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Comparing Gefitinib and Erlotinib With Regard To Brain Metastases Recurrence in EGFR-Mutant Non-Small Cell Lung Cancer Patients 吉非替尼和厄洛替尼对EGFR突变非小细胞肺癌癌症患者脑转移复发的比较
Pub Date : 2017-06-14 DOI: 10.4172/2324-9110.1000190
K. Nakahama, A. Tamiya, Y. Taniguchi, Yoko Naoki, M. Kanazu, S. Atagi
Brain metastases of lung cancer are associated with a poor prognosis. Little research has been conducted to directly compare erlotinib with gefitinib regarding the frequency of central nerve system recurrence. This is the first study to directly compare erlotinib with gefitinib in terms of brain metastases recurrence rates in patients with EGFR-mutant NSCLC who had no brain metastasis at the time of starting TKI treatment. This was a single-center retrospective study. Advanced or recurrent non-small cell lung cancer patients with no brain metastases at the time of starting initial tyrosine kinase inhibitor treatment who received either gefitinib or erlotinib monotherapy were selected. The primary endpoint was the incidence of brain metastases, and secondary endpoints included the objective response rate, progression-free survival, overall survival, and Post-Progression Survival in subgroups based on tyrosine kinase inhibitor treatment and the occurrence of brain metastases. There were 119 patients in the gefitinib group and 13 patients in the erlotinib group. Brain metastases at disease progression were observed in 16 patients in the gefitinib group, and in no patients in the erlotinib group (13.5% vs. 0%, p=0.37). The median overall survival was 29.2 months in the gefitinib group and was not reached in the erlotinib group (p=0.14). The median PPS was 15.5 months in the gefitinib group and 23.7 months in the erlotinib group (p=0.11). Based on the occurrence of brain metastases, Post-Progression Survival was significantly longer in the no brain metastases group (8.0 months vs. 17.9 months, p=0.01). These data showed the possibility of a lower central-nerve-system recurrence rate with erlotinib compared with gefitinib. Post-Progression Survival in patients with brain metastases was significantly shorter than that of patients without brain metastases.
癌症脑转移与预后不良有关。很少有研究直接比较埃洛替尼和吉非替尼的中枢神经系统复发频率。这是第一项直接比较埃洛替尼和吉非替尼在EGFR突变NSCLC患者脑转移复发率的研究,这些患者在开始TKI治疗时没有脑转移。这是一项单中心回顾性研究。选择接受吉非替尼或埃洛替尼单药治疗的癌症晚期或复发患者,在开始初始酪氨酸激酶抑制剂治疗时无脑转移。主要终点是脑转移的发生率,次要终点包括基于酪氨酸激酶抑制剂治疗和脑转移发生率的亚组的客观有效率、无进展生存率、总生存率和进展后生存率。吉非替尼组119例,埃洛替尼组13例。在吉非替尼组的16名患者中观察到疾病进展时的脑转移,埃洛替尼组无患者(13.5%对0%,p=0.37)。吉非替尼组的中位总生存期为29.2个月,埃洛替尼组未达到(p=0.14)。吉非替尼和埃罗替尼组PPS的中位分别为15.5个月和23.7个月(p=0.11)。根据脑转移的发生情况,无脑转移组的进展后生存期明显更长(8.0个月vs.17.9个月,p=0.01)。这些数据表明,与吉非替尼相比,埃洛替尼可能降低中枢神经系统复发率。脑转移患者的进展后生存期明显短于无脑转移患者。
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引用次数: 0
Will PD-1/PD-L1 Inhibitor Become a True Salvage Therapy for Relapsed or Refractory Patients with Hematological Malignancies? PD-1/PD-L1抑制剂会成为复发或难治性血液恶性肿瘤患者的真正救助性治疗吗?
Pub Date : 2017-06-13 DOI: 10.4172/2324-9110.1000E110
C. Schmidt, Mark A. Brown
Relating the Pendulum of Democracy with Oncology Research Abstract It has been over 40 years since President Richard M. Nixon signed the National Cancer Act. Considered radically progressive by some in 1971, few today recognize the political implications of this legislation for a conservative U.S. president. In retrospect, the signing of the National Cancer Act highlights how closely most U.S. politicians operate to political center, relative to their global counterparts. Thus, the rest of the world is often mystified by the ability of the pendulum of American democracy to drive revolutionary events with global impacts, following a subtle swing to the left or right of the political center. Herein, we reflect upon the relationship between this pendulum of democracy and oncology research.
