Efficacy of First-Line Immunotherapy Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients With Different Brain Metastases Status: A Systematic Review and Meta-Analysis.

Background: This study aims to evaluate the efficacy of first-line immunotherapy combined with chemotherapy in extensive-stage small cell lung cancer (ES-SCLC) patients with differing brain metastasis statuses. Methods: We conducted a comprehensive search in public databases, such as PubMed, EMBASE, and the Cochrane Library, to identify randomized controlled trials involving ES-SCLC patients, with or without brain metastases, who underwent first-line immunotherapy combined with chemotherapy. The primary outcome measure was progression-free survival (PFS), and the secondary outcome measure was overall survival (OS). Results: Our analysis incorporated seven high-quality randomized controlled trials, encompassing 398 patients with brain metastases and 3,533 without. Among patients without brain metastases, the combination of immunotherapy and chemotherapy led to significantly improved PFS (hazard ratio (HR) = 0.72, 95% confidence interval (CI): 0.62 - 0.84, P < 0.001) and OS (HR = 0.77, 95% CI: 0.67 - 0.88, P < 0.001) in comparison to chemotherapy alone. Conversely, for patients with brain metastases, the addition of immunotherapy to chemotherapy did not result in a significant improvement in PFS (HR = 1.03, 95% CI: 0.66 - 1.61, P = 0.887) or OS (HR = 1.03, 95% CI: 0.82 - 1.31, P = 0.776) when compared to chemotherapy alone. Conclusions: In ES-SCLC patients without brain metastases, first-line immunotherapy combined with chemotherapy demonstrated improved PFS and OS in contrast to chemotherapy alone. However, patients with brain metastases did not experience similar benefits.

Postoperative radiotherapy in pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy: A meta-analysis.

BACKGROUND: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with pIIIA-N2 non-small cell lung cancer after complete resection and adjuvant chemotherapy. METHODS: Electronic databases (PubMed, Web of Science databases, Embase, and the Cochrane Central Register of Controlled Trials) were systematically searched to extract randomized control trials comparing PORT with observation in pIIIA-N2 non-small cell lung cancer patients until October 2021. Main outcomes were disease-free survival (DFS), overall survival (OS), and local recurrence. RESULTS: Three-phase 3 randomized control trials involving 902 patients were included: 455 patients in the PORT group and 447 patients in the observation group. The methodological quality of the 3 randomized control trials were high quality. The pooled analysis revealed that PORT decreased local recurrence rate (odds ratio = 0.56, 95% confidence interval [CI]: 0.40-0.76). However, PORT did not improve median DFS (hazard ratio = 0.84, 95% CI: 0.71-1.00) and OS (hazard ratio = 1.02, 95% CI: 0.68-1.52). CONCLUSIONS: PORT decreased the incidence of local recurrence. However, PORT did not improve DFS and OS.

Physical Activity and Sedentary Behaviors among Chinese Children: Recent Trends and Correlates.

OBJECTIVE: This study was aimed at examining the trends and correlates of physical activity (PA) and sedentary behaviors among Chinese children. METHODS: A total of 4,341 subjects (6,936 observations) aged 6-17 years who participated in the China Health and Nutrition Survey (2004-2015) were included. Of the subjects, 41% participated in the survey twice or more. Random-effects ordinal regression models and repeated-measures mixed-effects models were used to examine the PA trends. Quantile regression models were applied to examine the factors influencing PA and sedentary behaviors. RESULTS: From 2004 to 2015, the prevalence of physical inactivity among Chinese children aged 6-17 years increased by 5.5% [odds ratio ( OR), 1.51; 95% confidence interval ( CI), 1.19-1.90; P < 0.001]. The PA volume declined by 5.8 metabolic equivalent of task-hr/week ( P < 0.001), and the time spent in sedentary behaviors increased by 1.8 hr/week ( P < 0.001). Age, ethnicity, and region showed significant effects on the PA volume across the quartiles ( P < 0.001). Across the quartiles, sedentary time was significantly higher in the children residing in urban areas ( P < 0.001) or areas with high urbanization levels ( P ≤ 0.005) than in their counterparts. CONCLUSIONS: A declining PA trend among Chinese children aged 6-17 years was observed from 2004 to 2015, and certain subgroups and geographical areas are at higher risk of physical inactivity.

