Background and Objectives: The association between fiber intake and pancreatic cancer risk is conflicting and poorly explored. The aim of study was to investigate the association between dietary ...fiber intake and the risk of pancreatic cancer by conducting a meta-analysis of epidemiological studies.
Methods and Study Design: Systematic search of PubMed and Embase databases up to April 2015 were conducted to identify relevant studies. Adjusted odds ratios (ORs) were combined using random-effects models to assess the risk of pancreatic cancer when comparing extreme categories of fiber intake. Dose-response meta-analysis was performed for studies reporting categorical risk estimates for at least 3 exposure levels.
Results: One cohort and thirteen case-control studies were identified. The overall analysis revealed a strong inverse association between risk of pancreatic cancer and high fiber intake (OR 0.52; 95% CI 0.44-0.61). No publication bias was detected by Egger's or Begg's test. The dose-response analyses showed that the summary OR for an increment of 10 g daily intake of fiber was 0.88 (0.84 to 0.92).
Conclusion: A high intake of dietary fiber was associated with a reduced risk of pancreatic cancer. Further well-designed prospective studies are warranted to confirm the inverse association and to identify the dietary fiber types involved.
The incidence of primary spinal cord melanoma (PSCM) is rare. Several case series and case reports have been published in the literature. However, the predictive factors of PSCM survival and ...management options are not discussed in detail.
We present a case of PSCM; total resection was achieved and chemotherapy was given postoperatively. A comprehensive search was performed on PubMed's electronic database using the words “primary spinal cord melanoma.” Survival rates with various gender, location, treatment, and metastasis condition were collected from the published articles and analyzed.
Fifty nine cases were eligible for the survival analysis; 54% were male and 46% were female. Patient sex did not influence overall survival. The most common location was the thorax. Patient sex and tumor location did not influence overall survival. The major presenting symptoms were weakness and paresthesia of the extremities. Metastasis or dissemination was noted in 45.16% of 31 patients. In the Kaplan-Meier survival analysis, patients who had metastasis had the worst prognosis. Extent of resection was not related to mortality. Patients who received surgery and surgery with adjuvant therapy had a better median survival than did those who had adjuvant therapy alone. Prognosis was worst in those patients who underwent only adjuvant therapy without surgery (5 months).
Surgery is the first treatment of choice in treating PSCM. The goal of tumor resection is to reduce symptoms. Adjuvant therapy after surgery had a beneficial effect on limiting the metastasis.
•The incidence of primary spinal cord melanoma (PSCM) is very rare.•Surgery is the first treatment of choice in treating PSCM.•The goal of tumor resection is to reduce the symptoms.•Adjuvant therapy after surgery had a beneficial effect in limiting the metastasis.•Metastasis is the factor predictive of poor OS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Epstein-Barr virus (EBV) is a human herpesvirus that latently infects approximately 95% of adults and is associated with a spectrum of human diseases including Infectious Mononucleosis and a variety ...of malignancies. However, understanding the pathogenesis, vaccines and antiviral drugs for EBV-associated disease has been hampered by the lack of suitable animal models. Tree shrew is a novel laboratory animal with a close phylogenetic relationship to primates, which is a critical advantage for many animal models for human disease, especially viral infections. Herein, we first identified the key residues in the CR2 receptor that bind the gp350 protein and facilitate viral entry. We found that tree shrew shares 100% sequence identity with humans in these residues, which is much higher than rabbits (50%) and rats (25%).
analysis showed that B lymphocytes of tree shrews are susceptible to EBV infection and replication, as well as EBV-enhanced cell proliferation. Moreover, results of
experiments show that EBV infection in tree shrews resembles EBV infection in humans. The infected animals exhibited transient fever and loss of weight accompanied by neutropenia and high viremia levels during the acute phase of the viral infection. Thereafter, tree shrews acted as asymptomatic carriers of the virus in most cases that EBV-related protein could be detected in blood and tissues. However, a resurgence of EBV infection occurred at 49 dpi. Nanopore transcriptomic sequencing of peripheral blood in EBV-infected animals revealed the dynamic changes in biological processes occurring during EBV primary infection. Importantly, we find that neutrophil function was impaired in tree shrew model as well as human Infectious Mononucleosis datasets (GSE85599 and GSE45918). In addition, retrospective case reviews suggested that neutropenia may play an important role in EBV escaping host innate immune response, leading to long-term latent infection. Our findings demonstrated that tree shrew is a suitable animal model to evaluate the mechanisms of EBV infection, and for developing vaccines and therapeutic drugs against EBV.