将民主的钟摆与肿瘤研究联系起来摘要理查德·M·尼克松总统签署《国家癌症法案》已经40多年了。1971年,一些人认为这是一项激进的立法,如今很少有人认识到这项立法对保守派美国总统的政治影响。回顾过去,《国家癌症法案》的签署突显了与全球同行相比,大多数美国政客与政治中心的关系是多么密切。因此,世界其他地区经常对美国民主的钟摆在政治中心微妙地向左或向右摆动后推动具有全球影响的革命事件的能力感到困惑。在此,我们反思民主的钟摆与肿瘤学研究之间的关系。
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引用次数: 5
Orphan Nuclear Receptor TR3/Nur77 is a Specific Therapeutic Target for Hepatic Cancers. 孤儿核受体TR3/Nur77是肝癌的特异性治疗靶点
Pub Date : 2017-06-01 Epub Date: 2017-05-09 DOI: 10.4172/2324-9110.1000184
Yingling Zeng, Xiaoguang Ye, Degui Liao, Shizhang Huang, Huinan Mao, Dezheng Zhao, Huiyan Zeng

Objective: Although great success has been achieved in cancer treatment, current cancer therapies, including anti-tumorigenesis and anti-angiogenesis, still face the problems of insufficient efficacy, resistance and intrinsic refractoriness, in addition to their toxic side effects. There is a demand to identify additional targets that can be blocked to turn off the downstream effects of most, if not all, pathways. Our previous studies suggest that orphan nuclear receptor TR3 (human) / Nur77 (mouse) is such a target. However, the correlation of TR3 expression and clinical tumor progression has not been studied.

Methods: The expression of TR3 was analysed in human primary hepatic cancer specimens from patients that have complete medical records with Immunohistochemical staining. The statistical analysis was used to assess the significance of TR3 expression in tumor tissues, paratumor tissues and normal tissues, and to investigate the correlation of TR3 expression and clincopathologic characteristics.

Results: TR3 is highly expressed in human hepatic cancer tissues, but not in normal liver tissues. The positive expression yields of TR3 are 67.67% (14/21), 19.05% (4/21) and 0% (0/10) in cancer tissues, para cancer tissues, and normal liver tissue, respectively, which are statistic significant (χ2=17.07, p<0.005). The expression of TR3 is significantly higher in cancer tissues than in para cancer tissues χ2=9.722, p<0.005) and in normal tissues (p<0.0005). The levels of TR3 expression in human hepatic cancer tissues correlates well with tumors that are at low/middle degree of tumor differentiation and have portal vein thrombosis, metastasis and recurrence, but not with age, gender, tumor number and Alpha-fetal protein (AFP) volume.

Conclusion: The results indicate that TR3 is a specific therapeutic target for hepatic cancers.

目的:虽然癌症治疗取得了巨大的成功,但目前的癌症治疗方法,包括抗肿瘤和抗血管生成,仍然面临着疗效不足、耐药和内在难治性的问题,以及毒副作用。有必要确定可以阻断的其他靶标,以关闭大多数(如果不是全部的话)途径的下游影响。我们之前的研究表明孤儿核受体TR3(人)/ Nur77(小鼠)就是这样一个靶点。然而,TR3表达与临床肿瘤进展的相关性尚未得到研究。方法:采用免疫组化染色法对病历完整的人原发性肝癌标本中TR3的表达进行分析。采用统计学方法评价TR3在肿瘤组织、瘤旁组织和正常组织中的表达,探讨TR3表达与临床病理特征的相关性。结果:TR3在人肝癌组织中高表达,而在正常肝组织中不表达。TR3在肝癌组织、癌旁组织和正常肝组织中的阳性表达率分别为67.67%(14/21)、19.05%(4/21)和0%(0/10),差异均有统计学意义(χ2=17.07, p)。结论:TR3是肝癌特异性治疗靶点。
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引用次数: 6
Antiangiogenic Activity of rTRAIL is Potentiated by Sflt-1, a VEGF Trap VEGF诱捕剂Sflt-1可增强rTRAIL的抗血管生成活性
Pub Date : 2017-05-30 DOI: 10.4172/2324-9110.1000185
B. Yashaswini, A. Mutahar, B. Salimath
Objective: Anti-angiogenesis and pro-apoptosis are the two processes which are strategically used to target tumors. The soluble form of VEGF receptor 1 (Flt-1) is a modulator of VEGF activity and could be useful as a trap to intrinsically sequester VEGF in tumor cells. In the present study, we have investigated the role of rTRAIL in inhibiting VEGF-mediated angiogenesis and its synergistic potentiation by sFlt-1. Methods: We have expressed human recombinant TRAIL, to study its role in anti-angiogenesis and a 2-domain active variant of sFlt-1 by bacterial expression to be used as a trap for VEGF. 3[H] thymidine incorporation assay was used to confirm the