Recent Trends in Physical Activity among Chinese Children Based on Their Demographic and Social Characteristics.

Aimed to explore the trends in physical activity among Chinese children, data of 4,341 children aged 6-17 years who participated in at least one round of "China Health and Nutrition Survey" from 2004 to 2015 were analyzed. Repeated measures mixed models were applied to test the trends in physical activity, which were further analyzed after applying stratification on gender, age, urbanization level, residential area and region. The volume of total physical activity in Chinese children aged 6-17 years showed a downward trend from 2004 to 2015, especially among children residing in medium and high urbanization communities, the south and urban areas of China, so that more efforts need to be put to promote their physical activity.

MicroRNA-1271-5p inhibits cell proliferation and enhances radiosensitivity by targeting CDK1 in hepatocellular carcinoma.

This study aims to determine whether miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity by targeting cyclin-dependent kinase 1 (CDK1) in hepatocellular carcinoma (HCC). Its expression levels in the HCC cell lines were significantly lower than those in normal human liver cell line. Bioinformatics analysis indicated CDK1 was a potential target of miR-1271-5p. Dual-Luciferase Reporter Assay confirmed that CDK1 is a direct target gene of miR-1271-5p. With overexpression of miR-1271-5p in SMMC-7721 and HuH-7 cells, cell proliferation was decreased, radiosensitivity was enhanced, cell cycle distribution was altered and the growth of transplanted tumours in nude mice was significantly reduced. miR-1271-5p overexpression enhanced radiosensitivity, which could be reduced by CDK1 overexpression. Overall, our findings suggested that miR-1271-5p inhibits cell proliferation and enhances the radiosensitivity of HCC cell lines by targeting CDK1.

Combined effects of physical activity and calcium on bone health in children and adolescents: a systematic review of randomized controlled trials.

BACKGROUND: A better understanding of the role of exercise and nutrition in bone health is significant for preventing osteoporosis. The aim of this review was to assess the combined effects of physical activity and calcium intake on improving bone mineral density in children and adolescents. METHODS: A search of electronic databases (MedLine, ISI Web of Science, Science Direct) and the literature references were performed. Randomized controlled trials published between 1997 and 2017, evaluating the effect of both physical activity and calcium intake intervention on bone mineral density or bone mineral content among children aged 3-18 years were selected. The Improved Jadad Rating Scale was used to assess the methodological quality of the included studies. Study characteristics were summarized in accordance with the review's PICO criteria. Changes in bone mineral content were detected at several different bone sites. RESULTS: A total of nine studies involving 908 participants were included in this review. The combined intervention of physical activity and calcium increased bone mineral in children and adolescents, especially when baseline calcium intake level was low and among participants on the stage of early puberty. CONCLUSIONS: Regular physical activity combined with high level of calcium intake is beneficial for bone health in young population. Further research is needed to evaluate the dose-response associations and long-term effects of the interaction between physical activity and calcium intake.

Antioxidant and Cytotoxic Activities of Distillates Purified by Means of Molecular Distillation from Ginger Extract Obtained with Supercritical CO2 Fluid.

