Association of status of mismatch repair protein expression and EB virus infection with clinicopathological parameters in 886 gastric adenocarcinoma patients / 中华胃肠外科杂志

Objective: To analyze the expression of mismatch repair (MMR) protein and the EB virus infection in gastric adenocarcinoma, and to examine the association of MMR expression and EB virus infection with clinicopathological parameters. Methods: A case-control study was performed. Clinicopathological data of patients who was pathologically diagnosed as gastric adenocarcinoma, received radical gastrectomy and had complete clinicopathological data from August 2017 to April 2020 in Tianjin Medical University Cancer Institute and Hospital were retrospectively collected and analyzed. The immunohistochemistry (IHC) of MMR proteins and in situ hybridization (ISH) of Epstein-Barr virus encoded RNA (EBER) were reviewed. The associations of MMR and EBER results with clinicopathological parameters were analyzed. The main observations of the study were MMR and EBER expression, and association of MMR and EBER results with clinicopathological parameters. Results: Eight hundred and eighty-six patients were enrolled, including 98 patients who received preoperative neoadjuvant chemoradiotherapy. Of 886 patients, 613 (69.2%) were males and the median age was 60 (22-83) years; 831 (93.8%) were mismatch repair proficiency (pMMR), and 55 (6.2%) were mismatch repair deficiency (dMMR). In dMMR group, 47 cases (85.5%) had the deficiency of both MLH1 and PMS2, 1 case (1.8%) had the deficiency of both MSH2 and MSH6, 4 cases (7.3%) had the deficiency only in PMS2, 2 cases (3.6%) had the deficiency only in MSH6, and 1 case (1.8%) had the deficiency only in MSH2. The deficiency rates of PMS2, MLH1, MSH6 and MSH2 were 5.8% (51/886), 5.3% (47/886), 0.3% (3/886) and 0.2% (2/886), respectively. Among the 871 cases with EBER results, 4.9% (43/871) were positive EBER. Univariate analysis showed that dMMR was more frequently detected in female patients (χ(2)=10.962, P=0.001), cancer locating in the antrum (χ(2)=9.336,P=0.020), Lauren intestinal type (χ(2)=9.718, P=0.018), stage T3 (χ(2)=25.866, P<0.001) and TNM stage II (χ(2)=15.470, P=0.002). The ratio of dMMR was not significantly associated with age, tumor differentiation, histological type, lymph node metastasis, distant metastasis or Her-2 immunohistochemical score (all P>0.05). Compared with negative EBER, positive EBER was more frequent in male patients (χ(2)=9.701, P=0.002), cancer locating in gastric fundus and corpus (χ(2)=17.964, P<0.001), gastric cancer with lymphoid stroma (χ(2)=744.073, P<0.001) and poorly differentiated cancer (χ(2)=13.739, P=0.010). Positive EBER was not significantly associated with age, depth of invasion, lymph node metastasis, distant metastasis, TNM stage or Her-2 immunohistochemical score (all P>0.05). In addition, all dMMR cases were EBER negative, and all cases of positive EBER were pMMR. Conclusions: The positive EB virus status is mutually exclusive with dMMR, indicating that different molecular subtypes of gastric adenocarcinoma are involved in different molecular pathways in tumorigenesis and progression. The overlapping of dMMR or positive EBER status and positive Her-2 expression is found in some cases of gastric adenocarcinoma. Patients with gastric adenocarcinoma after radical surgery should be tested for MMR status if they are female, the tumor locates in gastric antrum, the TNM staging is stage II or T3, or if the Lauren classification is intestinal type. And if patients are male, the tumor locates in the gastric fundus and corpus, the cancer is lymphoid stroma, or poor differentiated, the expression of EBER should be detected. Results of our study may provide evidence for further decision-making of clinical treatment.