inhibitory activity of sFlt-1 and/or rTRAIL on cell proliferation. The synergistic anti-migratory and anti-angiogenic activity of sFlt-1 and rTRAIL were assessed using endothelial cell wound healing and tube formation assay in-vitro and by rat corneal micropocket assay in-vivo. Results: Inhibition of cell proliferation was evident in sFlt-1 and rTRAIL treated cells in a dose -dependent manner with more than 60% reduction in proliferation rate as compared to the tumor cells treated with sFlt-1 and rTRAIL alone. Furthermore, the anti-metastatic and anti-angiogenic activity of sFlt-1 and rTRAIL in combination was evident in endothelial wound healing and tube formation with a significant reduction in the number of cells migrated into the wounded area and the number of honey comb-like structures with the length of the tubes formed to mimic blood vessel formation in-vitro respectively. The in-vivo corneal micropocket assay confirmed the anti-angiogenic effect of sFlt-1 and rTRAIL in combination. Conclusion: The synergistic role of sFlt-1 and rTRAIL as the potential inhibitors of VEGF- mediated angiogenesis could be therapeutically exploited.
目的:抗血管生成和促细胞凋亡是靶向肿瘤的两个重要过程。可溶性形式的VEGF受体1(Flt-1)是VEGF活性的调节剂,并且可以用作在肿瘤细胞中固有地螯合VEGF的陷阱。在本研究中,我们研究了rTRAIL在抑制VEGF介导的血管生成中的作用及其通过sFlt-1的协同增强作用。方法:我们表达了人重组TRAIL,以研究其在抗血管生成中的作用,并通过细菌表达来研究sFlt-1的2结构域活性变体作为VEGF的陷阱。3[H]胸苷掺入试验用于证实sFlt-1和/或rTRAIL对细胞增殖的抑制活性。sFlt-1和rTRAIL的协同抗迁移和抗血管生成活性通过体外内皮细胞伤口愈合和管形成测定和体内大鼠角膜微袋测定进行评估。结果:与单独用sFlt-1和rTRAIL处理的肿瘤细胞相比,sFlt-1或rTRAIL处理的细胞以剂量依赖性方式明显抑制细胞增殖,增殖率降低60%以上。此外,sFlt-1和rTRAIL的联合抗转移和抗血管生成活性在内皮伤口愈合和管形成中是明显的,迁移到损伤区域的细胞数量和蜂窝状结构的数量随着管的长度而显著减少,以分别模拟体外血管形成。体内角膜微袋测定证实了sFlt-1和rTRAIL联合使用的抗血管生成作用。结论:sFlt-1和rTRAIL作为VEGF介导的血管生成的潜在抑制剂具有协同作用,可用于治疗。
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引用次数: 1
Feasibility of Single Tumorspot Treatment in Peritoneal Carcinomatosis via Close Range Doxorubicin Impaction in Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC) 腹膜内加压气溶胶化疗(PIPAC)中阿霉素近距离介入治疗腹膜癌的可行性
Pub Date : 2017-05-26 DOI: 10.4172/2324-9110.1000187
T. Khosrawipour, Dan Wu, Alex, er Bellendorf, Nirushika Mohanaraja, E. Karabay, D. Díaz-Carballo, Veria Khosrawipour
Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a well-established, yet not fully evaluated new treatment approach for peritoneal carcinomatosis with the aim at enabling localized application of chemo aerosol within the abdominal cavity. Distribution inhomogeneity in PIPAC has been previously indicated in prior experiments. This study was conducted to investigate whether this finding can be used to achieve localized high drug concentrations into micro metastasis. Materials and Methods: PIPAC construct was built using a hermetic container system which mimics the abdominal cavity. Fresh parietal peritoneum portions from post-mortem swine were cut into samples and placed vertically in the center of a box. The Micropump© (MIP) was introduced via trocar at the side of the box and located at 1cm from the samples to enable close range impaction of the aerosolized doxorubicin with the samples. Doxorubicin penetration depth was radially measured by fluorescence microscopy from the center of targets to the outer rim. Results: Tissue doxorubicin penetration in the tissue was lower towards the outer rim and further away from the center of the sprayjet. Maximal penetration of drug was achieved in the midpoint of the sprayjet with 417± 87(SD) µm and a minimal penetration was reached at 3 cm from center with 45 ± 20 (SD) µm. Conclusions: Our ex vivo data indicated that it might be feasible and beneficial to treat single cancer nodules at close range using PIPAC as it increases local penetration rates and therefore might be advantageous prior or after the planned cytoreductive surgery.
