• 【接受腹膜内光动力疗法的患者的肿瘤和正常组织中的光敏蛋白摄取。】 复制标题 收藏 收藏
    DOI:10.1158/1078-0432.CCR-06-0953 复制DOI
    作者列表:Hahn SM,Putt ME,Metz J,Shin DB,Rickter E,Menon C,Smith D,Glatstein E,Fraker DL,Busch TM
    BACKGROUND & AIMS: PURPOSE:A phase II trial of Photofrin-mediated i.p. photodynamic therapy shown in a previous report limited efficacy and significant acute, but not chronic, toxicity. A secondary aim of this trial and the subject of this report is to determine Photofrin uptake in tumor and normal tissues. EXPERIMENTAL DESIGN:Patients received Photofrin, 2.5 mg/kg, i.v., 48 hours before debulking surgery. Photofrin uptake was measured by spectroflurometric analysis of drug extracted from tumor and normal tissues removed at surgery. Differences in drug uptake among these tissues were statistically considered using mixed-effects models. RESULTS:Photofrin concentration was measured in 301 samples collected from 58 of 100 patients enrolled on the trial. In normal tissues, drug uptake significantly (P<0.0001) differed as a function of seven different tissue types. In the toxicity-limiting tissue of intestine, the model-based mean (SE) Photofrin level was 2.70 ng/mg (0.32 ng/mg) and 3.42 ng/mg (0.24 ng/mg) in full-thickness large and small intestine, respectively. In tumors, drug uptake significantly (P=0.0015) differed as a function of patient cohort: model-based mean Photofrin level was 3.32 to 5.31 ng/mg among patients with ovarian, gastric, or small bowel cancer; 2.09 to 2.45 ng/mg among patients with sarcoma and appendiceal or colon cancer; and 0.93 ng/mg in patients with pseudomyxoma. Ovarian, gastric, and small bowel cancers showed significantly higher Photofrin uptake than full-thickness large and/or small intestine. However, the ratio of mean drug level in tumor versus intestine was modest (
    背景与目标: 目的:Photofrin介导的i.p.的II期临床试验。以前的报告中显示的光动力疗法疗效有限,且具有明显的急性但非慢性毒性。该试验和本报告主题的第二个目的是确定肿瘤和正常组织中的光敏蛋白摄取量。
    实验设计:患者在减容手术前48小时接受静脉注射2.5 mg / kg的Photofrin。通过分光光度法对从肿瘤和手术中切除的正常组织中提取的药物进行分光光度法分析来测量光蛋白的摄取。使用混合效应模型从统计学上考虑了这些组织之间的药物吸收差异。
