Building a Clinically Relevant Risk Model: Predicting Risk of a Potentially Preventable Acute Care Visit for Patients Starting Antineoplastic Treatment.

PURPOSE: To create a risk prediction model that identifies patients at high risk for a potentially preventable acute care visit (PPACV). PATIENTS AND METHODS: We developed a risk model that used electronic medical record data from initial visit to first antineoplastic administration for new patients at Memorial Sloan Kettering Cancer Center from January 2014 to September 2018. The final time-weighted least absolute shrinkage and selection operator model was chosen on the basis of clinical and statistical significance. The model was refined to predict risk on the basis of 270 clinically relevant data features spanning sociodemographics, malignancy and treatment characteristics, laboratory results, medical and social history, medications, and prior acute care encounters. The binary dependent variable was occurrence of a PPACV within the first 6 months of treatment. There were 8,067 observations for new-start antineoplastic therapy in our training set, 1,211 in the validation set, and 1,294 in the testing set. RESULTS: A total of 3,727 patients experienced a PPACV within 6 months of treatment start. Specific features that determined risk were surfaced in a web application, riskExplorer, to enable clinician review of patient-specific risk. The positive predictive value of a PPACV among patients in the top quartile of model risk was 42%. This quartile accounted for 35% of patients with PPACVs and 51% of potentially preventable inpatient bed days. The model C-statistic was 0.65. CONCLUSION: Our clinically relevant model identified the patients responsible for 35% of PPACVs and more than half of the inpatient beds used by the cohort. Additional research is needed to determine whether targeting these high-risk patients with symptom management interventions could improve care delivery by reducing PPACVs.

The Use of Technology to Support Precision Health in Nursing Science.

PURPOSE: This article outlines how current nursing research can utilize technology to advance symptom and self-management science for precision health and provides a roadmap for the development and use of technologies designed for this purpose. APPROACH: At the 2018 annual conference of the National Institute of Nursing Research (NINR) Research Centers, nursing and interdisciplinary scientists discussed the use of technology to support precision health in nursing research projects and programs of study. Key themes derived from the presentations and discussion were summarized to create a proposed roadmap for advancement of technologies to support health and well-being. CONCLUSIONS: Technology to support precision health must be centered on the user and designed to be desirable, feasible, and viable. The proposed roadmap is composed of five iterative steps for the development, testing, and implementation of technology-based/enhanced self-management interventions. These steps are (a) contextual inquiry, focused on the relationships among humans, and the tools and equipment used in day-to-day life; (b) value specification, translating end-user values into end-user requirements; (c) design, verifying that the technology/device can be created and developing the prototype(s); (d) operationalization, testing the intervention in a real-world setting; and (e) summative evaluation, collecting and analyzing viability metrics, including process data, to evaluate whether the technology and the intervention have the desired effect. CLINICAL RELEVANCE: Interventions using technology are increasingly popular in precision health. Use of a standard multistep process for the development and testing of technology is essential.

Using air-quality feedback to encourage disadvantaged parents to create a smoke-free home: Results from a randomised controlled trial.

OBJECTIVE: To determine if low-cost air-quality monitors providing personalised feedback of household second-hand smoke (SHS) concentrations plus standard health service advice on SHS were more effective than standard advice in helping parents protect their child from SHS. DESIGN: A randomised controlled trial of a personalised intervention delivered to disadvantaged mothers who were exposed to SHS at home. Changes in household concentrations of fine Particulate Matter (PM2.5) were the primary outcome. METHODS: Air-quality monitors measured household PM2.5 concentrations over approximately 6 days at baseline and at one-month and six-months post-intervention. Data on smoking and smoking-rules were gathered. Participants were randomised to either Group A (standard health service advice on SHS) or Group B (standard advice plus personalised air-quality feedback). Group B participants received personalised air-quality feedback after the baseline measurement and at 1-month. Both groups received air-quality feedback at 6-months. RESULTS: 120 mothers were recruited of whom 117 were randomised. Follow up was completed after 1-month in 102 and at 6-months in 78 participants. There was no statistically significant reduction in PM2.5 concentrations by either intervention type at 1-month or 6-months, nor significant differences between the two groups at 1-month (p = 0.76) and 6-month follow-up (p = 0.16). CONCLUSIONS: Neither standard advice nor standard advice plus personalised air-quality feedback were effective in reducing PM2.5 concentrations in deprived households where smoking occurred. Finding ways of identifying homes where air-quality feedback can be a useful tool to change household smoking behaviour is important to ensure resources are targeted successfully.

