Emerging Roles of Ruk/CIN85 in Vesicle‐Mediated Transport,Adhesion, Migration and Malignancy

Ruk/CIN85 is an adaptor protein. Similar to many other proteins of this type, Ruk/CIN85 is known to take part in multiple cellular processes including signal transduction, vesicle‐mediated transport, cytoskeleton remodelling, programmed cell death and viral infection. Recent studies have also revealed the potential importance of Ruk/CIN85 in cancer cell invasiveness. In this review we summarize the various roles of this protein as well as the potential contribution of Ruk/CIN85 to malignancy and the invasiveness of cancer cells. In the last section of the paper we also speculate on the utility of Ruk/CIN85 as a target for novel anti‐cancer therapies.     

药物作用靶点研究最新进展

通过对我国学者近2年在国内外发表的相关论文进行检索和整理,分类综述针对神经退行性疾病（如阿尔茨海默病、帕金森病等）、心血管疾病（如高血压、心律失常、心衰、冠心病、心肌梗死、动脉粥样硬化等）、脑血管疾病、代谢类疾病（如肥胖症、血脂异常、脂肪肝、糖尿病等）、感染性疾病（如艾滋病、流感、结核病等）、恶性肿瘤、自身免疫性疾病等多种疾病的药物作用靶点研究最新进展。     

金刚藤联合妇科千金片对慢性盆腔炎患者血液流变学和炎症因子的影响

目的:研究金刚藤联合妇科千金片对慢性盆腔炎(CPID)患者血液流变学和炎症因子的影响。方法:选择从2016年2月到2019年5月在我院接受治疗的CPID患者204例进行研究。依照随机数字表法将患者划分为观察组以及对照组各102例,对照组患者予以妇科千金片治疗,观察组患者在此基础上另予以金刚藤治疗,两组均治疗6周,对比两组的疗效、临床指标、血液流变学指标以及炎症因子的水平。结果:观察组的痊愈率、总有效率均分别高于对照组,观察组的无效率低于对照组,差异均有统计学意义(P0.05)。观察组体温恢复时间、腹痛消失时间、抗生素应用时间以及住院时间均短于对照组(P0.05)。治疗后两组的低切全血黏度、高切全血黏度、血浆黏度(PV)、纤维蛋白原(FIB)水平均明显低于治疗前,且观察组较对照组降低(P0.05)。治疗后两组的白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、粒-巨噬细胞集落刺激因子(GM-CSF)及C反应蛋白(CRP)水平均明显低于治疗前,且观察组较对照组降低(P0.05)。结论:CPID患者给予金刚藤及妇科千金片联合治疗可明显改善临床指标,且有助于其机体内血液流变学及炎症症状的改善,值得临床推广应用。     

Paradoxical oncogenesis: are all BRAF inhibitors equal?

Cutaneous squamous cell carcinoma (cSCC) is a concerning toxicity with BRAF inhibitors in the treatment for melanoma. While the two drugs shown to improve survival, vemurafenib, and dabrafenib, have similar efficacy, the reported rates of cSCC are quite different. Drawing upon preclinical and clinical trial data, this article discusses the potential factors behind the different cSCC incidences reported with the two BRAF inhibitors and provides a strategic approach to understand this issue further.     

Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category

A. Mahajan, X. Lin and R. Nayar Thyroid Bethesda reporting category, ‘suspicious for papillary thyroid carcinoma’, pitfalls and clues to optimize the use of this category Objective: The Bethesda System of Reporting Thyroid Cytopathology classifies the indeterminate categories based on their differing risks of malignancy, as atypia of undetermined significance (AUS), follicular neoplasm/suspicious for follicular neoplasm (FLUS) and suspicious for malignancy. The vast majority of cases of the last category are suspicious for papillary thyroid carcinoma (PTC). The aim of the present study was to identify the pitfalls and clues to improve the usage of the suspicious category as well as improve its outcome of malignancy. Methods: We reviewed the cytological features on air dried Diff‐Quik® and alcohol‐fixed Papanicolaou smears from 54 thyroid fine needle aspirates (FNAs) with surgical follow‐up that were originally diagnosed as suspicious. Procedure data/specimen adequacy was correlated and follow‐up histology reports were reviewed after our cytological review was completed. Incidental PTC that was not the target of the FNA was excluded from the calculations for correlation. Results: In our cytological review, we retained a diagnosis of suspicious in 18 of the 54 cases and the remaining 36 were re‐categorized as follows: 6 malignant, 10 neoplasm (which is used in our centre instead of FLUS) and 20 AUS. The reasons for overcall of suspicious cases included pseudopapillae, syncytial sheets, nuclear grooves and pinpoint nucleoli in chronic lymphocytic thyroiditis and Hürthle cell neoplasms, and intranuclear inclusions in parathyroid adenoma, hyalinizing trabecular adenoma and mesenchymal repair. The primary reasons for undercall of PTC as suspicious included cystic aspirates with minor features of PTC such as histiocytoid cells, bubblegum colloid, syncytial sheets and cellular swirls. Cases with cytoplasm similar to Hürthle cells were also noted to cause difficulty in accurate classification. Conclusions: Recognition of these pitfalls and clues can help improve diagnosis, patient treatment and consequently reduce the number of unnecessary thyroidectomies.     