背景:加压腹膜内气雾剂化疗(PIPAC)是一种公认的、但尚未完全评估的腹膜癌新治疗方法,旨在使化疗气雾剂能够在腹腔内局部应用。PIPAC中的分布不均匀性先前已经在先前的实验中指出。进行这项研究是为了研究这一发现是否可以用于实现微转移的局部高药物浓度。材料和方法:使用模仿腹腔的密闭容器系统构建PIPAC结构。将来自死后猪的新鲜腹膜壁部分切成样品,并垂直放置在盒子的中心。微型泵©(MIP)是通过套管针在盒子侧面引入的,位于距离样品1cm的位置,以使雾化的阿霉素能够与样品近距离碰撞。阿霉素的穿透深度通过荧光显微镜从靶的中心到外缘进行径向测量。结果:多柔比星在组织中的穿透力朝向外缘较低,并且远离喷雾器的中心。药物的最大穿透力在喷雾器的中点达到417±87(SD)µm,最小穿透力在距离中心3厘米处达到45±20(SD)μm。结论:我们的离体数据表明,使用PIPAC近距离治疗单个癌症结节可能是可行和有益的,因为它可以提高局部穿透率,因此在计划的细胞减灭术之前或之后可能是有利的。
{"title":"Feasibility of Single Tumorspot Treatment in Peritoneal Carcinomatosis via Close Range Doxorubicin Impaction in Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC)","authors":"T. Khosrawipour, Dan Wu, Alex, er Bellendorf, Nirushika Mohanaraja, E. Karabay, D. Díaz-Carballo, Veria Khosrawipour","doi":"10.4172/2324-9110.1000187","DOIUrl":"https://doi.org/10.4172/2324-9110.1000187","url":null,"abstract":"Background: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a well-established, yet not fully evaluated new treatment approach for peritoneal carcinomatosis with the aim at enabling localized application of chemo aerosol within the abdominal cavity. Distribution inhomogeneity in PIPAC has been previously indicated in prior experiments. This study was conducted to investigate whether this finding can be used to achieve localized high drug concentrations into micro metastasis. \u0000Materials and Methods: PIPAC construct was built using a hermetic container system which mimics the abdominal cavity. Fresh parietal peritoneum portions from post-mortem swine were cut into samples and placed vertically in the center of a box. The Micropump© (MIP) was introduced via trocar at the side of the box and located at 1cm from the samples to enable close range impaction of the aerosolized doxorubicin with the samples. Doxorubicin penetration depth was radially measured by fluorescence microscopy from the center of targets to the outer rim. \u0000Results: Tissue doxorubicin penetration in the tissue was lower towards the outer rim and further away from the center of the sprayjet. Maximal penetration of drug was achieved in the midpoint of the sprayjet with 417± 87(SD) µm and a minimal penetration was reached at 3 cm from center with 45 ± 20 (SD) µm. \u0000Conclusions: Our ex vivo data indicated that it might be feasible and beneficial to treat single cancer nodules at close range using PIPAC as it increases local penetration rates and therefore might be advantageous prior or after the planned cytoreductive surgery.","PeriodicalId":73658,"journal":{"name":"Journal of clinical & experimental oncology","volume":" ","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49488998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Knockdown of CD151 Gene Expression Reduces Survival of Estrogen Receptor Positive Breast Cancer Cells CD151基因表达下调可降低雌激素受体阳性乳腺癌细胞的存活率
Pub Date : 2017-05-26 DOI: 10.4172/2324-9110.1000186
Gayatri Devi, A. Badana, M. Ch, P. Muralimohan, Shail, Rakhi P. Naik, I. BhaskarReddy, Seema Kumari, R. Malla
Tetraspnin CD151 is involved in proliferation, motility, and invasion. Yet, the role of CD151 in estrogen receptor positive breast cancer is not reported. In the present study, the role of CD151 in survival of ER positive cell line and the underlying molecular partners was reported. CD151 shRNA expression vector was transfected into MCF-7 cells and its efficacy was evaluated by RT-PCR. The capacity of proliferation, migration, and invasion, cell adhesion, angiogenesis of MCF-7 cells was diminished by the knockdown of CD151 via CD151 specific shRNA. It arrested the cell cycle at G2/M phase and induced the apoptosis. The expressions of c-myc, α3β1 integrin, IL-8, Ras, FAK and VEGF were reduced by knockdown of CD151. The results conclude that CD151 gene silencing affects the expression of its network partner’s associate with survival of MCF-7 cells. Therefore, CD151 may be a potential target of luminal and basal subtypes.
