Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma / 中华病理学杂志

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

A retrospective analysis of clinical characteristics and prognostic factors for primary breast diffuse large B cell lymphoma / 临床与实验病理学杂志

Purpose To study the clinical features, immunophenotypes and prognostic factors of primary breast diffuse large B-celllymphoma (PBDLBCL). Methods The clinical pathological data of 49 cases of PBDLBCL during January 2006 to December 2016 were retrospectively analysed, and the basic clinical and pathologic data, pathologic types and the immunohistochemical slides by EnVision method for staining were summarized. Results 47 cases were women and 2 cases were men. The age ranged from 24 to 79 year old with the median age of 48 year old. On microscopic observation, tumor cells were large to medium-sized which characterized as diffuse infiltration between the lobules of mammary gland, around the duct, interstitial and fat tissue, some were single file cord pattern. The immunophenotype showed 37 cases were of non-GCB, 12 cases were GCB type. Ki-67 index were greater than 40％. According to Ann Arbor staging, 16 cases were stage I EA, 28 cases were stage Ⅱ EA, 5 cases were stage Ⅳ E. IPI score: 30 cases with 0 ～1 score, 10 cases with 2 score, 9 cases with 3 score. Patients were followed up from 5 to 146 months, The 3-year overall survival (OS) rate was 51.2％ and 5-year OS rate was 36.7％, Single factor analysis showed that there were statistically significant difference in clinical stage, levels of LDH, IPI score, BCL-2 protein expression, and BCL-6 protein expression in 3 and 5 years of OS rate. The multiple factor analysis of Cox regression showed that the increase of IPI risk classification was the independent adverse prognostic factor of primary breast diffuse large B-cell lymphoma. Conclusion The diagnosis of PBDLBCL is confirmed by pathological biopsy and immunohistochemical markers. The immunophenotype was mainly non-GCB type. Comprehensive treatment including surgery, chemotherapy and radiotherapy is appropriate. The prognosis should be comprehensively evaluated by multiple factors. IPI increase risk classification is the independent adverse prognostic factor.

OTX1 Contributes to Hepatocellular Carcinoma Progression by Regulation of ERK/MAPK Pathway

Orthodenticlehomeobox 1 (OTX1) overexpression had previously been associated with the progression of several tumors. The present study aimed to determine the expression and role of OTX1 in human hepatocellular carcinoma (HCC). The expression level of OTX1 was examined by quantitative real-time PCR (qRT-PCR) in 10 samples of HCC and paired adjacent non-cancerous tissues, and by immunohistochemistry (IHC) analysis in 128 HCC samples and matched controls. The relationship between OTX1 expression and the clinicopathological features werealso analyzed. Furthermore, the effects of OTX1 knockdown on cell proliferation and migration were determined in HCC cell lines. Axenograft mouse model was also established to investigate the role of OTX1 in HCC tumor growth. TheqRT-PCR and IHC analyses revealed that OTX1 was significantly elevated in HCC tissues compared with the paired non-cancerous controls. Expression of OTX1 was positively correlated with nodal metastasis status (P = 0.009) and TNM staging (P = 0.001) in HCC tissues. In addition, knockdown of OTX1 by shRNA significantly inhibited the proliferation and migration, and induced cell cycle arrest in S phase in vitro. Tumor growth was markedly inhibited by OTX1 silencing in the xenograft. Moreover, OTX1 silencing was causable for the decreased phosphorylation level of ERK/MAPK signaling. In conclusion, OTX1 contributes to HCC progression possibly by regulation of ERK/MAPK pathway. OTX1 may be a novel target for molecular therapy towards HCC.

Protective effect of total flavonoid C-glycosides from Abrus mollis extract on lipopolysaccharide-induced lipotoxicity in mice / 中国天然药物

Abrus mollis is a widely used traditional Chinese medicine for treating acute and chronic hepatitis, steatosis, and fibrosis. It was found that the total flavonoid C-glycosides from Abrus mollis extract (AME) showed potent antioxidant, anti-inflammatory, and hepatoprotective activities. To further investigate the hepatoprotective effect of AME and its possible mechanisms, lipopolysaccharide (LPS)-induced liver injury models were applied in the current study. The results indicated that AME significantly attenuated LPS-induced lipid accumulation in mouse primary hepatocytes as measured by triglyceride (TG) and total cholesterol (TC) assays and Oil Red O staining. Meanwhile, AME exerted a protective effect on LPS-induced liver injury as shown by decreased liver index, serum aminotransferase levels, and hepatic lipid accumulation. Real-time PCR and immunoblot data suggested that AME reversed the LPS-mediated lipid metabolism gene expression, such as sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase 1 (ACC1). In addition, LPS-induced overexpression of activating transcription factor 4 (ATF4), X-box-binding protein-1 (XBP-1), and C/EBP homologous protein (CHOP) were dramatically reversed by AME. Furthermore, AME also decreased the expression of LPS-enhanced interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2). Here, it is demonstrated for the first time that AME ameliorated LPS-induced hepatic lipid accumulation and that this effect of AME can be attributed to its modulation of hepatic de novo fatty acid synthesis. This study also suggested that the hepatoprotective effect of AME may be related to its down-regulation of unfolded protein response (UPR) activation.