The ginger extract obtained with supercritical CO2 fluid was purified by molecular distillation (MD), and the chemical compositions, antioxidant and cytotoxic activities of ginger extract and its distillates were investigated. Analysis revealed that the ginger extract was rich in terpene hydrocarbons, along with oxygenated terpenes and other non-volatile compounds. The MD distillates were prepared in a series of stages and the active compounds like terpenes and gingerols could be separated by MD. The major compounds of the distillates purified by MD at 40 °C, 80 Pa and 60 °C, 80 Pa were terpene hydrocarbons. Additional distillates obtained by MD at 80 °C, 80 Pa and 100 °C, 60 Pa were predominated by terpene hydrocarbons and oxygenated terpenes. Until the operating conditions of MD reached 150 °C and 2 Pa, some non-volatile compounds were concentrated in the final distillate. Moreover, antioxidant activities and the cytotoxic effects on three human cancer cells in final MD distillate were superior to other extracts, and this phenomenon could be mainly supported by the phenols. The MD could be used to prepare ginger distillates with better antioxidant and cytotoxic activities.

Esculetin enhances the inhibitory effect of 5-Fluorouracil on the proliferation, migration and epithelial-mesenchymal transition of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the most common malignant disease worldwide and thus new therapeutic approaches are needed. 5-Fluorouracil (5-FU) remains the most widely used agent to treat colorectal cancer (CRC). However, its clinical efficacy is currently limited by the development of drug resistance. Esculetin (EST), a coumarin, was found to have anti-proliferative and anti-migration activity in cancer. OBJECTIVE: This research aims to evaluated the influence and possible mechanism of EST on the proliferation, migration and epithelial-mesenchymal transition of CRC cell lines. MATERIALS AND METHODS: Human CRC cell lines HT-29, SW480, HCT-116, and Caco-2 were treated with various concentrations of EST (0.2, 2, 20, 200, 2000 µg/ml) or 5-FU (0.1, 1, 10, 100, 1000 µg/ml) for 48 h, and cell viability was determined by the MTT and CCK-8 assay. The motility of HCT-116 cells was detected by scratch assay. Western blot was applied to detect the protein expression. Besides, levels of Wnt3a and VEGF in HCT-116 cell culture medium supernatant were analyzed by ELISA. The anti-tumor effect was detected with HCT-116 subcutaneous tumor bearing tumor model by monitoring the tumor vomume in vivo. Finally, the tumoral expression of VEGF was measured by immunohistochemistry, and the expression of Ki67, PCNA, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 was measured by Western blot analysis. RESULTS: EST inhibited HCT-116 cell proliferation in a dose-dependent manner. Western blot analysis revealed that EST decreased the expression of Ki67, PCNA, N-cadherin, E-cadherin, vimentin, fibronectin, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7. Furthermore, EST reduced the release of Wnt3a and VEGF into HCT-116 cells culture medium. After EST treatment, the tumor volume was significant smaller than that of the control group, and the tumoral levels of VEGF were decreased. Moreover, western blot analysis indicated that the expression of Ki67, PCNA, ß-catenin, c-Myc, Cyclin D1, MMP2 and MMP7 were also significantly decreased after treated with EST. In addition, in vitro and in vivo anti-tumor results demonstrated that EST combined with 5-FU could increase the inhibitory effect of 5-FU on HCT-116 cells proliferation, migration and epithelial-mesenchymal transition. CONCLUSIONS: EST enhances the inhibitory effect of 5-FU on the proliferation, migration and epithelial-mesenchymal transition of CRC.

The protocol for the Prospective Urban Rural Epidemiology China Action on Spine and Hip status study.

The Prospective Urban Rural Epidemiology (PURE) China Action on Spine and Hip status (CASH) study focused on the prevalence of osteoporosis and spinal fracture in China. The aim of the PURE CASH study is to determine the prevalence of osteoporosis and spinal fracture, and explore the potential relationship between spinal fracture and bone mineral density (BMD). This study is a prospective large-scale population study with a community-based sampling and recruitment strategy. The aim is to determine the prevalence of osteoporosis and vertebral fracture in this population, to evaluate the association between vertebral fractures and BMD values, and to assess the prediction power of BMD for incident fractures. Participants in the PURE CASH study are all from the PURE study in China, recruited from 12 centers in 7 Chinese provinces. The inclusion criteria are that participants should be aged more than 40 years and able to give informed consent. Exclusion criteria are pregnant women, individuals with metal implants in the lumbar spine, use of medications or the existence of any disease or condition known to have a major influence on BMD, and inability to give informed consent. A total of 3,457 participants undergo a quantitative computed tomography (QCT) scan of the upper abdomen. The scanning parameters are as follows: 120 kVp at all centers, mAs between 75 and 200, FOV 40 cm×40 cm. The BMD values of L1 to L3 are measured, and the average BMD calculated. The American College of Radiology QCT criteria for the diagnosis of osteoporosis is applied to determine the presence of osteoporosis. The scout view images of T4-L4 vertebrae are reviewed by two experienced radiologists for semi-quantification of vertebral fractures according to Genant's method.

