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Cancer care professionals should pay more attention to the sexual aspects of cancer in men with a non-mainstream sexual orientation 癌症护理专业人员应该更多地关注非主流性取向男性癌症的性方面
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000286
W. Gianotten, H. Aars
Cancer and its treatment are known to be associated with much collateral damage in the areas of sexuality and intimacy. Since nature doesn’t discriminate, cancer happens also to gay and bisexual men. In men who have sex with men (MSM) cancer treatment can cause serious sexual impairments that are unknown to the average heterosexual health care provider (HCP). Because insufficient appropriate knowledge impairs good cancer care, this article will address relevant aspects of sexual lifestyle, relationships and sexual behavior of MSM and the typical areas where cancer treatment tends to damage. After prostate cancer treatment there is no more ejaculate, a very important part in the average MSM sexual play. Radical prostatectomy causes climacturia (urine loss during orgasm) in a substantial amount of men. This is a real killjoy for oral sex, which is in MSM the most common way to have sex. Prostate cancer and anorectal cancer treatment damage the possibilities for prostate orgasm, an intense variety of orgasm, common in many MSM. Anorectal cancer treatment can impair the possibilities for various ways of anal sex, especially in the ‘bottom man’ (the receptive partner). Cancer treatments that impair erection tend to damage more in MSM, not only because erections are in their sexual encounters very relevant for sexual identity, but also because one needs for anal penetration a firmer erection than for vaginal penetration. This review will successively deal with the prevalence of MSM; with relevant aspects of MSM sexuality and MSM lifestyle; with different cancer prevalence in MSM; with consequences of cancer treatment that are typical for the sexuality of MSM; and finally with some aspects of optimal care in MSM with cancer. The aim of the information in this article is both to improve the communication with MSM, and to improve the oncological care for MSM and their partners. *Correspondence to: Woet L Gianotten, MD, Psychotherapist, Emeritus Senior Lecturer in Medical Sexology, Consultant in Oncosexology, University Medical Centre, Utrecht, The Netherlands, E-mail: woetgia@ziggo.nl
众所周知,癌症及其治疗与性和亲密关系领域的许多附带损害有关。由于大自然没有歧视,癌症也会发生在同性恋和双性恋男性身上。在男男性行为者(MSM)中,癌症治疗可能导致严重的性障碍,而这是普通异性恋卫生保健提供者(HCP)所不知道的。由于缺乏适当的知识会影响良好的癌症治疗,本文将讨论性生活方式、关系和性行为的相关方面,以及癌症治疗往往受到损害的典型领域。前列腺癌治疗后不再射精,这是男男性接触者性行为中非常重要的一部分。根治性前列腺切除术导致大量男性出现性高潮(性高潮时尿量减少)。这对口交来说是一个真正的扫兴,而口交在男男性接触者中是最常见的性方式。前列腺癌和肛肠癌的治疗破坏了前列腺性高潮的可能性,前列腺性高潮是一种强烈的性高潮,在许多男男性接触者中很常见。肛肠癌的治疗可能会削弱肛交的各种方式,特别是在“底部男人”(接受伴侣)。损害勃起功能的癌症治疗对男男性接触者的伤害更大,不仅因为勃起在他们的性接触中与性身份非常相关,还因为一个人需要肛门插入比阴道插入更牢固的勃起。本文将依次讨论男男性行为的流行情况;与男男性接触者的性行为和生活方式有关的方面;男男性行为者癌症患病率不同;癌症治疗的后果是典型的男同性恋者的性行为;最后是男男性接触者癌症的最佳护理。本文信息的目的是提高与男男性行为者的沟通,并改善男男性行为者及其伴侣的肿瘤护理。*通信:Woet L Gianotten,医学博士,心理治疗师,医学性学荣誉高级讲师,肿瘤学顾问,荷兰乌得勒支大学医学中心,E-mail: woetgia@ziggo.nl
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引用次数: 2
PD-1/PD-L1 immune checkpoint inhibitors in advanced cervical cancer. 晚期宫颈癌中的 PD-1/PD-L1 免疫检查点抑制剂。
Pub Date : 2018-01-01 Epub Date: 2018-04-14 DOI: 10.15761/ICST.1000272
Ozlen Saglam, Jose Conejo-Garcia

