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Immunotherapeutic Approaches to Target Cancer Stem Cell: Progress and Challenges 靶向癌症干细胞的免疫治疗方法:进展和挑战
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000E136
S. Deshmukh
The success of immunotherapeutic approaches for melanoma and non-small cell lung cancer raised hope for the treatment of other malignancies as well. However, resistance to the cancer therapies developed by tumor cells is the biggest challenge in the cancer treatment. Due to the heterogeneous nature of cancer, the bulk tumor consists of diverse cells having distinct molecular, morphological and phenotypic signatures with differential levels of sensitivity to treatment [1,2]. The cancer stem cells (CSCs) that are rare immortal cells of bulk tumor have the capability to self-renew by dividing and give rise to many cell types that constitute the tumor. CSCs are increasingly identified as the source of tumor progression, metastasis, and cancer therapy resistance and relapse [2,3]. Treatment strategies that can eliminate CSCs and nonCSCs suggested improving the long-term clinical outcome for cancer patients. Since immunotherapy directly utilizes the immune cells and works in the distinct principle from chemotherapy or small molecule therapy, it can be an alternative therapeutic approach to target CSCs.
黑色素瘤和非小细胞肺癌的免疫治疗方法的成功也为其他恶性肿瘤的治疗带来了希望。然而,肿瘤细胞对癌症治疗的耐药性是癌症治疗的最大挑战。由于癌症的异质性,大块肿瘤由不同的细胞组成,具有不同的分子、形态和表型特征,对治疗的敏感性也不同[1,2]。肿瘤干细胞(cancer stem cells, CSCs)是肿瘤中罕见的不朽细胞,具有分裂自我更新的能力,并产生多种构成肿瘤的细胞类型。CSCs越来越多地被认为是肿瘤进展、转移、癌症治疗抵抗和复发的来源[2,3]。能够消除CSCs和非CSCs的治疗策略可以改善癌症患者的长期临床结果。由于免疫治疗直接利用免疫细胞,其工作原理与化疗或小分子治疗不同,因此它可以成为靶向CSCs的替代治疗方法。
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引用次数: 0
Nivolumab Induced Hemolitic Anemia in Patient with Advanced Squamous Cell Lung Cancer (SCC) 纳武单抗诱导晚期鳞状细胞肺癌(SCC)患者溶血性贫血
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000532
V. Scotti, V. Maragna, F. Meacci, M. Teriaca, J. Topulli, L. Visani, L. Livi, A. Bosi
Nivolumab, a humanized IgG4 programmed death-1 (PD-1) inhibitor antibody, is approved in Italy for advanced non small cell lung cancer (NSCLC), for advanced melanoma in association with ipilimumab, in second line renal cell carcinoma (RCC), in Hodgkin lymphoma relapsed after autologous stem cell transplantation and treatment with brentuximab vedotin, in head and neck squamous cell carcinoma progressed after platinum therapy and in locally advanced urothelial carcinoma unresectable or metastatic after failure of previous platinum therapy. Its immunogenic potential is well known, with described autoimmune-like syndromes, but no clear association is evident for hemolytic anemia. We report case of a 68-year-old man who developed hemolytic anemia after 28 cycles of treatment for advanced Squamous Cell Lung Cancer (SSC).
Nivolumab是一种人源化IgG4程序性死亡-1 (PD-1)抑制剂抗体,在意大利被批准用于晚期非小细胞肺癌(NSCLC)、与ipilimumab相关的晚期黑色素瘤、二线肾细胞癌(RCC)、自体干细胞移植和brentuximab vedotin治疗后复发的霍奇金淋巴瘤。头颈部鳞状细胞癌在铂治疗后进展,局部晚期尿路上皮癌在先前铂治疗失败后不可切除或转移。它的免疫原性潜力是众所周知的,与描述的自身免疫样综合征有关,但与溶血性贫血没有明显的明确联系。我们报告一例68岁的男子谁发展溶血性贫血后28周期治疗晚期鳞状细胞肺癌(SSC)。
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引用次数: 0
Cutaneous Plasmacytoma: An Uncommon Entity 皮肤浆细胞瘤:一种罕见的实体
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000I101
S. Nusrat, A. Shakir, A. Keruakous
Extramedullary plasmacytoma is a manifestation of multiple myeloma in which a discrete mass of neoplastic monoclonal plasma cells forms within soft tissue [1]. Cutaneous plasmacytoma remains an uncommon entity. We present a case of a 61-year-old female with a seven-year history of multiple myeloma diagnosed in the setting of a pathological fracture secondary to multiple lytic lesions. Patient initially went into remission after receiving Bortezomib-based chemotherapy followed by autologous stem cell transplant. Following transplant, she was noted to be in CR2 with no evidence of light chain disease for 3 years. She then developed an enlarging anterior abdominal wall mass which was consistent with plasmacytoma [2]. Core biopsy of the lesion showed CD138 positive and kappa-restricted plasma cells with a high proliferation index, thereby establishing disease relapse. The lesions continued to progress in size and number and she was hospitalized for concerns of superimposed infection. Vitals on admission were within normal limits. On exam, multiple foulsmelling, fungating tumors occupying a dimeter of 5 centimeters or more were noted on the infraumbilical region of the abdominal wall (Figures 1 and 2).