Plastrum Testudinis Extracts Promote BMSC Proliferation and Osteogenic Differentiation by Regulating Let-7f-5p and the TNFR2/PI3K/AKT Signaling Pathway.

BACKGROUND/AIMS: Plastrum testudinis extracts (PTE) show osteoprotective effects on glucocorticoid-induced osteoporosis in vivo and in vitro. However, the underlying molecular mechanism of PTE in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. METHODS: BMSC proliferation was investigated using the Cell Counting Kit-8 assay. BMSC differentiation and osteogenic mineralization were assayed using alkaline phosphatase and Alizarin red staining, respectively. The mRNA expression levels of Let-7f-5p, Tnfr2, Traf2, Pi3k, Akt, ß-catenin, Gsk3ß, Runx2, and Ocn were measured using real time quantitative polymerase chain reaction. Protein levels of TNFR2, TRAF2, p-PI3K, p-AKT, p-ß-CATENIN, and p-GSK3ß were analyzed by western blotting. The functional relationship of Let-7f-5p and Tnfr2 was determined by luciferase reporter assays. RESULTS: The optimum concentration for PTE was 30 µg/ml. PTE significantly promoted BMSC osteogenic differentiation and mineralization after 7 and 14 days in culture, respectively. The combination of PTE and osteogenic induction exhibited significant synergy. PTE upregulated Let-7f-5p, ß-catenin, Runx2, and Ocn mRNA expression, and downregulated Tnfr2, Traf2, Pi3k, Akt, and Gsk3ß mRNA expression. PTE inhibited TNFR2, TRAF2, and p-ß-CATENIN protein expression, and promoted p-PI3K, p-AKT, and p-GSK3ß protein expression. In addition, Tnfr2 was a functional target of Let-7f-5p in 293T cells. CONCLUSIONS: Our results suggested that PTE may promote BMSC proliferation and osteogenic differentiation via a mechanism associated with the regulation of Let-7f-5p and the TNFR2/PI3K/AKT signaling pathway.

Smoking and Its Relation to Metabolic Status among Chinese Adults: Analysis of a Nationwide Survey

OBJECTIVE: To update the estimated prevalence rates of smoking and examine major metabolic diseases associated with smoking status in Chinese adults. METHODS: Using a complex, multistage, probability sampling design, we recruited a nationally representative sample of 98,658 Chinese adults aged ⋝18 years in 2010. Information on current, former, never, and passive smoking status was obtained using a standard questionnaire. All estimates were weighted to represent the overall Chinese adult population. RESULTS: The estimated proportion of current smokers was 28.3% for Chinese adults aged ⋝18 years. The corresponding values of former and passive smokers were 5.1% and 21.4%, respectively. Additionally, former smokers were found to have a less favorable metabolic risk profile among all categories of smoking status in both men and women. The prevalence of metabolic diseases such as diabetes and hypertension also increased with a greater number of smoking pack-years in men. CONCLUSION: The prevalences of current smoking and passive smoking remain high in Chinese adults.

[Relationship between prevalent features of central obesity and clustering of cardiometabolic diseases among Chinese elder people].