Programmed cell death-1 and programmed cell death ligand-1 (PD-1/PD-L1) blockage has become an important treatment modality after approval of pembrolizumab and nivolumab by Food and Drug Administration in advanced cancers. Patients with metastatic and recurrent cervical cancer have limited treatment options and usually receive palliative platinum-based chemotherapy without significant survival benefit. Recent studies provided support for usage of immune checkpoint inhibitors in advanced cervical cancer. Around 35% of cervical squamous cell carcinoma (C-SCC) and 17% of adenocarcinomas expressed PD-L1. Human Papilloma Virus status was also correlated with PD-L1 expression. PD-1/PD-L1 expression in tumor infiltrating inflammatory cells was higher in cervical cancer in comparison to endometrial and ovarian adenocarcinomas. In C-SCC diffuse PD-L1 expression as compared to marginal PD-L1 expression on the interface between tumor and stroma was a risk factor for poor disease-free and disease-specific survival rates. Higher numbers of infiltrating regulatory T cells in PD-L1 positive tumors was associated with better prognosis. The studies performed on other cancer types revealed PD-L1 tumor heterogeneity and transient marker expression. Drug-resistance to immune checkpoint inhibitors is also a potential problem. Currently Phase I/II clinical trials evaluating effects of PD-1 therapy are in progress for cervical carcinoma. Additional studies are required to develop novel biomarkers and for standard evaluation of PD-L1 testing in order to predict response to immune checkpoint inhibitors in all cancer types including cervical carcinoma.

在美国食品药品管理局批准将pembrolizumab和nivolumab用于晚期癌症治疗后,程序性细胞死亡-1和程序性细胞死亡配体-1(PD-1/PD-L1)阻断已成为一种重要的治疗方式。转移性和复发性宫颈癌患者的治疗选择有限,通常接受以铂类药物为基础的姑息性化疗,但生存率并不高。最近的研究支持在晚期宫颈癌中使用免疫检查点抑制剂。约35%的宫颈鳞状细胞癌(C-SCC)和17%的腺癌表达PD-L1。人类乳头状瘤病毒状态也与 PD-L1 表达相关。与子宫内膜癌和卵巢腺癌相比,宫颈癌中肿瘤浸润性炎症细胞的 PD-1/PD-L1 表达更高。与肿瘤和基质界面的边缘PD-L1表达相比,C-SCC中弥漫性PD-L1表达是无病生存率和疾病特异性生存率较低的风险因素。PD-L1 阳性肿瘤中浸润调节性 T 细胞数量越多,预后越好。对其他癌症类型的研究显示,PD-L1肿瘤具有异质性和标记物表达的短暂性。免疫检查点抑制剂的耐药性也是一个潜在问题。目前,评估 PD-1 疗法对宫颈癌影响的 I/II 期临床试验正在进行中。为了预测包括宫颈癌在内的所有癌症类型对免疫检查点抑制剂的反应,还需要进行更多的研究来开发新的生物标记物,并对 PD-L1 测试进行标准评估。
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引用次数: 0
The role of PTH in mouse skin tumorigenesis PTH在小鼠皮肤肿瘤发生中的作用
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000271
K. Okumura, Megumi Saito, Y. Wakabayshi
Received: March 15, 2018; Accepted: April 03, 2018; Published: April 06, 2018 Vitamin D and calcium are known to regulate differentiation and proliferation of keratinocytes; they may potentially have roles in suppressing carcinogenesis in squamous epithelium [1]. Indeed, the importance of the vitamin D receptor (VDR) in regulating cellular proliferation and differentiation was verified when the skin of mice lacking the VDR was reported to be susceptible to tumor formation [1]. In addition, knockout of the calcium sensing receptor in addition to VDR accelerated the development of skin tumors [2]. However, the role of Parathyroid Hormone (PTH) in tumorigenesis is yet to be elucidated. PTH is a classical endocrine hormone that was first identified more than 80 years ago as a key regulator of blood calcium levels [3]. Serum PTH is a sensitive indicator of calcium and vitamin D deficiency.