Misery Loves Company: Presenting Symptom Clusters to Urgent Care by Patients Receiving Antineoplastic Therapy.

PURPOSE: The Centers for Medicare & Medicaid Services (CMS) identifies suboptimal management of treatment toxicities as a care gap and proposes the measurement of hospital performance on the basis of emergency department visits for 10 common symptoms. Current management strategies do not address symptom co-occurrence. METHODS: We evaluated symptom co-occurrence in three patient cohorts that presented to a cancer hospital urgent care center in 2016. We examined both the CMS-identified symptoms and an expanded clinician-identified set defined as symptoms that could be safely managed in the outpatient setting if identified early and managed proactively. The cohorts included patients who presented with a CMS-defined symptom within 30 days of treatment, patients who presented within 30 days of treatment with a symptom from the expanded set, and patients who presented with a symptom from the expanded set within 30 days of treatment start. Symptom co-occurrence was measured by Jaccard index. A community detection algorithm was used to identify symptom clusters on the basis of a random walk process, and network visualizations were used to illustrate symptom dynamics. RESULTS: There were 6,429 presentations in the CMS symptom-defined cohort. The network analysis identified two distinct symptom clusters centered around pain and fever. In the expanded symptom cohort, there were 5,731 visits and six symptom clusters centered around fever, emesis/nausea, fatigue, deep vein thrombosis, pain, and ascites. For patients who newly initiated treatment, there were 1,154 visits and four symptom clusters centered around fever, nausea/emesis, fatigue, and deep vein thrombosis. CONCLUSION: Uncontrolled symptoms are associated with unplanned acute care. Recognition of the complexity of symptom co-occurrence can drive improved management strategies.

The Spectrum of Caregiving in Palliative Care for Serious, Advanced, Rare Diseases: Key Issues and Research Directions.

Rare diseases are often life-limiting conditions, the majority of which require constant caregiving needs. The realization of a spectrum of palliative care throughout the trajectory of rare diseases could ensure individualized and caregiver-focused approaches to the care of patients and families. In June 2015, the National Institute of Nursing Research (NINR), the lead institute at the National Institutes of Health for end-of-life research, in conjunction with the National Center for Advancing Translational Sciences, Office of Rare Diseases Research (ORDR) held an interdisciplinary workshop on the unique challenges of caregiving and palliative care in adult and pediatric rare diseases. The panel identified gaps in current knowledge, and afforded suggestions for research opportunities in palliative care science to improve the care of individuals with serious, advanced, rare diseases and their caregivers. This meeting provided an in-depth opportunity to incorporate new concepts into palliative and end-of-life care for individuals with a range of rare diseases and their caregivers. This report presents a summary of the workshop.

Precision medicine in oncology standard of care.

OBJECTIVES: To review the histologic subtypes and staging of non-small cell lung cancer and metastatic melanoma, as well as the molecular markers used to direct standard therapy. DATA SOURCES: Book chapters and journal articles from medical and nursing literature, as well as published clinical guidelines. CONCLUSION: Patients with metastatic non-small cell lung cancer and metastatic melanoma have had a paucity of treatment options, most fraught with toxicity with limited benefit. Increased understanding of tumor genetics and molecular markers has expanded the treatment options for these patients, often providing them with durable responses and improved quality of life. IMPLICATIONS FOR NURSING PRACTICE: To provide education and support to their patients, nurses caring for these patients need to understand the role that genetics and molecular markers play in directing these therapies.