    结果:在从该试验的100名患者中的58名患者中收集的301个样品中测量了光敏蛋白的浓度。在正常组织中,药物吸收显着不同(P <0.0001),是七种不同组织类型的函数。在肠道毒性限制组织中,全厚度大肠和小肠中基于模型的平均(SE)Photofrin水平分别为2.70 ng / mg(0.32 ng / mg)和3.42 ng / mg(0.24 ng / mg),分别。在肿瘤中,药物吸收随患者队列的不同而有显着差异(P = 0.0015):卵巢癌,胃癌或小肠癌患者中基于模型的平均Photofrin水平为3.32至5.31 ng / mg。肉瘤,阑尾或结肠癌患者中2.09至2.45 ng / mg;假性粘液瘤患者为0.93 ng / mg。卵巢癌,胃癌和小肠癌的Photofrin摄取明显高于全厚度的大肠和/或小肠。然而,肿瘤与肠道中平均药物水平的比率是中等的(<或= 2.31)。
    结论:在肿瘤与腹膜腔正常组织之间的光敏蛋白摄取中发现了一些选择性,但是相对于毒性受限的正常组织(肠)而言,药物摄取的绝对差异很小。先前已经报道过,药物选择性的这种狭窄差异可能导致治疗应用中的狭窄窗口。
  • 【肝细胞癌患者中识别野生型p53衍生表位的CD8 T淋巴细胞频率增加与表位缺失肿瘤变体的存在相关。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22251 复制DOI
    作者列表:Cicinnati VR,Zhang X,Yu Z,Ferencik S,Schmitz KJ,Dworacki G,Kaczmarek E,Oldhafer K,Frilling A,Baba HA,Schmid KW,Grosse-Wilde H,Broelsch CE,DeLeo AB,Gerken G,Beckebaum S
    BACKGROUND & AIMS: :Wild-type (WT) sequence p53 peptides are attractive candidates for broadly applicable cancer vaccines. The aim of this study was to evaluate the potential of a WT p53-based immunotherapeutic approach for patients with hepatocellular carcinoma (HCC). Circulating CD8+ T cells specific for WT p53(149-157) and WT p53(264-272) HLA-A*0201 restricted epitopes were directly identified in the peripheral blood by the use of peptide/HLA-A2.1 tetramers in 24 HCC patients. Cytotoxic T lymphocyte (CTL) activity after WT p53 peptide-specific stimulation was assessed by analysis of granzyme B and interferon-gamma mRNA transcription, using a quantitative real-time polymerase chain reaction assay. Tumor immunophenotyping was performed to evaluate the p53 status, the expression of major histocompatibility complex (MHC) and costimulatory molecules in freshly isolated tumor cells. HCC patients exhibited significantly higher frequencies of WT p53-specific memory CD8+ T cells and stronger WT p53-specific CTL activity, when compared with healthy controls. Increased frequencies of p53-specific CD8+ T cells and their activity correlated with selective HLA-A2 allele loss and reduced costimulatory molecule expression of tumor cells. Moreover, augmented numbers of p53-specific T cells coincided with high MHC class II expression in tumor cells but were inversely related to the T status of the tumor node metastasis staging system. Our results indicate the existence of natural immunosurveillance and tumor immune evasion, involving a T cell response against WT p53 tumor antigen in patients with HCC. These findings may have important implications for the future development of cancer vaccines.