Application of dermoscopy to the evaluation of efficacy of 2940 nm Er pixel laser in the treatment of skin pore widening / 中华皮肤科杂志

Objective To explore and establish a method for quantitative evaluation of facial skin pores based on dermoscopy,and to evaluate the scientificity and practicability of this method.Methods Totally,30 patients with enlarged facial skin pores were enrolled from Department of Dermatology,Peking University Third Hospital between June 2017 and December 2017,and treated with 2 940 nm Er pixel laser.Photographs were taken,and dermoscopic images were collected before and after treatment.According to the standard photographs of facial pores,the improvement of enlarged facial pores was evaluated by comparing the photos before and after the treatment.A dermoscope-based pore detection system was established,and quantified indices for pore area and color difference before and after the treatment were evaluated by using this system.A pre-post self-contrast study was conducted,and statistical analysis was carried out by using paired t test for the comparison of measurement data and paired non-parametric test (Wilcoxon signed-rank test) for the comparison of ranked data.Results After the treatment,the standard photograph method for the assessment of facial pores showed score reduction by 3 grades in 1 of the 30 patients (3.3％),by 2 grades in 7(23.3％),by 1 grade in 21(70％),and no changes of grades in 1 (3.3％).Additionally,the differences between pre-and post-treatment grades were significant (Z =-4.94,P ＜ 0.01).The detection rate of skin pores by using the detection system was (70.59 ± 3)％.After the treatment,the quantified values of pore area and color difference both significantly decreased compared with those before the treatment (pore area:712.95 ± 87.45 vs.831.45 ± 88.92,t =5.70,P ＜ 0.05;color difference:23.82 ± 9.43 vs.28.92 ± 9.91,t =2.76,P ＜ 0.05).Conclusion The dermoscopy-based method for quantitative evaluation of skin pores after the treatment with 2 940 nm Er pixel laser showed highly consistent results with the standard photograph method,which can be further verified and popularized in the evaluation of enlarged skin pores.

The inhibitory effect of dihydroartemisinin on the growth of neuroblastoma cells

Objective: To evaluate the inhibitory effect of dihydroartemisinin on neuroblastoma cell line SH-SY5Y, explore the possible mechanism of dihydroartemisinin against neuroblastoma cells. Methods: The cell viability of dihydroartemisinin treated SH-SY5Y cells was examined by MTT assay and morphology of cells was observed by using inverted microscope. Cell cycle was examined with flowcytometry assay, then cyclin D1 and caspase-3 proteins expression was detected by ELISA and western blotting assay. Results: MTT analysis results showed that cell viability significantly decreased after exposure to 0.05, 0.50, 5.00 and 50.00 μmol/L dihydroartemisinin in a dose-dependent manner, and the lower density of cells was observed in treated groups. The number of cells in sub-G1 phase was increased after treatment with different doses of dihydroartemisinin compared with the control group. The expression of cyclin D1 protein was decreased, while the expression of caspase-3 protein was increased in treated group. Conclusions: Dihydroartemisinin could inhibit the proliferation through stopping the cell cycle and inducing the apoptosis in neuroblastoma SH-SY5Y cells.

Inhibitory effect of dihydroartemisinin on growth of neuroblastoma cells and its mechanism / 吉林大学学报(医学版)

Objective:To explore the inhibitory effect of dihydroartemisinin (DHA ) on the growth of neuroblastoma cells,and to clarify the anti-tumor mechanism of DHA.Methods:The experiment was divided into blank control group and DHA groups (the final concentrations of DHA were 0.05, 0.50, 5.00 and 50.00μmol·L-1 ).The proliferation rates of neuroblastoma SH-SY5Y cells after treated with DHA were examined by MTT assay;the changes of cell cycle of SH-SY5Y cells after treated with DHA were examined by flow cytometry;the expression levels of cyclin D1 and caspase-3 proteins were detected by ELISA and Western blotting methods.Results:The proliferation of SH-SY5Y cells 24,48,and 72 h after treated with different concentrations of DHA were inhibited.Compared with blank control group,the proliferation rates of SH-SY5Y cells in 0.50,5.00 and 50.00μmol·L-1 DHA groups were significantly decreased (P<0.05 or P<0.01).The density of cells was decreased with the increasing of DHA concentration.Compared with blank control group,the percentage of SH-SY5Y cells at SubG1 phase in 50.00μmol·L-1 DHA group was increased (P<0.05),and the percentage of cells at G0/G1 phase was increased first then was decreased;otherwise, the percentages of cells at S and G2/M phase were decreased.Compared with blank control group,the expression level of cyclin D1 protein in 50.00μmol·L-1 DHA group was decreased (P<0.05),but the expression level of caspase-3 protein in 50.00μmol· L-1 DHA group was increased (P<0.05).Conclusion:DHA could inhibit the proliferation through arresting the cell cycle and inducing the apoptosis of neuroblastoma cells.