Whole blueberry powder inhibits metastasis of triple negative breast cancer in a xenograft mouse model through modulation of inflammatory cytokines.

Triple negative breast cancer (TNBC) comprises approximately 15% of breast cancers and is associated with a poor prognosis. Many patients with TNBC relapse quickly and commonly develop metastases. There are no individualized targeted adjuvant or induction treatments for TNBC, and the current treatments are highly toxic. Development of chemoprevention methods using natural products would be beneficial to patients at risk of TNBC. To investigate the inhibitory effect of blueberries on inflammation-induced TNBC and identify the mechanism underlying modulation of inflammatory proteins by blueberries, we induced a proinflammatory microenvironment by feeding female MDA-MB-231 tumor-bearing mice a high fat western diet (W) with 5% whole blueberry powder (BB) and studied the effect on tumor formation and metastasis. We showed that mice fed a BB diet had significantly smaller tumors, less ulceration, and significantly less metastasis to the inguinal lymph nodes than mice fed a W diet. In BB-fed mice, serum levels of specific antiinflammatory cytokines were increased and specific cytokine expression was also altered. Together, these results suggest that blueberries may inhibit TNBC and TNBC-related metastasis by reducing inflammation via specific cytokine-driven pathways and thus reduce tumor growth and metastasis.

Whole blueberry powder modulates the growth and metastasis of MDA-MB-231 triple negative breast tumors in nude mice.

Previous studies in our laboratory demonstrated that blueberry (BB) extract exhibited antitumor activity against MDA-MB-231 triple negative breast cancer (TNBC) cells and decreased metastatic potential in vitro. The current study tested 2 doses of whole BB powder, 5 and 10% (wt:wt) in the diet, against MDA-MB-231 tumor growth in female nude mice. In this study, tumor volume was 75% lower in mice fed the 5% BB diet and 60% lower in mice fed the 10% BB diet than in control mice (P ≤ 0.05). Tumor cell proliferation (Ki-67) was lower in the 5 and 10% BB-fed mice and cell death (Caspase 3) was greater in the 10% BB-fed mice compared to control mice (P ≤ 0.05). Gene analysis of tumor tissues from the 5% BB-fed mice revealed significantly altered expression of genes important to inflammation, cancer, and metastasis, specifically, Wnt signaling, thrombospondin-2, IL-13, and IFNγ. To confirm effects on Wnt signaling, analysis of tumor tissues from 5% BB-fed mice revealed lower ß-catenin expression and glycogen synthase kinase-3ß phosphorylation with greater expression of the ß-catenin inhibitory protein adenomatous polyposis coli compared to controls. A second study tested the ability of the 5% BB diet to inhibit MDA-MB-231-luc-D3H2LN metastasis in vivo. In this study, 5% BB-fed mice developed 70% fewer liver metastases (P = 0.04) and 25% fewer lymph node metastases (P = 0.09) compared to control mice. This study demonstrates the oral antitumor and metastasis activity of whole BB powder against TNBC in mice.

Blueberry phytochemicals inhibit growth and metastatic potential of MDA-MB-231 breast cancer cells through modulation of the phosphatidylinositol 3-kinase pathway.

