The development of nanomaterials using green synthesis methods is gaining attention due to their potential to reduce environmental pollution and health risks associated with traditional chemical synthesis methods. Among the various transition metals, zirconia has gained significant interest as filling materials and implants in dentistry due to its excellent mechanical and chemical properties. In this study, we developed ecofriendly zirconium oxide nanoparticles using Biancaea sappan extract as a capping agent and then functionalized them with Quercetin. Further, their anti-inflammatory property and hemocompatibility were evaluated to target their application as filling materials. The biogenic zirconium oxide nanoparticles (B-ZrO2NPs) and quercetin functionalized biogenic zirconium oxide nanoparticles (BQZN) were characterized by UV–Vis Spectroscopy (UV–Vis), Fourier Transform Infrared Spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy X-ray analysis (EDX). B-ZrO2NPs showed maximum absorbance at 267nm and 383nm. FTIR showed characteristic stretching at 3381cm−1−1, confirming the O–H group in the extract and Quercetin used for BQZN formation. The FTIR spectra of BQZN displayed the presence of the characteristic peaks observed in the spectra of B-ZrO2NPs and Quercetin. The broad XRD pattern confirmed the amorphous nature of the zirconia. SEM revealed the spherical morphology of B-ZrO2NPs and BQZN with a size range of around 90nm and 120nm, respectively. EDAX of BQZN revealed the presence of 45.7wt.% Zr, 32.9% oxygen and 21.4% of carbon. In vitro bioactivity studies revealed that BQZN exhibited significant anti-inflammatory activity, as evidenced by the inhibition of protein denaturation. The nanoparticles were also demonstrated for their hemocompatibility with erythrocytes. These findings highlight the potential of BQZN as a promising hemocompatible dental filling with significant anti-inflammatory properties. Further in-depth in vivo studies are required to fully understand their efficacy and toxicity.
Inflammation is a critical defense mechanism that mainly occurs in the human body through arachidonic acid metabolism and is needed to maintain a healthy life, but uncontrolled inflammation leads to several diseases like asthma, osteoarthritis, etc. Machilus macrantha is an important Indian medicinal plant that is traditionally used as an anti-inflammatory, anti-rheumatic agent but has yet to be explored much. Hence, this study has been undertaken to elucidate the molecular mechanisms underlying its anti-inflammatory activity by using network pharmacology and molecular modeling studies. Several free online tools and databases like SEA, Swiss target prediction, OMIM, GeneCards, Venny 2.1.0 and STRING were utilized to predict, compile and filter the anti-inflammatory targets and a total of 23 targets were obtained throughout the process. Further, by using the topology parameters (degree, betweenness and closeness) in Cytoscape 3.10.0 software, a total of five hub nodes or genes named PTGS2, NFkβkβ1, MAPK1, CYP2C8 and CYP2C9 were identified which is mainly associated with arachidonic acid metabolism. KEGG and GO analyses were performed by using the SRplot tool and it was observed that arachidonic acid metabolism emerged as the top pathway with the lowest P-value and highest fold enrichment. The tissue enrichment studies of the hub genes were also performed using the Human eFP Browser. Finally, a ligand-target-pathway interaction network was created, which proved that the phytoconstituents of M. macrantha interact with multiple molecular targets of arachidonic acid metabolism and showed anti-inflammatory activity. Molecular docking and molecular dynamics simulation studies proved that a total of three ligands named machigline, machiline and quercetin exhibited moderate to good binding affinities toward the hub genes and machigline and quercetin showed stability in the binding cavity. From the present study, it can be concluded that the phytocompounds of M. macrantha have significant interactions with anti-inflammatory targets specifically on arachidonic acid metabolism, hence the same can act as an important source for developing novel anti-inflammatory agents.