Expression of indoleamine 2, 3-dioxygenase and its correlation with prognosis in breast cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of indoleamine 2, 3-dioxygenase (IDO) in breast cancer and its correlation with clinicopathologic factors and prognosis.</p><p><b>METHODS</b>The expression of IDO, CD31, CD105 proteins in 40 specimens of breast cancer were assessed by immunohistochemistry.</p><p><b>RESULTS</b>The overexpression rate of IDO in breast cancer was 67.5% (27/40), and expression of IDO was closely associated with clinical stage and lymph nodes metastasis. The disease-free survival rate in patients with IDO overexpression was not significantly lower than that in patients with negative or low expression of IDO (P > 0.05). Moreover, the expression of IDO was positively correlated with CD105-labeled microvessel density (r = 0.659, P < 0.05).</p><p><b>CONCLUSIONS</b>Expression of IDO is associated with clinical stage and lymph nodes metastasis, and microvessel densitty. IDO expression may promote the growth and metastasis of breast cancer, probably via the increased agiogenesis. A larger sample study is needed to verify whether the prognosis of beast cancer is significantly correlated with IDO expression.</p>

Relationship between EGFR and K-ras mutations and clinicopathological characteristics and response to erlotinib treatment in 301 Chinese patients with non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate gene mutations of epidermal growth factor receptor (EGFR) and K-ras in Chinese patients with non-small cell lung cancer (NSCLC) and its clinicopathological significance, and to analyze the correlation between these mutations and tumor response to erlotinib treatment.</p><p><b>METHODS</b>Mutations of exons 18, 19, 20 and 21 of the EGFR and codons 12, 13 of the K-ras in 301 cases of NSCLC were detected by PCR-amplification and gene sequencing. The relationship between the mutations and clinicopathological characteristics of the 301 patients was analyzed.</p><p><b>RESULTS</b>EGFR mutations were present in 32.9% (99/301) of the samples: 3 mutation in exon 18, 59 in exon 19, 2 in exon 20, and 35 in exon 21. Mutations of K-ras were present in 4.7% (14/301) of the samples: 13 in codon 12 and 1 in codon 13. EGFR mutations were never found in tumors with K-ras mutations, suggesting a mutually exclusive relationship. EGFR mutations were more common in adenocarcinomas, non-smokers and females. Seven out of 10 erlotinib-treated patients with disease control carried EGFR mutation.</p><p><b>CONCLUSION</b>The frequency of EGFR mutation in Chinese NSCLC patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite. Combined detection of EGFR gene and K-ras gene mutation may help clinicians to choose patients who may gain benefit from EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment, and to predict their response to erlotinib treatment and prognosis.</p>

Synthesis and antitumor activity of selenophosphocholine analogues containing tegafur / 药学学报

<p><b>AIM</b>To synthesize the selenophosphocholine analogues containing tegafur and test their antitumor activities.</p><p><b>METHODS</b>The cyclic glyceroselenophospholopid conjugate of tegafur was synthesized by the reaction of hexaethylphosphorous triamide with N1-(2-furanidyl)-N3-(hydroxyalkyl)-5-fluyorouracil and 1-O-hexadecyl glycerol as well as selenium in one-pot. Cyclic glyceroselenophospholopid conjugate of tegafur reacted with triethylamine to give title compounds.</p><p><b>RESULTS</b>Six new compounds have been synthesized. Their structures were confirmed by 1H NMR, 13P NMR and elemental analysis. Antitumor activity of the title compounds against PGA1 was tested.</p><p><b>CONCLUSION</b>The reaction of triethylamine with cyclic glyceroselenophospholopid conjugate of tegafur very readily occurred, which was finished within 2 h at room temperature. The opening-ring products of trans isomers showed antimutor activity against human uriaryl bladder cancer cell more effective than that of the tegafur.</p>