Progress on targets and therapeutic drugs for pancreatic cancer / 药学学报

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Research progress of tumor immune and tumor metabolic drug targets / 药学学报

The occurrence and development of tumors are closely related to the tumor microenvironment. Among them, tumor immune microenvironment and tumor metabolic microenvironment play important roles in tumor. Tumor immunotherapy is a way to kill tumor cells by activating the body's immune system. Tumor immunotherapy has shown good therapeutic effects in a variety of solid tumors. In recent years, significant progress has been made in tumor immunotherapy. The Warburg effect indicates that tumor cells use aerobic glycolysis to acquire energy. In the tumor, the energy metabolism pathway is abnormal, and the tumor microenvironment can induce the reprogramming of tumor cell metabolism. Therefore, targeting tumor metabolism is also of great significance for tumor treatment. In this paper, we reviewed the research progress of drug targets related to tumor immunology and tumor metabolism in recent years, as well as the progress of drug development.

Construction and identification of ST8Sial gene over-expression vector and its effect on proliferation of human melanoma cells / 中国药理学通报

Aim To construct different over-expression vectors of ST8Sial gene and establish a cell line with stable ST8Sial over-expression , and to check the proliferation of cells with ST8Sial over-expression. Methods Polymerase chain reaction ( PCR) was used to amplify the code region of ST8Sial. The amplified ST8Sial fragment and pEGFP-Cl vector, pHBLV-CMV-MCS-3flag-EFl-ZsGreen-T2A-Puro vector were digested with restriction enzymes. The target gene fragment and the different vectors were ligated to obtain the ST8Sial-pEGFP-Cl recombinant vector and the recombinant lentiviral vector, respectively. PCR and DNA sequencing were used to identify recombinant vectors. Melanoma cells WM451 were transfected with different vectors. Cell line with stable ST8Sial over-expressing was established. ST8Sial mRNA level was checked by real-time PCR. STSSial protein expression level was checked by Western blot. Proliferation of the stable cells was assayed by CCK-8 method. The clony formation of stable cells was also performed. Results Both ST8Sial-pEGFP-Cl recombinant plasmid and STSSial over-expression lentiviral vectors were successfully constructed. The transfection efficiency of ST8Sial over-expression lentiviral vector was much higher than that of ST8Sial-pEGFP-Cl recombinant plasmid. A WM451 cell line with stable ST8Sial over-expression lentiviral vectors was established. Results showed that the over-expression of ST8Sial promoted the proliferation and colony formation of cells. Conclusions ST8Sial over-expression vectors are successfully constructed. The over-expression of ST8Sial promotes the proliferation and colony formation of WM451 cells.

Preliminary study on adverse effects and mechanism of germ cells induced by Glyphosate / 局解手术学杂志

Objective To study the effects and mechanism of Glyphosate induced cell cycle arrest and apoptosis in mouse spermatogenic cells(GC-2).Methods Morphology of the GC-2 cells was observed by optical microscope and Transmission Electron Microscopy.Flow cytometry were used to detect cell cycle arrest and apoptosis.Cell cycle arrcst and apoptosis related proteins were detected by Western blot.Results Glyphosate could inhibit cell proliferation and impair endoplasmic reticulum and mitochondria significantly,which was associated with G1 phase arrest and apoptosis in GC-2 cells.Glyphosate lead to cell cycle arrest and apoptosis by regulating the expressions of G1/S phase checkpoint regulatory factor proteins such as p21,CyclinD1,CyclinE and activating caspase3.Conclusion Glyphosate has adverse effects on male germ cells by inducing cell cycle arrest and apoptosis.