Dietary phytochemicals are known to exhibit a variety of anticarcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple-negative breast cancer cell lines in vitro and in vivo. Blueberry decreased cell proliferation in HCC38, HCC1937, and MDA-MB-231 cells with no effect on the nontumorigenic MCF-10A cell line. Decreased metastatic potential of MDA-MB-231 cells by blueberry was shown through inhibition of cell motility using wound-healing assays and migration through a polyethylene terephthalate membrane. Blueberry treatment decreased the activity of matrix metalloproteinase-9 and the secretion of urokinase-type plasminogen activator while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion in MDA-MB-231 conditioned medium as shown by Western blotting. Cell signaling pathways that control the expression/activation of these processes were investigated via Western blotting and reporter gene assay. Treatment with blueberry decreased phosphatidylinositol 3-kinase (PI3K)/AKT and NFkappaB activation in MDA-MB-231 cells, where protein kinase C and extracellular signal-regulated kinase (ERK) were not affected. In vivo, the efficacy of blueberry to inhibit triple-negative breast tumor growth was evaluated using the MDA-MB-231 xenograft model. Tumor weight and proliferation (Ki-67 expression) were decreased in blueberry-treated mice, where apoptosis (caspase-3 expression) was increased compared with controls. Immunohistochemical analysis of tumors from blueberry-fed mice showed decreased activation of AKT and p65 NFkappaB signaling proteins with no effect on the phosphorylation of ERK. These data illustrate the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cells through modulation of the PI3K/AKT/NFkappaB pathway.

Pomegranate ellagitannin-derived compounds exhibit antiproliferative and antiaromatase activity in breast cancer cells in vitro.

Estrogen stimulates the proliferation of breast cancer cells and the growth of estrogen-responsive tumors. The aromatase enzyme, which converts androgen to estrogen, plays a key role in breast carcinogenesis. The pomegranate fruit, a rich source of ellagitannins (ET), has attracted recent attention due to its anticancer and antiatherosclerotic properties. On consumption, pomegranate ETs hydrolyze, releasing ellagic acid, which is then converted to 3,8-dihydroxy-6H-dibenzo[b,d]pyran-6-one ("urolithin") derivatives by gut microflora. The purpose of this study was to investigate the antiaromatase activity and inhibition of testosterone-induced breast cancer cell proliferation by ET-derived compounds isolated from pomegranates. A panel of 10 ET-derived compounds including ellagic acid, gallagic acid, and urolithins A and B (and their acetylated, methylated, and sulfated analogues prepared in our laboratory) were examined for their ability to inhibit aromatase activity and testosterone-induced breast cancer cell proliferation. Using a microsomal aromatase assay, we screened the panel of ET-derived compounds and identified six with antiaromatase activity. Among these, urolithin B (UB) was shown to most effectively inhibit aromatase activity in a live cell assay. Kinetic analysis of UB showed mixed inhibition, suggesting more than one inhibitory mechanism. Proliferation assays also determined that UB significantly inhibited testosterone-induced MCF-7aro cell proliferation. The remaining test compounds also exhibited antiproliferative activity, but to a lesser degree than UB. These studies suggest that pomegranate ET-derived compounds have potential for the prevention of estrogen-responsive breast cancers.

Phytochemicals for breast cancer prevention by targeting aromatase.

Aromatase is a cytochrome P450 enzyme (CYP19) and is the rate limiting enzyme in the conversion of androgens to estrogens. Suppression of in situ estrogen production through aromatase inhibition is the current treatment strategy for hormone-responsive breast cancers. Drugs that inhibit aromatase have been developed and are currently utilized as adjuvant therapy for breast cancer in post-menopausal women with hormone dependent breast cancer. Natural compounds have been studied extensively for important biologic effects such as antioxidant, anti-tumor and anti-viral effects. A significant number of studies have also investigated the aromatase inhibitory properties of a variety of plant extracts and phytochemicals. The identification of natural compounds that inhibit aromatase could be useful both from a chemopreventive standpoint and in the development of new aromatase inhibitory drugs. This review will discuss whole food extracts and the common classes of phytochemicals which have been investigated for potential aromatase inhibitory activity. We will review reported aromatase inhibition, kinetic data and possible structural variations that may inhibit or enhance the interaction of phytochemicals with the aromatase enzyme.

Putting evidence into practice: evidence-based interventions to prevent and manage anorexia.