Tetraspnin CD151参与增殖、运动和侵袭。然而,CD151在雌激素受体阳性乳腺癌中的作用尚未报道。在本研究中,我们报道了CD151在ER阳性细胞系及其潜在分子伴侣存活中的作用。将CD151 shRNA表达载体转染MCF-7细胞,采用RT-PCR方法评价其表达效果。MCF-7细胞的增殖、迁移、侵袭、细胞粘附和血管生成能力被CD151特异性shRNA敲除。将细胞周期阻滞在G2/M期,诱导细胞凋亡。敲低CD151可降低c-myc、α3β1整合素、IL-8、Ras、FAK、VEGF的表达。结果表明,CD151基因沉默影响其网络伴侣的表达,与MCF-7细胞存活相关。因此,CD151可能是管腔和基底亚型的潜在靶点。
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引用次数: 4
Anti Adeno-Associated Virus 2 (AAV) Antibody Profile in Ovarian Cancer Ascitic Fluid: Implications for AAV Intraperitoneal Gene Therapy 卵巢癌腹水抗腺相关病毒2 (AAV)抗体谱:对AAV腹腔内基因治疗的意义
Pub Date : 2017-05-26 DOI: 10.4172/2324-9110.1000183
J. Skubis-Zegadło, M. Kowalska, B. Śpiewankiewicz, Wacław Smiert Krzysztof Gawrychowski, M. Małecki
Objective: Recombinant adeno-associated virus (rAAV) type 2 is a common vector used in gene therapy. However, the presence of anti-AAV2 neutralizing antibodies or other neutralizing factors can significantly limit effective transduction. Intraperitoneal gene therapy could enable local delivery of the target gene directly to ovarian cancer cells. Until now, there have been no reports on the presence of anti-AAV antibodies in ascitic fluid, which might limit the effectiveness of rAAV as a candidate vector for intraperitoneal gene therapy. Thus, the characterization of the preexisting neutralization antibodies in ascitic fluid will provide insight into successful intraperitoneal gene therapy. Methods: The study was conducted on 23 ascitic fluid samples obtained from women with stage 3 and 4 ovarian cancer. The samples were collected to determine the presence of anti-AAV antibodies with ELISA test and the presence of neutralizing antibodies with neutralizing assay. Results: Our results indicate that anti-rAAV antibodies are present in 70%, whereas neutralizing factors/antibodies are present in 78% of analyzed ascitic fluid samples. This correlation provides evidence for the presence of additional, different from antibodies, currently unknown factors in ascites, which are able to inhibit AAV2 infection in the absence of anti-AAV antibodies. Conclusion: The presence of neutralizing antibodies against rAAV or other neutralizing factors in ascitic fluid should be taken into account during intraperitoneal gene therapy, because they might limit effective intraperitoneal gene therapy with rAAV as a vector.