Relations between doses cumulated in bone marrow and dose delivery techniques during radiation therapy of cervical and endometrial cancer

PurposeTo compare normal tissue complication probability (NTCP) and average doses in the bone marrow (BM), obtained for five different radiotherapy delivery and planning strategies of cervical and endometrial cancer.Material/methods50 patients were taken to analysis. For each case, 3 different dose delivery techniques were used: 4-field, X15MV, 3DCRT; 7-field, X6MV, IMRT; and 2-arc, X6MV, VMAT. Two optimization scenarios were used for the IMRT and VMAT plans generation: with (+) and without (−) the inclusion of the BM as an optimized structure. Average doses and dose-volume histogram parameters for the PTV, BM, bladder, rectum, bowels and femoral heads were compared. In addition, the BM doses were analyzed with respect to the PTV and/or volume of the BM, and NTCP for the BM were computed.ResultsThe dose in PTV for evaluated plans was similar. The worst doses in organs at risk were obtained for 3DCRT. Using the BM during the optimization of IMRT and VMAT reduces an average dose in BM without increasing the doses in the bladder, rectum and bowels. Differences between doses in BM for IMRT(+) and VMAT(+) plans were similar while NTCP was lower for VMAT(+). A correlation between average dose in BM and the volume ratio of BM and PTV was found for each technique.ConclusionUsing the BM during the optimization of the IMRT and VMAT plans effectively reduces the dose in BM without increasing the dose in the bladder, rectum and bowels. The VMAT(+) plans were characterized by the lowest NTCP.     

Role of Different Isoforms of Nitric Oxide Synthase in Development of Tumor Mutants in Drosophila melanogaster

We studied the role of nitric oxide synthase during tumor growth in oncovirus-induced tumor mutants of Drosophila melanogaster. The lines with different capacity for malignancy differed reliably in the level of enzymatic activity. It was shown using specific inhibitors of neuronal and inducible isoforms that the neuronal isoform was not involved in tumor formation, while the inducible one appears to play an important role in tumor growth inhibition. This isoform was identified with the help of immunoblotting and monoclonal antibodies against inducible nitric oxide synthase.     

MicroRNA-30e Functions as a Tumor Suppressor in Cervical Carcinoma Cells through Targeting GALNT7

Cervical cancer is the third most common cancer in women worldwide. However, the underlying mechanism of occurrence and development of cervical cancer is obscure. In this study, we observed that miR-30e was downregulated in clinical cervical cancer tissues and cervical cancer cells. Next, overexpression of miR-30e reduced the cervical cancer cell growth through MTT, colony formation, EdU, and Transwell assay in SiHa and Caski cells. Subsequently, UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase 7 (GALNT7) was identified as a potential miR-30e target by bioinformatics analysis. Moreover, we showed that miR-30e was able to bind to the 3′UTR of GALNT7 by luciferase reporter assay. In addition, the mRNA and protein levels of GALNT7 in cervical cancer cells were downregulated by miR-30e. And we validated that downregulation of GALNT7 repressed the proliferation of SiHa and Caski cells by MTT, colony formation, and Transwell assay. We identified that the restoration of GALNT7 expression was able to counteract the effect of miR-30e on cell proliferation of cervical cancer cells. Furthermore, we found that the expression levels of GALNT7 were frequently upregulated and negatively correlative to those of miR-30e in cervical cancer tissues. In addition, we validated that restoration of GALNT7 rescued the miR-30e–suppressed growth of cervical cancer xenografts in vivo. In conclusion, the current results suggest that miR-30e may function as tumor suppressors in cervical cancer through downregulation of GALNT7. Both miR-30e and its novel target, GALNT7, may play an important role in the process of cervical cancer.