Deoxynivalenol induces apoptosis in PC12 cells via the mitochondrial pathway

Deoxynivalenol (DON) has broad toxicity in animals and humans. In this study the impact of DON treatment on apoptotic pathways in PC12 cells was determined. The effects of DON were evaluated on (i) typical indicators of apoptosis, including cellular morphology, cell activity, lactate dehydrogenase (LDH) release, and apoptosis ratio in PC12 cells, and on (ii) the expression of key genes and proteins related to apoptosis, including Bcl-2, Bax, Bid, cytochrome C (Cyt C), apoptosis inducing factor (AIF), cleaved-Caspase9, and cleaved-Caspase3. DON treatment inhibited proliferation of PC12 cells, induced significant morphological changes and apoptosis, promoted the release of Cyt C and AIF from the mitochondria, and increased the activities of cleaved-Caspase9 and cleaved-Caspase3. Bcl-2 expression decreased with increasing DON concentrations, in contrast to Bax and Bid, which were increased with increasing DON concentration. These data demonstrate that DON induces apoptosis in PC12 cells through the mitochondrial apoptosis pathway.     

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.     

The role of WNT signalling in urothelial cell carcinoma

Urothelial cell carcinoma (UCC) of the bladder is one of the most common malignancies, causing considerable morbidity and mortality worldwide. It is unique among the epithelial carcinomas as two distinct pathways to tumourigenesis appear to exist: low grade, recurring papillary tumours usually contain oncogenic mutations in FGFR3 or HRAS whereas high grade, muscle invasive tumours with metastatic potential generally have defects in the pathways controlled by the tumour suppressors p53 and retinoblastoma. Over the last two decades, a number of transgenic mouse models of UCC, containing deletions or mutations of key tumour suppressor genes or oncogenes, have helped us understand the mechanisms behind tumour development. In this summary, I present my work investigating the role of the WNT signalling cascade in UCC.     

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.     

糖尿病小鼠小肠绒毛杯状细胞分泌黏原颗粒的变化

目的：观察糖尿病小鼠小肠绒毛杯状细胞分泌的黏原颗粒是否改变,为进一步研究糖尿病的消化系统并发症提供形态学基础。方法分别选取3,5,8,10月龄db/db糖尿病小鼠及相应年龄段的db/+m正常小鼠,每组6只,标本用4%多聚甲醛灌流固定后,从距Treitz韧带约10 cm处切下一段空肠,用PAS染色方法对小肠杯状细胞分泌的黏原颗粒进行观察。结果糖尿病组小肠绒毛易被破坏,糖尿病组中杯状细胞的分泌物比同月份正常对照组显著增加(P<0.05)；糖尿病组中3月龄的杯状细胞分泌物最多,8月龄最少,并且8月龄分别与3月龄、5月龄比较均存在着显著差异(P<0.05)；正常对照组随月龄增长无显著性差异(P>0.05)。结论糖尿病时杯状细胞分泌物增多可能对小肠绒毛有保护作用。