髓外浆细胞瘤是多发性骨髓瘤的一种表现,在软组织内形成离散的肿瘤单克隆浆细胞团块[1]。皮肤浆细胞瘤仍然是一种罕见的实体。我们提出一个病例61岁的女性与7年历史的多发性骨髓瘤诊断在设置病理性骨折继发多发性溶解性病变。患者在接受以硼替佐米为基础的化疗和自体干细胞移植后,最初进入缓解期。移植后,她被记录为CR2, 3年无轻链疾病的证据。随后,她出现前腹壁肿物增大,符合浆细胞瘤[2]。病灶核心活检显示CD138阳性,kappa限制性浆细胞增殖指数高,确定疾病复发。病变的大小和数量继续增加,她因担心合并感染而住院。入院时生命体征在正常范围内。检查时,腹壁脐下区可见多个恶臭、真菌性肿瘤,直径5厘米或更大(图1和2)。
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引用次数: 0
New Construction of an Electronic Nose Detects Volatile Organic Compounds from Blood, useful for the Diagnosis and Screening of Ovarian Carcinoma 新型电子鼻检测血液中挥发性有机化合物,用于卵巢癌的诊断和筛查
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000572
G. Horvath, J. Ranstam, M. Ottosson, Morgan Nilsen
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引用次数: 0
The use of the Appendix for Reconstruction of the Left Ureter: A Case Report 用阑尾重建左输尿管1例
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000530
H. Soliman
We present the case of a 38-year-old female with a locally advanced recto-sigmoid adenocarcinoma. Preoperative CT scan showed that the tumour is closely related to the left psoas muscle, with total encasement of the left ureter, causing Grade II left sided hydronephrosis. Exploration was done, and an extended left hemicolectomy, with en-bloc resection of a segment of about 6 cm from the left ureter was performed. After trying to approximate both cut ends, it was clear from the start that they will not reach, and a bridge would be needed to reconstruct the ureter.
我们提出的情况下,38岁的女性与局部进展直肠乙状结肠腺癌。术前CT扫描显示肿瘤与左侧腰肌密切相关,左侧输尿管完全包裹,左侧肾积水II级。探查后行左侧半结肠扩大切除术,整体切除距左侧输尿管约6cm的一段。在尝试近似切除两端后,从一开始就很清楚,它们无法到达,需要桥来重建输尿管。
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引用次数: 0
Anticancer Activity of Biosynthesized Silver Nanoparticles using Murraya koenigii Leaf Extract against HT-29 Colon Cancer Cell Line 木参叶提取物合成银纳米颗粒对HT-29结肠癌细胞的抗癌作用
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000521
K. Roshni, M. Younis, D. Ilakkiyapavai, Preethi Basavaraju, Vinayaga Moorthi Puthamohan
Plants extract from Murraya koenigii was used for the synthesis of silver nanoparticles (Ag NPs) using silver nitrate solution. Ag NPs were characterized by UV–vis spectrophotometer, scanning electron microscope (SEM), Energy Dispersive Spectroscopy (EDX) and Fourier Transform Infra-Red Spectroscopy (FT-IR). The formation of stable silver nanoparticles reduced to the colloidal solution are observed by UV–vis spectrophotometer analysis. SEM determination of the brown coloured samples with well dispersed nanoparticles seen after treatment with silver nitrate showed the presence of silver nanoparticle whereas the EDX analysis performed is to confirm the presence of silver molecules in the sample and FTIR measurement carried out identifies the biomolecules present in M. koenigii leaf responsible for capping leading to efficient stabilization of the silver nanoparticles. The anticancer potential of the nanoparticles was evaluated using MTT assay on HT-29 colon cancer cell line. Ag NPs showed potent cytotoxic activity against the human colorectal adenocarcinoma (HT-29) cell line at higher concentrations. This study insights the M. koenigii synthesized silver NP’s could be an effective applicability drug candidate for colon cancer.