收稿日期:2018年3月15日;录用日期:2018年4月3日;已知维生素D和钙可以调节角质形成细胞的分化和增殖;它们可能具有抑制鳞状上皮癌变的潜在作用。事实上,维生素D受体(VDR)在调节细胞增殖和分化中的重要性在缺乏VDR的小鼠皮肤易患肿瘤时得到了证实。此外,除VDR外,敲除钙敏感受体也会加速皮肤肿瘤[2]的发展。然而,甲状旁腺激素(PTH)在肿瘤发生中的作用尚未阐明。甲状旁腺激素是一种经典的内分泌激素,80多年前首次被发现是血钙水平的关键调节因子。血清甲状旁腺激素是钙和维生素D缺乏的敏感指标。
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引用次数: 0
Controversy regarding the functional conservation of cereblon CUL4-type E3 ligase substrate receptor 小脑cul4型E3连接酶底物受体功能保护的争议
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000283
A. Akuffo, A. Alontaga, H. Lawrence, N. Lawrence, P. Epling-Burnette
1Department of Immunology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA 2Cancer Biology Ph.D. Program, University of South Florida, Tampa, FL, USA 3Chemical Biology Core, Moffitt Cancer Center and Research Institute, Tampa, FL, USA 4Department of Oncologic Sciences, University of South, Tampa, FL, USA 5Department of Drug Discovery, Moffitt Cancer Center and Research Institute, Tampa, FL, USA
1美国佛罗里达州坦帕市莫菲特癌症中心和研究所免疫学系2美国佛罗里达州坦帕市南佛罗里达大学癌症生物学博士项目3美国佛罗里达州坦帕市莫菲特癌症中心和研究所化学生物学核心4美国佛罗里达州坦帕市南坦帕大学肿瘤科学系5美国佛罗里达州坦帕市莫菲特癌症中心和研究所药物发现系
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引用次数: 1
Use of chip-based PCR for 3D absolute digital quantification of microRNAs molecules for the non-invasive diagnostic screening of human colon cancer in stool 利用基于芯片的PCR技术对microRNAs分子进行三维绝对数字定量,用于人类粪便结肠癌的无创诊断筛查
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000274
F. Ahmed
Received: April 07, 2018; Accepted: April 24, 2018; Published: April 27, 2018 There is no validated approach to screen for colon cancer (CC) quantitativley on the marke, using molecular sensitive approach today, because of the complexity of fecal density, vulnerability of stool to daily changes, and the presence of three sources of miRNAs in stool (cell-free from fecal homogenates, exsosomal miRNAs from fecal exosomes, and fecal colonocytes). To address these obstacles for developing a sensitive, economical and a non-invasive molecular colon cancer screening test, we have first carried out a microarray miRNA qualitative study, using Affymetrix GeneChip miRNA 2.0 Arrays, on immunocaptured and eniched stool colonocytes of 15 subjects [three healthy controls and twelve colon cancer patients [three TNM stage 0-1 (e.g., polyps ≥ 1 cm, villous or tubvillous, or with high grade dysplasia), three stage 2, three stage 3, and three stage 4] in triplicates to select a smaller panel of 14 preferentially expressed mature miRNAs associated with colon cancer (12 Up-Regulated, miR-19a, miR-20a, miR-21, miR-31, miR34a, miR-96, miR-106a, miR-133a, miR-135b, miR-206, miR-224 and miR-302; and 2 Down-Regulated, miR-143 and miR-145). This was followed by an absolute quantitative digital PCR on these stool samples from the same stool samples. In which total small RNA extracted by immunocapture, followed by RT that employed TaqMan® miRNA Reverse Transcription (RT) Kit and a Custom TaqMan RT Primer Pool, and absolute quantification of miRNAs, in copies/μl, which was measured using a chip-based Absolute QuantStudio 3D Digital PCR analysis, to validate microarray results. To guarentee that we have used human and not bacterial small total RNA, we have carried out coextraction protocols with E. coli K1 strain RS18, compared Agilent electrophoretic patterns, and also sequenced random samples, using mRNA/miRNA sequencing.
