Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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自噬在前列腺癌发生发展和治疗中的研究进展

自噬是真核细胞通过溶酶体对其自身生物大分子和细胞器回收再利用的过程，其在维持细胞稳态中发挥重要作用，并参与多种病理生理过程。在肿瘤的发病过程中，自噬发挥“双面作用”，既可以抗癌也能促癌。前列腺癌是老年男性最常见的恶性肿瘤，研究表明前列腺癌的发生发展与自噬作用密切相关，放化疗、内分泌治疗等对肿瘤细胞造成的应激可通过自噬得以缓解，抵抗治疗，因而自噬抑制剂对于放化疗等具有协同促进作用。本文就自噬在前列腺癌中发病和治疗进行综述，以期为前列腺癌的诊治提供一些新的思路。     

Tumor-to-tumor metastases: Latent renal cell carcinoma discovered after elective surgical resection of a convexity meningioma

BackgroundTumor-to-tumor metastases are extremely rarely reported lesions, which usually involve an indolent lesion hosting a more aggressive neoplasm. We present an unusual initial manifestation of a previously unknown clear cell renal cell carcinoma as a tumor-to-tumor metastasis in a typical meningothelial meningioma.Case reportA 73-year old patient with transient left slight monoparesis was addressed to our Neurosurgical Department after being evaluated by his general practitioner and passing a cerebral MRI which revealed a right frontotemporal mass attached to the meninge. At presentation, no deficits were identified; therefore an elective surgery was proposed. Histological analysis revealed a typical meningothelial meningioma containing a metastatic clear cell renal cell carcinoma. Additional thoraco-abdominal computer tomography identified a 6 cm diameter lesion within the right kidney with radiological features highly suggestive of a primary clear cell renal cell carcinoma.ConclusionOur case highlights the need for a specialized neuropathological approach to clinical and imagistic indolent meningiomas, as they may require important differential diagnosis that can highly impact the treatment and follow-up of brain tumor patients.     

外泌体在肿瘤转移前微环境形成中的作用

肿瘤的转移前微环境（pre-metastatic niche，PMN）特指原发肿瘤灶为肿瘤细胞远处播散和定植准备的微环境，此微环境的六个特征包括炎症、免疫抑制、血管生成/血管通透性、亲器官性、重编程和淋巴管生成。PMN形成的关键成分包括肿瘤源性分泌因子、细胞外囊泡（含外泌体）、骨髓源性细胞、免疫抑制细胞和宿主基质细胞等，其中，外泌体作为细胞间重要的信使，在肿瘤PMN的形成中具有重要作用。本综述就外泌体在肿瘤PMN形成中的作用进行探讨。     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Hair shaft miRNA‐221 levels as a new tumor marker of malignant melanoma

miRNA‐221 (miR‐221) is known to be abnormally expressed in many human cancers. The serum levels of miR‐221 have been reported as a tumor marker for malignant melanoma (MM). We hypothesized that the hair shaft miR‐221 levels may be increased in patients with MM. We therefore assessed the possibility that hair shaft miR‐221 levels could be a marker for MM. The hair shaft miR‐221 levels were significantly higher in patients with MM than controls. The rates of increased hair shaft miR‐221 levels above the cut‐off value were comparable to those of serum 5‐S‐CD, which is a tumor marker commonly used for MM. Measurements of the hair shaft miR‐221 levels could have potential clinical value in the detection of MM. This is the first report investigating the hair shaft levels of an miRNA in patients with MM. Our investigations offer new insight into the relationship between miR‐221 and MM, and may provide a new, non‐invasive way to screen for melanoma.     

Does Outcome/Survival of Patients With Myelodysplastic Syndromes Should Be Predicted by Reduced Levels of ADAMTS-13? Results From a Pilot Study

IntroductionVon Willebrand factor (vWF) cleaving protease ADAMTS-13 has a key role for maintaining normal size of vWF. A deficiency or dysfunction of vWF cleaving protease is associated with ultra large vWF multimers and thrombotic microangiopathy. Patients with cancers have reduced levels of vWF cleaving protease. In this pilot study, we have evaluated whether or not deficiencies of ADAMTS-13 were present in myelodysplastic syndromes (MDS). Moreover, we assessed if a reduction in basal levels of ADAMTS-13 may play a role in the prognosis of MDS.Patients and MethodsWe measured and compared the levels of vWF cleaving protease ADAMTS-13 in 100 patients with MDS and 35 healthy controls. Patients were divided into 2 groups according to the International Prognostic Scoring System: group I consisting of 44 patients with low-risk MDS and group II of 56 patients with high-risk MDS. Patients with high-risk and low-risk MDS presented significantly lower levels of ADAMTS-13 than controls (P < .001 and P = .0177, respectively). High-risk patients had significantly lower levels of ADAMTS-13 when compared with the low-risk group (P < .001).ResultsWe found that reduced levels of ADAMTS-13 have a relationship with overall survival (P < .001). Statistical analysis showed that ADAMTS-13 correlates with cytogenetics (P < .001) and a tendency of slight correlation with platelet count and basal levels of ADAMTS-13 (R, 0.35; P value, 0.001). Moreover, we found that levels of ADAMTS-13 have correlation with response to treatment (P < .001).ConclusionsADAMTS-13 in MDS might represent a surrogate marker of prognosis, response to therapy, or disease progression. Further studies are needed.