Anorexia is defined as an involuntary loss of appetite.Approximately 50% of newly diagnosed patients with cancer experience the symptom, which often is accompanied by weight loss and most typically associated with advanced disease.Anorexia significantly affects the clinical course of cancer; it can lead to the development or exacerbation of disease- or treatment-related symptoms, decreased functional status, and diminished quality of life.As part of the Oncology Nursing Society's Putting Evidence Into Practice initiative, a team of oncology nurses examined and evaluated published research literature for the purpose of developing an evidence-based practice resource focused on the management of cancer-related anorexia.Even though anorexia is common among newly diagnosed patients and those with advanced disease, interventions to prevent, treat, and manage the symptom are limited.The evidence revealed that only two pharmacologic interventions, corticosteroids and progestins, can be recommended for use in clinical practice, and dietary counseling was identified as likely to be effective.This article summarizes selected empirical literature on interventions used to prevent and manage anorexia in patients with cancer.Familiarity with the literature will assist oncology nurses in proactively identifying and effectively managing patients experiencing this distressing symptom.

Eugenia jambolana Lam. berry extract inhibits growth and induces apoptosis of human breast cancer but not non-tumorigenic breast cells.

The ripe purple berries of the native Indian plant Eugenia jambolana Lam., known as Jamun, are popularly consumed and available in the United States in Florida and Hawaii. Despite the growing body of data on the chemopreventive potential of edible berry extracts, there is paucity of such data for Jamun fruit. Therefore our laboratory initiated the current study with the following objectives: (1) to prepare a standardized Jamun fruit extract (JFE) for biological studies and (2) to investigate the antiproliferative and pro-apoptotic effects of JFE in estrogen dependent/aromatase positive (MCF-7aro), and estrogen independent (MDA-MB-231) breast cancer cells, and in a normal/nontumorigenic (MCF-10A) breast cell line. JFE was standardized to anthocyanin content using the pH differential method, and individual anthocyanins were identified by high performance liquid chromatography with ultraviolet (HPLC-UV) and tandem mass spectrometry (LC-MS/MS) methods. JFE contained 3.5% anthocyanins (as cyanidin-3-glucoside equivalents) which occur as diglucosides of five anthocyanidins/aglycons: delphinidin, cyanidin, petunidin, peonidin and malvidin. In the proliferation assay, JFE was most effective against MCF-7aro (IC(50) = 27 microg/mL), followed by MDA-MB-231 (IC(50) = 40 microg/mL) breast cancer cells. Importantly, JFE exhibited only mild antiproliferative effects against the normal MCF-10A (IC(50) > 100 microg/mL) breast cells. Similarly, JFE (at 200 microg/mL) exhibited pro-apoptotic effects against the MCF-7aro (p

Mechanisms of nuclear vitamin D receptor resistance in Harvey-ras-transfected cells.

The hormone 1,25 dihydroxyvitamin D (1,25(OH)(2)D) binds to the nuclear vitamin D receptor (nVDR), which heterodimerizes with retinoid X receptor alpha (RXRalpha), and this complex interacts with specific response elements [vitamin D response elements (VDREs)] to regulate gene transcription. Previous results show a significant reduction in 1,25(OH)(2)D-induced nVDR transcriptional activity in fibroblast (C3H10T1/2) cells transfected with the Harvey ras gene (ras cells) compared with parental cells. The purpose of this study was to investigate the mechanisms by which the H-ras gene interferes with nVDR transcriptional activity. Similar to the ras cells, transcriptional activity of the nVDR was reduced following induction of the H-ras gene for 9 days. The ras cells expressed similar protein levels of RXRalpha with the parent cells, and overexpression of the wild-type RXRalpha plasmid did not restore 1,25(OH)(2)D-mediated nVDR activity in ras cells. Inhibiting activation of extracellular signal-regulated kinase (ERK1/2) had no effect on nVDR activity in ras cells. Furthermore, the binding of nVDR to VDREs was reduced in 1,25(OH)(2)D-treated ras cells. In addition, neither treatment of ras cells with an inhibitor (ketoconazole) of the 1,25(OH)(2)D degradative enzyme, 24-hydroxylase, nor the protein kinase C inhibitors, bisindoylmaleimide I and Gö 6976, had an effect on nVDR activity. In contrast, inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 resulted in a 1.6-fold significant increase in the nVDR activity in the ras cells. Taken together, these results indicate that PI3K may, at least in part, mediate the suppression of the 1,25(OH)(2)D regulation of nVDR transcriptional activity by the H-ras gene, leading to reduced ability to associate with response elements.

