Two autopsy cases of desmoplastic small round cell tumor

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignant tumor. It is a refractory tumor and the median overall survival is very short. We report two autopsy cases of DSRCT, both of which were already advanced and metastasized at the first medical examination. Both cases showed typical DSRCT findings in terms of localization of the lesions, histopathology and genetics, but the rate of disease progression was quite different. Survival after initial symptoms in Case 1 was only 12 months. On the other hand, survival after primary hospitalization in Case 2 was 42 months. The Case 2 patient initially received chemotherapy for advanced pancreatic carcinoma, because a nodule of the pancreatic tail was found on computed tomography (CT) scan. After chemotherapy, tumor regression was observed on CT scan. It is thus implied that adoption of the regimen for pancreatic carcinoma might have been one of reasons of the long survival in Case 2.     

Glucocorticoid receptor and serum‐ and glucocorticoid‐induced kinase‐1 in esophageal adenocarcinoma and adjacent Barrett's esophagus

Barrett's esophagus (BE) is a consequence of gastroesophageal reflux disease and is predisposed to esophageal adenocarcinoma (EAC). EAC is an exemplar model of inflammation‐associated cancer. Glucocorticoids suppress inflammation through glucocorticoid receptor (GR) and serum‐ and glucocorticoid‐induced kinase‐1 (Sgk1) expressions. Therefore, we immunolocalized GR and Sgk1 in EAC and the adjacent BE tissues and studied their association with clinical disease course in 87 patients with EAC who underwent surgical resection (N = 58) or endoscopic submucosal dissection (N = 29). Low GR and Sgk1 expressions in adjacent BE tissues were associated with adverse clinical outcomes (P = 0.0008 and 0.034, respectively). Patients with low Sgk1 expression in EAC cells exhibited worse overall survival (P = 0.0018). In multivariate Cox regression analysis, low GR expression in the adjacent nonmalignant BE tissues was significantly associated with worse overall survival (P = 0.023). The present study indicated that evaluation of GR and Sgk1 expressions in both the EAC cells and adjacent nonmalignant BE tissues could help to predict clinical outcomes following endoscopic and surgical treatments. In particular, the GR status in BE tissues adjacent to EAC was an independent prognostic factor.     

High expression of Twist is associated with tumor aggressiveness and poor prognosis in patients with renal cell carcinoma

Aims: Twist has been reported to play crucial roles for malignant aggressiveness; however, detailed pathological significance of Twist in renal cell carcinoma (RCC) is not fully understood. The present study was to clarify clinical significance and molecular functions of Twist in patients with RCC. Methods: Twist expression was examined by immunohistochemical techniques in 156 formalin-fixed specimens. Cell proliferation, angiogenesis, and apoptosis were measured as the percentage of Ki-67-positive cells (proliferation index, PI), CD31-stained vessels (microvessel density, MVD), and TUNEL-positive cells (apoptotic index, AI). In addition, semi-quantification of matrix metalloproteinase (MMP)-2 was performed. Macrophages were identified with anti-CD68 antibody, and the tumor associated macrophage (TAM) density was calculated as CD68-positive cells per high-power field. Results: Twist expression was positively associated with grade, pT stage, and metastasis (p<0.001). We also noticed that its expression was considerably higher in cancer cells of sarcomatoid RCC and in those at the edge of the tumors. Twist expression was positively correlated with PI, MVD, MMP2 expression, and TAM density (P<0.001), but not with AI, and MMP-2 expression and TAM density were independently correlate by multi-variate analyses. Kaplan-Meir survival curves showed high Twist expression was a worse predictor for cause-specific survival (P<0.001). Conclusions: Twist plays important roles in tumor growth, progression, and survival in patients with RCC patients. Such pathological mechanisms are significantly associated with increased cancer cell proliferation, angiogenesis, MMP2 expression, and macrophage recruitment. These findings are important information for discussion of treatment and observation strategies in these patients.     

A comprehensive study on the relieving effect of Lilium brownii on the intestinal flora and metabolic disorder in p-chlorphenylalanine induced insomnia rats

ContextThe bulb of Lilium brownii F. E. Brown (Liliaceae) (LB) is a common Chinese medicine to relieve insomnia.ObjectiveTo investigate the molecular mechanism of LB relieving insomnia.Materials and methodsInsomnia model was induced by intraperitoneally injection p-chlorophenylalanine (PCPA) in Wistar rats. Rats were divided into three groups: Control, PCPA (400 mg/kg, i.p. 2 days), LB (598.64 mg/kg, oral 7 days). The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE), melatonin (MT), and the expression of GABA_A, 5-HT1A and MT receptors, as well as pathological changes in hypothalamus, were evaluated. 16S rDNA sequencing and UPLC-MS/MS were used to reveal the change of the intestinal flora and metabolic profile.ResultsThe adverse changes in the abundance and diversity of intestinal flora and faecal metabolic phenotype altered by PCPA in rats were reversed after LB treatment, accompanied by the up-regulated levels of 5-HT as 8.14 ng/mL, MT as 16.16 pg/mL, 5-HT1A R and GABA_A R, down-regulated level of NE as 0.47 ng/mL, and the improvement of pathological phenomena of cells in the hypothalamus. And the arachidonic acid metabolism and tryptophan metabolism pathway most significantly altered by PCPA were markedly regulated by LB. Besides, it was also found that LB reduced the levels of kynurenic acid related to psychiatric disorders and trimethylamine-N-oxide associated with cardiovascular disease.ConclusionThe mechanism of LB relieving insomnia involves regulating flora and metabolites to resemble the control group. As a medicinal and edible herb, LB could be considered for development as a health-care food to relieve increasing insomniacs in the future.