    背景与目标: :野生型(WT)序列p53肽是广泛应用的癌症疫苗的诱人候选物。这项研究的目的是评估肝细胞癌(HCC)患者基于WT p53的免疫治疗方法的潜力。通过在24 HCC中使用肽/HLA-A2.1四聚体直接在外周血中鉴定出对WT p53(149-157)和WT p53(264-272)HLA-A * 0201限制性表位具有特异性的循环CD8 T细胞耐心。 WT p53肽特异性刺激后的细胞毒性T淋巴细胞(CTL)活性通过使用实时定量聚合酶链反应测定的颗粒酶B和干扰素-γmRNA转录分析来评估。进行肿瘤免疫表型分析以评估新鲜分离的肿瘤细胞中p53的状态,主要组织相容性复合体(MHC)的表达和共刺激分子。与健康对照相比,HCC患者表现出明显更高的WT p53特异性记忆CD8 T细胞频率和更强的WT p53特异性CTL活性。 p53特异性CD8 T细胞的频率增加及其活性与选择性HLA-A2等位基因缺失和肿瘤细胞共刺激分子表达降低有关。此外,p53特异性T细胞数量的增加与肿瘤细胞中II类MHC的高表达相吻合,但与肿瘤淋巴结转移分期系统的T状态呈负相关。我们的结果表明,在肝癌患者中存在自然免疫监视和肿瘤免疫逃避,涉及针对WT p53肿瘤抗原的T细胞应答。这些发现可能对癌症疫苗的未来发展具有重要意义。
  • 【缺氧条件下的肿瘤基质细胞相互作用通过肝细胞生长因子/ c-Met途径增加了胰腺癌细胞的侵袭性。】 复制标题 收藏 收藏
    DOI:10.1002/ijc.22178 复制DOI
    作者列表:Ide T,Kitajima Y,Miyoshi A,Ohtsuka T,Mitsuno M,Ohtaka K,Koga Y,Miyazaki K
    BACKGROUND & AIMS: :The hypoxic environment in tumor is reported to play an important role in pancreatic cancer progression. The interaction between stromal and cancer cells also contributes to the malignant behavior of pancreatic cancer. In the present study, we investigated whether hypoxic stimulation affects stromal as well as pancreatic cancer cells. Our findings demonstrated that hypoxia remarkably elevated the HIF-1alpha expression in both pancreatic cancer (PK8) and fibroblast cells (MRC5). Hypoxic stimulation accelerated the invasive activity of PK8 cells, and invasiveness was thus further accelerated when the hypoxic PK8 cells were cultured with conditioned medium prepared from hypoxic MRC5 cells (hypoxic conditioned medium). MMP-2, MMP-7, MT1-MMP and c-Met expressions were increased in PK8 cells under hypoxia. Hypoxic stimulation also increased the hepatocyte growth factor (HGF) secretion from MRC5 cells, which led to an elevation of c-Met phosphorylation in PK8 cells. Conversely, the elevated cancer invasion, MMP activity and c-Met phosphorylation of PK8 cells were reduced by the removal of HGF from hypoxic conditioned medium. In immunohistochemical study, the HIF-1alpha expression was observed in surrounding stromal as well as pancreatic cancer cells, thus indicating hypoxia exists in both of cancer and stromal cells. Moreover, the stromal HGF expression was found to significantly correlate with not only the stromal HIF-1alpha expression but also the c-Met expression in cancer cells. These results indicate that the hypoxic environment within stromal as well as cancer cells activates the HGF/c-Met system, thereby contributing to the aggressive invasive features of pancreatic cancer.
