Objective:To describe the special molecular and histopathological transformation of recurrent tumor in a patient with primary hepatocellular carcinoma(HCC)after liver transplantation.Methods:A case of HCC had recurrent tumor presenting special molecular and histopathological characteristics after liver transplantation.The diagnosis and treatment process of this case is reported.Results:A case of highly differentiated HCC received immune checkpoint inhibitors combined with antiangiogenic therapy after liver malignant tumor resection.Nearly one year later,due to severe liver cirrhosis,the case accepted allogeneic orthotopic transplantation of liver.More than two years later,elevated level of serum alpha fetoprotein was detected,then the PET-CT examination showed multiple suspected lesions with increased 18F-FDG metabolism in the right lobe of the liver.Liver biopsy and high-throughput sequencing were performed,and the results revealed poorly differentiated HCC with YAP1-MAML2 fusion gene.Chemotherapy with XELOX regimen and radiotherapy were administered,and no tumor progression was observed during follow-up.Conclusion:Recurrent tumors after liver transplantation in HCC patient developing into a special molecular and histopathological transformation is rarely reported.The underlying mechanism could be the dramatical alterations of immune microenvironment after liver transplantation,which consequently triggered genomic changes leading to generate novel YAP1-MAML2 fusion gene.The poor differentiation transformation after liver transplantation maybe driven by YAP1-MAML2 fusion gene.

Objective:To describe the special molecular and histopathological transformation of recurrent tumor in a patient with primary hepatocellular carcinoma(HCC)after liver transplantation.Methods:A case of HCC had recurrent tumor presenting special molecular and histopathological characteristics after liver transplantation.The diagnosis and treatment process of this case is reported.Results:A case of highly differentiated HCC received immune checkpoint inhibitors combined with antiangiogenic therapy after liver malignant tumor resection.Nearly one year later,due to severe liver cirrhosis,the case accepted allogeneic orthotopic transplantation of liver.More than two years later,elevated level of serum alpha fetoprotein was detected,then the PET-CT examination showed multiple suspected lesions with increased 18F-FDG metabolism in the right lobe of the liver.Liver biopsy and high-throughput sequencing were performed,and the results revealed poorly differentiated HCC with YAP1-MAML2 fusion gene.Chemotherapy with XELOX regimen and radiotherapy were administered,and no tumor progression was observed during follow-up.Conclusion:Recurrent tumors after liver transplantation in HCC patient developing into a special molecular and histopathological transformation is rarely reported.The underlying mechanism could be the dramatical alterations of immune microenvironment after liver transplantation,which consequently triggered genomic changes leading to generate novel YAP1-MAML2 fusion gene.The poor differentiation transformation after liver transplantation maybe driven by YAP1-MAML2 fusion gene.

Developing new therapeutic agents for cancer immunotherapy is highly demanding due to the low response ratio of PD-1/PD-L1 blockade in cancer patients. Here, we discovered that the novel immune checkpoint VISTA is highly expressed on a variety of tumor-infiltrating immune cells, especially myeloid derived suppressor cells (MDSCs) and CD8⁺ T cells. Then, peptide C1 with binding affinity to VISTA was developed by phage displayed bio-panning technique, and its mutant peptide VS3 was obtained by molecular docking based mutation. Peptide VS3 could bind VISTA with high affinity and block its interaction with ligand PSGL-1 under acidic condition, and elicit anti-tumor activity in vivo. The peptide DVS3-Pal was further designed by d-amino acid substitution and fatty acid modification, which exhibited strong proteolytic stability and significant anti-tumor activity through enhancing CD8⁺ T cell function and decreasing MDSCs infiltration. This is the first study to develop peptides to block VISTA/PSGL-1 interaction, which could act as promising candidates for cancer immunotherapy.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

