Pancreatic cancer remains one of the most lethal malignancies worldwide. The combination of the first-line standard agent gemcitabine (GEM) with the molecular-targeted drug erlotinib (Er) has emerged as a promising strategy for pancreatic cancer treatment. However, the clinical benefit from this combination is still far from satisfactory due to the unfavorable drug antagonism and the fibrotic tumor microenvironment. Herein, we propose a membrane-camouflaged dual stimuli-responsive delivery system for the co-delivery of GEM and Er into pancreatic cancer cells and tissues to block the antagonism, as well as reshapes profibrotic tumor microenvironment via simultaneous delivery of small interference RNA (siRNA) for synergistic pancreatic cancer treatment. This "all-in-one" delivery system exhibits sensitive GSH and pH-dependent drug release profiles and enhances the inhibitory effects on the proliferation and migration of tumor cells in vitro. Excitingly, the systemic injection of such a biomimetic drug co-delivery system not only resulted in superior inhibitory effects against orthotopic pancreatic tumor and patient-derived tumor (PDX), but also greatly extended the survival rate of tumor-bearing mice. Our findings provide a promising therapeutic strategy against pancreatic cancer through the enhanced synergistic effect of target therapy, chemotherapy and anti-fibrotic therapy, which represents an appealing way for pancreatic cancer treatment.

BACKGROUND: The incidence and mortality of lung cancer often rank first in all malignant tumors. DNA methylation, as one of epigenetics, often participates in the development and progression of tumors. CDO1 as a tumor suppressor gene always undergoes methylation changes early in tumor development. Therefore, this study aims to discuss the value of CDO1 methylation in the early diagnosis of lung cancer. METHODS: Peripheral blood samples were collected from tumor patients and healthy people. Detection of the methylation level of CDO1 in plasma by sulfite modification and quantitative real-time PCR. RESULTS: The level of gene methylation in peripheral blood of lung cancer patients was significantly higher than that of benign lung disease patients and healthy people. The methylation level of CDO1 was significantly different in the stratified comparison of gender, lymph node metastasis and tumor-node-metastasis (TNM) stage (P<0.05). The sensitivity and specificity of CDO1 were 52.2% and 78.6%, respectively. The overall accuracy of the diagnosis was significantly higher than that of the clinical tumor markers, and the sensitivity of CDO1 to stage I and II patients was the highest (40.8%, 47.1%). In addition, CDO1 could effectively increase the sensitivity of diagnosis in multiple joint examinations. CONCLUSIONS Detecting the methylation level of CDO1 has a potentially huge advantage for the early diagnosis of lung cancer.

Epigenetic modification is closely related to the occurrence and development of tumors. It mainly regulates gene function and expression level through DNA methylation, histone modification, regulation of non-coding RNA and chromatin structure reconstruction. At present, epigenetic drugs have been gradually applied to the treatment of malignant tumors. Common drug types include: DNA methyltransferase inhibitors and histone deacetylase inhibitors. However, these drugs still have many shortcomings and a wide range of clinical applications need further research. Encouragingly, the epigenetic drugs in combination with various anti-tumor drugs have shown great application potential. In this paper, we summarized the development mechanism of epigenetics in malignant tumors and the progress of related drugs.