OBJECTIVE: To study the relationship between prevalence of central obesity and clustering of cardiometabolic diseases among Chinese elder people over 60 years old. METHODS: A complex multistage stratified sampling survey on chronic diseases was conducted in 162 surveillance points, 31 provinces, China in 2010 by China CDC. The survey included face-to-face interview, physical measurement (body height, weight, waist circumference (WC) and blood pressure) and laboratory test (blood sugar, blood lipid and hemoglobin A1C), to collect the information about the prevalence of the risk factors as smoking, drinking, diet and physical activities and the prevalence of hypertension, diabetes and dyslipidemia. The survey selected 19 966 subjects who were over 60 years old. Central obesity was defined as WC ≥ 85 cm in males or ≥ 80 cm in females. The prevalence of central obesity among the elder people over 60 years old in different districts and populations was calculated; and the proportion of cardiometabolic diseases in groups of different WC was then analyzed. RESULTS: The prevalence of central obesity among elderly population over 60 years old was 48.6% (95%CI:46.1%-51.2%), including 39.7% (95%CI:37.2%-42.2%) males and 57.3% (95%CI:54.5%-60.1%) females. The proportion of females was higher than that of males (χ(2) = 474.63, P < 0.01). The higher the education level, the higher the prevalence of central obesity among elderly men. There was no significant association among females. The higher the family income, the higher the prevalence of central obesity. The prevalence of central obesity was 59.2% in urban area, which was much higher than that in rural area (43.5%) (χ(2) = 50.06, P < 0.01). The proportion of hypertension, diabetes and clustering of cardiometabolic disease was separately 18.8% (95%CI:16.1%-21.5%) , 66.2% (95%CI:63.0%-69.4%) and 47.5% (95%CI:44.1%-50.8%) among elderly men with WC between 85 and 89 cm, and separately 24.0% (95%CI:21.2%-26.8%), 78.2% (95%CI:75.6%-80.8%) and 64.0% (95%CI:60.3%-67.6%) among elderly men with WC ≥ 90 cm; which were both higher than those among elderly men with WC < 85 cm (separately 13.4% (95%CI:11.5%-15.3%) , 58.3% ( 95%CI:55.5%-60.1%) and 30.8% (95%CI:28.7%-32.9%) ). The proportion of hypertension, diabetes and clustering of cardiometabolic disease was 20.1% (95%CI:17.4%-22.7%) , 68.6% (95%CI:65.5%-71.8%) and 48.1% (95%CI:44.6%-51.6%) among elderly women with WC between 80 and 84 cm, and separately 31.7% (95%CI:28.9%-34.4%) , 81.0% (95%CI:78.5%-83.5%) and 61.8% (95%CI:58.9%-64.8%) among elderly women with WC ≥ 85 cm; which were both higher than those among elderly women with WC < 80 cm (separately 12.8% (95%CI:10.8%-14.8%) , 60.1% (95%CI:57.1%-63.0%) and 30.4% (95%CI:27.3%-33.5%)). CONCLUSION: Nearly half of the Chinese elder people were central obese. The proportion of cardiometabolic diseases among central obesity was significantly higher than that among non-obese population. We should pay more concern about them in the future prevention and control of chronic diseases.

The intracellular controlled release from bioresponsive mesoporous silica with folate as both targeting and capping agent.

A smart mesoporous silica nanocarrier with intracellular controlled release is fabricated, with folic acid as dual-functional targeting and capping agent. The folate not only improves the efficiency of the nanocarrier internalized by the cancer cells, but also blocks the pores of the mesoporous silica to eliminate premature leakage of the drug. With disulfide bonds as linkers to attach the dual-functional folate within the surface of mesoporous silica, the controlled release can be triggered in the presence of reductant dithiothreitol (DTT) or glutathione (GSH). The cellular internalization via folate-receptor-mediated endocytosis and the intracellular controlled release of highly toxic anticancer drug DOX were demonstrated with an in vitro HeLa cell culture, indicating an efficient cancer-targeted drug delivery.

