Matrine,oxymatrine, and compound Kushen injection from the roots of Sophora flavescens: an overview of their anticancer activities

In the present review, we updated current information on the chemistry, contents, and anticancer properties of matrine (MT), oxymatrine (OMT), and compound Kushen injection (CKI). The anticancer properties were focused on lung, breast, and liver cancer cells because they are most susceptible. Sources of information were from Google, Google Scholar, PubMed, PubMed Central, Science Direct, PubChem, J-Stage, Directory of Open Access Journals (DOAJ), and China National Knowledge Infrastructure (CNKI). Reference was also made on botanical websites, such as Flora of China and World Flora Online. MT and OMT are dominant quinolizidine alkaloids from the roots of Sophora flavescens (Kushen) of the family Fabaceae. Against lung, breast, and liver cancer cells, MT and OMT inhibit cell proliferation; induce cell cycle arrest, apoptosis, and autophagy; restrict angiogenesis; and inhibit cell metastasis, invasion, and migration. The processes involve various molecular targets and signaling pathways. CKI is a traditional Chinese medicine (TCM) composed of root extracts of S. flavescens and Smilax glabra (Baituling) of the family Smilacaceae. With MT and OMT as major components, CKI has been approved for the treatment of cancer in China more than 20 years ago. In recent years, systematic reviews and meta-analysis have been undertaken to evaluate the anticancer effects of CKI. When CKI is used alone and in combination with chemotherapy of western medicine, there is much to be learned concerning their interactions besides their individual and integrated efficacy. Some perspectives of MT, OMT, and CKI are discussed, and their suggestions for future research are provided.     

The use of Trichomonas vaginalis purine nucleoside phosphorylase to activate fludarabine in the treatment of solid tumors

Treatment with fludarabine phosphate (9-β-D-arabinofuranosyl-2-F-adenine 5′-phosphate, F-araAMP) leads to regressions and cures of human tumor xenografts that express Escherichia coli purine nucleoside phosphorylase (EcPNP). This occurs despite the fact that fludarabine (F-araA) is a relatively poor substrate for EcPNP, and is cleaved to liberate 2-fluoroadenine at a rate only 0.3% that of the natural E. coli PNP substrate, adenosine. In this study, we investigated a panel of naturally occurring PNPs to identify more efficient enzymes that may be suitable for metabolizing F-araA as part of experimental cancer therapy. We show that Trichomonas vaginalis PNP (TvPNP) cleaves F-araA with a catalytic efficiency 25-fold greater than the prototypic E. coli enzyme. Cellular extracts from human glioma cells (D54) transduced with lentivirus stably expressing TvPNP (D54/TvPNP) were found to cleave F-araA at a rate similar to extracts from D54 cells expressing EcPNP, although much less enzyme was expressed per cell in the TvPNP transduced condition. As a test of safety and efficacy using TvPNP, human head and neck squamous cell carcinoma (FaDu) xenografts expressing TvPNP were studied in nude mice and shown to exhibit robust tumor regressions, albeit with partial weight loss that resolved post-therapy. F-araAMP was also a very effective treatment for mice bearing D54/TvPNP xenografts in which approximately 10% of tumor cells expressed the enzyme, indicating pronounced ability to kill non-transduced tumor cells (high bystander activity). Moreover, F-araAMP demonstrated activity against D54 tumors injected with an E1, E3 deleted adenoviral vector encoding TvPNP. In that setting, despite higher F-araA cleavage activity using TvPNP, tumor responses were similar to those obtained with EcPNP, indicating factors other than F-Ade production may limit regressions of the D54 murine xenograft model. Our results establish that TvPNP is a favorable enzyme for activating F-araA, and support further studies in combination with F-araAMP for difficult-to-treat human cancers.     

Risk of Stroke-Associated Pneumonia With Acid-Suppressive Drugs: A Population-Based Cohort Study

Acid-suppressive drugs, including histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), are common medications used for treating upper gastrointestinal tract disorders. However, acid-suppressive drugs have been reported to increase the risk of pneumonia in numerous disease populations. However, the relationship between acid-suppressive drugs and stroke-associated pneumonia (SAP) remains controversial.The purpose of this study was to investigate the association between acid-suppressive drug usage and pneumonia among patients with stroke by using a nationwide data set.A population-based cohort study was conducted using a data set from the Taiwanese National Health Insurance Research Database. Data on patients with new-onset stroke from 2010 to 2011 were collected. Patients with and without acid-suppressive drug usage were followed up to identify the occurrence of any type of pneumonia. We estimated the adjusted hazard ratios (HRs) by using the Cox proportional hazards model.The study cohort comprised 7965 patients with new-onset stroke. The incidence of pneumonia was 6.9% (552/7965) and more than 40% (225/552) of patients developed pneumonia within 3 months after an acute stroke. Acid-suppressive drug usage was an independent risk factor of pneumonia. The adjusted HR for the risk of pneumonia in patients with new-onset stroke using acid-suppressive drugs was 1.44 (95% confidence interval [CI] = 1.18–1.75, P < 0.01). Only PPI usage increased risk of chronic SAP (adjusted HR = 1.46, 95% CI = 1.04–2.05).Acid-suppressive drug usage was associated with a slightly increased risk of SAP. Physicians should exercise caution when prescribing acid-suppressive drugs to patients with stroke, particularly at the chronic stage.     

Ebola Virus RNA Stability in Human Blood and Urine in West Africa’s Environmental Conditions

We evaluated RNA stability of Ebola virus in EDTA blood and urine samples collected from infected patients and stored in West Africa’s environmental conditions. In blood, RNA was stable for at least 18 days when initial cycle threshold values were <30, but in urine, RNA degradation occurred more quickly.     

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.