采用硝酸银溶液制备银纳米粒子(Ag NPs)。采用紫外-可见分光光度计、扫描电镜(SEM)、能量色散光谱(EDX)和傅里叶变换红外光谱(FT-IR)对Ag NPs进行了表征。通过紫外-可见分光光度计分析,观察了稳定的银纳米颗粒还原成胶体溶液的形成。用硝酸银处理后,对棕色样品和分散良好的纳米颗粒进行扫描电镜测定,显示了银纳米颗粒的存在,而进行的EDX分析是为了确认样品中银分子的存在,进行的FTIR测量确定了存在于M. koenigii叶子中的生物分子,这些生物分子负责封盖,导致银纳米颗粒的有效稳定。采用MTT法对HT-29结肠癌细胞株进行抑癌活性评价。Ag NPs对人结直肠癌(HT-29)细胞系具有较强的细胞毒活性。本研究揭示了M. koenigii合成的银NP可能是一种有效的适用于结肠癌的候选药物。
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引用次数: 12
Aflatoxins, Carcinogens in Food, as Etiological Factors in Human Malignant Neoplasias of the Lung 食物中的黄曲霉毒素和致癌物是人类肺部恶性肿瘤的病因
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000559
M. Carvajal-Moreno, E. Garcia-Hernandez, M. D. C. Gonzalez-Villasenor, A. González-Mendoza, Valentin A Rojas-Marin
Lung cancer is a malignant neoplasm of the lung or bronchial cells and is one of the primary causes of mortality in men and is the third leading cause of death in women worldwide. Active and passive tobacco smoking are considered the main risk factors for the development of lung cancer, but aflatoxins have also been considered important etiological factors. Aflatoxins, which are fungal secondary metabolites produced primarily by Aspergillus spp., are chemically bis or tetra-hydrodifuran coumarins that contaminate foods (cereals, oilseeds, spices, dry fruits and dairy products). Aflatoxins are better recognized as hepatocarcinogens, but they can cause lung cancer via the formation of links to DNA and by the formation of AFB1-DNA adducts, which can remain in the DNA for years and cause mutations and eventually cancers. The ingestion of aflatoxin-contaminated foods is the most common way in which individuals are exposed to these carcinogens, but other routes of exposure include nasal aerosol inhalation of AFB1, which damages the lung. Alveolar macrophages possess specific oxidase activity for the epoxidation of AFB1. In the biotransformation of the lung by AFB1, AFB1 requires a catalyzed metabolic activation of cytochrome P450 (CYP), the levels of which are low in the lung, to exert its carcinogenic activity. AFB1 activation in the lung is achieved by prostaglandin H-synthetize, lipoxygenases, and CYP2A13 enzymes, the last of which catalyzes metabolic activation. CYP2A13 also plays a critical role in human lung carcinogenesis associated with inhalation exposure to AFB1 and is highly efficient in the activation of AFB1 in situ. Aflatoxins (AFB1 and AFG1) cause point mutations in K-Ras and H-Ras as well as in the p53 tumor suppressor gene, which can cause lung cancer. This article summarizes the known etiology of lung cancer with respect to the human food carcinogens AFB1 and AFG1, the molecular mechanisms of aflatoxins, and the known point mutations in the K-Ras, H-ras and p53 genes. This article also discusses a possible biocontrol (creosote bush or Larrea tridentata), the use of which is limited by its toxicity.