    背景与目标: :据报道肿瘤中的低氧环境在胰腺癌的进展中起重要作用。基质细胞与癌细胞之间的相互作用也有助于胰腺癌的恶性行为。在本研究中,我们调查了低氧刺激是否影响基质以及胰腺癌细胞。我们的发现表明,低氧显着提高了胰腺癌(PK8)和成纤维细胞(MRC5)中HIF-1alpha的表达。低氧刺激加速了PK8细胞的侵袭活性,因此,当用由低氧MRC5细胞制备的条件培养基(低氧条件培养基)培养低氧PK8细胞时,侵袭性进一步加快。在缺氧条件下,PK8细胞中的MMP-2,MMP-7,MT1-MMP和c-Met表达增加。缺氧刺激还增加了MRC5细胞的肝细胞生长因子(HGF)分泌,从而导致PK8细胞中c-Met磷酸化的升高。相反,通过从低氧条件培养基中去除HGF,可以降低PK8细胞的癌浸润,MMP活性和c-Met磷酸化水平的升高。在免疫组织化学研究中,在周围的基质细胞和胰腺癌细胞中均观察到了HIF-1alpha的表达,因此表明在癌细胞和基质细胞中均存在缺氧。此外,发现基质HGF表达不仅与癌细胞中的基质HIF-1α表达而且与c-Met表达显着相关。这些结果表明基质以及癌细胞内的低氧环境激活了HGF / c-Met系统,从而促进了胰腺癌的侵袭性侵袭性。
  • 【骨髓嵌合体小鼠的肿瘤浸润基质细胞的制备和功能分析。】 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: :肿瘤浸润基质细胞(TISC)以及肿瘤本身都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,由于在已建立的肿瘤中TISC的比例很小,因此TISC的制备是困难的。因此,通常被认为与肿瘤相关的免疫抑制有关的细胞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)小鼠和移植有GFPTg小鼠骨髓(BM)细胞的C57BL / 6小鼠,我们检测到TISC的三个亚群:一个与源自BM的未成熟髓样细胞(ImC)相容。其他两个亚群CD11b()细胞和CD11b(-)细胞并非源自BM。在存在GM-CSF的情况下与肿瘤培养后,TISC包括这些亚群,但并非每个亚群独立地抑制由抗CD3诱导的T细胞增殖。在我们的系统中,肿瘤并未直接抑制T细胞反应,但来自肿瘤的未知因素影响了TISC的免疫抑制。
  • 【P53基因的等位基因缺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: 背景:我们检查了膀胱癌中P53基因的杂合性(LOH)缺失,并研究了P53基因在乳头状瘤恶性进展中的作用。另外,检查了复发性膀胱癌的克隆性。
    方法:分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定,石蜡包埋的组织中提取DNA,在P53基因的3个多态性位点处通过聚合酶链反应(PCR)进行扩增,并通过非放射性同位素单链构象多态性(Non-RI SSCP)分析。
    结果:在40个信息量样本中,在13个样本中检测到LOH,其中3个7级中有4个(57%),2个23级中有9个(39%),1个10级中没有10个(10%)。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明,3例(60%)在原发性肿瘤中显示LOH,2例在复发性肿瘤中显示LOH。 ,与LOH在19例(16%)的3例中未显示出恶性进展的情况相反。 4例异时复发表现为LOH。在复发性肿瘤中2个,仅在初始肿瘤中1个,在两个肿​​瘤中1个。
    结论:P53基因的改变被认为与肿瘤的分级有关,并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。
  • 【PedsQL脑肿瘤模块:初始可靠性和有效性。】 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: 背景:脑肿瘤(BT)仅次于急性淋巴细胞白血病,是儿童癌症的最普遍形式,其BT 5年生存率接近70%。随着生存率的提高,生活质量已成为一种必不可少的健康结果。这项研究检查了儿童生命质量量表(PedsQL)脑肿瘤模块的内部一致性可靠性和构建效度。