White button mushroom (Agaricus bisporus) exhibits antiproliferative and proapoptotic properties and inhibits prostate tumor growth in athymic mice.

White button mushrooms are a widely consumed food containing phytochemicals beneficial to cancer prevention. The purpose of this research was to evaluate the effects of white button mushroom extract and its major component, conjugated linoleic acid (CLA) on prostate cancer cell lines in vitro and mushroom extract in vivo. In all cell lines tested, mushroom inhibited cell proliferation in a dose-dependent manner and induced apoptosis within 72 h of treatment. CLA inhibited proliferation in the prostate cancer cell lines in vitro. DU145 and PC3 prostate tumor size and tumor cell proliferation were decreased in nude mice treated with mushroom extract, whereas tumor cell apoptosis was increased compared to pair-fed controls. Microarray analysis of tumors identified significant changes in gene expression in the mushroom-fed mice as compared to controls. Gene network analysis identified alterations in networks involved in cell death, growth and proliferation, lipid metabolism, the TCA cycle and immune response. The data provided by this study illustrate the anticancer potential of phytochemicals in mushroom extract both in vitro and in vivo and supports the recommendation of white button mushroom as a dietary component that may aid in the prevention of prostate cancer in men.

Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro.

Berry fruits are widely consumed in our diet and have attracted much attention due to their potential human health benefits. Berries contain a diverse range of phytochemicals with biological properties such as antioxidant, anticancer, anti-neurodegerative, and anti-inflammatory activities. In the current study, extracts of six popularly consumed berries--blackberry, black raspberry, blueberry, cranberry, red raspberry and strawberry--were evaluated for their phenolic constituents using high performance liquid chromatography with ultraviolet (HPLC-UV) and electrospray ionization mass spectrometry (LC-ESI-MS) detection. The major classes of berry phenolics were anthocyanins, flavonols, flavanols, ellagitannins, gallotannins, proanthocyanidins, and phenolic acids. The berry extracts were evaluated for their ability to inhibit the growth of human oral (KB, CAL-27), breast (MCF-7), colon (HT-29, HCT116), and prostate (LNCaP) tumor cell lines at concentrations ranging from 25 to 200 micro g/mL. With increasing concentration of berry extract, increasing inhibition of cell proliferation in all of the cell lines were observed, with different degrees of potency between cell lines. The berry extracts were also evaluated for their ability to stimulate apoptosis of the COX-2 expressing colon cancer cell line, HT-29. Black raspberry and strawberry extracts showed the most significant pro-apoptotic effects against this cell line. The data provided by the current study and from other laboratories warrants further investigation into the chemopreventive and chemotherapeutic effects of berries using in vivo models.

Anti-aromatase activity of phytochemicals in white button mushrooms (Agaricus bisporus).