The leaf of Strobilanthes cusia (Acanthaceae), popularly known as Da-Ching-Yeh, has been commonly used in traditional Chinese medicine. It is used for influenza, epidemic cerebrospinal meningitis, encephalitis B, viral pneumonia and mumps. It is also used to treat sore throat, aphthae and inflammatory diseases with redness of skin, etc. In this study, we evaluated the antinociceptive, anti-inflammatory and antipyretic effects of methanol extract of Strobilanthes cusia leaf. The results showed that the extract significantly inhibited the writhing responses of mice and decreased the licking time on both the early and late phases of the formalin test in a dose-dependent manner. It also reduced the paw edema induced by carrageenan in rats. In addition, it potently attenuated pyrexia induced by lipopolysaccharide.
CML-1 is a purified extract from a mixture of 13 Oriental herbs (Achyranthis Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex, Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori Graminei Rhizoma) that have been widely used for the treatment of inflammatory diseases in Asia. The aim of this study was to investigate the anti-inflammatory and analgesic potential of CML-1. The animals used in this study were administered either vehicle or CML-1 (30, 100, 300 and 600 mg/kg) orally. The vascular permeability induced by acetic acid was significantly reduced by CML-1 in all doses. The swelling of the rat's hind paw induced by carrageenan was significantly inhibited by CML-1 in doses of 100, 300 and 600 mg/kg. In the case of rheumatoid arthritis induced by complete Freund's adjuvant in rats, the treatment with CML-1 at a dose level of 300 mg/kg inhibited edema. CML-1 at a dose level of 600 mg/kg inhibited acetic acid-induced writhing syndrome, however it did not have any anti-nociceptive action in the Randall-Selitto assay or the hot plate test. Our findings suggest that CML-1 has a potent anti-inflammatory activity.
Neoandrographolide, one of the principal diterpene lactones, isolated from a medicinal herb Andrographis paniculata Nees, was tested in vivo and in vitro for its anti-inflammatory activities and mechanism. Oral administration of neoandrographolide (150 mg/kg) significantly suppressed ear edema induced by dimethyl benzene in mice. Oral administration of neoandrographolide (100–150 mg/kg) also reduced the increase in vascular permeability induced by acetic acid in mice. In vitro studies were performed using the macrophage cell line RAW264.7 to study the effect of neoandrographolide on suppressing phorbol-12-myristate-13-acetate (PMA)-stimulated respiratory bursts and lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-α). Respiratory bursts were quantified by chemiluminescence (CL) measurements.Results showed that neoandrographolide suppressed PMA-stimulated respiratory bursts dose-dependently from 30 μM to 150 μM. Neoandrographolide also inhibited NO and TNF-α production in LPS-induced macrophages, contributing to the anti-inflammatory activity of A. paniculata. These results indicate that neoandrographolide possesses significant anti-inflammatory effects, which implies that it would be one of the major contributing components to participate in the anti-inflammatory effect of A. paniculata. and a potential candidate for further clinical trial.
Armillariella mellea (AM), also known as Mi-Huan-Ku, a popular medicinal fungus used in the traditional Chinese medicine for treating headache, neurasthenia and insomnia. In the present study, our aim was to determine the effects of aqueous (AAM) and ethanol (EAM) extracts of A. mellea on lipopolysaccharide (LPS)-induced inflammatory response by measuring the inducible nitric oxide synthase (iNOS), cyclooxygenase-1 and -2 (COX-1 and COX-2) protein expression, cytokines (TNF-α, IL-4 and IL-8) formation, nitric oxide (NO) release and prostaglandin (PGE2) production in human monocytic (THP-1) cells. At concentration of 100 μg/ml, EAM, but not AAM, effectively protected against LPS-induced cell death in THP-1 cells. At concentrations of 10~100 μg/ml, EAM showed a potent anti-inflammatory activity as demonstrated by a dose-dependent inhibition of LPS (1 μg/ml)-induced release of NO and PGE2, and significantly decreased the transcription of proinflammatory cytokines. EAM at 100 μg/ml significantly blocked the LPS induction of iNOS and COX-2 expression, but not COX-1. Therefore, the protective effect of EAM against LPS-induced inflammatory mediators release could explain, at least in part, its effectiveness in alleviating certain inflammatory related diseases.