Fructose-1,6-bisphosphatase (FBPase), as a key rate-limiting enzyme in the gluconeogenesis (GNG) pathway, represents a practical therapeutic strategy for type 2 diabetes (T2D). Our previous work ...first identified cysteine residue 128 (C128) was an important allosteric site in the structure of FBPase, while pharmacologically targeting C128 attenuated the catalytic ability of FBPase. Herein, ten approved cysteine covalent drugs were selected for exploring FBPase inhibitory activities, and the alcohol deterrent disulfiram displayed superior inhibitory efficacy among those drugs. Based on the structure of lead compound disulfiram, 58 disulfide-derived compounds were designed and synthesized for investigating FBPase inhibitory activities. Optimal compound 3a exhibited significant FBPase inhibition and glucose-lowering efficacy in vitro and in vivo. Furthermore, 3a covalently modified the C128 site, and then regulated the N125–S124–S123 allosteric pathway of FBPase in mechanism. In summary, 3a has the potential to be a novel FBPase inhibitor for T2D therapy.
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•Alcohol deterrent disulfiram was repurposed as FBPase covalent inhibitor.•Derivative 3a showed potent FBPase inhibition activity both in vitro and in vivo.•Derivative 3a could ameliorate glucose tolerance both in ICR mice and diabetic db/db mice.•Derivative 3a covalently modified the C128 site of FBPase and affected the catalytic activity of FBPase.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
RNA activation is a promising discovery that promoter-targeted double-stranded small RNAs, termed small activating RNAs (saRNAs), can induce gene expression, which represents a novel approach to gene ...over-expression without traditional vector-based systems. PAWR is a tumor suppressing gene essential for apoptosis and a cancer-selective target for cancer therapeutics. Here our study identified synthetic saRNAs that could activate the expression of PAWR in human cancer cells. Functional analysis of PAWR induction revealed that saRNA treatment induced growth inhibition and apoptosis of cancer cells, and predictably modulated the expression of known downstream target gene Bcl-2. New functional saRNAs can also be harvested by one or two-base shifting of the original target sites. Chromatin immunoprecipitation assays indicated that activation of PAWR is accompanied by reduced dimethylation at histone H3K9 and increased dimethylation at histone H3K4. Moreover, the existence of transcripts in PAWR promoter was detected but its relationship with RNA activation needs more lucubration. These data have enlarged the gene pool of RNAa and hold great promise as an alternative for PAWR-targeted therapeutics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The aim of the present study was to collect published studies and compare the diagnostic accuracy of different markers for nasopharyngeal carcinoma (NPC). We systematically searched PubMed/MEDLINE, ...EMBASE, Cochrane Library, CNKI, and Wanfang for relevant studies until April 29, 2020. The revised Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was used to evaluate the methodological quality of the studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) values of the diagnostic markers were combined by a bivariate mixed effect model to compare their diagnostic accuracy. We explored heterogeneity through meta-regression. In total, 244 records from 101 articles were included, with 49,432 total study subjects (13,109 cases and 36,323 controls). EA-IgG, Zta-IgG, and Epstein-Barr virus (EBV) DNA load in non-invasive nasopharyngeal brushings (EBV-DNA brushings) have both high sensitivity and specificity, EBNA1-IgG and VCA-IgG have only high sensitivity, and EBNA1-IgA, VCA-IgA, Rta-IgG, Zta-IgA, HSP70, and serum sialic acid (SA) have only high specificity. The bivariate mixed effect model of EA-IgA had a significant threshold effect. Meta-regression analysis showed that ethnicity affected EBNA1-IgA, EBNA1-IgG, VCA-IgA, and EBV DNA load in plasma, test methods affected EBNA1-IgG, publication year affected VCA-IgA, and sample size affected Rta-IgG. There was significant publication bias for VCA-IgA and Rta-IgG (P < 0.05). EA-IgG, Zta-IgG, and EBV-DNA brushings are good diagnostic markers for NPC. The diagnostic accuracy was influenced by publication year, sample size, test methods, and ethnicity.