目的:重组腺相关病毒(rAAV) 2型是基因治疗中常用的载体。然而,抗aav2中和抗体或其他中和因子的存在会显著限制有效转导。腹腔内基因治疗可以使靶基因直接局部递送到卵巢癌细胞。到目前为止,还没有关于腹水中存在抗aav抗体的报道,这可能限制了rAAV作为腹膜内基因治疗候选载体的有效性。因此,腹水中预先存在的中和抗体的表征将为成功的腹膜内基因治疗提供见解。方法:对23例3期和4期卵巢癌患者的腹水样本进行研究。采集标本,采用ELISA法检测抗aav抗体的存在,中和法检测中和抗体的存在。结果:我们的结果表明,抗raav抗体存在于70%的腹水样本中,而中和因子/抗体存在于78%的腹水样本中。这种相关性为腹水中存在其他与抗体不同的未知因素提供了证据,这些因素能够在缺乏抗aav抗体的情况下抑制AAV2感染。结论:腹水中是否存在针对rAAV的中和抗体或其他中和因子,可能会限制以rAAV为载体进行腹水基因治疗的有效性,因此在进行腹水基因治疗时应考虑这些抗体的存在。
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引用次数: 1
Lack of Response to Vismodegib in a Patient with Advanced Basal Cell Carcinoma: A Case Report 一例晚期基底细胞癌患者对Vismodegib缺乏反应
Pub Date : 2017-03-23 DOI: 10.4172/2324-9110.1000177
C. Rodríguez-Cerdeira, Munoz-Garzon
Purpose: Basal cell carcinoma (BCC), the most common type of skin cancer in humans, rarely progresses to locally advanced or metastatic BCC. The size, extent, and location of the lesion should be carefully considered when selecting a treatment option for patients with BCC. Methods: Moreover, clinicians should review the potential for significant deformity and anticipated morbidity, when considering radiation therapy and surgery for treatment. Vismodegib, the first approved oral therapy for advanced BCC, is a treatment option that clinicians might consider for patients with BCC lesions that exhibit the clinical characteristics as described above. Results: In this manuscript, we reviewed the mechanism of action, clinical efficacy, and safety of vismodegib and consider the possible causes for a lack of response to the drug. Conclusion: The therapeutic response to these tumors may be limited by the challenge of acquired resistance against smoothened antagonists.
目的:基底细胞癌(BCC)是人类最常见的皮肤癌症类型,很少发展为局部晚期或转移性BCC。在选择BCC患者的治疗方案时,应仔细考虑病变的大小、范围和位置。方法:此外,临床医生在考虑放射治疗和手术治疗时,应审查严重畸形和预期发病率的可能性。Vismodegib是第一种被批准的晚期基底细胞癌口服治疗方法,临床医生可能会考虑对具有上述临床特征的基底细胞癌病变患者进行治疗。结果:在这篇文章中,我们回顾了vismodegib的作用机制、临床疗效和安全性,并考虑了对该药物缺乏反应的可能原因。结论:对这些肿瘤的治疗反应可能受到对平滑拮抗剂的获得性耐药性的挑战的限制。
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引用次数: 0
Cripto-1 and RUNX2 Expressions in Non-small Cell Lung Cancer, their Roles in its Progression and Patients Outcome Cripto-1和RUNX2在非小细胞肺癌癌症中的表达及其在进展和患者预后中的作用
Pub Date : 2017-03-23 DOI: 10.4172/2324-9110.1000182
O. Harb, S. Shorbagy, Nehal S. Abouhashem, O. Elfarargy, S. Balata, L. Gertallah, Mohammed M.N. Abozaid, W. Galal, Sameh Saber
Background: Non-small cell carcinoma of lung (NSCLC) is the commonest and most lethal lung cancer type; it includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma subtypes. The five-year survival rate in NSCLC patients is still very low although improvements in treatment modalities are still emerging. Hence, new prognostic markers and therapies need to be brought to light aiming to improve patients' outcome. Cripto-1 (CR-1) is one of the family members of epidermal-growth-factor; cripto FRL1 cryptic-(EGF-CFC) is needed for embryogenesis. Runt-related-transcription-factor [RUNX] family members make core-binding factor complex (CBFC) that attach to DNA to stimulate or inhibit many genes transcription, regulate the survival, differentiation and maturation of many tissues. The aim of this work is to detect the clinical significance and prognostic role of CR-1 and RUNX2 expressions in NSCLC using immunohistochemistry. Method: CR-1 and RUNX2 expressions were evaluated in 59 paraffin blocks sections of NSCLC. The relationship between their level of expressions and patient's prognosis was analyzed. Results: CR-1 and RUNX2 were highly expressed in NSCLC patients, 59.3% and 67.8%, respectively. There was a significant positive association between their expressions in NSCLC patients (p=0.015). Both markers were significantly correlated with size, grade, stage, site of the tumor within the lung, malignant (pleural and/or pericardial) effusion, presence of distant metastases, ECOG performance status of the patients (p<0.001) and existence of hepatic metastases (p=0.004). Both markers expressions were significantly correlated with poor response to treatment (p<0.001). After a median follow up of 30 months, mean PFS of NSCLC patients having elevated CR-1 and RUNX2 expressions was shorter (p<0.001). Patients with high RUNX2 expressing have significantly shorter mean OS (p=0.025). High CR-1 expression negatively affected OS but that was not statistically significant (p=0.2). Conclusion: NSCLC patients with elevated CR-1 and RUNX2 expression values had unfavorable prognosis.