Anti-inflammatory and hepatoprotective effects of total flavonoid C-glycosides from Abrus mollis extracts / 中国天然药物

The aim of this study was to evaluate the anti-inflammatory and hepatoprotective effects of the total flavonoid C-glycosides isolated from Abrus mollis extracts (AME). In the anti-inflammatory tests, xylene-induced ear edema model in mice and carrageenan-induced paw edema model in rats were applied. The hepatoprotective effects of AME were evaluated with various in vivo models of acute and chronic liver injury, including carbon tetrachloride (CCl4)-induced hepatitis in mice, D-galactosamine (D-GalN)-induced hepatitis in rats, as well as CCl4-induced hepatic fibrosis in rats. In the acute inflammation experiment, AME significantly suppressed xylene-induced ear edema and carrageenan-induced paw edema, respectively. In the acute hepatitis tests, AME significantly attenuated the excessive release of ALT and AST induced by CCl4 and D-GalN. In CCl4-induced hepatic fibrosis model, AME alleviated liver injury induced by CCl4 shown by histopathological sections of livers and improved liver function as indicated by decreased liver index, serum ALT, AST, TBIL, and ALP levels and hydroxyproline contents in liver tissues, and increased serum ALB and GLU levels. These results indicated that AME possesses potent anti-inflammatory activity in acute inflammation models and hepatoprotective activity in both acute and chronic liver injury models. In conclusion, AME is a potential anti-inflammatory and hepatoprotective agent and a viable candidate for treating inflammation, hepatitis, and hepatic fibrosis.

Clinicopathological features and prognostic factors of 216 cases with primary gastrointestinal tract non-Hodgkin's lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological features of primary gastrointestinal non-Hodgkin's lymphomas (PGI-NHL) and their prognostic values.</p><p><b>METHODS</b>The clinical and pathological data of 216 patients diagnosed as PGI-NHL from Zhejiang Cancer Hospital were analyzed retrospectively. χ² test, log-liner model analysis, COX proportional hazard regression analysis and Life-table survival analysis were used to analyze the survival status of the patients by SAS 8.2 software, and Log-rank test was performed to couple the overall survival rates with different prognostic factors.</p><p><b>RESULTS</b>Totally, the age of onset was 8 to 89 years with the median age of 56.5 years. Male versus female was 1.27∶1(121∶95). The most frequently involved location was stomach (147 cases, 68.1%), followed by ileocecus (25 cases, 11.6%), large intestine (20 cases, 9.3%), small intestine (17 cases, 7.9%) and multiple GI involvement (5 cases, 2.3%). 182 cases were classified as B cell lymphomas, 22 cases as T cell lymphomas, and 12 cases not classified exactly due to insufficient data. The 3-year and 5-year survival rates of the patients were 69.4% and 53.3%, respectively. Univariate analysis revealed that age＞60 years, ECOG≥2, high LDH level, stage Ⅲ-Ⅳ, IPI≥2, T cell type and intestinal involvement were predictors for poor prognosis. IPI≥2, T cell type and intestinal involvement were independent adverse predictors for prognosis by multiple COX proportional hazard regression analysis. Among different treatment groups, cases received chemotherapy combined with local radiotherapy gained the best survival status.</p><p><b>CONCLUSION</b>B-cell lymphoma was the main pathological type in PGI-NHL; IPI≥2, T-cell type and intestinal involvement are independent adverse predictors for prognosis; chemotherapy combined with local radiotherapy might be the choice of approach for advanced stage and aggressive PGI-HNL.</p>

Synchronous primary cancer of the endometrium and ovary / 中华肿瘤杂志

<p><b>UNLABELLED</b>To investigate the clinical and pathological characteristics, treatment, and The data of 12 patients prognosis of synchronous primary cancer of the endometrium and ovary. Methods with synchronous primary cancer of the endometrium and ovary were retrospectively reviewed . Results Eight patients had the same histological type of endometrioid carcinoma in both uterus and ovary, 4 patients had different histological types in uterus and ovary. Synchronous primary cancer of the endometrium and ovary was difficult to be dignosed preoperatively. All ovarian tumors were small with an average diameter of 7 cm. Infertility was common among these patients(40.7%). Most of them had early stage I lesion (66.7%). endometrioid carcinomas was the main pathologic type (66.7%). All patients were treated surgically followed by chemotherapy with a 3-year survival rate of 66.7% (8/12).</p><p><b>CONCLUSION</b>Synchronous primary endometrium and ovary cancer is a specific kind of tumor different from either the primary endometrium carcinoma or ovary carcinoma, and usually can be detected in early stage with a good prognosis.</p>