肤覆盖。无腹股沟淋巴结肿大。通过广泛的手术切除切除病变; 由于组织弹性,可以进行一次闭合。病理结果报告为增殖性毛囊癌,边缘无瘤。尽管广泛切除后的局部复发很少见,但由于复发的可能性,我们建议完全切除治疗PTT并进行长期随访。
  • 【晚期癌症患者对肿瘤基因组分析中次级种系发现的兴趣和态度。】 复制标题 收藏 收藏
    DOI:10.1200/JOP.2016.020057 复制DOI
    作者列表:Hamilton JG,Shuk E,Genoff MC,Rodríguez VM,Hay JL,Offit K,Robson ME
    BACKGROUND & AIMS: PURPOSE:Tumor genomic profiling (TGP) can reveal secondary findings about inherited disease risks in a patient with cancer. Little is known about how patients with advanced cancer, currently the primary users of TGP, perceive the benefits and harms of secondary germline findings. METHODS:We conducted semistructured interviews with 40 patients with advanced breast, bladder, colorectal, or lung cancer who had TGP. Qualitative interview data were evaluated by using a thematic content analysis approach. RESULTS:Most participants expressed interest in the prospect of learning their secondary germline findings (57%), although a minority was equivocal (29%) or disinterested (14%). Reasons for these preferences varied but were influenced by participants' perceptions of diverse benefits and harms of this information, which they regarded as relevant to themselves; their families; and other patients with cancer, medical science, and society. These attitudes were uniquely shaped by participants' personal disease experiences and health status. CONCLUSION:Many patients with advanced cancer are interested in learning secondary germline findings and hold optimistic and perhaps unrealistic beliefs about the potential health benefits. Patients also have important concerns about clinical and emotional implications of this information. These perceptions are necessary to address to ensure that patients make informed decisions about learning secondary germline findings.
    背景与目标:
  • 10 Organizing hematoma mimicking brain tumor. 复制标题 收藏 收藏