[Association between frequency of fruit and vegetable intake and chronic obstructive pulmonary disease].

OBJECTIVE: To explore the association between frequency of fruit and vegetable intake and chronic obstructive pulmonary disease (COPD). METHODS: In 2007, 48 974 Chinese residents aged 15 - 69 years were selected as study participants by multistage stratified proportionate to size random sampling from the 161 sites of Disease Surveillance Points System. Standardized questionnaires were used to collect relevant information to compare the risk for self-reported physician diagnosed COPD between different frequency groups for fruit (< 2, 2 - 4, 5 - 7 d/week) and vegetable (< 4, 4 - 5, 6 - 7 d/week) intake. RESULTS: The proportion of vegetable intake was 89.9% (44 019/48 974) and 4.6% (2262/48 974) for individuals with frequency of 6-7 and < 4 d/week respectively. The proportion of fruit intake was 30.8% (15 072/48 974) and 31.5% (15 432/48 974) for individuals with frequency of 5 - 7 and < 2 d/week respectively. The prevalence of self-reported COPD was 2.9% (1412/48 974). After adjusting for age, sex, urban/rural areas, passive smoking exposure and family history, the risk of COPD decreased among those with high frequency (5 - 7 d/week) of fruit intake (OR = 0.80, 95%CI: 0.66 - 0.98 for never smokers; OR = 0.80, 95%CI: 0.64 - 0.99 for ever smokers), compared to subjects with low frequency of fruit intake (< 2 d/week). Among never smokers, those with high frequency of vegetable intake (6 - 7 d/w) had a low risk of developing COPD (OR = 0.65, 95%CI: 0.48 - 0.89). CONCLUSION: There were beneficial effects of fruit and vegetable intake on COPD.

The chemotactic interaction between CCL21 and its receptor, CCR7, facilitates the progression of pancreatic cancer via induction of angiogenesis and lymphangiogenesis.

BACKGROUND: In this study, we report the influence of CCL21 and its receptor, CCR7, on the progression of pancreatic cancer and illuminates the correlation between the CCL21/CCR7 axis and the angiogenesis and lymphangiogenesis of pancreatic adenocarcinoma (PAC). METHODS: A total of 30 patients with pancreatic cancer was involved in the current study. The expression of CCL21 and CCR7 in cancerous tissues, paracancerous tissues and normal pancreas were investigated using real-time PCR, Western blot and immunohistochemistry, respectively. In addition, we assessed microvessel density (MVD) and microlymphatic vessel density (MLVD) in tumor tissues using immunohistochemistry. RESULTS: Compared to paracancerous tissues and normal pancreas, CCL21 expression in cancerous tissues was detected at a significantly low level. In contrast, the CCR7 expression was considerably higher in cancerous tissues than in normal pancreas and paracancerous tissues. Additionally, a significant correlation between the expression pattern of the CCL21/CCR7 axis and clinicopathological features, such as lymph node metastasis, was identified. Furthermore, we found that CCL21 expression was significantly associated with MVD but not significantly associated with MLVD, while CCR7 expression was significantly associated with MLVD but not significantly associated with MVD. CONCLUSIONS: The chemotactic interaction between CCR7 and its ligand, CCL21, may be a critical event during progression in pancreatic cancer, and its underlying mechanism may be induction of angiogenesis and lymphangiogenesis regulated by this chemotactic interaction.

[Quantitative analysis and significance of CXCL12 and CXCR4 expression with lymphangiogenesis of pancreatic adenocarcinoma].