Objective:Platelet-derived growth factor alpha (PDGFRA) mutations are respectively rare in gastrointestinal stromal tumors (GIST). Most GIST with PDGFRA exon 18 mutations including D842V mutation are highly resistant to imatinib. The treatment of GIST harboring PDGFRA primary drug-resistant mutation is a major challenge. This article aims to investigate clinicopathologic features of GIST with PDGFRA-D842V mutation and the efficacy of comprehensive treatment, providing a reference for clinical practice. Methods:A retrospective cohort study was conducted to collect the clinicopathological and follow-up data of patients with GIST harboring PDGFRA mutation who were diagnosed and treated in the GIST Clinic of Renji Hospital from January 2005 to May 2020. According to the mutation site, the enrolled patients were divided into D842V mutation group and non-D842V mutation group. The differences of clinicopathologic characteristics between the two groups were compared. Furthermore, overall survival and prognostic factors were analyzed. Results:A total of 71 patients with PDGFRA-mutant GIST were included in this study, including 47 cases of D842V mutation (66.2%) and 24 cases of non-D842V mutation (33.8%). There were 28 male patients and 19 female patients in D842V mutation group, with a median age of 60 (36-82) years. There were 16 male patients and 8 female patients in non-D842V mutation group, with a median age of 62 (30-81) years. There were no significant differences in age, gender, primary location, surgical procedure, tumor size, mitotic count, expression of CD117 and DOG1, Ki-67 proliferation index and modified NIH grade between the two groups (all P>0.05). The positive rate of CD34 was 89.4% (42/47) and 62.5% (15/24) in the D842V mutation group and the non-D842V mutation group, respectively, with a statistically significant difference (χ 2=5.644, P=0.018). Among all the cases, 66 cases underwent R0 resection without preoperative treatment; two cases underwent emergency operation with R1 resection because of tumor rupture; 2 cases were not operated after the pathological and mutation types were confirmed by biopsy (one case received avapritinib treatment and obtain partial remission). One case was diagnosed as wild-type GIST per needle biopsy in another institute, and underwent R0 resection after preoperative imatinib treatment for 6 months. After surgery, 5 high-risk GIST patients with D842V mutation and 5 high-risk GIST patients with non-D842V mutation were treated with imatinib for more than one year. The median follow-up time was 37 (1-153) months. As of the last follow-up among the patients who received R0 resection, 4 patients with D842V mutation had relapse, of whom 1 was in the period of imatinib administration, and the 3-year relapse-free survival rate was 94.2%; none of the patients with non-D842V mutation had relapse. There was no statistically significant difference in relapse-free surivval between two groups ( P=0.233). Univariate analysis revealed that mitotic count ( P=0.002), Ki-67 proliferation index ( P<0.001) and modified NIH grade ( P=0.025) were the factors associated with relapse-free survival of patients with D842V mutation after R0 resection (all P<0.05). However, the above factros were not testified as independant prognostic facors in multivariate Cox analysis (all P<0.05). Conclusion:Clinicopathologic features and the efficacy of radical resection in patients with PDGFRA-D842V mutation are similar to those in patients with non-D842V mutation.

OBJECTIVES: To investigate the distribution of serum calcium and the relationship between serum calcium and serum metabolic parameters in endometrial carcinoma (EC) patients. METHODS: Retrospective assessment of patients diagnosed with endometrial cancer from Peking University People's Hospital from 2004 to 2009. Clinical characteristics as well as pretreatment serum calcium, albumin, fasting plasma glucose (FPG), serum triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC) value were extracted from patient records. Serum calcium was corrected for albumin. Unpaired t test and analysis of covariance were used to compare serum calcium among categorical variables. Simple correlation analyses and partial correlation analyses were used to assess the associations between serum calcium and continuous variables. RESULTS: Two-hundred twenty patients were included in this study. After adjusting for confounders, postmenopausal patients had higher total serum calcium (p=0.002) and albumin-corrected serum calcium (p=0.012) than premenopausal patients, endometrioid endometrial carcinoma (EEC) patients had higher total serum calcium than non-endometrioid endometrial carcinoma (NEEC) patients (p=0.037). Significant positive correlations were found between total serum calcium and FPG (p=0.017), TG (p=0.043), HDL (p=0.042), LDL (p < 0.001), and TC (p < 0.001) after adjusting for multiple variables, and the corrected serum calcium showed no significant correlation with metabolic parameters. CONCLUSION: Total serum calcium might be a more sensitive parameter for metabolic syndrome in endometrioid endometrial cancer patients than lipids.
Beijing ; Blood Glucose ; Calcium* ; Cholesterol ; Endometrial Neoplasms* ; Fasting ; Female ; Humans ; Lipoproteins ; Retrospective Studies ; Triglycerides