    【组织血肿模仿脑肿瘤。】 复制标题 收藏 收藏
    DOI:10.1016/j.clinimag.2012.04.006 复制DOI
    作者列表:Ilica AT,Rodrigues F,Maluf F,Aygun N
    BACKGROUND & AIMS: :A 64-year-old man was referred to our hospital with progressive loss of function in his right upper and lower extremities. Unenhanced computed tomographic showed a high-density nodular lesion in the left basal ganglion with surrounding hypoattenuation. Brain magnetic resonance imaging demonstrated a predominantly cystic mass with multiple internal septa and an eccentric solid component showing enhancement. Histological examination revealed organizing blood clot and piloid gliosis. This unusual appearance of a mass-like organizing blood clot should be considered in the differential diagnosis when an encapsulated cystic mass with nodular component following the signal characteristics of old blood on MRI is encountered.
    背景与目标: : 一名64岁的男子因右上下肢功能逐渐丧失而被转诊至我们医院。未增强的计算机断层扫描显示左基底神经节有高密度结节病变,周围有衰减。脑磁共振成像显示主要是囊性肿块,多个内部间隔和偏心固体成分显示增强。组织学检查显示有组织的血块和纤毛样胶质增生。在鉴别诊断疾病中,当遇到带有结节成分的包囊性囊性肿块时,应考虑这种不寻常的肿块样组织血块的外观,该囊性肿块遵循MRI上旧血液的信号特征。
  • 【补充精氨酸可增加正常和鼠肉瘤病毒接种小鼠的胸腺细胞性,并增加对鼠肉瘤病毒肿瘤的抵抗力。】 复制标题 收藏 收藏
    DOI:10.1177/014860717900300601 复制DOI
    作者列表:Rettura G,Padawer J,Barbul A,Levenson SM,Seifter E
    BACKGROUND & AIMS: :Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.
    背景与目标: : 在接种鼠肉瘤病毒莫洛尼肉瘤病毒 (MSV) 之前的3天,对6周龄的CBA小鼠给予精氨酸补充剂。尽管基础饮食含有1.8% 精氨酸,因此并不缺乏精氨酸,但饮食和饮用水中添加0.5% 精氨酸HCl可降低肿瘤发生率,延长潜伏期,减小肿瘤大小,并加速肿瘤消退。精氨酸还增加了正常和接种MSV的小鼠的胸腺重量和细胞性。精氨酸的抗肿瘤作用可能与其对胸腺的作用有关。
  • 【RCC2的过表达通过诱导上皮-间质转化增强肺腺癌的细胞运动并促进肿瘤转移。】 复制标题 收藏 收藏
    DOI:10.1158/1078-0432.CCR-16-2909 复制DOI
    作者列表:Pang B,Wu N,Guan R,Pang L,Li X,Li S,Tang L,Guo Y,Chen J,Sun D,Sun H,Dai J,Bai J,Ji G,Liu P,Liu A,Wang Q,Xiao S,Fu S,Jin Y
    BACKGROUND & AIMS: :Purpose: Investigate the role of regulator of chromosome condensation 2 (RCC2) on lung adenocarcinoma (LUAD) metastasis.Experimental Design: Clinical specimens were used to assess the impact of RCC2 on LUAD metastasis. Mouse models, cytobiology, and molecular biology assays were performed to elucidate the function and underlying mechanisms of RCC2 in LUAD.Results: RCC2 expression was frequently increased in LUADs (88/122, 72.13%). It was confirmed by analysis of a larger cohort of TCGA RNA-seq data containing 488 LUADs and 58 normal lung tissues (P < 0.001). Importantly, increased level of RCC2 was significantly associated with T status of tumor (P = 0.002), lymph node metastasis (P = 0.004), and advanced clinical stage (P = 0.001). Patients with LUAD with higher expression of RCC2 had shorter overall survival. Cox regression analysis demonstrated that RCC2 was an independent poorer prognostic factor for patients with LUAD. Moreover, forced expression of RCC2 promoted intrapulmonary metastasis in vivo and significantly enhanced LUAD cell migration, invasion, and proliferation in vitro Further study found that RCC2 induced epithelial-mesenchymal transition (EMT) and also stimulated the expression of MMP-2 and MMP-9. In addition, RCC2 was able to activate JNK, while inhibition of JNK suppressed the effect of RCC2 on LUAD cell migration, invasion, EMT, and the expression of MMP-2 and MMP-9.Conclusions: RCC2 plays a pivotal role in LUAD metastasis by inducing EMT via activation of MAPK-JNK signaling. Clin Cancer Res; 23(18); 5598-610. ©2017 AACR.
