OPRM1(A118G)基因多态性与肺癌癌痛患者镇痛效果的相关性

目的:探讨阿片样物质受体(μ1 opioid receptor,OPRM1)(A118G)基因多态性与肺癌癌痛患者镇痛效果的相关性。方法:选取本院2017年3月至2019年10月收治的360例肺癌患者作为研究对象,判断患者阿片耐受与不良反应发生情况。收集患者血液指标,检测OPRM1(A118G)基因多态性情况并进行相关性分析。结果:在360例患者中,阿片耐受78例(耐受组),耐受率为21.7%;耐受组的性别、年龄、体重指数、肿瘤最大直径等与非耐受组对比差异无统计学意义(P0.05),两组临床分期与淋巴结转移等对比差异有统计学意义(P0.05)。OPRM1(A118G)基因共有AA、AG、GG三种基因型,两组人群的OPRM1(A118G)基因型分布均符合Hardy-Weinberg平衡定律;两组OPRM1(A118G)基因型分布差异具有统计学意义,耐受组的OPRM1(A118G)基因GG基因型比例显著高于非耐受组(P0.05),等位基因G频率显著高于非耐受组(P0.05);耐受组的呼吸抑制、恶心呕吐、头晕、皮肤瘙痒等不良反应发生率为35.9%,显著高于非耐受组的2.8%(P0.05)。直线相关性分析显示OPRM1(A118G)基因GG基因型与阿片耐受、淋巴结转移、临床分期都呈现相关性(P0.05);二分类变量Logistic回归分析显示OPRM1(A118G)基因GG基因型、临床分期、淋巴结转移为影响阿片耐受的主要因素(P0.05)。结论:肺癌癌痛患者在镇痛中存在阿片耐受情况,与患者的OPRM1(A118G)基因多态性与治疗不良反应显著相关,OPRM1(A118G)基因GG基因型、临床分期、淋巴结转移为影响阿片耐受的主要因素。     

Complexities and pitfalls in analyzing and interpreting mitochondrial DNA content in human cancer

Mutations in the human mitochondrial genome have been observed in all types of human cancer, indicating that mutations might contribute to tumorigenesis, metastasis, recurrence, or drug response. This possibility is appealing because of the known shift from oxidative metabolism to glycolysis, known as the Warburg effect, that occurs in malignancy. Mitochondrial DNA (mtDNA) mutations could either be maternally inherited and predispose to cancer (germ line mutations) or occur sporadically in the mtDNA of specific tissues (tissue- or tumor-specific somatic mutations) and contribute to the tumor initiation and progression process. High-throughput sequencing technologies now enable comprehensive detection of mtDNA variation in tissues and bodily fluids, with the potential to be used as an early detection tool that may impact the treatment of cancer. Here, we discuss insights into the roles of mtDNA mutations in carcinogenesis, highlighting the complexities involved in the analysis and interpretation of mitochondrial genomic content, technical challenges in studying their contribution to pathogenesis, and the value of mtDNA mutations in developing early detection, diagnosis, prognosis, and therapeutic strategies for cancer.     

The advent of de novo proteins for cancer immunotherapy

Engineered proteins are revolutionizing immunotherapy, but advances are still needed to harness their full potential. Traditional protein engineering methods use naturally existing proteins as a starting point, and therefore, are intrinsically limited to small alterations of a protein's natural structure and function. Conversely, computational de novo protein design is free of such limitation, and can produce a virtually infinite number of novel protein sequences, folds, and functions. Recently, we used de novo protein engineering to create Neoleukin-2/15 (Neo-2/15), a protein mimetic of the function of both interleukin-2 (IL-2) and interleukin-15 (IL-15). To our knowledge, Neo-2/15 is the first de novo protein with immunotherapeutic activity, and in murine cancer models, it has demonstrated enhanced therapeutic potency and reduced toxicity compared to IL-2. De novo protein design is already showcasing its tremendous potential for driving the next wave of protein-based therapeutics that are explicitly engineered to treat disease.     

COVID-19 pandemic and patients with cancer: The protocol of a Clinical Oncology center in Tehran,Iran

AimTo provide recommendations for the management of patients with cancer in the COVID-19 era.BackgroundThe current global pandemic of COVID-19 has severely impacted global healthcare systems. Several groups of people are considered high-risk for SARS-CoV-2 infection, including patients with cancer. Therefore, protocols for the better management of these patients during this viral pandemic are necessary. So far, several protocols have been presented regarding the management of patients with cancer during the COVID-19 pandemic. However, none of them points to a developing country with limited logistics and facilities.MethodsIn this review, we have provided a summary of recommendations on the management of patients with cancer during the COVID-19 pandemic based on our experience in Shohada-e Tajrish Hospital, Iran.ResultsWe recommend that patients with cancer should be managed in an individualized manner during the COVID-19 pandemic.ConclusionsOur recommendation provides a guide for oncology centers of developing countries for better management of cancer.     