BACKGROUND: Venous thromboembolism (VTE) is a recognized complication in lung cancer patients with higher morbidity and mortality. The purpose of this study is to determine the incidence of lower extremity venous thrombosis (LEDVT) in lung cancer patients and to reveal the risk factors for LEDVT during admission in our center. METHODS: We first connected 231 patients with lung cancer admitted to the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital from July 2017 to December 2017. All these patients underwent color ultrasound examination of lower extremity vein on admission to analyze the incidence of LEDVT. At the same time, the incidence of LEDVT in patients with benign lung diseases on admission was used as control. In order to explore the possible risk factors for LEDVT in these patients with lung cancer, we further analyze the correlations between LEDVT and their clinical features. At the same time, we also analyze the relationship between LEDVT and Plasma D-Dimmer, fibrinogen (FIB), thrombin time (TT), activated partial thrombin time (APTT), prothrombin time (PT) and platelet (PLT) in these patients with lung cancer. RESULTS: Among 231 patients with lung cancer, the incidence rate of LEDVT on admission was 5.2% (12/231), and in 77 patients with benign lung disease, there was none of patients with LEDVT on admission. This result indicated that the admitted incidence rate of LEDVT in patients with lung cancer was significantly higher than that in patients with benign lung disease (P<0.05). Further analysis in patients with lung cancer found that there was higher incidence rate of LEDVT in distant metastasis group (including N3 lymph node metastasis) compared to in non-distant metastasis group (11.29%, 7/62 vs 2.96%, 5/169) (P<0.05). In patients with lung cancer, the median value of D-Dimer in LEDVT group was 1,534 mg/L (369 mg/L-10,000 mg/L), which was significantly higher than that in the non-LEDVT group (539 mg/L, 126 mg/L-1,000 mg/L) (P<0.05). There was no statistically significant difference in FIB, TT, APTT, PT and PLT between these two groups (P>0.05). CONCLUSIONS The overall incidence of LEDVT in our central lung cancer patients was approximately 5%, significantly higher than that in patients with benign lung disease. Lung cancer patients with distant metastasis (including N3 lymph node metastasis) at admission were more likely to develop LEDVT, and these patients with higher D-Dimer values should be considered the possibility of VTE events.
Female ; Humans ; Incidence ; Lower Extremity ; Lung Neoplasms ; surgery ; therapy ; Male ; Middle Aged ; Patient Admission ; Risk Factors ; Tomography, X-Ray Computed ; Venous Thrombosis ; diagnostic imaging ; etiology

Objective To investigate the relationship between vaspin,Apelin,leptin and polycystic ovary syndrome.Methods We determined the serum vaspin,Apelin and leptin levels of 40 cases of PCOS patients and 30 cases of control group,and divided the PCOS group into three subgroups (normal weight,overweight and obesity) according to WHO criteria for obesity.Then we compared the serum vaspin,Apelin and leptin levels in PCOS and control group,and the differences in body weight index (body mass index,BMI) in women with polycystic ovary syndrome,and analyzed roles of adipokine vaspin,Apelin and leptin in the pathogenesis of PCOS.Results In PCOS patients adipokine vaspin,Apelin,leptin,insulin resistance index (Homeostasis model assessment for insulin index in resistence,HOMA-IR),fasting insulin (INS) and blood glucose,blood lipid were higher than those of the control group and increased with the increase of body mass index (BMI),and three kinds of adipokines and PCOS patients with HOMA-IR were positively correlated,there were statistically significant differences (P ＜ 0.05).Conclusion The results of vaspin,Apelin and leptin may be involved in the occurrence of PCOS.

OBJECTIVETo observe the change of peripheral blood Th17 cells in patients with different kinds of CRSwNPs and the relationship between the frequency of Th17 cells and inflammatory cell density in nasal polyps tissue, and to explore the correlation between levels of peripheral blood Th17 cells and prognosis of patients with CRSwNPs.METHODSEighty one patients with CRSwNPs and 20 controls were recruited in this research. Flow cytometer was used to detect the expression of peripheral blood Th17 cells. The number per 10000μm2 of infiltrated inflammatory cells in nasal polyp tissue (including eosinophils, neutrophils, lymphocytes and plasma cells) was counted at a high-power field. The CT scores were evaluated by Lund-Mackay system and the nasal endoscopy scores were graded according to Lund-Mackay methods. RESULTSThe percentages of Th17 cells in patients with E-CRSwNPs and NE-CRSwNPs were 2.10% (3.75%, 1.40%)和1.10% (1.70%, 0.73%). There was significant difference between the two groups (Mann-WhitneyU=358.0,Z=-2.965, P=0.001). Furthermore, a positive association between the percentage of Th17 cells in peripheral blood and the eosinophil density of nasal polyp (r=0.408,P<0.001) was demonstrated. The percentage of Th17 cell in peripheral blood was significantly correlated with the endoscopic score of CRSwNPs at third month after the operation (r=0.458, P<0.001).CONCLUSIONThl7 might be involved in the pathogenesis and prognosisof eosinophilic CRSwNPs.

OBJECTIVETo investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.

METHODSThe expressions of RLIP76 protein and gene were detected by Western blotting and real-time PCR (RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively. siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression. The drug-sensitivity of cells to chemotherapeutic drugs (ADM, DDP, VP-16) were detected by CCK8 assay. The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry. The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.

