Comparison of rivaroxaban and dalteparin for the long-term treatment of venous thromboembolism in patients with gynecologic cancers.

OBJECTIVES: Two randomized, controlled studies comparing outcomes in patients treated with direct oral anticoagulants or low-molecular weight heparin for cancer-associated venous thromboembolism (VTE) have previously been performed. However, gynecologic cancers accounted for approximately 10% of the study populations. We compared the outcomes of patients with primary gynecological cancers who were treated for cancer-associated VTE with either rivaroxaban or dalteparin. METHODS: The 162 eligible patients with gynecologic cancers who were treated with either dalteparin (n=60) or rivaroxaban (n=102) were reviewed. The primary outcome was a composite event, which included recurrence or clinically relevant bleeding events during the therapeutic period. Secondary outcomes were recurrence, clinically relevant bleeding events, and mortality. RESULTS: During the therapeutic period, there were no significant differences between the groups in the proportion of composite events, recurrence, or clinically relevant bleeding. Multivariate analysis using the Cox proportional hazards model also showed no significant difference in the number of composite events and clinically relevant bleeding between the groups. In the rivaroxaban group, 44.0% of patients experienced gastrointestinal bleeding and 24.0% experienced urinary tract bleeding. In the dalteparin group, bleeding was most common in the urinary tract (44.4%) and at the injection site (22.2%). CONCLUSION: In this study, although there were no significant differences in effectiveness or safety between the rivaroxaban and dalteparin groups, rivaroxaban use was associated with a higher rate of clinically relevant bleeding than dalteparin. Therefore, caution should be taken when prescribing rivaroxaban for gynecologic cancer-associated VTE and bleeding events should be carefully monitored.

Rivaroxaban versus Low-Molecular-Weight Heparin for Venous Thromboembolism in Gastrointestinal and Pancreatobiliary Cancer.

BACKGROUND: Low-molecular-weight heparin (LMWH) is the standard treatment for venous thromboembolism (VTE) in patients with active cancer. However, use of factor Xa inhibitors, such as rivaroxaban, is increasing on the basis of limited clinical evidence. The present single-center study compared the incidence of bleeding and other treatment outcomes in gastrointestinal and pancreatobiliary cancer (GI tract cancer) patients administered rivaroxaban or LMWH for the treatment of VTE. METHODS: Retrospective data from 281 GI tract cancer patients who were treated for VTE with rivaroxaban (n = 78) or LMWH (n = 203) between 1 January 2012 and 31 December 2016, were analyzed. Primary end-point was the incidence of major and clinically relevant bleeding. Secondary outcomes included the incidence of recurrent VTE and mortality. RESULTS: Clinically relevant bleeding occurred in 19 patients (24.4%) in the rivaroxaban group and 31 (15.3%) in the LMWH group (P = 0.074). No inter-group difference was observed for rate of VTE recurrence (3.8% with rivaroxaban vs. 3.9% with LMWH; P > 0.999) or incidence of major bleeding (5.1% with rivaroxaban vs. 8.9% with LMWH; P = 0.296). Multivariate Cox proportional hazards analysis for age, cancer type, metastasis, history of chemotherapy or recent surgery, and Eastern Cooperative Oncology Group performance status revealed a 1.904-fold higher risk of bleeding with rivaroxaban than LMWH (1.031-3.516; P = 0.040). No significant inter-group difference was found in terms of hazard ratio for all-cause mortality. CONCLUSION: Compared to LMWH, rivaroxaban was associated with a higher incidence of clinically relevant bleeding in GI tract cancer patients presenting with VTE.

A Retrospective Study on Efficacy and Safety of Rivaroxaban and Dalteparin for Long-Term Treatment of Venous Thromboembolism in Patients with Lung Cancer.

BACKGROUND: Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES: We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS: A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS: The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS: There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

Nardostachys jatamansi Ethanol Extract Ameliorates Aß42 Cytotoxicity.

The Nardostachys jatamansi DC (NJ) root has been used as a sedative or analgesic to treat neurological symptoms and pain in traditional Korean medicine. Here, we investigate the potential effects of NJ on Alzheimer's disease (AD) and reveal the molecular mechanism through which NJ exerts its effects. The neuroprotective effect of the NJ root ethanol extract against ß amyloid (Aß) toxicity was examined in vitro using a cell culture system and in vivo using a Drosophila AD model. The NJ extract and chlorogenic acid, a major component of NJ, inhibited Aß-induced cell death in SH-SY5Y cells. Moreover, the NJ extract rescued the neurological phenotypes of the Aß42-expressing flies (decreased survival and pupariation rate and a locomotor defect) and suppressed Aß42-induced cell death in the brain. We also found that NJ extract intake reduced glial cell number, reactive oxygen species level, extracellular-signal-regulated kinase (ERK) phosphorylation, and nitric oxide level in Aß42-expressing flies, without affecting Aß accumulation. These data suggest that the neuroprotective activity of NJ might be associated with its antioxidant and anti-inflammatory properties, as well as its inhibitory action against ERK signaling; thus, NJ is a promising medicinal plant for the development of AD treatment.