Mutational spectra in the tk gene of mouse lymphoma cells induced by acrylamide / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of acrylamide (AA)-induced mutational spectra in the tk gene of mouse lymphoma cells.</p><p><b>METHODS</b>L5178Y3.2.7c-tk(+/-) cells were treated with AA at different concentrations. Mutational spectra of tk locus were analyzed by the mouse lymphoma assay (microtiter procedure), and frequency of loss of heterozygosity (LOH) analysis with allele special PCR. Subsequently determined the DNA sequence of negative LOH's colonies induced by AA.</p><p><b>RESULTS</b>The LOH of mutants derived from AA induction was 78.8%, and showed a good dose-response relationship in large colonies. The occurrence of LOH of large colonies at lower doses (150 microg/ml and 300 microg/ml) were 25.0% and 33.3% respectively which were significantly different from those of control (66.7%), and at higher doses (600 microg/ml and 750 microg/ml) were 77.8% and 85.7%. By Sequence analysis showed that AA-induced point mutations were mainly base substitutions, and most of them were T:G-->G:T transversions.</p><p><b>CONCLUSION</b>Functional tk allele gene loss is major mutational event in both spontaneous and induced tk mutants. And point mutations were base substitution.</p>

Gene expression profiles in early stage of BALB/c 3T3 cells' transformation promoted with 12-O-tetradecanoylphorbol-13-acetate / 中华预防医学杂志

<p><b>OBJECTIVE</b>To elucidate the potential molecular mechanism responsible for the early time of tumor promotion, gene expression profile was studied in the transformed BALB/c 3T3 cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA).</p><p><b>METHODS</b>The two-stage cell transformation model was established by using the initiator of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and promoter of TPA. Cell proliferation was measured by trypan blue staining and cell cycle analysis was carried out by flow cytometry assay. A cDNA microarray representing 1 152 genes was used to investigate the gene expression profiles of BALB/c 3T3 cells exposed to TPA at 4 h and 24 h respectively.</p><p><b>RESULTS</b>TPA could effectively inhibit cell proliferation and induce the G1 and S cell cycle arrested in the early time. Moreover 19 genes were found differentially expressed at least twofold in the TPA treated cells as compared with the control cells, 9 of them were upregulated and 10 downregulated. Most of the differentially expressed genes were involved in cell proliferation, differentiation or apoptosis, and related to ras or p53 signal transduction pathway.</p><p><b>CONCLUSION</b>TPA could influence the transcriptional expression of some genes related to cell cycle modulation and ultimately result in the cell growth arrest.</p>

Hypermethylation of p16 gene in clinical specimens of patients with lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate aberrant methylation of the p16 promoter as a useful biomarker of lung cancer.</p><p><b>METHODS</b>A modified methylation-specific semi-nested PCR was performed to detect p16 hypermethylation in the matched samples of tumor tissue, blood plasma and sputum derived from 51 cases of lung cancer patients.</p><p><b>RESULTS</b>Hypermethylation of p16 promoter was demonstrated in 84.3% of the tumor tissues, 70.6% of the blood plasma and 76.5% of the sputum specimens, respectively. Only the patients whose tumor tissues had p16 hypermethylation exhibited aberrant methylation in their plasma and/or sputum specimens. Combining with cytological examination, 92.2% of the patients with lung cancer could be detected by p16 hypermethylation assay in both sputum and plasma samples.</p><p><b>CONCLUSION</b>The results indicate that p16 hypermethylation in plasma and sputum identified by semi-nested PCR is a biomarker of lung cancer which can be useful as an auxillary diagnostic parameter.</p>

Detection of hypermethylation of p16 gene in plasma DNA from lung cancer patients / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To detect hyper methylation of p16 gene in plasma DNA from patients with lung cancer, and to assess its potential as a malignant marker.</p><p><b>METHODS</b>Using a modified semi-nested methylation-specific PCR (MSP), the status of methylation of the p16 was investigated in plasma DNA from 137 lung cancer patients and 112 matched tumor tissues.</p><p><b>RESULTS</b>Hypermethylation of the p16 was present in 75.2% (103/137) of the plasma samples and 80.4% (90/112) of the tumor tissues. Hypermethylation of the p16 in the plasma was detected in 77.9% squamous-cell carcinoma, 65.1% adenocarcionma, 75.1% adeno-squamous-cell carcinoma, and 91.7% small-cell lung cancer. Only in those patients whose tumor tissues had hypermethylation of p16 gene, similar changes could be detected in their plasma samples. Hypermethylation of the p16 in plasma and the corresponding tumor tissues was not significantly correlated with the clinical stage and pathological type of the tumor.</p><p><b>CONCLUSION</b>The result indicates that hypermethylation of the p16 may be a useful marker in the auxiliary diagnosis of lung cancer.</p>