The extract of Angelicae Dahuricae Radix has traditionally been used as an anti-noceptive remedy in China. In this study, the methanol extract of Angelicae Dahuricae Radix (MEAD) was evaluated to determine if it has anti-noceptive and anti-inflammatory action. The anti-nociceptive activities of MEAD were evaluated by determining the writhing response and sleeping time, as well as by a formalin test. In addition, the anti-inflammatory activities of MEAD were evaluated by a vascular permeability test as well as by measuring the carrageenan-induced paw edema and conducting a myeloperoxidase (MPO) assay. MEAD (600 and 1200 mg/kg) exhibited anti-inflammatory effects on acetic acid-induced vascular permeability, carrageenan-induced paw edema, and MPO activity. Moreover, the results of the formalin test, the acetic acid-induced writhing response and the pentobarbital-induced sleeping time indicated that MEAD had anti-nociceptive effects that occurred in a concentration-dependent manner. To determine the mechanism by which MEAD exerted its effects on the expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO) by treated murine macrophage RAW 264.7 cells was evaluated. Similar to the in vivo activities, both the iNOS expression and NO production were significantly suppressed by MEAD in a dose-dependent manner. Furthermore, MEAD inhibited the activating phosphorylation of ERK1/2. These results provide a scientific basis that explains the mechanism by which Angelicae Dahuricae Radix relieves inflammatory pain.
In order to explore the anti-inflammatory effects of Nodosin from Isodon serra, a traditional Chinese herb medicine, mouse T lymphocytes were incubated with Nodosin. In the current study, Nodosin suppressed the overproduction of the T lymphocytes; moreover, cell mitosis cycle was modulated by interfering with DNA replication in G1 stages via inhibition of IL-2 cytokine secretion at the mRNA level by Nodosin. Interestingly, Xylene-induced mouse tumescence model results suggested Nodosin depressed the murine ear-swelling extent and the level of IL-2 in the blood serum. Finally, Nodosin possessed significant anti-inflammatory effects and is a potential candidate for further clinical trial.
Lobelia chinensis Lour (LcL) is a popular herb that has been widely used as folk medicine in China for the treatment of fever, lung cancer, and inflammation for hundreds of years. Recently, several studies have shown that the anti-inflammatory properties were correlated with the inhibition of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) from the NF-κB pathway. The aim of this study was to evaluate the anti-oxidative and anti-inflammatory activities of L. chinensis. Both suppressive activities on LPS-induced nitric oxide production in RAW264.7 macrophages in vitro and the acute rat lung injury model in vivo were studied. The results showed that the methanol extract of LcL and its fractions within the range of 62.5–250 μg/mL did not induce cytotoxicity (p < 0.001). The ethyl acetate fraction of LcL showed better NO inhibition activity than other fractions. On the other hand, the Lc-EA (62.5, 125, 250 mg/kg) pretreated rats showed a decrease in the pro-inflammatory cytokines (TNF-α, IL-β, IL-6) and inhibited iNOS, COX-2 expression through the NF-κB pathway. These results suggested that L. chinensis exhibited an anti-inflammatory effect through the NF-κB pathways.
Medicinal plants have played a major role as a functional food and pharmacological source of active substances. Barley grass (BG) is young green barley leaves. It is the young grass of the common barley plant Hordeum vulgare L. of the family Poeaceae (Graminae). It is a type of green grasses, and the only vegetation on the earth that can supply sole nutritional support from birth to old age. It contains a wide spectrum of vitamins, minerals, as well as eight essential amino acids that we must get from our diets. BG possesses several pharmacological activities as anticancer activity, anti-oxidant activity and anti-inflammatory activity. It has been argued that BG helps blood flow, digestion and general detoxification of the body. The major pharmacologic interest of BG is its use in the treatment of chronic diseases. The beneficial effects observed in chronic disease may be related to bioactive compounds contained in BG such as superoxide dismutase (SOD) and bioflavonoids (lutonarin and saponarin). Thus, this paper is focused on the various studies that emphasize the therapeutic potential of BG in the prevention and treatment of chronic diseases.