Terpenes from Forests and Human Health.

Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.

Coriandrum sativum Suppresses Aß42-Induced ROS Increases, Glial Cell Proliferation, and ERK Activation.

Alzheimer's disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD. In the present study, we investigated the neuroprotective effects of an ethanol extract of Coriandrum sativum (C. sativum) leaves on A[Formula: see text] cytotoxicity and examined the molecular mechanisms underlying the beneficial effects. Although recent studies have shown the benefits of the inhalation of C. sativum oil in an animal model of AD, the detailed molecular mechanisms by which C. sativum exerts its neuroprotective effects are unclear. Here, we found that treatment with C. sativum extract increased the survival of both A[Formula: see text]-treated mammalian cells and [Formula: see text]42-expressing flies. Moreover, C. sativum extract intake suppressed [Formula: see text]-induced cell death in the larval imaginal disc and brain without affecting A[Formula: see text]42 expression and accumulation. Interestingly, the increases in reactive oxygen species levels and glial cell number in AD model flies were reduced by C. sativum extract intake. Additionally, C. sativum extract inhibited the epidermal growth factor receptor- and A[Formula: see text]-induced phosphorylation of extracellular signal-regulated kinase (ERK). The constitutively active form of ERK abolished the protective function of C. sativum extract against the [Formula: see text]-induced eye defect phenotype in Drosophila. Taken together, these results suggest that C. sativum leaves have antioxidant, anti-inflammatory, and ERK signaling inhibitory properties that are beneficial for patients with AD.

In Vivo Screening of Traditional Medicinal Plants for Neuroprotective Activity against Aß42 Cytotoxicity by Using Drosophila Models of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder, characterized by progressive neuronal loss with amyloid ß-peptide (Aß) plaques. Despite several drugs currently used to treat AD, their beneficial effects on AD progress remains under debate. Here, we established a rapid in vivo screening system using Drosophila AD models to assess the neuroprotective activities of medicinal plants that have been used in traditional Chinese medicine. Among 23 medicinal plants tested, the extracts from five plants, Coriandrum sativum, Nardostachys jatamansi, Polygonum multiflorum (P. multiflorum), Rehmannia glutinosa, and Sorbus commixta (S. commixta), showed protective effects against the Aß42 neurotoxicity. We further characterized the neuroprotective activity of ethanol extracts from P. multiflorum and S. commixta. Aß42-expressing flies that we used showed AD neurological phenotypes, such as decreased survival and motility and increased cell death and reactive oxygen species level. However, feeding these flies extracts from P. multiflorum or S. commixta showed strong suppression of such phenotypes. Similar results were observed in human cells, so that the treatment of P. multiflorum and S. commixta extracts increased the viability of Aß-treated SH-SY5Y cells. Moreover, 2,3,5,4'-tetrahydroxystilbene-2-O-ß-D-glucoside, one of the main constituents of P. multiflorum, also showed similar protective activity against Aß42 cytotoxicity in both Drosophila and human cells. Taken together, our results suggest that both P. multiflorum and S. commixta have therapeutic potential for the treatment of neurodegenerative diseases, such as AD.

Characteristics of Korean ginseng varieties of Gumpoong, Sunun, Sunpoong, Sunone, Cheongsun, and Sunhyang.

BACKGROUND: Ginseng (Panax ginseng Meyer) is an important medicinal herbs in Asia. However, ginseng varieties are less developed. METHOD: To developed ginseng varieties, a pure line selection method was applied in this study. RESULTS: Gumpoong was testing of 4-yr-old specimens in 2002, the proportions of the below-ground roots that were rusty colored for Gumpoong was 1.29 in Daejeon and 1.45 in Eumseong, whereas the proportions for its yellow berry variant were 2.60 and 2.45 in the two regions, respectively. Thus the Gumpoong was resistant to root rust. Sunpoong has a high yielding property. Its average root weight is 70.6 g for 6-yr-old roots. Its yield is 2.9 kg/1.62m(2) and the rate of heaven- and earth-grade product is 20.9%, which is very high compared to 9.4% for Yunpoong. Sunone is resistance to root rot and the survival rate of 4-yr-old roots was 44.4% in 1997, whereas that of the violet-stem variant landrace was 21.7%. Sunhyang has content of arginyl-fructosyl-glucose (AFG), which produces the unique scent of red ginseng, is 95.1 µmol/g and greater than the 30.8 µmol/g of Chunpoong in 6-yr-old plants. Sunun and Cheongsun are being nurtured to protect genetic resources. CONCLUSION: Developed ginsneg varieties will be used as the basis for the protection of genetic resources and breeding.