    背景与目标: 目的: 探讨染色体浓缩调节因子2 (RCC2) 在肺腺癌 (LUAD) 转移中的作用。实验设计: 临床标本用于评估RCC2对LUAD转移的影响。进行小鼠模型、细胞生物学和分子生物学试验以阐明RCC2在LUAD中的功能和潜在机制。结果: RCC2表达在LUAD中经常增加 (88/122,72.13%)。通过对包含488个LUADs和58个正常肺组织的TCGA RNA-seq数据的较大队列的分析证实了这一点 (P <0.001)。重要的是,RCC2水平的升高与肿瘤的T状态 (P = 0.002),淋巴结转移 (P = 0.004) 和晚期临床分期 (P = 0.001) 显着相关。具有较高RCC2表达的LUAD患者的总生存期较短。Cox回归分析表明,RCC2是LUAD患者的独立较差预后因素。此外,RCC2的强制表达促进了体内肺内转移,并显着增强了LUAD细胞的迁移,侵袭和增殖。进一步研究发现,RCC2诱导了上皮-间质转化 (EMT),也刺激了MMP-2和MMP-9的表达。此外,RCC2能够激活JNK,而JNK的抑制抑制了RCC2对LUAD细胞迁移、侵袭、EMT以及MMP-2和MMP-9.Conclusions表达的影响: RCC2通过MAPK-JNK信号的激活诱导EMT在LUAD转移中起关键作用。临床癌症研究; 23(18); 5598-610。©2017 AACR.
  • 【紫杉醇联合cyclooxygenase-1和cyclooxygenase-2选择性抑制剂对体内卵巢肿瘤生长的抗肿瘤特性。】 复制标题 收藏 收藏
    DOI:10.3727/096504012x13473664562466 复制DOI
    作者列表:Li W,Zhai L,Tang Y,Cai J,Liu M,Zhang J
    BACKGROUND & AIMS: :The present study was designed to investigate whether taxol in combination with cyclooxygenase (COX) inhibitors could be superior on inhibitory effect of ovarian cancer growth than taxol alone as drug therapy of mice implanted with human ovarian carcinoma cell line SKOV-3. The animals were treated with 100 mg/ kg celecoxib (a COX-2 selective inhibitor) alone or in combination with 3 mg/kg SC-560 (a COX-1 selective inhibitor) by gavage twice a day, 20mg/kg taxol alone by intraperitoneal (IP) once a week or in combination with celecoxib, or SC-560/celecoxib/taxol for 3 weeks. To test the mechanism of the combination treatment, the index of cell proliferation, expression of cyclin D1, and microvessel density (MVD) in tumor tissues were determined by immunohistochemistry and the index of apoptotic cells by the terminal-deoxynucleotidyl-transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) method. Mean tumor volume in the SC-560/celecoxib/taxol group was first significantly lower than control at day 14 (p < 0.05). In the SC-560/celecoxib/taxol group, the index of cell proliferation and apoptosis and quantification of cyclin D1-postive cells were 6.93%, 69.62%, and 19.14%, respectively, which are statistically significant compared with those of the control group (29.85%, p < 0.001; 32.81% and 36.99%, both p < 0.05). Statistical significance on MVD was observed between the SC-560/celecoxib/taxol (39.57 +/- 4.98) and the control (73.2 +/- 1.96) group (p < 0.001). Our results suggest that the combined antitumor efficacy of taxol and COX inhibitors may be superior to taxol alone as drug therapy against ovarian cancer in mice, and that synergism of the combination treatment in part may be mediated through accelerated apoptosis and suppression of cell proliferation and angiogenesis.
    背景与目标: 本研究旨在研究紫杉醇联合环氧合酶 (COX) 抑制剂对卵巢癌生长的抑制作用是否优于单独使用紫杉醇作为植入人卵巢癌细胞系SKOV-3的小鼠的药物治疗。分别用100 mg/kg塞来昔布 (一种COX-2选择性抑制剂) 单独或与3 mg/kg SC-560 (一种COX-1选择性抑制剂) 联合每天两次灌胃,单独用20mg/kg紫杉醇腹腔 (IP) 每周一次或与塞来昔布联合治疗,或SC-560/塞来昔布/紫杉醇3周。为了测试联合治疗的机制,采用免疫组织化学方法测定肿瘤组织中细胞增殖指数,细胞周期蛋白D1的表达和微血管密度 (MVD),并通过末端脱氧核苷酸-转移酶介导的三磷酸脱氧尿苷缺口末端标记 (TUNEL) 方法测定凋亡细胞的指数。在第14天,SC-560/塞来昔布/紫杉醇组的平均肿瘤体积首先显着低于对照组 (p <0.05)。在SC-560/塞来昔布/紫杉醇组中,细胞增殖和凋亡指数以及细胞周期蛋白D1-postive的定量分别为6.93% 、69.62% 和19.14%,与对照组相比有统计学意义 (29.85%,p <0.001; 32.81% 和36.99%,均p <0.05)。SC-560/塞来昔布/紫杉醇 (39.57 +/- 4.98) 和对照组 (73.2 +/- 1.96) 之间的MVD有统计学意义 (p <0.001)。我们的结果表明,紫杉醇和COX抑制剂的联合抗肿瘤疗效可能优于单独的紫杉醇作为小鼠卵巢癌的药物治疗,并且联合治疗的协同作用部分可能通过加速凋亡和抑制细胞增殖和血管生成来介导。
  • 【抗雌激素LY117018对结膜瘤和结肠癌细胞的体外生物效应。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Picariello L,Fiorelli G,Benvenuti S,Brandi ML,Galli G,Malentacchi C,Montali E,Bigozzi U,Ficari F,Tonelli F
    BACKGROUND & AIMS: BACKGROUND:Clinical and experimental evidence suggest that estrogen has a role in the natural history of desmoid tumor (DT) and colorectal carcinoma.