OBJECTIVETo study the chemical constituents of Daphne odora var. margirmta.

METHODThe compounds were isolated and purified by column chromatography of silica gel, ODS, Sephadex LH-20, and their structures were identified by UV, 1H-NMR, 13C-NMR, MS and CD spectroscopic methods.

RESULTTen compounds were elucidated as wikatrols B (1), kaempferol (2), daphnodorin B (3), daphnodorin D2 (4), daphnodorin A (5), daphnodorin C (6), daphnodorin D1 (7), daphnodorin I (8), daphnetin (9), daphnoretin (10).

CONCLUSIONCompounds 1,2,4 were obtained from this plant for the first time,and compound 1 was isolated firstly from the genus Daphne.

The effects of adsorption time, solid-liquid ratio, sample concentration, flow rate on the adsorption properties of supported ionic liquids(the N-methylimidazolium functionalized silica, SilprMin) for flavonoids were investigated. The results indicated that the adsorption equilibrium for tested compounds, genistein, luteolin and quercetin, was achieved within 30 min, the adsorption efficiencies of these three compounds were improved with the increase of solid-liquid ratio, and decreased with the increase of their concentrations. Moreover, the adsorption isotherm data of the three tested compounds were in good concordance with the Langmuir model. The saturated adsorption capacity of SilprMim for genistein, luteolin and quercetin was 47.7, 52.5 and 63.2 mg/g, respectively. Adsorption efficiency of SilprMim could reach more than 90% at a sample flow rate of 0.5～1.5 mL/min. Using methanol as eluent, the saturated desorption efficiencies of genistein, luteolin and quercetin were 86.1%, 83.3% and 84.6%, respectively. The elution order of the three tested flavonoids was genistein, luteolin and quercetin. SilprMim had strong adsorption and separation capacity for three tested flavonoids, which was hopeful to be applied in separation and purification of naturally occurring flavonoids.

Objective: To study the effect of sulforaphane (SUL) on cell growth inhibition, cell cycle, apoptosis and its mechanism in different breast cancer cell lines. Methods: By means of MTT assay, flow cytometry and Western blotting, the effects of the SUL different concentrations on cell growth inhibition, cell cycle arrest, F3Ⅱapoptosis and expression of p34cdc2 and Cdc25C were studied. Results: (1) SUL had strong inhibition effects on the cell growth of tested mammary cancer cell lines, in which the sensitivity of ERP cell lines to SUL was stronger than that of ERN cell line. (2) SUL exhibited obviously G2/M cell cycle arrest to F3Ⅱ and two kinds of ERP cell lines at 5-10?mol/L, whereas no effect on the cell cycle of ERN cell line. (3)The mechanism of hindering transition of F3 Ⅱ cells from G2 phase to M phase was enhancing the phosphorylation of Cdc2, down-regulating the expression of Cdc25C, and inducing inhibition to thedephosphorylation of cyclin B1-Cdc2 complex. (4) No apoptosis was observed under tested conditions. Conclusion: Sulforaphane exhibited obvious differences in the inhibiting effects on the cell proliferation and cell cycle arrests of four different tested breast cancer cell lines, and did not induce apoptosis in F3Ⅱcell line under tested conditions. The mechanism of cell cycle arrest of F3Ⅱcell line appears to involve enhancing the phosphorylation of Cdc2, and down-regulating the expression of Cdc25C.