OBJECTIVE: To investigate the expression of CXCL12, its receptor CXCR4 and its correlations with clinical pathology and lymphangiogenesis in pancreatic adenocarcinoma (PAC). METHODS: The tissue samples were obtained from 30 patients with PAC by surgery between January 2005 and December 2007, which including PAC, the cancerous peripheral tissues, the normal pancreatic tissues and peripheral lymph nodes. The patients age ranged from 35 to 78 years old (median 57.2 years old). The expressions of CXCL12 and CXCR4 in these tissues were assayed by immunohistochemical staining, RT-PCR and fluorescence quantitative real-time PCR. RESULTS: In the immunohistochemical staining, the CXCL12 protein mainly located in the normal pancreatic cell envelopes and/or cytolymphs. In the immunohistochemical staining, the CXCR4 protein mainly located in the cell envelopes and/or cytolymphs of PAC. The results of RT-PCR and fluorescence quantitative real-time PCR indicated that the expression levels of CXCR4 mRNA in PAC tissues, the cancerous peripheral tissues and peripheral lympho nodes were higher than that in the normal pancreatic tissues (P < 0.01). The MLVD in PAC were detected by morphometric analysis respectively. The level of MLVD in III-IV stages was higher than I-II stages of PAC (P < 0.01), and in these cases which had lymphatic metastasis, the level of MLVD significantly increased (P < 0.01). And there was no correlation between the differentiation and histology types of PAC (P > 0.05). There was 22 samples that the CXCR4 protein was positive, and among these samples the MLVD was higher than that in negative group of CXCR4 protein (P = 0.003). CONCLUSIONS: The expression of CXCR4 was significantly associated with lymphatic metastasis of PAC, and the higher expression of CXCR4 in PAC tissues was significantly associated with lymphangiogenesis of PAC.

Effect of 5-LOX/COX-2 common inhibitor DHDMBF30 on pancreatic cancer cell Capan2.

AIM: To study the effect of 5-lipoxygenase/cyclooxygenase-2 (5-LOX/COX-2) dual inhibitor 7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 and the effect of DHDMBF30 on human pancreatic cancer in a nude mouse model. METHODS: Investigate the effect of 5-LOX/COX-2 dual inhibitor DHDMBF30 on proliferation and apoptosis of the pancreatic cancer cell line Capan-2 by RT-PCR, MTT assay, FCM and electron microscope. Cell line Capan-2 was inoculated percutaneously on the outer thigh of 12 nude mice. The VEGF mRNA of transplantation tumor was detected by RT-PCR. RESULTS: DHDMBF30 inhibits the proliferation of cell line Capan2, reduces the expression of 5-LOX, COX-2 and VEGF. After Capan2 was treated with DHDMBF30, we found that the apoptosis peak of the experimental group was significantly higher than that of the contrast group (3.08 +/- 1.89 vs 27.67 +/- 0.52, P < 0.001). The tumor weight of the DHDMBF30 group was significantly lower than PBS control groups (1.35 +/- 0.47 vs 2.92 +/- 0.73, P < 0.01). Expression of VEGF in the DHDMBF30 group was significantly decreased. CONCLUSION: DHDMBF30 inhibits the proliferation of the pancreatic cell line Capan2, and induces apoptosis and inhibits the growth of pancreatic cancer in nude mice.

The novel inhibitory effect of Pangdahai on fatty acid synthase.

Recently, animal fatty acid synthase (FASN) is reported as a potential therapeutic target for obesity and cancer. Considerable interest has been developed in searching for novel inhibitors of this enzyme. An extract from Pangdahai has been found to inhibit FASN in both reversible and irreversible manners, with an IC(50) of 3.5 microg/ml and an apparent inactivation rate constant of k(obs) of 2.2 x 10(-3)/min. The kinetic study showed that the Pangdahai extract inhibited the overall FASN reaction uncompetitively with acetyl-CoA, but it presented in a mixed manner both with NADPH and with malonyl-CoA. Its major reacting site on this enzyme, as compared between two IC(50) values, is not in the beta-ketoacyl reduction domain. A weight reducing experiment in rats showed that the extract significantly reduced the adipose and food intake, but in view of statistics (P < 0.05), a correlation between the reductions in the adipose and in the food consumption and the inhibition of hepatic FASN could not be established. Three known flavonoid compounds were isolated from the extract and the structure-activity relationship was discussed.