肺癌是肺或支气管细胞的恶性肿瘤,是全世界男性死亡的主要原因之一,也是女性死亡的第三大原因。主动和被动吸烟被认为是肺癌发生的主要危险因素,但黄曲霉毒素也被认为是重要的病因。黄曲霉毒素是主要由曲霉产生的真菌次生代谢物,是一种化学上的二氢或四氢二呋喃香豆素,会污染食品(谷物、油籽、香料、干果和乳制品)。黄曲霉毒素更被认为是肝癌致癌物,但它们可以通过与DNA的连接以及AFB1-DNA加合物的形成而导致肺癌,这些加合物可以在DNA中保留多年,导致突变,最终导致癌症。摄入受黄曲霉毒素污染的食物是个人接触这些致癌物的最常见方式,但其他接触途径包括通过鼻腔雾化吸入AFB1,这会损害肺部。肺泡巨噬细胞对AFB1的环氧化具有特异性氧化酶活性。在AFB1对肺的生物转化过程中,AFB1需要催化代谢激活细胞色素P450 (CYP),而CYP在肺中的水平较低,才能发挥其致癌活性。肺中AFB1的激活是通过前列腺素h合成、脂氧合酶和CYP2A13酶实现的,CYP2A13酶催化代谢激活。CYP2A13在与吸入暴露于AFB1相关的人类肺癌发生中也起着关键作用,并且在AFB1的原位激活中效率很高。黄曲霉毒素(AFB1和AFG1)引起K-Ras和H-Ras以及p53肿瘤抑制基因的点突变,可导致肺癌。本文综述了人类食物致癌物AFB1和AFG1的已知肺癌病因,黄曲霉毒素的分子机制,以及K-Ras、H-ras和p53基因的已知点突变。本文还讨论了一种可能的生物防治方法(木馏油灌木或三叉戟Larrea tridentata),其使用受到其毒性的限制。
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引用次数: 0
Up-regulation of Mismatch Repair Pathway by Suicide Gene Therapy: Implications on the use of Temozolomide Treatment in Malignant Glioma 自杀基因疗法上调错配修复通路:替莫唑胺治疗恶性胶质瘤的意义
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000547
H. Samaranayake, Venla Olsson, Jere Kurkipuro, A. Määttä, H. Stedt, H. Kärkkäinen, M. Kaikkonen, M. Taavitsainen, Taina Vuorio, Nigel R. Parker, S. Ylä-Herttuala
Objective: The dependency of the efficacy of temozolomide (TMZ) on cellular DNA repair activities makes it therapeutically effective in approximately half of malignant glioma (MG) patient population with a dysfunctional DNA repair system. Adenovirus-mediated Herpes simplex virus thymidine kinase and ganciclovir (AdHSV-tk/GCV) suicide gene therapy is effective in those as well as in MG patients with a functional DNA repair system. When administered together, these two therapies show evidence of synergistic cytotoxicity. However, the validity of such claims has been questioned as the exact mechanism has been unknown. Methods: The underlying mechanism was studied in rat and human MG cell lines and in an immunocompetent, orthotopic, syngeneic rat MG model. Results: The results, for the first time, revealed an up-regulation of mismatch repair (MMR) pathway in MG cells by AdHSV-tk/GCV therapy, an adjunct effect to AdHSV-tk/GCV’s pro-apoptotic therapeutic mode of action that enhanced the cytotoxicity of TMZ. When combined with AdHSV-tk/GCV therapy, initially resistant MG cells were sensitized to TMZ treatment. The enhancement of TMZ’s efficacy was also seen in vivo as a significant increase in survival and a reduction in tumor growth rate, without affecting the adverse effect profile. Conclusion: This study demonstrates a synergistic outcome of AdHSV-tk/GCV and TMZ treatment combination, underlying mechanism for the synergy and a possible improved therapeutic protocol for enhanced efficacy. The findings may have an impact on future clinical use of this treatment combination, as well as benefit other chemotherapies, which depend on MMR pathway for action.