收稿日期:2018年4月07日;录用日期:2018年4月24日;目前,由于粪便密度的复杂性、粪便对日常变化的易变性以及粪便中存在三种mirna来源(粪便均质物的无细胞、粪便外泌体的外泌体mirna和粪便结肠细胞),市场上还没有经过验证的方法来使用分子敏感方法定量筛查结肠癌(CC)。为了解决这些障碍,开发一种敏感、经济和非侵入性的分子结肠癌筛查试验,我们首先进行了一项微阵列miRNA定性研究,使用Affymetrix GeneChip miRNA 2.0阵列,对免疫捕获和富集的15名受试者(3名健康对照和12名结肠癌患者)的粪便结肠细胞进行了微阵列miRNA定性研究[3名TNM 0-1期(例如,息肉≥1厘米,绒毛状或管状,或高度不典型增生),3名2期,3名3期,3名2期,3名3期。和三个阶段4],在三个重复中选择14个优先表达的与结肠癌相关的成熟mirna(12个上调,miR-19a, miR-20a, miR-21, miR-31, miR34a, miR-96, miR-106a, miR-133a, miR-135b, miR-206, miR-224和miR-302;2下调,miR-143和miR-145)。随后对来自相同粪便样本的这些粪便样本进行绝对定量数字PCR。其中,通过免疫捕获提取总小RNA,然后使用TaqMan®miRNA逆转录(RT) Kit和Custom TaqMan RT引物池进行RT,并使用基于芯片的absolute QuantStudio 3D数字PCR分析测量miRNA的绝对定量,以拷贝数/μl为单位,以验证微阵列结果。为了确保我们使用了人类而不是细菌的小总RNA,我们与大肠杆菌K1菌株RS18进行了共提取方案,比较了Agilent电泳模式,并对随机样本进行了mRNA/miRNA测序。
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引用次数: 1
Rationale for the design of a novel tool for immunotherapy based on an emulsion of glycosaminoglycan 基于糖胺聚糖乳剂的新型免疫治疗工具的设计原理
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000285
M. Ruggiero, S. Pacini
In this article, we describe the rationale behind the design of an innovative immunotherapeutic tool designated imunoTM that is an emulsion of microbial, lowmolecular-weight chondroitin sulfate non-covalently bound to pure phosphatidylcholine with vitamin D3 intercalated in the ensuing multi-molecular structure. The rationale for this design derives from the decade-old observation that chondroitin sulfate is the active principle responsible for the immune-stimulatory, anti-cancer properties of cartilage extracts and from the more recent observation that a known immunotherapeutic compound, the Gc protein-derived Macrophage Activating Factor (GcMAF), works as an adjuvant similar, in principle, to the incomplete Freund’s adjuvant. From these premises, we designed an innovative tool that uses an ultrapure, low-molecular-weight chondroitin sulfate, thus overcoming all limitations associated with blood-derived or animal-derived non-ultrapure extracts, at the same time guaranteeing constant sulfation profile and charge density. This novel form of chondroitin sulfate is non-covalently bound to pure phosphatidylcholine in a self-assembly manner that is coherent with the principles of negentropy. Vitamin D3 is then intercalated in this structure that resembles protocells made of a phosphatidylcholine bilayer. Such an association