Macroautophagy is repressed during mitosis – seeing is believing

ABSTRACT

For the last two decades there has been wide ranging debate about the status of macroautophagy during mitosis. Because metazoan cells undergo an “open” mitosis in which the nuclear envelope breaks down, it has been proposed that macroautophagy must be inhibited to maintain genome integrity. While many studies have agreed that the number of autophagosomes is greatly reduced in cells undergoing mitosis, there has been no consensus on whether this reflects decreased autophagosome synthesis or increased autophagosome degradation. Reviewing the literature we were concerned that many studies relied too heavily on autophagy assays that were simply not appropriate for a relatively brief event such as mitosis. Using highly dynamic omegasome markers we have recently shown unequivocally that autophagosome synthesis is repressed at the onset of mitosis and is restored once cell division is complete. This is accomplished by CDK1, the master regulator of mitosis, taking over the function of MTORC1, to ensure autophagy is repressed during mitosis.     

A ROCK inhibitor promotes keratinocyte survival and paracrine secretion,enhancing establishment of primary human melanocytes and melanocyte–keratinocyte co‐cultures

Primary melanocytes isolated from skin and expanded in culture have been widely used for laboratory research and clinical applications. The conventional method to isolate primary melanocytes from skin usually requires about 3–4 weeks of culture for melanocytes to grow sufficiently to passage. Considering that melanocytes comprise only 3%–7% of epidermal cells in normal human skin, it would be extremely helpful to increase the isolation efficiency and shorten the initial culture time to quickly meet various application needs. Here, we report that adding Y‐27632, a Rho kinase inhibitor, into the initial culture medium for 2 days can dramatically increase the yield of melanocytes. We found that Y‐27632 can promote keratinocyte attachment and survival in the melanocyte culture system, resulting in not only better recovery, but also increased proliferation of melanocytes by a paracrine signaling pathway. More specifically, Y‐27632 significantly induced keratinocyte expression of stem cell factor, which played an important role in enhancing the growth of melanocytes. In summary, Y‐27632 could profoundly enhance the yield of primary melanocytes in the initial culture through paracrine effects on keratinocytes.     

Improving NK1R-targeted gene delivery of stearyl-antimicrobial peptide CAMEL by conjugating it with substance P

Specificity is a crucial condition that hampers the application of non-viral vectors for cancer gene therapy. In a previous study, we developed an efficient gene vector, stearyl-CAMEL, using N-terminal stearylation of the antimicrobial peptide CAMEL. Substance P (SP), an 11-residue neuropeptide, rapidly enters cells after binding to the neurokinin-1 receptor (NK1R), which is expressed in many cancer cell lines. In this study, the NK1R-targeted gene vector stearyl-CMSP was constructed by conjugating SP to the C-terminus of stearyl-CAMEL. Our results indicated that stearyl-CMSP displayed significant transfection specificity for NK1R-expressing cells compared with that shown by stearyl-CAMEL. Accordingly, the stearyl-CMSP/p53 plasmid complexes had significantly higher antiproliferative activity against HEK293-NK1R cells than they did against HEK293 cells, while the stearyl-CAMEL/p53 plasmid complexes did not show this specificity in antiproliferative activity. Consequently, conjugation of the NK1R-targeted ligand SP is a simple and successful strategy to construct efficient cancer-targeted non-viral gene vectors.     

miRNA和lncRNA在动物脂肪沉积中的研究进展

微小RNA(MicroRNA,miRNA)是一类由18–25个核苷酸组成的高度保守的核苷酸序列,它可以特异性结合信使RNA (mRNA)的3′-非编码区域,进而发挥降解mRNA或阻遏mRNA翻译的负调控作用。长链非编码RNA (Long non-coding RNA,lncRNA)是一类长度超过200个核苷酸、不能编码蛋白质或只能编码蛋白质微肽的核苷酸序列,它可以在表观遗传、转录水平和转录后水平调控基因表达。脂肪作为一种重要的储能物质,在调节动物体能量平衡过程中发挥着重要的作用,并与动物产肉量、肉品质等产肉性状密切相关。而脂肪功能的紊乱可导致高血脂、Ⅱ型糖尿病以及一系列心血管疾病发生,因此动物脂肪沉积的分子调控机制备受人们关注。近年来,越来越多的研究发现miRNA和lncRNA在动物脂肪沉积中发挥重要作用。文中就现阶段miRNA和lncRNA在动物脂肪沉积中的研究进展进行综述,以期为进一步揭示动物脂肪沉积的分子调控机制提供理论指导和新思路。