    方法:将PedsQL 4.0通用核心量表,PedsQL多维疲劳量表和PedsQL脑肿瘤模块应用于99个家庭。 56名男孩和43名女孩的平均年龄为9.76岁(范围= 2-18岁)。样本包括肿瘤位于后颅窝/脑干(N = 62,62.6%),幕上(N = 15,15.2%)和中线(N = 22,22.2%)的儿童。儿童正在接受治疗(N = 46,46.5%),未接受治疗<12个月(N = 19,19.2%)或接受过治疗> 12个月/长期幸存者(N = 34,34.3%)。治疗包括放疗(N = 61,61.6%),手术(N = 83,83.8%),化学疗法(N = 87,87.9%)和骨髓移植(N = 5,5.1%)。
    结果:24项PedsQL脑肿瘤模块具有内部一致性可靠性(平均α= 0.78-0.92,父母代理报告,n = 99;平均α= 0.76-0.87,孩子自我报告,n = 51)。通过分析通用核心量表和疲劳量表之间的相互关系,支持了PedsQL脑肿瘤模块的构建效度。
    结论:这些发现为PedsQL脑肿瘤模块的测量特性提供了支持。
  • 【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: :除了在细胞稳态中的作用外,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,了解在治疗的癌细胞中自噬的调控与发现抗癌药物的分子靶标有关。我们最近的报告指出,辐射诱导的mTOR途径失活是人类乳腺癌细胞系MCF-7辐射诱导的自噬的潜在机制。最重要的是,此途径的辐射诱导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)的水平降低以及p53磷酸化的增加有关。进一步分析这些事件之间的相互关系以及它们各自在放射后的细胞存活中所起的作用,将提高我们在抗癌治疗中采用mTOR途径的能力。
  • 【视频内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:经肛门切除良性和恶性直肠肿瘤是一种广为接受的手术技术。如Buess等人在1984年最初描述的,使用立体显微外科技术已显示可通过允许距肛门边缘长达24 cm的精确,全层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)未能获得广泛的普及,其原因有两个:专有的器械套件昂贵且复杂(68,000美元,包含30个组件),并且该过程在技术上难以掌握。我们通过修改TEM仪器(结合标准腹腔镜和摄像机以及标准腹腔镜仪器)展示我们的结果。

    方法:到目前为止,已经培训了四名外科医生。介绍了培训课程的详细信息。描述了视频内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。

    结果:1994年8月至1996年6月,四名外科医生进行了27例VTEM病例。平均年龄为69岁。年,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),在外科医生的前5例中以及距肛门边缘16厘米以上的病变中,手术时间更长。手术中很少有手术问题(4%),术后并发症(尿失禁2,晚期出血1,腺瘤复发1)占15%。

    结论:可以教VTEM使用类似于高级腹腔镜课程的格式成功地向胃肠道和结直肠外科医生使用。使用已经可用的腹腔镜和仪器可降低安装的初始成本。结果良好,并发症和复发率低,住院时间很短。患者可以从有效,微创的替代开放手术中受益。

  • 【大鼠横纹肌肉瘤R1H的放射生物学:辐照场大小对肿瘤反应,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区域,用15 Gy X射线单剂量照射:R1H肿瘤。通过分析至十倍治疗体积(GD10vo)的生长延迟和净生长延迟来分别确定对肿瘤细胞和肿瘤基质的损伤。 GD10vo包括对肿瘤实质细胞和肿瘤基质的辐射作用,而净生长延迟仅能测量对肿瘤实质细胞的作用。观察到间质损伤随田间大小的增加而增加。然而,对肿瘤实质细胞的影响与视野大小无关。观察到GD10vo的增加,每厘米田径直径增加13天。由此计算出被辐照的肿瘤床的新血管形成速度为每天0.30至0.38mm。
  • 【WT1 Wilms的肿瘤抑制基因是PC12细胞中胰岛素样生长因子I(IGF-1)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与ras-raf-连接的跨膜异四聚体IGF-I受体(IGF-IR)激活而介导的。丝裂原活化蛋白激酶(MAPK)和磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(PKB)/ Akt信号转导级联反应。威尔姆斯的肿瘤抑制基因(wt1)编码锌指转录因子WT1,该因子已参与多种细胞过程,包括增殖,分化和凋亡。在本研究中,我们证明了IGF-1以剂量和时间依赖性的方式调节神经源性PC12细胞中WT1基因的表达。这种作用是通过MAPK和PI3激酶信号传导途径介导的,如特异性抑制剂UO126和LY294002消除IGF-1作用的能力所示。此外,使用RT-PCR和瞬时转染试验,我们证明了IGF-I的作用与WT1 mRNA水平和WT1启动子活性的相应变化有关。此外,本研究结果表明,高WT1水平与凋亡诱导相关,而低WT1水平与凋亡抑制相关,如聚ADP核糖聚合酶(PARP)裂解,Bax表达,膜联蛋白所证明的。 V-FITC染色,并使用针对WT1的反义寡核苷酸。总而言之,我们的结果表明wt1基因是神经衍生细胞中IGF-I作用的新靶标。