目的:替莫唑胺(temozolomide, TMZ)对细胞DNA修复活性的依赖性使其对大约一半DNA修复系统功能失调的恶性胶质瘤(malignant glioma, MG)患者有效。腺病毒介导的单纯疱疹病毒胸苷激酶和更昔洛韦(AdHSV-tk/GCV)自杀基因治疗对具有功能DNA修复系统的MG患者和这些患者都有效。当一起使用时,这两种疗法显示出协同细胞毒性的证据。然而,这种说法的有效性受到质疑,因为确切的机制尚不清楚。方法:采用大鼠、人MG细胞系和免疫活性、原位、同基因大鼠MG模型研究其作用机制。结果:研究结果首次揭示了AdHSV-tk/GCV对MG细胞错配修复(MMR)通路的上调作用,这是AdHSV-tk/GCV的促凋亡治疗模式的辅助作用,增强了TMZ的细胞毒性。当与AdHSV-tk/GCV联合治疗时,最初耐药的MG细胞对TMZ治疗敏感。在体内,TMZ疗效的增强也被认为是生存率的显著提高和肿瘤生长速度的降低,而不影响不良反应的特征。结论:本研究证明了AdHSV-tk/GCV与TMZ联合治疗具有协同效果,协同作用的潜在机制和可能改进的治疗方案以增强疗效。这一发现可能会对这种联合治疗的未来临床应用产生影响,也会对其他依赖MMR途径起作用的化疗有好处。
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引用次数: 1
Combined Angiotensin Receptor Blocker Losartan and the CXCR4 Inhibitor AMD3100 Increases the Efficacy of Radiotherapy in a Metastatic Osteosarcoma Mouse Model 血管紧张素受体阻滞剂氯沙坦联合CXCR4抑制剂AMD3100提高转移性骨肉瘤小鼠模型的放疗疗效
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000570
Sen Li, Wende Li, C. Leung, Shuji Kitahara, Yujiao Liu, Sebastian Klein, D. Fukumura, L. Gerweck, J. Loeffler, R. Jain, D. Duda, Peigen Huang
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引用次数: 1
Novel Revolution in Diagnosis and Therapy of Breast and prostat e Cancer 乳腺癌和前列腺癌诊断和治疗的新革命
Pub Date : 2018-01-01 DOI: 10.4172/1948-5956.1000527
Sherif Salah Hesen, N. Sherif
New cancer markers have been discovered in the form of male and female oncogene peptide protein and its anti-peptide antibodies. They were found in both salvia and blood samples of females with breast cancer and males with prostate cancer, in a pilot study for fifteen married patients having cancer in advanced-stage and their Husbands and Wives. Ten females, their age ranging from 32 to 58 for breast cancer (group A), five males for prostate cancer their age ranging from 54 to 71 years (group B), and four normal persons [two male and two female], their age ranging from 23 to 34 years] (as control group), were recruited into a controlled study to investigate the presence of the new suspected oncogene peptide proteins and their specific anti-oncogene antibodies in their blood and saliva. Tumour markers, C.T scan, ultrasound, and mammogram reports were completely collected before the study for each subject in the three groups. The collection data revealed the presence of male oncogene peptide protein [MOP] in serum and saliva samples of male Husbands in group A and its specific anti-oncogene antibodies [AMOP] in the serum samples of each female affected with breast cancer in group A, and the presence of female oncogene peptide protein [FOP] in all five female Wives and its specific anti-oncogene antibodies [AFOP] in each male affected with prostate cancer in group B, and the differences between normal controls and cancer patients were estimated by different in vitro and in vivo experimental trails. Our conclusions showed that a direct relation exists between the increases in concentration levels of OPP and its AOAbs, and the stage of malignancy. These promising results can open the doors for a new challenge, by developing a therapeutic and prophylactic cancer vaccine as well as new biological markers for breast and prostate cancer.
新的肿瘤标志物以男性和女性癌基因肽蛋白及其抗肽抗体的形式被发现。在一项针对15名晚期癌症已婚患者及其丈夫和妻子的初步研究中,研究人员在女性乳腺癌患者和男性前列腺癌患者的鼠尾草和血液样本中发现了这些物质。选取年龄32 ~ 58岁乳腺癌患者10例(A组),年龄54 ~ 71岁前列腺癌患者5例(B组),年龄23 ~ 34岁正常人群4例(2男2女)作为对照组,研究血液和唾液中新型疑似癌基因肽蛋白及其特异性抗癌基因抗体的存在情况。在研究前,我们收集了三组受试者的肿瘤标志物、ct扫描、超声和乳房x光检查报告。收集数据显示,A组男性丈夫的血清和唾液样本中均存在男性癌基因肽蛋白(MOP)及其特异性抗癌基因抗体(AMOP), A组每名女性乳腺癌患者的血清样本中均存在女性癌基因肽蛋白(FOP)及其特异性抗癌基因抗体(AFOP), B组5名女性妻子均存在女性癌基因肽蛋白(FOP)及其特异性抗癌基因抗体(AFOP)。通过不同的体外和体内实验,估计正常对照和癌症患者之间的差异。我们的结论表明,OPP及其AOAbs浓度水平的升高与恶性肿瘤分期存在直接关系。通过开发治疗性和预防性癌症疫苗以及乳腺癌和前列腺癌的新生物标志物,这些有希望的结果可以为新的挑战打开大门。
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引用次数: 0
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Journal of Cancer Science & Therapy
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