Astragalus membranaceus is a major medicinal herb commonly used in many herbal formulations in the practice of traditional Chinese medicine (TCM) to treat a wide variety of diseases and body disorders. Among its diversified clinical applications, the potential use of this herb and its chemical constituents in treatments of inflammatory diseases and cancers has been actively investigated in recent years. Astragalus-based treatments have demonstrated significant amelioration of the toxicity induced by other concurrently administered orthodox drugs (e.g., immunosuppressants and cancer chemotherapeutics). The major components of Astragalus membranaceus are polysaccharides, flavonoids, and saponins. Contemporary use of Astragalus membranaceus mainly focuses on its immunomodulating, anti-oxidant, and anti-inflammatory, as well as anticancer effects. In this paper, we summarize the properties of Astragalus membranaceus and its major constituents in the biological system based on experimental and clinical studies. The antitumorigenic mechanisms of a novel Astragalus saponins extract called AST in treating various gastrointestinal cancers are highlighted. We discuss in detail how the Astragalus herb and AST influence the immune system, modulate various cancer signaling pathways, and interact with specific transcription molecules during protection against gastrointestinal inflammation and cancers. This information could help clinicians and scientists develop novel target-specific and effective therapeutic agents that are deprived of major systemic side effects, so as to establish a better treatment regimen in the battle against inflammatory diseases and cancers of the gut.
Inflammatory diseases of the periodontal tissues are known health problems worldwide. Therefore, anti-inflammatory active compounds are used in oral care products to reduce long-term inflammation. In addition to inducing inflammation, pathogen attack leads to an increased production of reactive oxygen species (ROS), which may lead to oxidative damage of macromolecules. Magnolia officinalis L. bark extract (MBE) has been shown to possess antioxidant and anti-inflammatory potential in vitro. In the present study, the influence of MBE-fortified chewing gum on the resistance against lipopolysaccharide (LPS)-induced inflammation and oxidative stress of oral epithelial cells was investigated in a four-armed parallel designed human intervention trial with 40 healthy volunteers. Ex vivo stimulation of oral epithelial cells with LPS from Porphyromonas gingivalis for 6h increased the mRNA expression and release of the pro-inflammatory cytokines IL-1αα, IL-ββ, IL-8, MIP-1ββ, and TNFαα. Chewing MBE-fortified gum for 10min reduced the ex vivo LPS-induced increase of IL-8 release by 43.8 ±± 17.1% at the beginning of the intervention. In addition, after the two-week intervention with MBE-fortified chewing gum, LPS-stimulated TNFαα release was attenuated by 73.4 ±± 12.0% compared to chewing regular control gum. This increased resistance against LPS-induced inflammation suggests that MBE possesses anti-inflammatory activity in vivo when added to chewing gum. In contrast, the conditions used to stimulate an immune response of oral epithelial cells failed to induce oxidative stress, measured by catalase activity, or oxidative DNA damage.
The aim of the present review is to comprehensively outline the botanical description, traditional uses, phytochemistry, pharmacology and toxicology of Patrinia, and to discuss possible trends for the further study of medicinal plants from the genus Patrinia. The genus Patrinia plays an important role in Asian medicine for the treatment of erysipelas, conjunctival congestion with swelling and pain, peri-appendicular abscesses, lung carbuncle, dysentery, leucorrhea, and postpartum disease. More than 210 chemical constituents have been isolated and identified from Patrinia plants, especially P. scabiosaefolia Fisch., P. scabra Bunge, P. villosa Juss., P. heterophylla Bunge and P. rupestris(Pall.) Juss.. Of these compounds, triterpenoids and saponins, iridoids, flavonoids, and lignans are the major or active constituents. Both in vitro and in vivo studies have indicated that some monomer compounds and crude extracts from the genus Patrinia possess wide pharmacological activities, including antitumor, anti-inflammatory, antibacterial, and antiviral effects. In addition, they have been shown to have valuable and positive effects on the immune and nervous system in experimental animals. There are also some reports on the clinical uses and toxicity of these species. However, few reports have been published concerning the material identification or quality control of Patrinia species, and the clinical uses and toxic effects of these plants are relatively sparse. More attention must be given to these issues.