背景:非小细胞肺癌(NSCLC)是癌症最常见、最致命的类型;它包括鳞状细胞癌、腺癌和大细胞癌亚型。NSCLC患者的五年生存率仍然很低,尽管治疗方式仍在不断改进。因此,需要揭示新的预后标志物和治疗方法,以改善患者的预后。Cripto-1(CR-1)是表皮生长因子的家族成员之一;胚胎发生需要隐式FRL1(EGF-CFC)。Runt相关转录因子[RUNX]家族成员形成核心结合因子复合体(CBFC),该复合体附着在DNA上,刺激或抑制许多基因的转录,调节许多组织的生存、分化和成熟。本工作的目的是通过免疫组织化学检测CR-1和RUNX2在NSCLC中的表达的临床意义和预后作用。方法:对59例NSCLC石蜡切片中CR-1和RUNX2的表达进行评价。分析其表达水平与患者预后的关系。结果:CR-1和RUNX2在NSCLC患者中的高表达率分别为59.3%和67.8%。它们在NSCLC患者中的表达之间存在显著的正相关(p=0.015)。这两种标志物与肿瘤的大小、级别、分期、肺部部位、恶性(胸腔和/或心包)积液、远处转移的存在、,患者的ECOG表现状态(p<0.001)和肝转移的存在(p=0.004)。这两种标志物的表达与治疗反应差显著相关(p<001)。在中位随访30个月后,CR-1和RUNX2表达升高的NSCLC患者的平均PFS更短(p<0.001)。RUNX2表达高的患者的平均OS显著更短(p=0.025)。CR-1表达高对OS产生负面影响,但无统计学意义(p=0.2)。
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引用次数: 1
High Extra-Tumoral 99mTc-Macroaggregated Albumin Accumulation in a Fatty Liver in a Candidate for Transarterial Radioembolization Treatment 脂肪肝中高肿瘤外99mTc大聚集白蛋白的积聚作为经动脉放射栓塞治疗的候选者
Pub Date : 2017-03-23 DOI: 10.4172/2324-9110.1000180
V. Lyra, K. Palialexis, Chrisostomos Constantos, L. Reppas, E. Brountzos, S. Chatziioannou
A patient with non-alcoholic fatty liver disease (NAFLD) and unresectable small-sized (≤3cm) diffuse liver metastases from adenocarcinoma of the rectosigmoid junction was assessed for treatment with transarterial radioembolization (SIRT). The right hepatic arteriogram demonstrated several hypervascular lesions. However, the planar and the SPECT images of the subsequent right hepatic arterial 99mTc-MAA perfusion scintigraphy, revealed significantly heterogeneous distribution of 99mTc-MAA particles and “hot spots”, not corresponding to lesion-specific sites. The no coincidence of the angiographic and the scintigraphic findings could be possibly influenced by hemodynamic changes, due to the presence of significant NAFLD. Because of the high risk-benefit ratio, the patient was considered to be an inappropriate candidate for SIRT.
我们对1例非酒精性脂肪性肝病(NAFLD)合并直肠乙状结肠连接处腺癌不可切除的小尺寸(≤3cm)弥漫性肝转移患者进行了经动脉放射栓塞(SIRT)治疗评估。右肝动脉造影显示多处血管增生病变。然而,随后的右肝动脉99mTc-MAA灌注显像的平面和SPECT图像显示99mTc-MAA颗粒和“热点”分布明显不均匀,与病变特异性部位不对应。由于存在明显的NAFLD,血管造影和血管造影结果不一致可能受到血流动力学变化的影响。由于风险收益比高,该患者被认为不适合进行SIRT。
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Journal of clinical & experimental oncology
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