Evaluating the Cost-Effectiveness of Hydrogel Rectal Spacer in Prostate Cancer Radiation Therapy

Purpose

A hydrogel rectal spacer (HRS) is a medical device that is approved by the U.S. Food and Drug Administration to increase the separation between the prostate and rectum. We conducted a cost-effectiveness analysis of HRS use for reduction in radiation therapy (RT) toxicities in patients with prostate cancer (PC) undergoing external beam RT (EBRT).

Ribosomal S6 kinase (RSK) modulators: a patent review

Introduction: The p90 ribosomal S6 kinases (RSK) are a family of Ser/Thr protein kinases that are downstream effectors of MEK1/2-ERK1/2. Increased RSK activation is implicated in the etiology of multiple pathologies, including numerous types of cancers, cardiovascular disease, liver and lung fibrosis, and infections.

Areas covered: The review summarizes the patent and scientific literature on small molecule modulators of RSK and their potential use as therapeutics. The patents were identified using World Intellectual Property Organization and United States Patent and Trademark Office databases. The compounds described are predominantly RSK inhibitors, but a RSK activator is also described. The majority of the inhibitors are not RSK-specific.

Expert opinion: Based on the overwhelming evidence that RSK is involved in a number of diseases that have high mortalities it seems surprising that there are no RSK modulators that have pharmacokinetic properties suitable for in vivo use. MEK1/2 inhibitors are in the clinic, but the efficacy of these compounds appears to be limited by their side effects. We hypothesize that targeting the downstream effectors of MEK1/2, like RSK, are an untapped source of drug targets and that they will generate less side effects than MEK1/2 inhibitors because they regulate fewer effectors.     

Polymorphisms of HLA-DM genes in Japanese patients with psoriasis vulgaris

We analysed the polymorphisms of HLA-DM genes in 85 unrelated Japanese patients with psoriasis vulgaris and 52 healthy controls using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of DMA*0101 was decreased (79% vs. 89%, P < 0.05) and that of DMA*0102 was increased (20% vs. 11%, P < 0.05) in the patients. However, neither of these remained significant after P-values were corrected for the number of comparisons made (Pc > 0.05). As we reported previously, HLA-C molecules are assumed to play a more important part than HLA-DM genes in the development of psoriasis vulgaris.     

miR‐197‐5p inhibits sarcomagenesis and induces cellular senescence via repression of KIAA0101

The abnormal expressions of microRNAs (miRNAs) are known to be associated with various pathophysiological processes that lead to the development of a plethora of diseases including cancer. Among several miRNAs studied so far, miR‐197 has been reported to play a vital role either as an oncogene or tumor suppressor in different cancers. However, its role in carcinogenesis of fibrosarcoma has not yet been elucidated. Therefore, the current study investigated the role of miR‐197‐5p, which is significantly downregulated in HT1080 fibrosarcoma cells compared to IMR90‐tert fibroblast cells. The transient overexpression of miR‐197‐5p causes a significant decrease in viability and proliferation of fibrosarcoma cells in both concentration‐ and time‐dependent manners. Interestingly, we did not observe any significant changes in cell cycle pattern or apoptotic cell populations, but rather noticed cellular senescence of fibrosarcoma cells upon overexpression of miR‐197‐5p. Further, this miRNA suppresses the metastatic properties, such as migration, invasion, and anchorage‐independent growth of fibrosarcoma possibly through targeting KIAA0101, which is a proliferating cell nuclear antigen‐associated factor and overexpressed in the malignancy. In nutshell, our result revealed that miR‐197‐5p acts as an oncosuppressor miRNA in fibrosarcoma through target regulation of KIAA0101, which can be exploited for developing RNA‐based therapeutic strategies for the cure of this malignancy.     

Synthesis and Structure–Activity Relationship Study of 5a-Carbasugar Analogues of SL0101

l-cyclitol analogues were found to inhibit RSK2 in in vitro kinase activity with a similar efficacy to that of SL0101, however, the analogues were not specific for RSK in cell-based assays. In contrast, the d-isomers showed no RSK inhibitory activity in in vitro kinase assay.     

小干扰RNA沉默KIAA0101的表达对皮肤鳞状细胞癌SCL-1细胞增殖和迁移的影响

目的 探讨KIAA0101蛋白表达下调对皮肤鳞状细胞癌（SCC）SCL-1细胞增殖和细胞侵袭能力影响的分子机制。方法 将KIAA0101 siRNA和对照siRNA分别转染SCL-1细胞,将SCL-1细胞分为3组：未转染组、对照siRNA组和KIAA0101 siRNA组。Western印迹检测3组细胞中KIAA0101蛋白的表达,CCK-8试剂检测细胞增殖,用Boyden小室检测细胞侵袭能力, Western印迹检测细胞增殖和细胞侵袭相关蛋白的表达。结果 KIAA0101 siRNA组中KIAA0101蛋白的相对表达量为0.062 ± 0.095,显著低于未转染组（0.359 ± 0.044）和对照siRNA组（0.379 ± 0.025）,P < 0.05,SCL-1细胞的增殖和侵袭能力亦降低（P < 0.05）。此外,与未转染组和siRNA对照组相比,KIAA0101 siRNA组中p21蛋白表达显著上升,而基质金属蛋白酶2表达显著下调（P < 0.05）。结论 KIAA0101表达下调介导的SCL-1细胞增殖抑制和侵袭能力降低与p21和基质金属蛋白酶2表达变化相关。 【关键词】 癌,鳞状细胞; 基因,KIAA0101; RNA,小分子干扰     

shRNA干扰A549细胞KIAA0101基因表达的初步研究

目的探讨小发卡RNA(small hairpin RNA,shRNA)真核表达质粒介导的RNA干扰技术对人肺腺癌A549细胞KIAA0101基因表达的抑制作用。方法应用pSIREN-RetroQ载体构建KIAA0101基因shRNA重组质粒,经脂质体法导入A549细胞,分别设置为空白对照组、阴性对照组、干扰A组和干扰B组,采用实时定量PCR法和免疫印迹(Western blot)法检测检测转染后细胞KIAA0101基因mRNA与表达蛋白质的变化,四唑盐(MTT)比色法测定各组干扰细胞活性。结果成功构建KIAA0101基因shRNA重组质粒,相对阴性对照组与空白对照组,干扰B组KIAA0101的mRNA与蛋白质表达水平均下降达70%(P≤0.05)以上,MTT法结果显示降低KIAA0101的表达可抑制肺癌细胞的生长活性。结论shRNA干扰质粒可以显著降低细胞内KIAA0101mRNA与蛋白质的表达水平,并且抑制癌细胞的生长活性,为该基因在肺癌中的深入研究奠定了基础。