Resveratrol, which is highly concentrated in the skin of grapes and is abundant in red wine, has been demonstrated to account for several beneficial properties, including antioxidant, anticoagulant, ...anti‐inflammatory and anticancer effects. Taxol is a microtubule‐stabilizing drug that has been extensively used as effective chemotherapeutic agents in the treatment of solid tumors. Here, we investigated whether the combination of the two compounds would yield increased antitumor efficacy in human cancer cells. Unexpectedly, resveratrol effectively prevented tumor cell death induced by taxol in 5637 bladder cancer cells. This pronounced antagonistic function of resveratrol against taxol was associated with changes in multiple signal transduction pathways, but not with tubulin polymerization. Importantly, cell cycle analysis showed that resveratrol prevented the cells from entering into mitosis, the phase in which taxol exerts its action. Furthermore, resveratrol blocked the cytotoxic effects of vinblastine but not cisplatin in 5637 cells. Interestingly, resveratrol pre‐treatment followed by taxol resulted in synergistic cytotoxicity. Finally, we extended our studies to various human cancer cell lines. Taken together, our results indicate that resveratrol may have the potential to negate the therapeutic efficacy of taxol and suggest that consumption of resveratrol‐related products may be contraindicated during cancer therapy with taxol.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In this study, we performed RNA sequencing of Prx II
+/+
and Prx II
−/−
dermal mesenchymal stem cells (DMSCs) to identify differentially expressed genes (DEGs). To explore the role of Prx II in ...DMSCs, we performed Gene Ontology analysis of the DEGs. The results showed that the DEGs were mainly involved in the biological processes of cell migration, intercellular adhesion, and coordination of the regulation of stem cell homing. Through the construction of protein–protein interaction network, four hub genes
Cd274
,
Ccl5
,
Il1b
, and
Stat1
involved in cell adhesion and cell homing were screened. Quantitative reverse transcription PCR analysis showed that
Cd274
,
Ccl5
,
Il1b
, and
Stat1
were down regulated in Prx II
−/−
DMSCs. miRwalk and Starbase databases were further used to screen the upstream molecules miRNA and lncRNA regulating hub gene. Prx II was found to be involved in the regulation of stem cell homing via the Tctn2/miR-351/Stat1/Il1b axis. Thus, we demonstrated that Prx II is a key molecule in the regulation of the homing ability of DMSCs. Our results provide a theoretical foundation for improving the homing ability of DMSCs by targeting Prx II.
Studies investigating the association of milk consumption with bladder cancer risk have reported inconsistent findings. We conducted a meta-analysis of published cohort and case-control studies to ...pool the risk estimates of the association between milk intake and bladder cancer. We quantified associations with bladder cancer using meta-analysis of odds ratio (OR) associated with the highest vs. the lowest category of milk intake using fixed- or random-effect models depending on the heterogeneity of effects among studies. Nineteen cohort and case-control studies were eligible for inclusion. High milk intake was significantly associated with decreased risk of bladder cancer (OR, 0.84; 95% CI, 0.71-0.97) when comparing the highest with the lowest category of milk intake. The inverse association was stronger in Asia (OR, 0.60; 95% CI, 0.40-0.81) than North America (OR, 0.89; 95% CI, 0.76-1.03), and no association was observed in Europe (OR, 1.05; 95% CI, 0.85-1.26). This relationship also varied significantly by specific dairy products. Our results suggest that milk may be related to the reduction of bladder cancer risk. Further studies need to clarify the biological mechanisms.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Cancer metastasis is a highly coordinated and dynamic multistep process in which cancer cells interact with a variety of host cells. Morphological studies have documented the association of ...circulating tumor cells with host platelets, where a surface coating of platelets protects tumor cells from mechanical trauma and the immune system. Cantharidin is an active constituent of mylabris, a traditional Chinese medicine. Cantharidin and norcantharidin are potent protein phosphatase 2A (PP2A) inhibitors that exhibit in vitro and in vivo antitumor activity against several types of cancer, including breast cancer. We investigated whether cantharidin and norcantharidin could repress the ability of MCF-7 breast cancer cells to adhere to platelets. Using MTT, clone formation, apoptosis, adhesion and wound-healing assays, we found that cantharidin and norcantharidin induced apoptosis and repressed MCF-7 cell growth, adhesion and migration. Moreover, we developed a flow cytometry-based analysis of tumor cell adhesion to platelets. We proved that cantharidin and norcantharidin repressed MCF-7 cell adhesion to platelets through downregulation of α2 integrin, an adhesion molecule present on the surface of cancer cells. The repression of α2 integrin expression was found to be executed through the protein kinase C pathway, the activation of which could have been due to PP2A inhibition.
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