Astragalus membranaceus (Fisch) Bge (Huang-Qi) is a well-known herbal medicine with tonic property and has been widely used to treat cancer and other immune disorders in China and Southeast Asia for thousands of years. Accumulating evidence suggests that Huang-Qi possesses both immune-boosting and anti-inflammatory/immune-regulatory effects clinically, leaving the mechanism elusive. Recently, we discovered that Astragaloside (ASI), a major active component of Huang-Qi, is able to increase CD45 phosphatase activity. In this paper, we reviewed the recent progress of ASIs in immunoregulatory and anti-inflammatory activities, including the induction of T-cell activation, regulation of effector/regulatory T-cell balance, enhancement of CD45 phosphatase activity, inhibition of pro-inflammatory cytokine and, NF-κκB pathway. Finally, we hypothesized that inducing interferon-γγ (IFN-γγ) activity by activating CD45 protein tyrosine phosphatase (PTPase) may be involved in the protective role of ASI in two contrary immune-associated diseases. These pharmacological properties highlight the traditional uses of Astragalus and provide a new direction for subsequent research and the clinical application of this traditional herbal.
Lilium bulbs have long been used as Chinese traditional medicines to alleviate the symptoms of various human inflammatory diseases. However, mechanisms of Lilium bulb-mediated anti-inflammatory activity and the bioactive components in Lilium bulbs remain unknown. In the present study, the anti-inflammatory activity of Lilium bulbs and the underlying mechanism of action were investigated in macrophages using Lilium bulb ethanol extracts (Lb-EE). In a dose-dependent manner, Lb-EE inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and bone marrow-derived macrophages (BMDMs) without causing significant cytotoxicity. Lb-EE also down-regulated mRNA expression of inflammatory genes in LPS-stimulated RAW264.7 cells, which included inducuble nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and tumor necrosis factor-αα (TNF-αα). Furthermore, Lb-EE markedly restored LPS-induced morphological changes in RAW264.7 cells to a normal morphology. HPLC analysis identified quercetin, luteolin, and kaempferol as bioactive components contained in Lb-EE. Mechanistic studies in LPS-stimulated RAW264.7 cells revealed that Lb-EE suppressed MyD88- and TRIF-induced NF-κκB transcriptional activation and the nuclear translocation of NF-κκB transcription factors. Moreover, Lb-EE inhibited IKKαα/ββ-induced activation of the NF-κκB signaling pathway and IKK inhibition significantly reduced NO production in LPS-stimulated RAW264.7 cells. Taken together, these results suggest that Lb-EE plays an anti-inflammatory role by targeting IKKαα/ββ-mediated activation of the NF-κκB signaling pathway during macrophage-mediated inflammatory responses.
Inflammatory macrophages stimulated by LPS disrupt homeostasis in the production of inflammatory cytokines and nitric oxide (NO). These are the causes of inflammation-related diseases and various cancers. The present study aimed to evaluate the protective effects of Korean ginseng berry extract (KGB) on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophage cells. NO and prostaglandin E2 (PGE2)2) production was elevated in response to LPS stimulation and was dose-dependently reduced by pretreatment with KGB. The expression levels of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNA and protein were also reduced by KGB treatment. KGB treatment significantly suppressed the LPS-induced gene expression and production of cytokines, including interleukin (IL)-1ββ, IL-6, and tumor necrosis factor-αα (TNF-α)α). Furthermore, KGB inhibited the translocation of nuclear expression of nuclear factor-kappa B (NF-κκB) by preventing inhibitory factor-kappa B (IκκBα)α) phosphorylation and suppressing the phosphorylation of extracellular signal-related kinase (ERK1/2), c-Jun N-terminal kinase (JNK), and p38. Additionally, decreased reactive oxygen species (ROS) generation and increased glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities were observed following KGB treatment. Taken together, these results indicated that KGB possesses anti-inflammatory and anti-oxidant effects, mediated by the inhibition of the mitogen-activated protein kinases (MAPKs) signaling pathway in LPS-induced RAW264.7 macrophages. KGB may represent a potential therapeutic agent for inflammatory and oxidative stress-related diseases.