reduces the main side effect of vitamin D3 that is the induction of hypercalcemia, at the same time maximizing its immunotherapeutic potential. In addition, we describe the mechanism of action of this immunotherapeutic tool with particular reference to stimulation of innate immunity through a mechanism shared by adjuvants such as Freund’s adjuvant. Finally, we describe an example of a transdermal delivery system and we discuss possible applications. *Correspondence to: Marco Ruggiero, Silver Spring Sagl, Via Raimondo Rossi 24, Arzo-Mendrisio 6864, Switzerland, Tel: +41 79 230 9283, E-mail: marco.drruggiero@gmail.com
在这篇文章中,我们描述了一种创新的免疫治疗工具设计背后的基本原理,该工具被称为imunnotm,它是一种微生物乳液,低分子量硫酸软骨素与纯磷脂酰胆碱非共价结合,维生素D3插入随后的多分子结构中。这种设计的基本原理源于十年前的观察,即硫酸软骨素是软骨提取物具有免疫刺激和抗癌特性的活性原理,以及最近的观察,即一种已知的免疫治疗化合物,Gc蛋白衍生的巨噬细胞激活因子(GcMAF),原则上类似于不完整的弗氏佐剂。基于这些前提,我们设计了一种使用超纯、低分子量硫酸软骨素的创新工具,从而克服了与血源性或动物源性非超纯提取物相关的所有限制,同时保证了恒定的硫酸化轮廓和电荷密度。这种新型硫酸软骨素以一种与负熵原理相一致的自组装方式与纯磷脂酰胆碱非共价结合。维生素D3被嵌入到这个类似于磷脂酰胆碱双分子层的原始细胞的结构中。这种关联减少了维生素D3的主要副作用,即诱导高钙血症,同时最大化其免疫治疗潜力。此外,我们描述了这种免疫治疗工具的作用机制,特别提到了通过佐剂(如弗氏佐剂)共享的机制来刺激先天免疫。最后,我们描述了一个透皮给药系统的例子,并讨论了可能的应用。*通讯:Marco Ruggiero, Silver Spring Sagl, Via Raimondo Rossi 24, Arzo-Mendrisio 6864,瑞士,电话:+41 79 230 9283,E-mail: marco.drruggiero@gmail.com
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引用次数: 5
Progress of novel compounds with anticancer activity 具有抗癌活性的新型化合物研究进展
Pub Date : 2018-01-01 DOI: 10.15761/icst.1000270
Jianping Yong, Mingxue Yang, Canzhong Lu, Xiaoyuan Wu
Received: March 05, 2018; Accepted: March 30, 2018; Published: April 03, 2018 Cancer is one of the major causes of human death worldwide. The death caused by cancer mainly is lung cancer, breast cancer, liver cancer, carcinoma of colon and rectum. It is estimated that about 1,688,780 new cancer cases will be diagnosed in the United States in 2017 and 600,920 cancer cases are expected to die, which is about 1,650 people per day. For all sites combined, the cancer incidence rate is 20% higher in men than in women, while the cancer death rate is 40% higher [1]. It has been reported that 4,292,000 new cancer cases and 2,814,000 cancer deaths occurred in 2015 in China, with lung cancer being the most common incident cancer and the leading cause of cancer death. Stomach, esophageal, and liver cancers were also commonly diagnosed and were identified as leading causes of cancer death [2].