White button mushrooms (Agaricus bisporous) are a potential breast cancer chemopreventive agent, as they suppress aromatase activity and estrogen biosynthesis. Therefore, we evaluated the activity of mushroom extracts in the estrogen receptor-positive/aromatase-positive MCF-7aro cell line in vitro and in vivo. Mushroom extract decreased testosterone-induced cell proliferation in MCF-7aro cells but had no effect on MCF-10A, a nontumorigenic cell line. Most potent mushroom chemicals are soluble in ethyl acetate. The major active compounds found in the ethyl acetate fraction are unsaturated fatty acids such as linoleic acid, linolenic acid, and conjugated linoleic acid. The interaction of linoleic acid and conjugated linoleic acid with aromatase mutants expressed in Chinese hamster ovary cells showed that these fatty acids inhibit aromatase with similar potency and that mutations at the active site regions affect its interaction with these two fatty acids. Whereas these results suggest that these two compounds bind to the active site of aromatase, the inhibition kinetic analysis indicates that they are noncompetitive inhibitors with respect to androstenedione. Because only conjugated linoleic acid was found to inhibit the testosterone-dependent proliferation of MCF-7aro cells, the physiologically relevant aromatase inhibitors in mushrooms are most likely conjugated linoleic acid and its derivatives. The in vivo action of mushroom chemicals was shown using nude mice injected with MCF-7aro cells. The studies showed that mushroom extract decreased both tumor cell proliferation and tumor weight with no effect on rate of apoptosis. Therefore, our studies illustrate the anticancer activity in vitro and in vivo of mushroom extract and its major fatty acid constituents.

Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines.

Herbal medicines are often combinations of botanical extracts that are assumed to have additive or synergistic effects. The purpose of this investigation was to compare the effect of individual botanical extracts with combinations of extracts on prostate cell viability. We then modeled the interactions between botanical extracts in combination isobolographically. Scutellaria baicalensis, Rabdosia rubescens, Panax-pseudo ginseng, Dendranthema morifolium, Glycyrrhiza uralensis and Serenoa repens were collected, taxonomically identified and extracts prepared. Effects of the extracts on cell viability were quantitated in prostate cell lines using a luminescent ATP cell viability assay. Combinations of two botanical extracts of the four most active extracts were tested in the 22Rv1 cell line and their interactions assessed using isobolographic analysis. Each extract significantly inhibited the proliferation of prostate cell lines in a time- and dose-dependent manner except S. repens. The most active extracts, S. baicalensis, D. morifolium, G. uralensis and R. rubescens were tested as two-extract combinations. S. baicalensis and D. morifolium when combined were additive with a trend toward synergy, whereas D. morifolium and R. rubescens together were additive. The remaining two-extract combinations showed antagonism. The four extracts together were significantly more effective than the two-by-two combinations and the individual extracts alone. Combining the four herbal extracts significantly enhanced their activity in the cell lines tested compared with extracts alone. The less predictable nature of the two-way combinations suggests a need for careful characterization of the effects of each individual herb based on their intended use.

Pomegranate juice, total pomegranate ellagitannins, and punicalagin suppress inflammatory cell signaling in colon cancer cells.

Phytochemicals from fruits such as the pomegranate (Punica granatum L) may inhibit cancer cell proliferation and apoptosis through the modulation of cellular transcription factors and signaling proteins. In previous studies, pomegranate juice (PJ) and its ellagitannins inhibited proliferation and induced apoptosis in HT-29 colon cancer cells. The present study examined the effects of PJ on inflammatory cell signaling proteins in the HT-29 human colon cancer cell line. At a concentration of 50 mg/L PJ significantly suppressed TNFalpha-induced COX-2 protein expression by 79% (SE = 0.042), total pomegranate tannin extract (TPT) 55% (SE = 0.049), and punicalagin 48% (SE = 0.022). Additionally, PJ reduced phosphorylation of the p65 subunit and binding to the NFkappaB response element 6.4-fold. TPT suppressed NFkappaB binding 10-fold, punicalagin 3.6-fold, whereas ellagic acid (EA) (another pomegranate polyphenol) was ineffective. PJ also abolished TNFalpha-induced AKT activation, needed for NFkappaB activity. Therefore, the polyphenolic phytochemicals in the pomegranate can play an important role in the modulation of inflammatory cell signaling in colon cancer cells.