Ginkgolic acids (GAs) are distinctive secondary metabolites of Ginkgo biloba (G. biloba) primarily found in its leaves and seeds, with the highest concentration located in the exotesta. GAs are classified as long-chain phenolic compounds, and exhibit structural similarities to lignoceric acid. Their structural diversity arises from variations in the length of side chains and their number of double bonds, resulting in six distinct forms within G. biloba extracts (GBE). Of these, GA (C15:1) is the most prevalent. As inhibitors of SUMOylation, GAs demonstrate significant antitumor activity, and can exert antineoplastic effects through multiple pathways, which positions them as potentially promising therapeutic agents for cancer treatment. Additionally, GAs exhibit notable anti-inflammatory, antibacterial, and antiviral properties, highlighting their multifaceted medicinal potential. Although the pharmacological properties of GAs have been extensively investigated, the associated risks of liver and kidney damage must not be overlooked. GAs can induce significant hepatic damage by promoting cellular apoptosis, oxidative stress, and the disruption of various metabolic processes. Furthermore, a limited number of studies have indicated that GAs may exhibit nephrotoxicity, as well as adverse effects on the skin and nervous system. Due to their recognized toxicity, the concentration of GAs is typically regulated to within 5ppm in the standardized G. biloba leaf extract EGb 761. Currently, there is no definitive evidence supporting the mutagenic toxicity of GAs. This review primarily synthesizes recent advancements in understanding the pharmacological and toxicological effects of GAs, along with their underlying mechanisms. It is anticipated that this review will stimulate scholarly discourse and elicit valuable insights.
Autogen Obtains Australian Patent for Obesity Gene.
Prima Biomed Adds to its Anti-inflammatory IP Portfolio.
Nicholas Piramal’s First NCE Patent Filed.
Advanced Ocular Systems Offered AusIndustry Commercial Ready Grant.
Australia's Medivac Collaborates with Germany's Logmed Technologie.
Genetic Technologies Partners with MetaMorphix.
Phylogica and Garvan Collaborate on Phylomer Development.
Sydney Scientists Discover and License Breakthrough Anti-inflammatory Treatment.
Zenyth Announces In-Licensing Agreement from Ludwig Institute for Cancer Research.
Japan's Bioventures Today: Oxygenix Co Ltd.
Edwards Lifesciences Breaks Ground on New Heart Valve Manufacturing Facility in Singapore.
Illumina in Singapore.
Leading Singapore Insurer, NTUC Income, to Provide Insurance Policy for CordLife Customers.
MDS Sciex Opens Manufacturing Facility in Singapore.
INDIA – Lack of access to technology ‘hampers detection of substandard drugs’.
JAPAN – Daiichi Sankyo announces development of nucleic acid treatment for Duchenne muscular dystrophy utilizing proprietary technology.
SINGAPORE – IBN creates unlimited source of human kidney cells.
SINGAPORE – Dyesol and Singapore's NTU sign agreement.
THE PHILIPPINES – Global biotech/GM crop plantings increase 100-fold from 1996.
AUSTRALIA – Phosphagenics further expands pain portfolio.
AUSTRALIA – Primary Health Care signs Australia distribution agreement for iGeneScreen™ prenatal test.
AUSTRALIA – Folic acid in pregnancy linked with reduced autism risk.
AUSTRALIA – Phylogica and Bio-Link collaborate to commercialize anti-inflammatory Phylomers.
AUSTRALIA – ABRAXANE® plus gemcitabine improves survival in Phase III study of patients with advanced pancreatic cancer.
CANADA – Verisante Technology, Inc. announces first sales of aura, a revolutionary medical device for the detection of skin cancer.
EUROPE – Project eyes robust medical technology for poor countries.
UNITED KINGDOM – Asthma sufferers have more lung fungi.
UNITED KINGDOM – Pioneering drug discovery gets major funding to move to next stage.
UNITED STATES – Gilead's sofosbuvir for hepatitis C meets primary endpoint in fourth pivotal Phase III study.
UNITED STATES – Eleven Biotherapeutics publishes data on EBI-005, a novel IL-1 inhibitor protein for topical treatment of dry eye disease.
UNITED STATES – Phase I/II trial of ADXS-HPV in anal cancer conducted by Brown University Oncology Group.
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