RESULTSThe expression of RLIP76 in H69AR cells was 13.675 ± 0.983, significantly higher than 1.074 ± 0.107 in the H69 cells (P < 0.01). The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated (P< 0.001). The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression (P = 0.003). The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively (P < 0.01). The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients (P < 0.05).

CONCLUSIONSOur results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance. RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

ATP-Binding Cassette Transporters ; metabolism ; physiology ; Antineoplastic Agents ; pharmacology ; Cisplatin ; pharmacology ; Down-Regulation ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; Etoposide ; pharmacology ; GTPase-Activating Proteins ; metabolism ; physiology ; Humans ; Lung Neoplasms ; drug therapy ; metabolism ; RNA, Small Interfering ; Real-Time Polymerase Chain Reaction ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; Transfection ; Up-Regulation

Objective To investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.Methods The expressions of RLIP 76 protein and gene were detected by Western blotting and real-time PCR ( RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively.siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression.The drug-sensitivity of cells to chemotherapeutic drugs ( ADM, DDP, VP-16) were detected by CCK8 assay.The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry.The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.Results The expression of RLIP76 in H69AR cells was 13.675 ±0.983, significantly higher than1 .074±0.107 in the H69 cells ( P<0.01) .The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated ( P<0.001) .The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression ( P=0.003 ) .The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively ( P<0.01 ) .The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients ( P<0.05) .Conclusions Our results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance.RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

Objective To investigate the role of RLIP76 in regulating multi-drug resistance in small cell lung cancer (SCLC), and to analyze the relationship between its expression and prognosis.Methods The expressions of RLIP 76 protein and gene were detected by Western blotting and real-time PCR ( RT-PCR) in both the chemosensitive SCLC H69 cell line and chemoresistant H69AR cell line, respectively.siRNA was transfected into the H69AR cells to inhibit RLIP76 expression, and eGFP-RLIP76 was transfected into the H69 cells to enhance RLIP76 expression.The drug-sensitivity of cells to chemotherapeutic drugs ( ADM, DDP, VP-16) were detected by CCK8 assay.The expression of RLIP76 in the SCLC tissues was detected by immunohistochemistry.The relationship of RLIP76 expression with clinicopathological features and prognosis of the patients was analyzed.Results The expression of RLIP76 in H69AR cells was 13.675 ±0.983, significantly higher than1 .074±0.107 in the H69 cells ( P<0.01) .The drug-sensitivities of H69AR cells to chemotherapeutic drugs were significantly increased when the expression of RLIP76 was down-regulated ( P<0.001) .The sensitivities of H69 cells to chemotherapeutic drugs ADM, DDP and VP-16 were significantly decreased after transfection with eGFP-RLIP76 up-regulating the RLIP76 expression ( P=0.003 ) .The positive expression rates were 61.3% and 9.4% in the SCLC tumor tissues and para-cancerous tissues, respectively ( P<0.01 ) .The expression of RLIP76 was significantly correlated with clinical stage, chemosensitivity and overall survival of the SCLC patients ( P<0.05) .Conclusions Our results suggest that RLIP76 is involved in the regulation of small cell lung cancer multidrug resistance.RLIP76 may serve as a potential target gene to evaluate the chemosensitivity and clinical prognostic for small cell lung cancer.

This study was aimed to show the extraction research of cpDNA in Gentiana straminea Maxim. and G. crassicaulis Duthie ex Burk., which will increase the knowledge about the chloroplast genome sequence characteris-tics, understand its genetic diversity and improve the efficiency of breeding schemes. G. straminea Maxim. and G. crassicaulis Duthie ex Burk. were taken as study objects. The improved sucrose-gradient centrifugation and purifica-tion methods were used to obtain the cpDNA, measure the concentration, detect the OD value, and amplify the ITS2 sequence to verify the nucleus pollution. The results showed that the high quality and purity cpDNA (0.1 - 0.4 μg/10 g) was demonstrated without other pollution after ITS2 sequence amplification, which met to the subsequent effi-cient sequencing of chloroplast genomes. The purity and mass have an important influence on the accuracy and cred-ibility of the cp genome sequencing. It was concluded that this study improved the sucrose-gradient centrifugation and purification with great effect of the purity and mass of cpDNA, and guaranteed the obtaining of complete cpDNA of Gentiana.