    METHODS:The biological effects of LY117018, a nonsteroidal antiestrogen benzothiophene derivative, were assessed on a human adenocarcinoma cell line (HCT8 cells), and on DT cells and colorectal cancer derived fibroblasts in primary culture.

    RESULTS:LY117018 inhibited cell proliferation and collagen type I synthesis in DT cells. The compound also reduced cell growth in HCT8 cells and colorectal cancer fibroblasts. Binding experiments revealed the presence of estrogen binding sites in DT cells and frozen tissues but LY117018 did not displace [3H]17 beta E2 binding to DT cells.

    CONCLUSIONS:Present results demonstrate that LY117018 inhibits epithelial and fibroblastic colon cancer cells proliferation and proliferation and differentiation of desmoid cells in vitro. The lack of displacement of [3H]17 beta E2 binding to desmoid cells by LY117018 suggests the existence of distinct LY117018 binding sites.

    背景与目标: 背景 : 临床和实验证据表明,雌激素在结膜瘤 (DT) 和大肠癌的自然史中起作用。
    方法 : 非甾体类抗雌激素苯并噻吩衍生物LY117018的生物学作用,在人腺癌细胞系 (HCT8细胞) 以及原代培养物中的DT细胞和大肠癌衍生的成纤维细胞上进行了评估。
    结果 :LY117018抑制DT细胞中的细胞增殖和I型胶原合成。该化合物还降低了HCT8细胞和大肠癌成纤维细胞的细胞生长。结合实验表明,在DT细胞和冷冻组织中存在雌激素结合位点,但LY117018并未取代 [3H] 17βe2与DT细胞的结合。
    结论 : 目前的结果表明,LY117018在体外抑制上皮和成纤维细胞结肠癌细胞的增殖以及结膜样细胞的增殖和分化。LY117018缺乏与结膜细胞结合的 [3H] 17βe2的位移,表明存在不同的LY117018结合位点。
  • 【腹膜内,静脉内和静脉内给药单克隆抗 β-FGF抗体对大鼠软骨肉瘤肿瘤血管形成和生长的影响。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Coppola G,Atlas-White M,Katsahambas S,Bertolini J,Hearn MT,Underwood JR
    BACKGROUND & AIMS: The growth and vascularization of many tumours has been reported to be associated with the overexpression of the potent mitogenic and angiogenic polypeptide basic fibroblast growth factor (beta-FGF). Consequently, it has been proposed that inhibition of beta-FGF action would prevent the growth of beta-FGF-dependent tumours. In this study, cell culture assays were established to assess the ability of mouse monoclonal DG-2 anti-beta-FGF antibodies to inhibit the mitogenic action of beta-FGF in vitro. Following in vitro characterisation, the monoclonal DG-2 antibodies were used to evaluate the role of beta-FGF in promoting the vascularization and growth of rat chondrosarcoma tumours. The effect the monoclonal anti-B-FGF antibodies had on tumour vascularization and growth in vivo were monitored using a 99m Technetium (99mTc)-labelled red blood cell procedure. The characterization studies confirmed that the DG-2 monoclonal antibody recognised beta-FGF and inhibited its mitogenic action on mouse Balb/c cells and bovine endothelial cells in vitro. When examined in vivo, intralesional administration of mouse monoclonal DG-2 antibody significantly inhibited rat chondrosarcoma growth and vascularization. However when the monoclonal DG-2 antibody was administered intraperitoneally or intravenously no attenuation of rat chondrosarcoma tumour vascularization or growth was observed. This report has confirmed the potential effectiveness of anti-beta-FGF antibodies in the regulation of tumour growth. It has also demonstrated that further studies on the pharmacokinetics of administered antibodies and their mode of delivery are required so that the effectiveness of such anti-growth factor immunotherapy can be assured.

    背景与目标: 据报道,许多肿瘤的生长和血管化与有效的有丝分裂和血管生成多肽碱性成纤维细胞生长因子 (β-FGF) 的过表达有关。因此,已经提出抑制 β-FGF作用将阻止 β-FGF依赖性肿瘤的生长。在这项研究中,建立了细胞培养试验以评估小鼠单克隆DG-2抗 β-FGF抗体在体外抑制 β-FGF的促有丝分裂作用的能力。在体外表征之后,使用单克隆DG-2抗体来评估 β-FGF在促进大鼠软骨肉瘤肿瘤的血管化和生长中的作用。使用99m tech (99mTc) 标记的红细胞程序监测单克隆抗B-FGF抗体对体内肿瘤血管化和生长的影响。表征研究证实,DG-2单克隆抗体在体外识别 β-FGF并抑制其对小鼠Balb/c细胞和牛内皮细胞的促有丝分裂作用。当在体内检查时,小鼠单克隆DG-2抗体的病灶内给药可显着抑制大鼠软骨肉瘤的生长和血管形成。然而,当腹膜内或静脉内施用单克隆DG-2抗体时,未观察到大鼠软骨肉瘤肿瘤血管化或生长的减弱。该报告证实了抗 β-FGF抗体在调节肿瘤生长中的潜在有效性。还表明,需要对所给药抗体的药代动力学及其传递方式进行进一步研究,以便可以确保这种抗生长因子免疫疗法的有效性。

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