  • 【复发性外阴三叉神经增生性肿瘤:一例报道。】 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: :增生性三腕膜肿瘤(PTT)是一种罕见的但形态上明显不同的肿瘤,通常出现在老年妇女的头皮上。它由鳞状上皮组成的多个囊肿组成,具有三足动物的角质化作用,无颗粒层插入。外阴增生性三腕膜囊肿非常罕见,据我们所知,文献中仅报道了3例。我们描述了一个39岁的女性,其外阴左唇唇上有反复的PTT,这是5年前从同一侧切除的。她有一个明显的结节,大小约2厘米,结实,活动且不嫩。没有红斑和溃疡;并被外阴的正常皮肤覆盖。没有腹股沟淋巴结肿大。通过广泛的外科手术切除病变。由于组织的弹性,可以进行初次闭合。据报道该病理结果为具有无肿瘤切缘的增殖性三叶膜癌。尽管广泛切除后局部复发很少见,但由于复发的可能性,我们建议完全切除以治疗PTT和长期随访。
  • 【关于晚期肿瘤患者的兴趣和态度,关于肿瘤基因组分析的继发性生殖细胞发现。】 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: 目的:肿瘤基因组图谱(TGP)可以揭示有关癌症患者遗传疾病风险的次要发现。目前尚不了解晚期癌症患者(目前是TGP的主要使用者)如何感知次级种系发现的利弊。
    方法:我们对40名患有TGP的晚期乳腺癌,膀胱癌,结直肠癌或肺癌患者进行了半结构化访谈。使用主题内容分析方法对定性访谈数据进行了评估。
    结果:大多数参与者对学习其次生种系发现的前景表示兴趣(57%),尽管少数人模棱两可(29%)或不感兴趣(14%)。这些偏好的原因各不相同,但受到参与者对这些信息的各种利弊的看法的影响,他们认为这与自己有关。他们的家人;以及其他患有癌症,医学和社会的患者。这些态度是由参与者的个人疾病经历和健康状况独特地塑造的。
    结论:许多晚期癌症患者对学习继发生殖系发现感兴趣,并对潜在的健康益处抱有乐观甚至不切实际的信念。患者还对该信息的临床和情感含义有重要的担忧。这些认识是解决以确保患者就学习次生种系发现做出知情决定所必需的。
  • 13 Organizing hematoma mimicking brain tumor. 复制标题 收藏 收藏

    【组织模仿脑瘤的血肿。】 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岁男子因右上肢和下肢渐进性功能丧失而被转诊到我们医院。未增强的计算机体层摄影术显示左基底神经节有高密度的结节性病变,周围低衰减。脑磁共振成像显示主要是囊性肿块,内部有多个隔垫,偏心的固体成分增强。组织学检查显示有组织的血块和小胶质细胞胶质增生。当在MRI上遇到遵循旧血信号特征的具有结节性成分的囊状囊性肿块时,在鉴别诊断中应考虑这种类似肿块状组织血块的异常出现。
  • 【补充精氨酸可增加正常和鼠肉瘤病毒感染小鼠的胸腺细胞性,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3天,向6周大的CBA小鼠补充精氨酸。尽管基础饮食中含有1.8%的精氨酸,因此并非精氨酸缺乏,但饮食和饮用水中添加0.5%的精氨酸HCl可以降低肿瘤的发生率,延长潜伏期,减小肿瘤的大小并加速肿瘤的消退。精氨酸还增加了正常小鼠和接种MSV的小鼠的胸腺重量和细胞数量。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-间质转化增强了肺腺癌的细胞运动性并促进了肿瘤转移。】 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:研究染色体凝集2调节剂(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。进行了小鼠模型,细胞生物学和分子生物学实验,以阐明RCC2在LUAD中的功能及其潜在机制。结果:RCA2在LUAD中的表达频繁增加(88 / 122,72.13%)。通过分析大量包含488 LUAD和58正常肺组织的TCGA RNA-seq数据证实了这一点(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)和晚期临床阶段(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患者的独立不良预后因素。此外,RCC2的强制表达在体内促进肺内转移,并在体外显着增强LUAD细胞的迁移,侵袭和增殖。进一步的研究发现RCC2诱导上皮-间质转化(EMT)并刺激MMP-2和MMP-9的表达。 。此外,RCC2能够激活JNK,而抑制JNK则抑制了RCC2对LUAD细胞迁移,侵袭,EMT以及MMP-2和MMP-9表达的影响。结论:RCC2在LUAD转移中起关键作用。通过激活MAPK-JNK信号传导来诱导EMT。临床癌症研究; 23(18); 5598-610。 ©2017 AACR。

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