收稿日期:2018年03月05日;录用日期:2018年3月30日;癌症是全球人类死亡的主要原因之一。癌症导致的死亡主要是肺癌、乳腺癌、肝癌、结肠癌和直肠癌。据估计,2017年美国将新诊断出约1,688,780例癌症病例,预计将有600,920例癌症病例死亡,每天约有1,650人死亡。所有这些部位加起来,男性的癌症发病率比女性高20%,而癌症死亡率比女性高40%。据报道,2015年中国有429.2万例新发癌症病例和281.4万例癌症死亡,肺癌是最常见的癌症,也是癌症死亡的主要原因。胃癌、食管癌和肝癌也被普遍诊断出来,并被确定为癌症死亡的主要原因。
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引用次数: 0
Solubilization and penetration enhancement of water-soluble and amphiphilic phospholipid polymer aggregate for poorly soluble drugs 水溶性和两亲性磷脂聚合物聚集体对难溶性药物的增溶和增透作用
Pub Date : 2018-01-01 DOI: 10.15761/icst.1000282
T. Konno, K. Ishihara
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引用次数: 0
Mitochondrial Lon protease-unique structure and essential function in mammalian cells 线粒体Lon蛋白酶——哺乳动物细胞的独特结构和基本功能
Pub Date : 2018-01-01 DOI: 10.15761/ICST.1000296
E. Kutejova
Lon protease belongs to the family of ATP dependent proteases. The Lon protease was first characterized by Prof. Alfred Goldberg in E. coli in 1981 [1]. Since then, it has been found in almost all living cells except some parasites like Trypanosoma brucei. In eukaryotes Lon is localized mainly in mitochondria, however peroxisomes as well as chloroplasts have their own Lon proteases. Although several eukaryotes can exist without Lon protease, for mammals it is an essential enzyme whose dysfunction has been identified in a number of diseases. Downregulation of this key mitochondrial component was observed in association with aging. Lon protease plays an important role also in malignant transformation that requires the adaptation to new sources of energy and is connected to hypoxia. This is the reason why Lon is highly expressed in aggressive tumors [2].
Lon蛋白酶属于ATP依赖性蛋白酶家族。1981年,Alfred Goldberg教授首次在大肠杆菌中发现了Lon蛋白酶。从那时起,除了一些寄生虫,如布鲁氏锥虫,几乎在所有活细胞中都发现了它。在真核生物中,Lon主要定位于线粒体,但过氧化物酶体和叶绿体也有自己的Lon蛋白酶。尽管一些真核生物可以在没有Lon蛋白酶的情况下生存,但对于哺乳动物来说,它是一种必需的酶,其功能障碍已被确定在许多疾病中。这一关键线粒体成分的下调与衰老有关。Lon蛋白酶在需要适应新的能量来源并与缺氧有关的恶性转化中也起着重要作用。这就是为什么Lon在侵袭性肿瘤[2]中高度表达的原因。
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引用次数: 0
GY II represses proliferation and metastasis and promotes apoptosis in laryngeal squamous cell carcinoma GYⅱ抑制喉鳞癌的增殖和转移,促进细胞凋亡
Pub Date : 2018-01-01 DOI: 10.15761/icst.1000298
Yunfei Bai, Ru Wang, X. Cui, Ling Feng, Q. Shi, Hongzhi Ma, M. Lian, X. Shen, Yifan Yang, Chen Tan, Jugao Fang
Traditional Chinese Medicine (TCM) has been considered to provide certain advantages in the treatment of cancer. Guben Yiliu II (GY II) has been widely used for clinical treatment of cancer in China. The current study investigated the effects of GY II on proliferation, apoptosis, invasion, and metastasis of laryngeal squamous cell carcinoma via MTT assays, Transwell assays, and flow cytometry, respectively, in Hep-2 and cells from clinical samples. Results of MTT assays revealed that GY II inhibited the growth of cells via arresting the cell cycle at G0/G1 phase. The addition of GY II significantly suppressed cell migration and invasion. Additionally, GY II treatment significantly promoted apoptosis of tumor cells. Present findings have significant implications regarding the understanding of mechanisms and targets of GY II in terms of tumors.
人们一直认为中医在治疗癌症方面具有一定的优势。固本益流II (GY II)在中国已广泛应用于临床治疗癌症。本研究分别通过MTT法、Transwell法和流式细胞术对Hep-2和临床样本细胞进行了GY II对喉鳞癌增殖、凋亡、侵袭和转移的影响。MTT实验结果显示,GY II通过将细胞周期阻滞在G0/G1期来抑制细胞的生长。添加GY II可显著抑制细胞迁移和侵袭。此外,GY II治疗可显著促进肿瘤细胞凋亡。目前的发现对于理解GY II在肿瘤中的作用机制和靶点具有重要意义。
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引用次数: 1
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Integrative cancer science and therapeutics
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