Suppressive effects of SuHeXiang Wan on amyloid-ß42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease.

SuHeXiang Wan (SHXW), a Chinese traditional medicine, has been used to treat infantile convulsions, seizures and strokes. Previously, we reported that modified SHXW, called KSOP1009, suppressed the hyper-activation of c-Jun N-terminal kinase (JNK) and Alzheimer's disease (AD)-like phenotypes in amyloid-ß42 (Aß42)-expressing Drosophila AD models. In the present study, we, further, investigated the detailed mechanism by which KSOP1009 suppresses the AD-like phenotypes of the model flies. As seen in the brains of AD patients, pan-neuronal expression of Aß42 in Drosophila increased activation of extracellular signal-regulated kinase (ERK), which was monitored by its phosphorylation level, and the number of glial cells in the brain. Suppression of caspase activity did not affect these phenomena, suggesting that Aß42 induces ERK activation and glial cell proliferation independently of apoptotic processes. KSOP1009 intake significantly reduced the level of ERK activation and the number of glial cells. Moreover, KSOP1009 intake also effectively decreased the defects in the wing vein formation induced by Epidermal growth factor receptor (Egfr) overexpression in fly wings, suggesting that it may contain an inhibitory substance that inhibits the EGFR/ERK signaling pathway. In addition, the Aß42-induced locomotive defect was partially rescued by inhibition of the elevated ERK activity through its antagonistic drug treatment. Taken together, these results suggest that KSOP1009 exerts its therapeutic effect by inhibiting the EGFR/ERK pathway and glial cell proliferation and by suppressing the JNK pathway and apoptosis.

Neuroprotective effect of SuHeXiang Wan in Drosophila models of Alzheimer's disease.

AIM OF THE STUDY: SuHeXiang Wan (SHXW) is a Chinese traditional medicinal prescription that consists of 15 crude herbs. SHXW has been used to treat central nervous depression, seizures, infantile convulsion and stroke, and its essential oil has been shown to have anticonvulsant and antioxidative activity. The goal of this study was to investigate the beneficial effects of SHXW on the neurological phenotypes of Drosophila AD models. MATERIALS AND METHODS: We evaluated the effects of a modified SHXW (called KSOP1009) intake on the AD-like phenotypes of Drosophila AD models, which express human Aß42 in their developing eyes or neurons. RESULTS: When the flies were kept on the media containing 5 µg/ml of KSOP1009 extract, Aß42-induced eye degeneration, apoptosis, and the locomotive dysfunctions were strongly suppressed. However, Aß42 fibril deposits in the Aß42 overexpressing model were not affected by treatment with KSOP1009 extract. Conversely, KSOP1009 extract intake significantly suppressed the constitutive active form of hemipterous, a JNK activator, while it induced eye degeneration and JNK activation, which has been recognized as an important mediator of Aß42-associated neuro-cytotoxicity. CONCLUSIONS: In conclusion, the results of this study suggest that KSOP1009 confers a therapeutic potential to AD-like pathology of Aß42 overexpressing Drosophila model via suppression of the hyperactivation of JNK activity and apoptosis.

Desiccation sensitivity and cryopreservation of Korean ginseng seeds.

Korean ginseng germplasm is maintained as clonal germplasm since there is no practical method for long-term seed conservation. The aim of this study was to establish a cryopreservation protocol for Korean ginseng seeds. Desiccation of undehisced ginseng seeds to a moisture content (MC) of 7.1 % did not decrease their dehiscence and germination. After cryopreservation, the dehiscence percentage of desiccated seeds decreased for MC above 12.5%; it was 26% for 22.6% seed MC and nil for 41.9% seed MC. Germination percentage did not decrease significantly between 12.5-22.6% seed MC, while germination percentage of dehisced seeds decreased below 7.2% MC, reaching 25.8% at 3.8% MC. After cryopreservation, the germination percentage decreased from 90.5-92.9% at 8.3-10.6% MC to 84.8% at 12.5% MC. At MCs below 8.3%, germination rapidly decreased from 85.0% at 7.2% MC to 34.9% at 5.3% MC. Therefore, the hydration window for cryopreservation of ginseng seeds is around 8-11% MC. Undehisced Korean ginseng seeds were characterized by their high lipid and protein content (lipids, 42.6% FW; proteins, 41.0% FW). When using thermal analysis, during the cooling phase, exothermic ice crystallization peaks were observed with dehisced ginseng seeds above 13.5% MCs (3.3 J/g FW). A second crystallization peak was detected following ice crystallization peaks.